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i notes

Ophthalmology PG Exam Notes


1st Edition

CORNEA
Dhaval Patel
MD (AIIMS)
I notes
(Ophthalmology PG Exam Notes)

Dhaval Patel MD (AIIMS)


drdpatel87@gmail.com

by inotesforPG.blogspot.com
1st edition, February 2014

This is a compilation effort from my preparation notes and other sources, thus
any contributions or comments are welcomed in the effort to improve this book.
Therefore, feel free to e‐mail me at
drdpatel87@gmail.com
I notes

(Ophthalmology PG Exam Notes)

Thank you GOD

This manual is collection of the notes I made, found in books or internet while
studying for the Final MD exams for ophthalmology.

I have segregated topics just like book chapters to find them back easily. Though these all
might be far less then other preparation notes available, I am proud of what I have made
and I feel nice to present them to my upcoming ophthalmology friends.

Good luck!

-Dhaval Patel MD
drdpatel87@gmail.com
February 2014
I notes CORNEA Dhaval Patel MD

CORNEA
Evaluation of the Cornea and External Eye ........................................................... 4

DD in Cornea ................................................................................................15

Eye Banking .................................................................................................26

Diseases of the Lid .........................................................................................32

Disorders of Tear Production ............................................................................36

Conjunctival Tumors ......................................................................................42

Conjunctivitis ...............................................................................................43

Developmental Abnormalities of Cornea ..............................................................65

Noninflammatory Ectatic Disorders ....................................................................69

Keratoconus .................................................................................................72

Iridocorneal Endothelial Syndrome ....................................................................79

Corneal and Conjunctival Degenerations .............................................................81

Corneal Dystrophy .........................................................................................88

PUK ...........................................................................................................99

Corneal Infections ....................................................................................... 100

Pterygium.................................................................................................. 116

Corneal Complications of Intraocular Surgery ..................................................... 120

Mechanical Injury ........................................................................................ 124

Chemical Injuries of the Eye .......................................................................... 126

Keratoplasty .............................................................................................. 133

Keratoprosthesis ......................................................................................... 186

Ocular Surface Transplantation ....................................................................... 193

Amniotic membrane Transplantation ................................................................ 202

Refractive Surgery ....................................................................................... 205

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Evaluation of the Cornea and External Anterior Corneal Dystrophies


Eye Stromal Dystrophies
Examination of the Lids Descemet's Membrane and Endothelial
Tear Film Evaluation Dystrophies
Corneal Diagnostic Techniques PUK
Keratometry and Topography Corneal Infections
Specular Microscopy Herpes Simplex Keratitis
Confocal Microscopy Acanthamoeba Keratitis
High-Resolution Ultrasound Bacterial Keratitis (lecture notes)
ASOCT Fungal Keratitis (lecture notes)
DD in Cornea Viral Keratitis (Lecture notes)
Congenital Corneal Opacities Akanthamoeba Keratitis (lecture notes)
Peripheral Corneal Disease Stages of Corneal Ulcer
Corneal Ulcer Pterygium
Corneal Edema Corneal Complications of Intraocular
Corneal Deposits Surgery
Red Eye Aphakic/Psudophakic bullous
Eye Banking keratopathy
Corneal Storage Media Brown-McLean syndrome
Diseases of the Lid TASS
Anatomic Abnormalities Mechanical Injury
Blepharitis Chemical Injuries of the Eye
Meibomian Gland Dysfunction Acid Injury
Disorders of Tear Production Alkali Injuries of the Eye
Conjunctival Tumors Autologous Serum Eyedrops
Squamous Neoplasms of the Conjunctiva Keratoplasty
Conjunctivitis Decision-Making in Keratoplasty
Bacterial Conjunctivitis Penetrating Keratoplasty
Viral Conjunctivitis Femtosecond Laser-assisted Penetrating
Chlamydial Infections Keratoplasty
Ophthalmia Neonatorum Keratoplasty Suturing Techniques
Parinaud's Oculoglandular Syndrome Intraoperative Complications of
Allergic Conjunctivitis Penetrating Keratoplasty
Giant Papillary Conjunctivitis Postoperative Management
Cicatricial Pemphigoid Early Postoperative Complications
EM, SJS & TEN Postkeratoplasty Astigmatism
Toxic Conjunctivitis Corneal Allograft Rejection
Superior Limbic Keratoconjunctivitis Infections after Penetrating
Ligneous Conjunctivitis Keratoplasty
Conjunctivochalasis Retrocorneal Membranes
Developmental Abnormalities of Cornea Glaucoma after Penetrating
Anomalies of Size and Shape Keratoplasty
ARS and PA Pediatric Penetrating Keratoplasty
Noninflammatory Ectatic Disorders Large-Diameter Corneal Grafts
Keratoconus PK in Herpes Simplex Disease
Management High-Risk Penetrating Keratoplasty
Iridocorneal Endothelial Syndrome Anterior Lamellar Keratoplasty
Corneal and Conjunctival Degenerations Endothelial Keratoplasty
Corneal Dystrophy Management of Corneal Perforations
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Therapeutic Lamellar Keratoplasty Refractive Surgery


Therapeutic Keratoplasty Patient Evaluation and Selection
Surgical Management of Superficial Topographic Analysis
Corneal and Conjunctival Disease Incisional Corneal Surgery
Phototherapeutic Keratectomy Onlays and Inlays
Conjunctival Flaps Photoablation
Iris Reconstruction Surgery Collagen Shrinkage
Keratoprosthesis C3R
Postoperative Management of All FemtoSecond Sx
Keratoprosthesis INTRACOR
Ocular Surface Transplantation Intraocular Surgery
Limbal Stem Cell Deficiency
Amniotic membrane Transplantation
Prokera

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Evaluation of the Cornea and External Eye

Examination of the Lids


 History of Patient

 Dermatologic Examination

 Eyelid Position: ectropion and entropion, Floppy Eyelid Syndrome

 Tear Meniscus and Puncta

 Anterior Eyelid: A collarette, which forms in areas of inflammation or


hyperkeratinization, is simply mucous debris, Lice, Demodex

 Posterior Eyelid

 Meibomian Gland Expression: normal diameter of each dome is 0.5–0.7 mm, The volume
of lipid is increased if any of the lipid domes are 0.8 mm or larger; this finding is sufficient
to diagnose seborrheic meibomian gland dysfunction viscosity and opacity of the
expressed lipid are important signs

 After instilling lissamine green, rose Bengal or fluorescein onto the ocular surface, a
visible line of demarcation, called the Marx line, is often apparent on the lid margin. This
line is thought to represent the mucocutaneous junction, and anterior displacement
relative to the meibomian gland orifices may correlate with gland dysfunction.

 Meibomian Gland Imagery: The most obvious change seen with transillumination is gland
dropout. Dropout is associated with obstructive meibomian gland dysfunction and is not
associated with infectious blepharitis, allergic phenomenon, or seborrheic meibomian
gland dysfunction.

Tear Film Evaluation


 General Inspection: Alterations in the eyelid structure

 Inferior marginal tear strip: normally about 0.5 mm in width and has a concave upper
aspect. If this strip is thin (<0.25mm) or discontinuous, it is evidence of deficient aqueous
tear volume.

 Tear Stability:

o The interval between the last complete blink and the appearance of the first
random dry spot is the break-up time (BUT). Normally 10–30 seconds. Values of
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less than 10 seconds are considered abnormal. Seen in aqueous tear deficient and
in evaporative dry eye.

o Noninvasive BUT that employs reflective devices with a grid projected onto the
corneal surface.

o Video-recorded BUT: Values below 7 seconds are considered abnormal and


reflective of the presence of dry eye disease.

o Ocular Protection Index (OPI): OPI = BUT/IBI. Values below 1 are characteristic of
tear film instability and dry eye disease. Blink rate, which is calculated by dividing
60 by the number of observed blinks per second. (IBI: Inter-Blink Interval)

 Tear Production

o Schirmer's test: Schirmer's II (with anesthesia) has been purported to measure


‘basal’ tear secretion, i.e. nonstimulated tears. Values below 5.5 mm of wetting
are diagnostic of aqueous tear deficiency.

o A Schirmer's I (without anesthesia) has become the generally accepted method


for assessing aqueous tear production.

o Without anesthesia, wetting of less than 15 mm indicates dry eyes, and less than 5
mm indicates very severe dry eyes.

o The phenol red test: phenol red impregnated cotton thread is inserted over the
inferior lid margin into the temporal conjunctival sac. At the end of 15 seconds,
the dye, which is pH sensitive, turns color from yellow to orange, indicating the
length of the thread wetted by tears. This test has been reported to be less
uncomfortable and more specific in the diagnosis of aqueous tear-deficient dry eye
disease.

 Tear Composition and Characteristics

o tear lysozyme levels are decreased in aqueous tear-deficient dry eye disease

o tear protein lactoferrin: Touch MicroAssay,

o Tear ferning: normally there is crystalline pattern of tear mucin. In aqueous tear
deficiency, this pattern resembles ferns

Ocular Ferning Test: Crystallization of a drop of tear fluid on a glass slide at room
temperature. (DES display type III and IV pattern)

o Tear osmolarity: single diagnostic test with the highest accuracy in identifying
patients with dry eye disease. Cutoff- 316mOsm (DEWS Report)

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 Meibomian Gland Structure and Excreta

o Expression of Meibum

o transillumination of the eyelid

 Tear Clearance Tests

o Dye dilution studies: concentration of the dye is measured over time.

o Fluorescein Clearance Test [FCT]:

o This tear function index (TFI) is the ratio of the value of the Schirmer's test over
the tear clearance rate. The use of the TFI in the diagnosis of dry eye disease is
reported to demonstrate a specificity of 91% and a sensitivity of 79%.

 Staining of the Ocular Surface

o Fluorescein, which stains damaged epithelial cells, is best visualized on the corneal
surface.

o Staining of the conjunctiva is seen when there are disruptions in the protective
mucin coating; RB and LG are used.

 Tests of visual function

o tear stability analysis system (TSAS), serial videokeratographic images are


collected each second between blinks.

o functional visual acuity (FVA) device has been developed which measures visual
acuity by way of rapid presentation of optotypes.

Corneal Diagnostic Techniques


 Corneal Staining

o Fluorescein and rose Bengal: both dyes can stain living cells, rose Bengal does so
more effectively and is intrinsically toxic. healthy preocular tear film will block
rose Bengal staining of healthy and damaged cells. Cell degeneration or death
increases membrane permeability to both dyes, but rose Bengal diffusion into the
stroma is limited. Fluorescein stains BM of epithelial defect, while RB stains dead
epithelial cells even without epithelial defect.

o Lissamine green: better tolerated than rose Bengal.

 Pachymetry

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o thinnest part of the cornea is usually located about 1.5 mm temporal to the
center of the cornea

o Mean thickness is 515 µm in the central cornea.

o cornea with a central thickness greater than the thickness in the midperipheral
should be considered suspicious for endothelial dysfunction centrally or thinning in
the midperiphery

o If the intraocular pressure is normal, epithelial edema develops when the stroma
has swollen about 40%, to a corneal thickness greater than 700 µm.

o corneal striae become visible at 4–8%, folds are seen at 11–12% swelling, and loss of
transparency can occur at greater than 20% swelling.

o Techniques for measuring CCT include optical pachymetry, ultrasound pachymetry,


confocal microscopy, ultrasound biomicroscopy, optical ray path analysis or
scanning slit corneal topography, and optical coherence tomography.

 Aesthesiometry

o cotton-tipped swab

o Cochet-Bonnet aesthesiometer: 6.0 cm-long adjustable nylon monofilament,


Measurements are taken by advancing nylon filament smoothly and perpendicularly
toward the center of the cornea. Contact is detected by the slightest bend of the
nylon; sensitivity is measured as the length of the filament that gives a 50%
positive response from a minimum of four stimuli. The normal cutoff is 4.5 cm,
and measurements below this are compatible with decreased sensation.

o jet of warm saline

o noncontact air puff technique

o Ocular sensitivity is greatest in the central cornea except in elderly patients, in


whom the peripheral cornea is the most sensitive.

Keratometry and Topography

 1619, Father Christopher Scheiner observed that shiny glass spheres of different radii
produced reflected images of different sizes

 Ramsden later added a magnification system and also introduced the doubling device

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 1854, Helmholtz extended this work and constructed a complex instrument that he called
an ophthalmometer.

 1881, Javal and Schiotz introduced a simplified ophthalmometer  keratometer

 P = 0.3375/r

 Principle:

o Anterior corneal surface to behave like a convex mirror and reflect light. The
optical design of the keratometer allows the examiner to measure the size of the
reflected image and thereby determine the radius of curvature of the anterior
corneal surface.

 Limitations:

o assumes that the mires are measuring an area directly over the pupil.

o assumption that the cornea has a sphero-cylindrical surface with a single radius of
curvature in each meridian and a major and minor axis separated by 90 degrees.

o no information about areas central or peripheral to the points measured

o only analyzes approximately 6% of the corneal surface

 Series of instrument developments that began with the keratoscope, followed by the
photokeratoscope, and finally the videokeratoscope now called the corneal
topographer.

Keratoscopy

 Cuignet first described the technique of keratoscopy in the 1820

 Henry Goode described the first keratoscope in 1847

 Antonio Placido was the first to photograph the corneal reflections of a series of
illuminated concentric rings in the 1880s.

 In 1896, Gullstrand was the first to quantitatively analyze photokeratoscopic images of


the cornea.

 evaluate about 70% of the total corneal area (limited by the optics of the reflecting
system itself)

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 Types

o flat-target keratoscope: rings of the target are located in the same plane

o Collimating keratoscope: rings in different planes along the interior of a column


and in this way are able to maximize the amount of corneal surface that can
reflect the target mires

 Limitation

o to produce an obviously distorted image, the cornea must be quite distorted itself

o astigmatism of at least 3 diopters (D) must be present to be detected by


traditional keratoscopy.

Videokeratoscopy = Topography

 Klyce in 1984: union of rapid computer analysis and digital video

 Two approaches are in general use currently: the Placido disk or reflection-based
topographers, and the scanning slit-based tomographers.

o Placido disk-based topographers:

 vast majority of the older units

 transilluminated cone acting as a modified Placido ring

 Most systems can be divided into ‘near-design’ and ‘distant-design.’

 sensitive to disruptions in the tear film

o Slit scanning tomography

 elevation of each surface can be measured directly with slit beam


technology

 The PAR CTS (PAR Technology, New Hartford, NY) was the first ‘topography
system’ to produce a true topographic map, using elevation data from the
corneal surface.

 Bausch & Lomb Orbscan: Orbscan is a hybrid system – both a topographer


and a tomographer – that uses Placido disk technology to display
conventional corneal topography. Is is limited in its ability to reliably
measure the postoperative posterior cornea, the Oculus Pentacam had
greater success in this area.

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 Oculus Pentacam uses a scanning slit but with Scheimpflug optics, which
increases the depth of focus. In doing so, simultaneous imaging of the
cornea, lens, and iris is possible; this permits corneal, anterior chamber,
and lens geometry to be imaged and analyzed.

 Zeimer Galilei, also a Scheimpflug imaging device, has similar advantages


with regard to image registration and measurement of the posterior corneal
surface.

 The main uses of corneal topography

o Preoperative evaluation to rule out certain corneal abnormalities, establish


refractive stability, determine whether the patient's corneal shape will allow
surgery to be performed safely, and determine whether the surgical outcome is
likely to allow acceptable visual performance.

o Operative assessment to determine surgical parameters, plan complicated ‘re-op’


cases, and input data for customized ablations.

o Postoperative evaluation to monitor the surgeon's and laser's performance.

o Aid in the calculation of IOLs for patients who have undergone refractive surgery.

 Presentation Methods

o Color-coded maps: The ‘warmer’ colors represent higher dioptric powers (steeper
curvatures), while the ‘cooler’ colors are used to represent the lower dioptric
powers (flatter curvatures). Similar color-coded maps can be used to present
changes in elevation.

 topographies of fellow eyes tend to be mirror images of each other: enantiomorphs

 The Universal Standard Scale has been adopted by the ANSI standard on corneal
topography.

 Axial = sagital Curvature Maps: The cornea has a prolate shape, so power is higher in the
center than in the periphery.

 Refractive Power Map: normal cornea will have a higher calculated power peripherally
than in the center. This is due to the natural residual spherical aberration of the cornea.

 Instantaneous or Tangential Power Map: not recommended for routine clinical use,
extremely useful in the demonstration and measurement of the optical zone size in
modern refractive surgery as they emphasize transition zone power changes

 Difference Maps: Progression of keratoconus

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 Elevation Maps: Commonly, the best-fitting sphere or toroidal surface is subtracted from
the elevation data. Posterior elevation values can be used to distinguish normal and
keratoconic corneas, but posterior elevations are not sensitive enough a measure to
separately classify forme fruste keratoconus and normal corneas.

 Pachymetric Maps: thinnest areas of the corneal stroma are generally inferotemporal to
the fixation-reflex

o Simulated Keratometry: power derived from the corneal topography.

o Surface Regularity Index (SRI): irregularity of the corneal topography over the
pupil, correlated to potential visual acuity

o I-S index: introduced by Rabinowitz and McDonnell

o Contact lens warpage can mimic mild keratoconus and needs to be ruled out

Specular Microscopy

 images light reflected from an optical interface.

 confocal or nonconfocal /contact or noncontact.

 first direct visualization of the endothelium was demonstrated by Vogt in 1918

 in 1968, David Maurice described the first laboratory specular microscope that could be
used to study excised living corneas

 Optical Principles:

o Light striking a surface can be reflected, transmitted, or absorbed or


Combination of 3

o primary importance in clinical specular microscopy is the light that is reflected


specularly

o four zones of reflection can be seen  Zone 3 is the endothelial region

 Instrumentation

o Konan NonCon Robo Series (Torrance, CA)

o sequential images (Tomey, Inc., Phoenix, AZ)

o live view (HAI Labs, Inc., Lexington, MA)


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 Qualitative Specular Microscopy

o Epithelium:

o Endothelium (miscellaneous bright and dark structures)  Guttae are excrescences


of Descemet's membrane. Guttae, however, can also be seen in the far periphery
of young individuals. In this case, they are called Hassall-Henle warts.

o Endothelium: morphometry

 Quantitative Specular Microscopy

o endothelial cell density (ECD) (measured as cells/mm2), mean cell area (measured
as µm2/cell), coefficient of variation (CV) (standard deviation of cell areas/mean
cell area), and pleomorphism (usually measured as a percentage of 6, <6 or >6-
sided cells).

o The variable-frame analysis is more accurate than fixed-frame analysis because


only whole cells are counted and it is not necessary to include portions of cells
located on the frame boundary.

o Cell density alone is not the most sensitive measure of endothelial health, as the
endothelium functions even at low ECDs (under 500 cells/mm2).

o polymegathism (variation in cell area as determined by the CV) and pleomorphism


(variation in cell shape as represented by the percentage of hexagonal cells) are a
more sensitive measure of the endothelium under stress.

o The corners method

o The Center method (Konan Medical USA)

o the center-flex method

 Clinical Applications

o The ECD at which corneal edema occurs is quite variable, but has been estimated
to be between 300 and 700 cells per mm2.

o Difference between two eyes: greater than 280 cells per mm2 is abnormal

o A cornea with a CV greater than 0.40 or the presence of less than 50%
hexagonal cells should be considered abnormal and at increased risk for
postoperative edema.

o age-related cell loss is approximately 0.5% per year.

o Combined surgery is considered if CCT>600 and Specular <1000


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o The most striking abnormality in keratoconus, however, is elongation of


endothelial cells

o FDA-approved Artisan/Verisyse phakic intraocular lens (IOL) has found acceptable


mean cell loss rates of 1.8% per year after insertion to correct high myopia.

o Cell loss after PKP: 10% after 2 week, 33% at 3 months, 50 % at 1 year

o Cell loss after EK: 34% cell loss after 6 months, and 38% at 1 year

o vitreous contact mechanically injures the endothelium and interferes with its
physiologic function.

Confocal Microscopy

 The optical sectioning ability of confocal microscopy allows images to be obtained from
different depths within a thick tissue specimen, thereby eliminating the need for
processing and sectioning procedures.

 principle of Lukosz, which states that resolution may be improved at the expense of field
of view.

 In 1955, Marvin Minsky developed the first confocal microscope for studying neural
networks in the living brain

 Because both condenser and objective lenses had the same focal point, the microscope
was termed ‘confocal.’

 Because the illumination and detection of light through conjugate pinholes occurs in
tandem, this microscope was named the tandem scanning confocal microscope (TSCM).

 There are three main confocal imaging systems used clinically:

1. the TSCM

2. the HRT III (a scanning laser system)

3. the Confoscan 4 (a scanning slit system)

High-Resolution Ultrasound

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 University of Toronto: UBM

 frequency range of 25–100 MHz

 resolution ranging from 20 to 100 µm

 penetration to the 4–15-mm range.

 For diagnosis of: Corneal edema, DMD, IOL malposition, Imaging the anterior segment
behind corneal opacities, Corneal dystrophies, Peripheral corneal degenerations,
Keratoconus, Corneal Tumors, post- Keratoplasty, Refractive surgery,

ASOCT

 Fujimoto, Huang, and colleagues

 The optical delay of the reflected light is determined by interferometry to generate a


ranging measurement called the axial scan (A-scan)

 The original OCT technology is now classified as time-domain OCT (TD-OCT), in which the
reference mirror is moved through a range of delay, and the resulting inference
patterns between the sample and reference beams are processed into an axial image.

 new technology called Fourier-domain OCT (FD-OCT) has been developed. In FD-OCT, the
reference mirror is stationary and the A-scan is generated by Fourier transformation
of spectral interference patterns between the sample and reference reflections.

 5 pachymetric parameters for Keratoconus Screening:

1. minimum – median thickness < −63 µm

2. I − S < −31 µm

3. IT − SN < −48 µm

4. Minimum corneal thickness is less than 492 µm.

5. The thinnest region of the cornea is outside of the central 2-mm area.

 Keratoconus Screening, Refractive Surgery Evaluation, Corneal Power Calculation, Corneal


Opacities, Cornea Transplant, Phakic Intraocular Lenses

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DD in Cornea

Congenital Corneal Opacities

 3-6 per 100000

 STUMPED classification (Waring)

o Sclerocornea

o Tears in Descemet's membrane: Congenital glaucoma, Birth trauma

o Ulcer: Herpes simplex virus, Bacterial, Neurotropic

o Metabolic (rarely present at birth): Mucopolysaccharidoses, Mucolipidoses,


Tyrosinosis

o Posterior corneal defect: Peters’ anomaly, Posterior keratoconus, Staphyloma

o Endothelial dystrophy: Congenital hereditary, Posterior polymorphous corneal


dystrophy, Stromal: congenital stromal corneal dystrophy

o Dermoid

 Sclerocornea

o scleralization of the peripheral or the entire part of the cornea

o sporadically, familial or autosomal dominant

o bilateral but commonly asymmetric

o opacification of the cornea is smooth, white, and vascular; it appears to be an


extension of the sclera without limbal landmarks

o four groups (Waring et al)

1. Isolated peripheral sclerocornea

2. Sclerocornea plana: <38D, High Hyperopia, Shallow AC, Pseudoptosis

3. Sclerocornea associated with anterior chamber cleavage anomalies: Peter’s


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4. Total sclerocornea: the most common form causing congenital corneal


opacity,

o Histopathology in sclerocornea

1. Corneal stroma resembles sclera morphologically

2. Precise arrangement of stromal lamellae absent

3. Irregular arrangement of collagen fibers; variable in diameter

4. Collagen fibrils thickened (up to 1500 Å in diameter); resemble scleral


fibrils

5. Diameter of collagen fibrils decreases in posterior stroma

6. Changes in posterior cornea may resemble those seen in Peters’ anomaly

o somatic abnormalities such as mental retardation, anomalies of the skin, facies,


ears, cerebellum, and testes.

o DD: arcus juvenilis, interstitial keratitis, Peters’ anomaly, and microcornea

 Congenital glaucoma

o epiphora, photophobia, and blepharospasm

o first signs are elevated intraocular pressure, corneal enlargement and clouding,
and optic nerve cupping

o increased corneal diameter

o tears in Descemet's membrane can be single or multiple, and appear as elliptical,


glassy, parallel ridges on the posterior cornea, either peripherally or across the
visual axis. In congenital glaucoma these breaks have a random distribution, most
commonly horizontal or concentric to the limbus, in contrast to the oblique and
vertical orientation of the breaks in Descemet's membrane seen in birth
trauma

 Birth trauma

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o Left eyes seem to be affected more commonly than right eyes because neonates
usually present in the left-occiput-anterior position

o The Descemet's tears in birth trauma are usually unilateral, central and, in
contrast to congenital glaucoma, line up in a vertical or oblique pattern,
presumably because the tip of the forceps has slipped over the rim of the orbit and
compressed the globe vertically, stretching it horizontally to create the tears.

o corneal edema usually clears within weeks to months.

o high residual corneal astigmatism, which may range from 4 to 9 diopters, requires
urgent correction and amblyopia treatment.

 HSV Infection

o 80% HSV type 2 and 20% by type 1.

o primary ocular infection that can later become recurrent

o CNS involvement are common and are associated with significant mortality

o usually apparent within 2 days to 2 weeks

o macrodendrites, geographic epithelial defects, and punctate keratopathy.

o An oral ACV–cesarean combination provides maximal protection for the neonate.

o The treatment for neonatal HSV keratitis or conjunctivitis is intravenous aciclovir.

 Congenital rubella

o Congenital rubella infection, however, causes microphthalmia, cataract, retinitis,


iridocyclitis, corneal clouding, strabismus, nystagmus, nasolacrimal duct
obstruction, and viral dacryoadenitis.

 Bacterial corneal ulcers

o exceedingly rare in the neonate

o Gonorrheal ophthalmia neonatorum usually presents as a unilateral conjunctivitis


with an incubation period of a few hours to 2–3 days.

o Ophthalmia neonatorum caused by Chlamydia: systemic erythromycin


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o Congenital syphilis is not a cause of congenital corneal opacification.

 Neurotrophic keratitis

o Familial dysautonomia (Riley–Day syndrome)

 Metabolic diseases: They are all autosomally recessive, with the exception of
mucopolysaccharidosis type II (Hunter's syndrome), which is X-linked recessive.

o Mucopolysaccharidosis

 Hurler's syndrome (MPS I-H) or gargoylism is caused by a deficiency of alfa-


l-iduronidase and the gene involved with this error is mapped to 4p16.3.
Corneal clouding is significant and helps differentiate this disease from
Hunter's syndrome.

 Hurler's, Scheie's, Morquio's, and Maroteaux-Lamy syndromes all


demonstrate progressive corneal clouding. Hunter's and Sanfilippo's
syndromes do not demonstrate clouding grossly, but may have slit lamp
evidence of clouding at a later age.

o Mucolipidosis

 Episodic ocular pain is an important symptom in mucolipidosis type IV. It is


caused by corneal epithelial cytoplasmic accumulation of abnormal
material with subsequent corneal surface irregularities.

o Cystinosis: AR, needle-like cystine crystals in the cornea and conjunctiva is usually
seen by 1 year of age.

o Fabry's disease: sphingolipidosis caused by a lack of alfa-galactosidase A

o Tyrosinemia: type II (Richner–Hanhart syndrome) is a rare congenital error of


metabolism characterized by a triad of dendriform keratitis, hyperkeratotic lesions
of the palms and soles, and mental retardation.

 Peters’ anomaly:

o Sporadic, AR, AD

o central corneal opacity with corresponding defects in the posterior stroma,


Descemet's membrane, and the endothelium.
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o Synechiae frequently extend from the iris collarette to the edge of the
posterior corneal defect

o glaucoma 50–80%  incomplete development of angle

o bilaterally 80%, asymmetric

o Type I: Corneal opacity + iridocorneal adhesions

 systemic abnormalities are uncommon

o Type II: Corneal opacity + iridocorneal adhesions + lens abnormality (position or


transparency)

 Peters’-plus syndrome: Peters’ anomaly + short stature, brachymorphy,


mental retardation, abnormal ears, and, in some patients, cleft lip and
palate

 Krause-Kivlin syndrome: Peters’ anomaly + facial abnormalities,


disproportionate short stature, retarded skeletal maturation and
developmental delay (probably inherited in an autosomal recessive manner)

o Histopathology of Peters’ anomaly

 Central concave defect in the posterior corneal stroma (posterior ulcer)

 Disorderly stromal lamellae in ulcer bed

 Absence of corneal endothelium and Descemet's membrane in the posterior


ulcer

 Corresponding area of central corneal edema and opacification

 Keratolenticular adhesions to posterior cornea in some cases

 Iridocorneal adhesions to margin of ulcer in some cases

 Bowman's layer thickened or absent

o differential diagnosis: Von Hippel's internal corneal ulcer, sclerocornea, dermoid,


CHED, and PPCD

o proposed causes: incomplete central migration of corneogenic mesenchyme (i.e.,


neural crest cells), accounting for posterior endothelial and stromal defects

 Posterior keratoconus

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o very uncommon, mildest variant of Peters’ anomaly

o nonprogressive and usually sporadic

o unilateral/ bilateral

o Descemet’s excrescences can also be present in or just outside of the area of


involvement. The corneal endothelium and Descemet's membrane are present.

 Congenital anterior staphyloma

o protuberant congenital corneal opacity.

o secondary to an intrauterine infection or related to a developmental abnormality


such as a severe type of Peters’ anomaly

 CHED

o 1960 by Maumenee

o CHED 1: AD, 20p11.2-q11, clouding is slowly progressive over 1–10 years. presents
with photophobia and epiphora and the subsequent development of corneal
clouding.

o CHED 2: AR, 20p13 (Solute Carrier Family), previously referred to as Maumenee


cornea dystrophy. bilateral corneal clouding at birth or shortly thereafter. The
corneal changes are stable and do not progress or regress. There are no associated
symptoms, such as epiphora or photophobia, but patients often develop
nystagmus.

o DD: CSCD, congenital glaucoma, PPCD, Peters’ anomaly, and inborn errors of
metabolism, especially the mucopolysaccharidoses

 PPCD

o bilateral, nonprogressive, asymptomatic disease that rarely requires penetrating


keratoplasty.

o One form may present with congenital corneal edema, It is important to


differentiate PPCD from CHED, because the treatment is different

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 CSCD

o decorin gene on chromosome 12

o anterior stroma demonstrates a diffuse, flaky-feathery opacification caused by


corneal lamellar irregularities

 Congenital Dermoids

o solid benign congenital tumors  choristomas

o yellowish-white, solid, vascularized, elevated nodules straddling the corneal


limbus.

o Sporadic, genetically mapped to chromosome Xq24-qter

o grade 1: small, usually measuring 5 mm in diameter or less, single, limbal or


epibulbar, 1/3 Goldenhar's syndrome  epibulbar dermoids, preauricular
appendages, and pretragal fistulas.

o grade 2: larger, covering part of or the entire corneal surface, with varible depth,
generally does not involve Descemet's membrane or the corneal endothelium. It is
the most important type in the differential of congenital corneal opacities.

o grade 3: entire anterior segment, Microphthalmos is common, and posterior


segment abnormalities

o Mx: limbal dermoids are more of cosmetic problem  cut flush with the corneal
surface, but it may recur. Penetrating keratoplasty for central dermoids if they are
7 mm or less. Larger central dermoids require a two-stage procedure: first the
tumor is excised and a large lamellar graft is placed in the bed; once that is
healed, a smaller central penetrating keratoplasty is performed

 Corneal Keloids

o fibrous tissue proliferations that represent the exuberant response of embryonic


connective tissue to injury.

o white, sometimes protuberant, glistening, masses

o presence of myofibroblasts in these lesions, differentiating them from Salzmann's


nodules.

o can be associated with Lowe's syndrome


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Peripheral Corneal Disease

 portion located between the central 50% of the cornea and the limbus.

 thickest region of the cornea, which is directly adjacent to the corneal limbus and
internal angle structures

 Congenital/Developmental/Inherited Disorders:

o Lattice dystrophy type II is associated with systemic amyloidosis and primarily


involves the peripheral cornea.

o Wilson's disease: orangey-brown ring in the periphery of the cornea, Kayser–


Fleischer ring consists of copper which is deposited in Descemet's membrane.

o Sclerocornea and cornea plana:

o posterior embryotoxon: a thickened, prominent Schwalbe's line, which is more


anteriorly located than normal. 15% of the normal eyes. When it is associated with
other peripheral corneal abnormalities, including multiple peripheral iris strands,
it is termed Axenfeld–Rieger anomaly

 Inflammatory/Autoimmune Disorders

o rheumatoid arthritis: KCS, sclerosing keratitis, peripheral corneal furrow

o Polyarteritis nodosa: eye in 20% of cases, bilateral peripheral keratitis

o Wegener's granulomatosis: Two forms of the ocular disease have been described:
a severe progressive disease, which has a 1-year mortality of 82% if untreated; and
a limited, less severe form.

o Marginal keratitis: ocular hypersensitivity reactions to toxins produced by bacteria


that commonly colonize the eyelids

o Phlyctenulosis is an inflammatory disorder which is similar to marginal keratitis


but involves a more severe reaction

o Mooren's ulcer produces a painful progressive peripheral ulceration of the cornea.


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o vascular pannus: blood vessels and fibrous connective tissue from the limbus grow
onto the peripheral cornea

o Superior limbal keratoconjunctivitis (SLK): inflammatory disorder of unknown


etiology which is associated with a peripheral corneal pannus, a punctuate
keratopathy, a thickened superior conjunctiva which is chemotic and hyperemic,
and a filamentary keratitis.

 Neoplastic Disorders

o Pterygium:

o pyogenic granuloma

o Dermoid tumors

o squamous metaplasia

o carcinoma in situ or intraepithelial neoplasia (CIN)

 Degenerative Disorders

o Corneal arcus

o Lipid keratopathy: primary & secondary

o White limbal girdle of Vogt: type 1 & 2

o Calcific band keratopathy: intraocular inflammation, trauma, multiple eye


surgeries, elevated serum calcium, or other systemic disorders. The deposition
initially begins in the peripheral cornea, with a clear margin separating the deposit
from the limbus. The clear interval is thought to represent the anatomic limit of
Bowman's layer. Throughout the band are clear, small holes that give a ‘Swiss
cheese’ appearance. The holes occur at sites where corneal nerves penetrate
Bowman's layer.

o Calcific degeneration: the calcium may be associated with a fibrovascular pannus


or may occur deep in the corneal stroma, as opposed to calcific band keratopathy
in which the calcium deposition is confined to the region of Bowman's membrane.

o Corneal epithelial stem cell deficiencies

o Terrien's marginal degeneration

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o Pellucid marginal degeneration

o Furrow degeneration: elderly, not a true thinning but rather an optical illusion

o Dellen: areas of thinning or excavation. The overlying epithelium is usually intact,

 Infectious Disorders

o Microbial keratitis

o Herpes

Corneal Ulcer

Always search for 

1. infectious agent

2. local host factors

3. exogenous risk factors

4. endogenous factors: autoimmune disease, inflammatory, immunocompromised

Corneal Edema

1. Primary endothelial failure: FECD, CHED, PPCD, ICE

2. Secondary endothelial failure: Trauma, chemical, hypoxia

3. Normal endothelium: increased IOP

4. Epithelial failure: Epithelial Defect

 Ancillary tests

o Pachymetry

o Specular microscopy
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o In vivo confocal microscopy

o Anterior segment optical coherence tomography

 Treatment

o Treatment of inflammation and the underlying cause of inflammation

o decreasing the pressure can improve or resolve corneal edema and prevent further
damage to endothelial cells. Inhibition of corneal carbonic anhydrase pumps by
topical CAIs may lead to decreased fluid flow from stroma to aqueous and
progression to corneal edema.

o Hypertonic agents

o Bandage contact lens

o Anterior stromal cautery: Application of light burns to Bowman's layer using a


thermal cautery (Salleras procedure)

o Conjunctival flap

o Amniotic membrane

o Excimer laser

o Penetrating keratoplasty

o Endothelial keratoplasty

Corneal Deposits

 three depths: superficial, stromal, and deep stromal.

 three categories: pigmented, nonpigmented, and refractile/crystalline.

(see tables in prints)

 Epithelial iron lines: Iron lines can be seen in the palpebral fissure (Hudson-Stahli), at
the head of a pterygium (Stocker), surrounding the cone in keratoconus (Fleischer), at
the head of a filtering bleb (Ferry), adjacent to areas of corneal elevation such as

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Salzmann's nodular degeneration, anterior to the sutures in keratoplasty (Mannis), and


after keratorefractive surgery.

 Coat's white ring is a superficial ring of iron deposition that remains after a metallic
foreign body is removed. Small white opacities may be seen inside the ring. These rings
develop when a rust ring from an iron foreign body is not entirely removed.

Red Eye

 Redness is not a symptom, but a nonspecific sign. The three major processes responsible
for the majority of cases are subconjunctival hemorrhages, inflammation, and vascular
abnormalities.

Eye Banking

 first formally organized eye bank established in New York in 1944

 The FDA required testing includes:

1. HIV 1–2 antibody

2. Hepatitis B & C antibody

3. Syphilis testing

4. HIV & HCV NAT testing (nucleactic acid DNA/MNA)

 The Uniform Anatomical Gift Act (UAGA) of 1968 stated that a signed and witnessed donor
card was sufficient legal permission for organ or tissue removal after death.

 CMV, HSV is not contraindications

 Eye malignancy like RB, Anterior segment Carcinoma like Adenocarcinoma etc. are
contraindication. Systemic malignancies are not contraindications except lymphoma/
leukemia.
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 Primary Graft Failure: currently believed to be about 1%. Causes include pre-existing
corneal endothelial abnormalities, damage during recovery or storage, and surgical
trauma.

Corneal Storage Media

 First corneal preservation was done by Magitot in 1911. He stored cornea in Hemolyzed
blood serum at 5-7deg.centigrade and Cornea was viable for 2 days. (JAMA)

 BASE MEDIA

o Tissue-culture199-aminoacids, salts, buffer & energy to support life.

o Minimum Essential Media(MEM) with Earles salt- matches natural salts & buffers
of human tissue, electrolytes similar to aqueous

 BUFFER: HEPES(N-2-hydroxyethyl-piperazine-N-2ethane-sulfonic acid)

o used for cultivation of sensitive mammalian cells

o provides optimal physiological PH in the range7-7.2

 ANTIBIOTIC: Gentamicin only /& Streptomycin

 DEXTRAN

o Polysaccharide, negatively charged.

o Prevents tissue swelling.

o Used alone does not provide sufficient tissue stability & viability for extended
storage.

 CHONDROTIN SULFATE

o Polysaccharide, negatively charged

o Endothelial integrity & acts as osmotic agent. Superior to dextran. Longer storage
time

 ENRICHED

o Various salts, amino acids essential &non-essential, vitamins, phosphates &


antioxidants to enhance cell & tissue viability & health during storage.

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 ATP precursors  Provide energy for pumping function.

 Anti-Oxidants Neutralize metabolic waste, maintain DNS synthesis

 Vitamins Provides additional nutritional cell supplements.

 Sodium Pyruvate & Glucose  Energy supply

 Color Phenol Red-->Visual aid for pH indication.

 CHECK MEDIA

o The cornea which is stored in MKmedia, Dexol, optisolGS.

o The following parameters to be checked before using

o Intact seal, Expiry date, Turbity, Colour (rose red),precipitates & FB.

o COLOUR CHANGE INDICATES

 Yellow-- Bacterial contamination.

 Red--- Unacceptable Ph.

 Cloudy—Contamination

 STORAGE TYPES

o SHORT-4deg.C(days)

 Moist chamber(1day)

 Filatov & Castroviejo.

 Whole globe is stored in a sterile jar having saline Humidification at


Temp of 4 degrees C.

 Popular until 1970.

 M.K. Media (4days)

 Tc199

 Dextran 40 1%

 PH 7.0-7.5
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 Osmolality 295-355

 gentamycin sulphate 75-150 micro gm/ml

 HEPES as buffer.

 Phenol red as indicator.

o INTERMEDIATE-14days- 4deg.C(wks)

 K-Sol

 Tc 199, MEM & Earles media, HEPES, Gentamicin, Chondroin


sulphate 2.5%

 1988 proprionibacteria contamination

 Dexol

 MEM

 1.35%Chondrotin Sulphate

 1mM Sodium pyruvate,

 1mM non- essential amino acids

 Antioxidants

 1% dextran40.

 Optisol GS

 Introduced in 1991

 MEM

 1.35% Chondrotin Sulphate

 1mM Sodium pyruvate

 1 mM non-essential aminoacids

 Antioxidants

 1%dextran40, ATP, Iron, cholestrol,

 L-hydroxyproline, Vitamins

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 2 antibiotics- Gentamycin, Streptomycin

 Procell

 MEM,1.35%chondrotin sulphate,1mM sodium pyruvate1mM,Non-


essential aminoacids,Antioxidants,Dextran40,

 Humen insulin10mic.g/ml & Human epidermal growth


factor(hEGF10ng/ml) to improve long term endothelial survival after
PKP.

 Eusol-C

 Store at 4deg.C

 Storage time 14 days

 SIMILAR TO DEXOL

 Dextran, Sodium Piruvate, Glucose, Essential & non-essential


aminoacids, mineral salts, Vitamins, Gentamin, hepes buffer,
Bicarbonate, Phenol Red.

o LONG(months)

 Organ culture

 1936, by Archer & Trevor-Roper.

 Being used since1974.

 Refrigeration not required.

 Complicated, expensive & well trained microbiologist.

 Contents: Eagles media, Earles salt without L-glutamine,L-


glutamine1%final conc, Decomlemented calf serum10%final conc.
Penicilllin 100 units/ml,, Gentamicin100microgram/ml.
Amphoterician B 0.25% microgram/ml.

 European Organ culture-120days(37deg.C)

 31-37deg.C, EMEM, MEM, IMDM ,

 HEPES, NaHCO3,Peni,Strep,Ampo-B,

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 BOVINE SERUM 2-10ML,Dextran4-10%

 Eurosol-31deg.C-28days(New)

 Duration of storage 28days.

 Temp 31deg.C.

 Better than the European culture media.

 Maintains intact endothelium, epithelium & Keratocyte

 Cryopreservation-Unlimited-(-80degC)

 Kaufman & Capella.1954

 Cornea is stored in Liquid Nitrogen with Dimethyl Sulfoxide (DMSO).

 DMSO, Prevents intracellular damage by ice crystals.

 Not a procedure used.Holds a lot of research interest.

 GLYCERINE PRESERVATION

 Patch graft or Lamellar Keraoplasty.

 Corneo-scleral button.

 100%glycerine.

 Enothelium is nonviable

 Use with in 1 year.

 Stored at room temp.

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Diseases of the Lid

Anatomic Abnormalities

 Entropion

 Ectropion

 Trichiasis and Distichiasis

 Floppy Eyelid Syndrome

o primarily a disorder of sleeping position

o ocular irritation, mucous discharge, and papillary conjunctivitis.

o histopathologic features of the floppy eyelid syndrome point primarily to a marked


reduction in eyelid tarsal elastin

o Identification of sleep apnea and institution of CPAP to allow a supine sleep


position is paramount

 Lid Imbrication Syndrome

o abnormality of lid apposition in which the upper lid overrides the lower,
thereby allowing the lower lashes and keratinized epithelium to rub chronically
against the upper eyelid marginal tarsal conjunctiva.

 Lagophthalmos

 Eyelid Retraction

Blepharitis

 Numerous classifications

o Fuchs

 blepharitis squamosa, which is characterized by small, dry scales

 blepharitis ulcerosa, characterized by marginal crusting covering frank


ulceration
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o Duke-Elder and MacFaul

 squamous blepharitis, which they described as a superficial, nondestructive


dermatitis with eczema-like inflammation

 Follicular blepharitis characterized as a deeply seated, purulent process

o McCulley

1. staphylococcal disease

2. seborrheic blepharitis

3. both staphylococcal and seborrheic diseases

4. meibomian seborrhea

5. Seborrheic with secondary meibomitis

6. Primary meibomitis (also known as meibomian keratoconjunctivitis)

7. blepharitis associated with other conditions such as psoriasis and atopy.

o practical standpoint of McCulley’s

 anterior blepharitis (comprising the first three)

 posterior blepharitis (comprising the remaining meibomian-related groups).

 four principal arms of therapy for all of the categories of blepharitis

1. lid hygiene

2. topical antibiotics

3. systemic antibiotics (specifically tetracycline)

4. corticosteroids

Meibomian Gland Dysfunction

 term first suggested by Korb and Henriquez.

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 The meibomian gland secretion, which is distinct from sebum has been termed meibum by
Nicolaides et al.

 Meibography is a technique that uses transillumination biomicroscopy of the everted


eyelid with infrared photography

 Meibomian gland dysfunction increases tear electrolytes uniformly

lacrimal gland disease  sodium ions rise disproportionately in secretion at low flow rates

 The lipid layer is about 40–100 nm thick.

 Blinking is important for the excretion of meibomian lipid.

 Meibometry is used to measure the amount of lipid on the lid margin by determining the
degree of translucency induced on plastic tape applied to the lid margin.

 Tear film break-up time is reduced in meibomian gland dysfunction.

 Classification

 McCulley et al. (1982)

 Mathers et al. (1991)

 Seborrheic:

 Obstructive:

 Obstructive with sicca:

 Sicca:

 Bron et al. (1991)

 Reduced number (congenital deficiency)

 Replacement (trichiasis, metaplasia)

 Hyposecretion

 Obstructive meibomitis subdivided into focal, primary, secondary to local


disease or systemic disease, and chalazia

 Hypersecretory (seborrhea)

 Neoplastic

 Suppurative

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 Diagnosis

 burning, irritation, itching, red eyes, and decreased or fluctuating vision

 The lid margin is often rounded with thickening, erythema, hyperkeratinization,


vascularization, telangiectasia, or notching.

 An increase or reduction in the number of orifices may be seen.

 orifices are frequently less well defined or may show pouting

 secretion instead of being clear, it is turbid, granular, or toothpaste-like

 meibography  narrowing or occlusion of the glandular orifices and glandular


distortion or dilation

 meibometer: lipid imprint is then analyzed using a density measuring device

 Associated Conditions

 lacrimal insufficiency

 Rosacea

 Giant papillary conjunctivitis (GPC)

 Contact lens intolerance

 Chalazia

 Histopathology

 Obstruction, hyperkeratinization

 Lipid Composition

 neutral sterol and wax esters with lesser amounts of polar lipids, diesters,
triesters, triglycerides, free fatty acids, and free sterols.

 cholesterol esters are always present in patients with meibomian gland dysfuncton

 Unlike meibomian gland secretion, sebum contains more triglycerides and free
fatty acids and considerably less sterol esters. Squalene is present in sebum and
absent in meibomian gland secretion. The wax ester proportion is similar in both
secretions. Overall, sebum is much more polar and will contaminate the tear film
when mixed with it.

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 Three of the bacteria commonly isolated from eyelids, S. aureus, Corynebacterium species
(CN-S), and P. acnes, produce lipases that can alter the composition of meibomian lipids.

 Tetracycline reduces lipase production in S. epidermidis, S. aureus, and P. acnes. It also


decreases serum cholesterol in mice, has antichemotactic effects on neutrophils, and has
activity against collagenase and other metalloproteinases. Any of these properties may
produce a marked therapeutic effect in many patients with meibomian gland dysfunction
and rosacea.

 Treatment

 lid hygiene

 Warm compresses:

 Lid massage:

 Lid scrubs:

 Systemic antibiotic therapy consists of oral tetracycline, 250 mg four times a day;
doxycycline, 50–100 mg twice a day, or minocycline, 50 mg twice a day.

 Topical therapy consists of antibiotics and anti-inflammatory drugs.

 treatment of associated conditions.

Disorders of Tear Production

 1995 National Eye Institute (NEI)/Industry Dry Eye Workshop: Dry eye is a disorder of the
tear film due to tear deficiency or excessive evaporation, which causes damage to the
interpalpebral ocular surface and is associated with symptoms of ocular discomfort.

 International Dry Eye WorkShop (DEWS) in 2007: dry eye is defined as multifactorial
disease of the tears and ocular surface that results in symptoms of discomfort, visual
disturbance, and tear film instability with potential damage to the ocular surface

 Lacrimal Functional Unit (LFU): ocular surface (cornea, conjunctiva, accessory lacrimal
and meibomian glands), the main lacrimal glands, the blink mechanism that spreads tears,
and the sensory and motor nerves.

 Pathophysiology

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1. Tear hyperosmolarity is regarded as the central mechanism causing ocular surface


inflammation, damage, and symptoms, and the initiation of compensatory events
in dry eye.

2. Tear film instability can arise secondary to hyperosmolarity, or can be the


initiating event

The core mechanisms responsible for dry eye disease are tear hyperosmolarity and
tear film instability. The major causes of tear hyperosmolarity are reduced
aqueous tear flow and/or increased tear evaporation. Tear hyperosmolarity
induces cascades of inflammatory events that result in damage to the surface
epithelium, nerve endings, and ultimately tear film instability. This instability
exacerbates ocular surface hyperosmolarity and completes the vicious circle. Tear
film instability can also be initiated by other etiologies, including xerophthalmia,
ocular allergy, topical preservative use, and contact lens wear.

 Dry Eye Diseases DED  aqueous tear-deficient dry eye (ADDE) and evaporative dry eye
(EDE)

 aqueous tear-deficient dry eye (ADDE)

Sjögren's syndrome dry eye (SSDE)


Non-Sjögren's syndrome dry eye (NSSDE)
 Primary lacrimal gland deficiencies
o Age-related dry eye (ARDE)
o Congenital alacrima:
 Secondary lacrimal gland deficiencies
o Lacrimal gland infiltration:
o Obstruction of the lacrimal gland ducts
 Reflex hyposecretion
o Reflex sensory block: DM, Neurotrophic Keratitis
o Reflex motor block
 Evaporative dry eye (EDE)

 Intrinsic causes
 Meibomian gland dysfunction
 Disorders of lid aperture and lid/globe congruity or dynamic
 Low blink rate
 Extrinsic causes
 Ocular surface disease
 Contact lens wear

 Diagnosis:

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o History: foreign body sensation, burning, stinging, itching, dryness, soreness,


heaviness of the lids, photophobia, and ocular fatigue. An important clue is
exacerbation of symptoms by certain activities or environmental conditions.

o Physical examination

 dynamics of blinking: a) frequency of blinking; b) variation of blink


intervals; c) size of the palpebral aperature, and d) adequacy of lid closure.

 Malposition of the lids: a) entropion; b) ectropion; c) eversion of the


lacrimal puncta; d) cicatrical malposition; e) dermatochalasis; and f)
swelling of the lacrimal gland.

o Diagnostic tests

 Tear film stability:

 tear breakup time (TBUT) test:

 noninvasive breakup time, or NIBUT: It involves projecting a target


onto the convex mirror surface of the tear film and recording the
time following a blink for the image to break up. The test has been
performed using custom-built devices such as Tearscope or
keratometry devices.

 arbitrary cutoff time of 10 s for both fluorescein-added and


noninvasive techniques appears quite specific

 Ocular Ferning Test

 Impression cytology

 Diagnostic dye staining:

 Fluorescein sodium: dye diffuses rapidly in the intercellular spaces


and staining indicates increased epithelial permeability

 Rose Bengal: more sensitive for staining the conjunctiva; however,


it is not tolerated as well and frequently causes irritation, stains
devitalized epithelial cells as well as epithelial cells that lack a
healthy layer of protective mucin coating.

 Lissamine green B is similar to rose Bengal in its staining


characteristics, and produces much less irritation after topical
administration than rose Bengal

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 Van Bijsterveld reported a grading scale that evaluates the intensity


of staining based on a scale of 0–3 in three areas: nasal conjunctiva,
temporal conjunctiva, and cornea.

 Corneal sensation

 cotton swab

 Cochet–Bonnet esthesiometer

 Tear film composition

 Osmolarity: well-validated cutoff value of 316 mmol/L for dry eye


disease.

 Tear protein analysis:

o tear lysozyme: sensitivity and specificity >95%

o Lactoferrin: Lactocard relative indicator of lacrimal gland


function

 Aqueous tear flow and turnover

 Schirmer test: Van Bijsterveld selected 5.5 mm strip wetting in 5


minutes for the Schirmer test without anesthesia to diagnose
aqueous tear deficiency.

 phenol red-impregnated thread test (PRT): cutoff value of 10 mm


at 15 seconds, the sensitivity and specificity of the PRT have been
shown to be 56% and 69%.

 Delayed tear clearance: increased tear cytokine concentration, which may


contribute to chronic inflammation

 fluorescein clearance test (FCT): detect the amount of residual


fluorescein by Schirmer strip or use a fluorophotometer

 Other noninvasive methods

 Tear meniscus height (meniscometry): meniscus radius of


curvature <0.25 mm suggests a dry eye condition.

 Interferometry of the tear film lipid layer is useful in screening and


evaluating dry eye.

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o Systemic Work-Up: anti-SS-A, anti-SS-B, rheumatoid factor, ANA, ESR, CRP

 Management

o Tear supplementation: lubricants

 electrolytes, surfactants, and various types of viscosity agent

 Osmolarity: 181 to 354 mmol/L

 Compatible solutes are small nonionic molecules (e.g., glycerin) Optive and
Refresh Endura (with 0.9% and 1% glycerin)

 Colloid osmolality (which relates to macromolecule concentration)

 Viscosity agents: Macromolecular complexes  carboxymethylcellulose,


polyvinyl alcohol, polyethylene glycol, propylene glycol, hydroxypropyl-guar
(HP-guar), and lipids such as those that make up castor oil or mineral oil.

 Lipid-containing artificial tear products such as Refresh Endura (with castor


oil) and Soothe XP (with mineral oil) are intended to reduce tear
evaporation by restoring the lipid layer of the tear film; this may be
particularly useful in patients with MGD.

 HP-guar (in products such as Systane) is believed to form a bioadhesive gel


when exposed to ocular pH, increasing aqueous retention and protecting
the ocular surface by mimicking the mucous layer of the tear film.

 two main types of preservative:

1. Detergent preservatives act by altering bacterial cell membrane


permeability.

- BAK

2. Oxidative preservatives penetrate the bacterial cell membrane and act by


interfering with intracellular processes. They are sometimes referred to as
‘vanishing’ preservatives because they dissipate on contact with the eye
and are therefore less likely than detergents to cause ocular damage.

- Stabilized oxychloro complex

o Tear retention

 Punctal occlusion: Punctal and intracanalicular plugs, argon laser,


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2 types: absorbable are made of collagen or polymers and last for variable
periods (3 days to 6 months). The nonabsorbable ‘permanent’ plugs include
the Freeman style, which consists of a surface collar resting on the punctal
opening, a neck, and a wider base, and are made of silicone or hydrophilic
acrylic.

 Moisture chamber spectacles:

 Contact lenses: Boston scleral lens, Mini-scleral lens (Jupiter Lens)

o Tarsorrhaphy

o Tear stimulation: secretagogues

 diquafosol (P2Y2 receptor agonists)

 Orally administered cholinergic agonists, in particular pilocarpine and


cevilemine

o Biological tear substitutes

 Serum: Concentrations between 20% and 100% o

 Salivary gland autotransplantation

o Anti-inflammatory therapy

 Ciclosporin

1. Decreases proinflammatory cytokines (e.g., conjunctival IL-6 levels)

2. Decreases activated lymphocytes in the conjunctiva

3. Decreases conjunctival inflammatory and apoptotic markers

4. increases conjunctival goblet cell numbers.

 0.05% and 1%, 2%

 Corticosteroids: inhibition of the activity of transcription factors such as


activator protein-1 (AP-1) and nuclear factor κB (NFκB), that are involved in
the activation of proinflammatory genes

 loteprednol etabonate 0.5%

 androgenic steroids

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 Tetracyclines: antibacterial, anti-inflammatory, inhibits MMPs and IL1


production and protease inhibitory properties.

 Essential fatty acids: a higher omega-6:omega-3 ratio was associated with


a significantly greater DED risk. omega-3 fatty acids (e.g., EPA found in fish
oil) inhibit the synthesis of these lipid mediators and block the production
of IL-1 and TNF-alfa.

o Topical vitamin A (retinol)

 Reversal of squamous metaplasia

 Increased production of type I collagen

 Promotes regeneration of conjunctival goblet cells and can re-establish


intracellular conjunction of conjunctival epithelium

o Mucolytics: Inhalational acetylcysteine is diluted to concentrations of 5–20% (most


commonly 10%) for off-label use as a topical ophthalmic agent.

 Treatment Guidelines

o In 2007 the Management and Therapy Subcommittee of the International Dry Eye
WorkShop (DEWS) adopted a modified form of the ITF (International Task Force)
severity grading. (DELPHI Panel)

o ITF- ciclosporin at level 2 & Plugs at level 3

o DEWS- ciclosporin & Plugs at level 2

Conjunctival Tumors

Squamous Neoplasms of the Conjunctiva

Read OSSN article form DOS

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Conjunctivitis

 The conjunctival epithelium is contiguous with the corneal epithelium and also lines the
lacrimal passages and glands, a fact that has significant clinical implications.

 The substantia propria is composed of a superficial adenoid layer and a deeper fibrous
layer.

o The adenoid layer: lymphoid tissue from which follicles are formed. Within the
lymphoid tissue are germinal centers with lymphoblasts in the center.

o The fibrous layer: connective tissue, which attaches to the tarsal plate and
contributes to the characteristic appearance of papillae.

 Conjunctival injection: superficial bright red blood vessels, most conspicuous in the
fornices and fade toward the corneoscleral limbus

 Conjunctival hyperemia: secondary to dilation of the conjunctival blood vessels without


accompanying exudation or cellular infiltration. Due to environmental factors including
smoke, smog or chemical fumes, wind, ultraviolet radiation, and prolonged topical
instillation of vasoconstrictors.

 Conjunctivitis: inflammation of the conjunctiva and is characterized by cellular


infiltration and exudation in addition to vascular dilation.

 Chemosis: accumulation of fluid within or beneath the conjunctiva, is frequently present.

 Morphologic responses

o Papillae: where the conjunctiva is attached to the underlying tissue by anchoring


septae, folds or projections of hypertrophic epithelium that contain a central
fibrovascular core whose blood vessels arborize on reaching the surface.
Micropappile < 1 mm

giant papillae > 1 mm: vernal conjunctivitis, atopic keratoconjunctivitis, and as a


foreign body reaction to suture material, contact lenses, or prostheses.

o Follicles: yellowish-white, discrete, round elevations of conjunctiva produced by a


lymphocytic response. Unlike a papilla, the central portion of the follicle is
avascular. 0.5–2.0 mm in diameter.

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Acute follicular conjunctivitis: Adenovirus, Inclusion conjunctivitis, Herpesviruses

Chronic follicular conjunctivitis: Chlamydial infections, Molluscum contagiosum,


Moraxella

o Membranes: primarily of fibrin that has attached to the epithelial conjunctival


surface. True membranes leave a raw surface and cause bleeding when peeled off,
which differentiates them from pseudomembranes.

C. diphtheria, β-hemolytic streptococci, adenoviral, HSV, vernal conjunctivitis,


inclusion conjunctivitis, and Candida. Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN)

o Cicatrizing changes: Scar formation ensues only when there is destruction of


stromal tissue.

o Conjunctival granulomas: affect the stroma.

o Conjunctival exudates may be classified as: (1) purulent or hyperacute; (2)


mucopurulent or catarrhal; and (3) watery.

o Anatomic localization:

 Upper tarsal: trachoma, contact lens wearers, patients wearing prostheses,


or from exposed suture material.

 upper palpebral: SLK, FES

 upper pretarsal: VKC, AKC (can be in lower lid)

 lower tarsal: toxic papillary conjunctivitis and the ‘mucus-fishing


syndrome.’ The follicular response in inclusion conjunctivitis is more
pronounced inferiorly than superiorly.

Bacterial Conjunctivitis

 Disruption of the host's defense mechanisms are predisposing factors for the development
of bacterial conjunctivitis:

 Risk factors

o Dry eye

o Exposure

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o Nutritional deficiency/malabsorption

o Local or systemic immune deficiency often after topical and systemic


immunosuppressive therapy

 An organism may be isolated in as many as 90% of normal subjects, with more than one
organism found in up to 35%. In most subjects, the flora is composed of aerobic
staphylococci (>60%) (mostly Staphylococcus epidermidis), diphtheroids (>35%), and
the anaerobe Propionibacterium acnes, but the spectrum of bacteria and sensitivity to
antibiotics varies among major age groups.

 Manifestations

o Discharge

o Membranes and pseudomembranes

o Papillae and follicles

 Classification

o Hyperacute: lid edema, marked conjunctival hyperemia, chemosis, and copious


amounts of purulent discharge. N. gonorrhoeae and N. meningitidis.

 Treatment

 Systemic treatment is mandatory for patients with Neisseria


conjunctivitis; concomitant topical antibiotic therapy is optional.

 single-dose intramuscular (IM) regimen of 1 g of ceftriaxone

 To treat N. gonorrhoeae conjunctivitis in the newborn, 25–50 mg/kg


intravenous (IV) or IM ceftriaxone administered in a single dose not
exceeding 125 mg is currently recommended

o Acute conjunctivitis: velvety papillary reaction, 10-14 days

 S. aureus, the most frequent cause

 H. influenzae (nonencapsulated) is the most common cause of bacterial


conjunctivitis in young children

 Treatment

 topical antibiotic therapy hastens resolution, improves microbiologic


cure, and may reduce morbidity, especially in culture-proven cases

o Chronic conjunctivitis:

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 foreign body sensation, mild stickiness and matting of the lashes, and
minimal discharge.

 S. aureus and M. lacunata

 short-term topical therapy is often ineffective.

 Long-term therapy is required and, if there is concomitant blepharitis, the


therapeutic regimen should include lid hygiene, lid margin cleansing with a
mild baby shampoo diluted 50% with water, and the nightly application of
an antibiotic ointment with good Gram-positive coverage, such as
bacitracin, to the lid margins.

 Adjunctive oral therapy with 100 mg doxycycline one to two times a day.

Viral Conjunctivitis

 Hallmark: follicular reaction of the conjunctiva

 RNA: benign forms of conjunctivitis

o Picornaviruses: most common causes of acute hemorrhagic conjunctivitis (AHC).

o Paramyxoviruses: measles, Newcastle disease, and mumps

Measles: Catarrhal conjunctivitis, superficial keratitis, and photophobia are the


most common clinical features in healthy individuals. Keratitis is usually severe in
patients with vitamin A deficiency.

Newcastle disease is limited to poultry workers and laboratory personnel.

Mumps is an acute viral infection characterized by swelling (more commonly


bilateral) of the parotid salivary glands.

o Togaviruses: Rubella (German measles)

o Flaviviruses: Yellow fever

 DNA: associated with vision-threatening forms of inflammation

o Adenoviruses: MCC of viral conjunctivitis. six subgenera (A–F). D is most common.

1. Pharyngoconjunctival fever (PCF) is characterized by pharyngitis, follicular


conjunctivitis, fever, and adenopathy (preauricular and cervical).

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2. Epidemic keratoconjunctivitis (EKC) is the severest ocular disease caused by


adenoviruses. 8,19,37

3. Acute nonspecific follicular conjunctivitis may be caused by many serotypes


of adenovirus, including those classically associated with PCF and EKC.

4. Chronic conjunctivitis is the least common form of adenovirus


conjunctivitis.

Stages: 0 to 5

Treatment: preventing the transmission and complications. Cold


compresses, Pseudomembranes and membranes should be removed, topical
antiinflammatory agent- Steroids/ NSAIDs.

o Herpes simplex virus (HSV)

 usually a benign condition except in neonates when the herpetic infection


can be associated with fatal disease and should be promptly treated.

 commonly diagnosed in dendritic/geographic ulcers, disciform keratitis, and


keratouveitis

 Treatment of HSV conjunctivitis in the neonate is mandatory and should


include both topical antiviral and intravenous acyclovir. A pediatric
consultation should be obtained.

o Varicella-zoster virus (VZV)

o Molluscum contagiosum is a human host-specific poxvirus.

Chlamydial Infections

 In humans the largest burden of ocular disease is caused by C. trachomatis.

o Serovars A, B,Ba and C are associated with trachoma.

o Serovars D–K are causative of adult or neonatal inclusion conjunctivitis as well as


urogenital diseases.

o serovars L1–3 are associated with lymphogranuloma venereum.


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 It uses the cellular machinery of the host to provide it with energy for metabolic activity.

 The RB is the classic metabolically active intracellular form. In contrast, the EB exists only
in an extracellular form. This form is metabolically inactive, possessing a rigid cell wall
which is relatively impermeable to stimuli in its extracellular environment.

 EB  IB  RB  binary fission of RB and increase in number  release

 Trachoma

 third most common cause of blindness worldwide after cataract and glaucoma.

 Transmission: directly from eye to eye, fomites, flies, eye make-up, low socioeconomic
status, lack of water, and poor hygiene

 WHO classification: FISTO

 Trachomatous inflammation – follicular (TF): the presence of five or more follicles


in the upper tarsal conjunctiva. Follicles must be at least 0.5 mm in diameter to be
considered.

 Trachomatous inflammation – intense (TI): pronounced inflammatory thickening of


the tarsal conjunctiva that obscures more than half of the normal deep tarsal
vessels.

 Trachomatous scarring (TS): the presence of scarring in the tarsal conjunctiva.

 Trachomatous trichiasis (TT): at least one eyelash rubs on the eyeball. Evidence of
recent removal of inturned eyelashes should also be graded as trichiasis.

 Corneal opacity (CO): easily visible corneal opacity over the pupil.

 The follicles around the limbus may eventually break down, and necrosis of the tissue can
occur with subsequent scarring. These scars are referred to as Herbert's pits.

 Linear or stellate scarring on the upper tarsus can coalesce and form an ‘Arlt's line’,
which is suggestive of prior trachoma infection

 Pathophysiology

o following the initial infection with ocular C. trachomatis, a hypersensitive state


occurs such that subsequent infections results in more intense inflammation

o Candidate antigens for inducing this hypersensitive state include the 60 kDa
chlamydial heat shock protein, the major outer membrane protein surface
antigen, and lipopolysaccharide from the bacterial cell membrane,
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o reduced interferon (IFN), interleukin (IL)-2, and increased IL-4 secretion have been
found to exist in subjects who progress to develop significant scarring

 Treatment:

o TF/ TI  e/o azithromycin BD for 6 weeks = single dose 1000 mg oral azithromycin
= 2-week course of oral tetracycline 250 mg four times daily or doxycycline 100 mg
twice daily

o TS/ TT  conservative, with ocular lubricants as well as close observation,


managing trichiasis in order to avoid subsequent bacterial ulcers and corneal
scarring

o TO  manage the disability and to restore vision.

 WHO's GET 2020 program (Global Elimination of Trachoma by the year 2020) has adopted
the so called ‘SAFE’ strategy (Surgery for entropion/trichiasis, Antibiotics for infectious
trachoma, Facial cleanliness to reduce transmission, and Environmental improvements
such as access to clean water and control of disease-spreading flies)

 The currently accepted WHO guidelines include community-wide antibiotic treatment if


there is >10% active trachoma in children aged 1–9 years. This treatment should be
reinstituted annually for 3 years, with reassessment at that time.

 Neonatial inclusion conjunctivitis (NIC)

 also known as ophthalmia neonatorum

 0.4% and 5%

 C. trachomatis is the single most common etiologic agent, accounting for up to 40% of
cases. Other causes include Neisseria gonorrhoeae, other bacterial infections, herpes
simplex virus (HSV), and chemical toxins

 NIC is associated with serovars D–K

 first manifestation is often bilateral conjunctival hyperemia, occurring 5–14 days after
birth. Other typical yet nonspecific signs include mucoid or mucopurulent discharge, lid
edema, pseudomembranes, papillary reaction and not a follicular reaction, all
occurring within the same timeframe

 Because of the systemic risk, the treatment for NIC should include systemic antibiotics.
The current recommended therapy is oral erythromycin 50 mg/kg/day in four divided
doses for 10–14 days.

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 Adult Inclusion Conjunctivitis

 D–K, 5-14 days

 Lymphogranuloma Venereum

 L1–3

 Parinaud's oculoglandular syndrome, a condition in which patients present with a severe


papillary conjunctivitis as well as massive tender posterior cervical and preauricular
lymphadenopathy.

Ophthalmia Neonatorum

1. Chemical: 1–36 hours

2. Neisseria gonorrhoeae: 1–2 days

3. Bacterial (Staphylococcus, Streptococcus, Haemophilus): 2–5 days

4. Viral: 3–15 days

5. Chlamydia: 5–14 days

Parinaud's Oculoglandular Syndrome

 The most common bacterial cause, Bartonella henselae, is particularly difficult to


culture.

Allergic Conjunctivitis

 Ocular allergy may be classified into five categories –


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1. seasonal and perennial allergic conjunctivitis

2. vernal keratoconjunctivitis

3. atopic keratoconjunctivitis

4. giant papillary conjunctivitis

5. contact allergic conjunctivitis

 Immunopathophysiology

 Mast cells, the primary inflammatory cells involved in ocular allergy, normally
reside within the vascular stroma (substantia propria), but can be present within
the conjunctival epithelium in pathologic situations.

 early-phase response (EPR) and a dose related late-phase response (LPR)

 two components of mast cell activation. The first is the release of preformed
mediators, including histamine. The second is the synthesis of arachidonic acid and
the subsequent metabolic cascade, resulting in the production of prostaglandins
and leukotrienes

 Seasonal allergic conjunctivitis (SAC)

 the most common form of ocular allergy

 Tree and flower pollen in the spring, grass pollen in the late spring and early
summer, and ragweed during the late summer and early fall

 hallmark symptom, ocular itching.

 clear, ropy discharge is characteristic

 nasal and pulmonary symptoms, as the same allergens could trigger rhinitis and
asthma

 Skin testing, both prick and intradermal methods, is the most widely accepted
method for allergy testing.

 Perennial allergic conjunctivitis (PAC)

 a year-round variant of seasonal allergic conjunctivitis

 79% of these patients have seasonal exacerbations

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 most common aeroallergens implicated in PAC are found indoors, and include
animal dander, dust mites, and feathers.

 Treatment

 Avoiding known allergen triggers is critical.

 itch–rub cycle: Encouraging patients to stop rubbing their eyes

 Over-the-counter topical decongestants containing vasoconstrictors with or without


antihistamines

 The more potent topical antihistamines, levocabastine hydrochloride 0.05% and


emedastine difumarate 0.05%, selectively block H1 receptors.

 The dual-acting medications, including olopatadine hydrochloride 0.1% and 0.2%,


azelastine hydrochloride 0.05%, ketotifen fumarate 0.025% (available over the
counter), and epinastine hydrochloride 0.05%, have antihistamine and mast cell
stabilizing properties

 Traditional mast cell stabilizers include sodium cromoglycate 4% and lodoxamide


tromethamine 0.1%.

 Ketorolac tromethamine 0.5% and diclofenac are NSAIDs, which decrease the
activity of cyclooxygenase, an enzyme responsible for arachidonic acid
metabolism. This, in turn, reduces prostaglandin production, most notably the
highly pruritic PGE2 and PGI2.

 Topical corticosteroids are highly effective therapy for ocular allergy, blocking
most allergic inflammatory cascades

 Oral antihistamines are seldom used to treat isolated seasonal or perennial allergic
conjunctivitis

 Vernal Keratoconjunctivitis

 chronic, bilateral, conjunctival inflammatory condition found in individuals


predisposed by their atopic background

 onset: 2-10 year  lasts till puberty

 Young males in dry, hot climates

 family history of atopy is found in 40–60%

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 Symptoms: Severe itching and photophobia, foreign body sensation, ptosis, thick
mucus discharge, and blepharospasm

 Signs:

1. papillary response, principally of the limbus or upper tarsus, classic


‘cobblestone’ papillae.

2. Limbal papillae tend to be gelatinous and confluent  Horner-Trantas


dots, which are collections of epithelial cells and eosinophils

3. punctate epithelial keratitis  frank epithelial erosion  shield ulcer (due


to its shape)  subepithelial ring-like scar

 Pathophysiology:

1. epithelium contains large numbers of mast cells (mast cells predominantly


of the type containing the neutral proteases tryptase and chymase) and
eosinophils

2. Basophils are found in the epithelium, and may indicate that one form of a
delayed-type hypersensitivity reaction is occurring

3. substantia propria contains elevated numbers of mast cells

 Diagnosis: intense photophobia, ptosis, and the characteristic finding of giant


papillae.

 DD: AKC

 Treatment

1. avoidance of allergens

2. Hyposensitization in VKC has limitations (due to multiple allergens)

3. short-term, high-dose pulse regimen of topical steroids

4. Cromolyn sodium, a mast cell stabilizer, has repeatedly been shown to be


effective in VKC

5. Topical calcineurin inhibitors of ciclosporin A (CsA) and tacrolimus have


been demonstrated effective in the treatment of VKC

6. Climatotherapy

7. Cryoablation of upper tarsal cobblestones is reported to render short-term


improvement

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 Atopic Keratoconjunctivitis

 bilateral, chronic inflammation of the conjunctiva and lids associated with atopic
dermatitis

 15% to 67.5% of patients with atopic dermatitis have ocular involvement

 Male: female = 2.4: 1

 Symptoms: Itching >> watering, mucus discharge, redness, blurring of vision,


photophobia, and pain

 Signs

1. periocular skin often shows a scaling, flaking dermatitis with a reddened


base

2. Lateral canthal ulceration, cracking, and madarosis

3. lid margins may show loss of cilia, meibomianitis, keratinization, and


punctal ectropion

4. In contrast to VKC, the papillary hypertrophy of AKC is more prominent


in the inferior conjunctival fornix.

5. perilimbal, gelatinous hyperplasia

6. Punctate epithelial keratopathy  Persistent epithelial defects  scarring


 microbial ulceration  neovascularization

 Pathophysiology

1. both type I and type IV hypersensitivity

2. conjunctival epithelium containing Mast cells (tryptase) and eosinophils

3. increase in the CD4:CD8 ratio 

4. substantia propria: increased number of mast cells, Eosinophils (never


found normally), Increased fibroblasts

 Treatment

1. opical application of a vasoconstrictor–antihistamine combination

2. topical administration of steroids

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3. Mast cell stabilizers two to four times daily is recommended year-round

4. Ciclosporin A and tacrolimus, both orally and topically, have been shown
effective in treating AKC

Giant Papillary Conjunctivitis

 noninfectious inflammatory disorder involving the superior tarsal conjunctiva.

 currently defined as papillae greater than 0.3 mm in diameter

 average length of time: soft contact lenses  8 months, hard contact lenses  8 years

 mild irritation, scant mucous discharge, and occasionally mild itching

 slow, progressive character  ropy, whitish, mucoid discharge

 Allansmith has divided the superior tarsal surface into three zones.

o Zone 1 is located proximally along the uppermost edge of the tarsal plate;

o Zone 2 is upper tarsal plate

o zone 3 is located distally adjacent to the lid margin.

 Papillae with soft contact lens  zone 1 to 3

 Papillae with RGP contact lens  zone 3

 Pathophysiology:

o combined effect of mechanical trauma and the subsequent immune response


to antigens in the form of contact lens surface deposits

 Treatment:

o Discontinuation of offending irritant if appropriate

o Modifying the patient’s contact lens care routine and wearing schedule

o appropriate surfactant cleaner and a ‘rub’ routine becomes mandatory

o Reducing contact lens wearing time

o Treat if any meibomian gland disease

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o Histamine antagonists and receptor blocking agent

o Topical corticosteroids have not proved particularly effective

o Suprofen, an NSAID, has been studied topically in contact lens-associated GPC.

o Cromolyn sodium has been studied extensively and has been shown to promote
resolution of early giant papillary conjunctivitis when combined with
meticulous lens hygiene.

Cicatricial Pemphigoid

 chronic cicatrizing autoimmune disease of the mucous membranes and skin.

 OCP affects primarily the conjunctiva and the mucosae, including oral, nasal, and
esophageal, in lesser frequency

 average age at onset of OCP is 65 years

 Scarring (Brusting-Perry dermatitis) occurs in approximately 25% of cases, and


cicatrizing conjunctivitis develops in 70–75%

 Histology: the conjunctival lesions show submucosal scarring, chronic inflammation,


perivasculitis, and squamous metaplasia of the epithelium, with loss of goblet cells; mast
cell participation in the inflammation is surprisingly great.

 Pathogenesis

o autoimmune disease with a genetic predisposition and probably a ‘second-hit’


environmental requirement to trigger the onset

o increase in frequency in the HLA-DR4 and HLA-DQw3

o second-hit  microbial or chemical

o β4 subunit of α6β4 integrin, 205 kilodalton (kDa) protein molecule in the BMZ
of the conjunctiva  the target of attack

 The diagnosis is confirmed by the demonstration of one or more immunoreactants at the


epithelial BMZ. Additional confirmation can be sought from immunoblot analysis of patient
serum, an identifying autoantibody that binds to the 205-kDa protein band from
conjunctival or epidermal lysates: anti-β4 antibody.

 Ocular Manifestations

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o chronic, recurrent unilateral conjunctivitis.

Stages:

1. Subepithelial fibrosis

2. fornix foreshortening

3. Symblepharon

4. end-stage disease, is characterized by ankyloblepharon and surface


keratinization

 Therapy

o Sicca syndrome: lubricants without preservatives, Punctal occlusion, Topical


retinoid (0.01% tretinoin) ointment

o Chronic blepharitis and meibomitis: vigorous warm compresses and lid


hygiene, oral doxycycline, 100 mg BD

o Immunomodulatory therapy (minimum 2 years)

 prednisone 1 mg/kg/day, and cyclophosphamide 2 mg/kg/day.

 Methotrexate (15–25 mg once weekly) and mycophenolate mofetil (1–


3 g/day) are used for cases that are less active and are not rapidly
progressing.

 Dapsone and prednisone can also be used for such cases; the initial daily
dose of dapsone employed is 1 mg/kg/day

 intravenous immunoglobulin (IVIG) alone and especially in combination


with rituximab therapy

 surgical treatment: tarsectomy for correction of entropion, strip


peritomy to provide an avascular barrier against corneal
neovascularization, superficial keratectomy for removal of corneal
vascular and scar tissue, and fornix incision for release of
symblepharon.

EM, SJS & TEN

 across-the-spectrum manifestations of the same clinical entity, affecting the skin and
mucous membranes.
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 international classification was adopted in 1993

 Ferdinand von Hebra, in 1866, first described erythema multiforme

 Incidence: 4.2 per million person-years

 M:F = 1:1.5/2

 Drugs and infections are the most frequent identifiable precipitating factors

 Clinical Features:

 Eye findings

 Acute eye findings

o nonspecific conjunctivitis: may precede the skin eruption

o may be catarrhal or pseudomembranous

o severe anterior uveitis

o corneal ulceration (uncommon)

 Chronic eye findings

o Scarring, symblepharon formation, and cicatrization of the conjunctiva

o entropion formation, trichiasis, and instability of the tear film

o corneal scarring, neovascularization, and, in severe cases, keratinization

o Keratin not only on the corneal surface but also along the posterior lid margin.

o Subepithelial fibrosis of the conjunctiva

o Cicatrization of the lacrimal ducts

o destruction of the conjunctival goblet cells

 Diagnostic criteria for bullous skin diseases

o Erythema multiforme minor

1. Target (iris) lesions (typical or atypical)

2. Individual lesions less than 3 cm in diameter

3. No or minimal mucous membrane involvement

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4. Less than 20% of body area involved in reaction

5. Biopsy specimen compatible with erythema multiforme minor

o Stevens-Johnson syndrome (erythema multiforme major)

1. Less than 20% of body area involved in first 48 hours

2. Greater than 10% body area involvement

3. Target (iris) lesions (typical or atypical)

4. Individual lesions <3 cm in diameter (lesions may coalesce)

5. Mucous membrane involvement (at least two areas)

6. Fever

7. Biopsy specimen compatible with erythema multiforme major

o Toxic epidermal necrolysis

1. Bullae and/or erosions over 20% of body area

2. Bullae develop on erythematous base

3. Occurs on non-sun-exposed skin

4. Skin peels off in >3 cm sheets

5. Mucous membrane involvement frequent

6. Tender skin within 48 hours of onset of rash

7. Fever

8. Biopsy specimen compatible with toxic epidermal necrolysis

 Incidence of ocular complications: average of 24% had ocular manifestations during their
hospitalization

 DD

o Ocular disorders: cicatricial pemphigoid, chronic keratoconjunctivitis caused by


bacteria or viruses, medications, allergies, chemical burns, avitaminosis A, and
trachoma, drug reaction.

o Dermatologic: SSSS, urticarial viral exanthema, drug reaction, toxic shock


syndrome, Kawasaki disease, Leiner disease, erythroderma secondary to other
causes, contact dermatitis, thermal burns, or poisonings
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 Etiology

o Drug-related cases

o certain infections

o malignancy

 Pathogenesis

o immune-mediated responses to certain drugs and infectious organisms

o keratinocyte death occurs from extensive apoptosis

o suicidal interaction between Fas and Fas ligand

o soluble FasL is secreted by peripheral blood mononuclear cells

o Cytokines released by T lymphocytes, macrophages, or keratinocytes may enhance


the expression of Fas and FasL on keratinocytes or enhance skin recruitment of
lymphocytes by up-regulating adhesion molecules

o SJS: significantly increased incidence of HLA-B12, HLA-Aw33, and DRw53

o HSV EM: HLA-DQw3

o TEN: HLA-B12

o ocular lesions of SJS: HLA-B44

 Histopathology

o Skin: lymphocytic infiltrate at the dermal–epidermal junction with a characteristic


vacuolization of epidermal cells and necrotic keratinocytes within the epidermis

o Eye: nonspecific inflammatory response is seen in the acute phases. In chronic


phase, absence of the mucus-producing goblet cells as sequel of cicatrization.

 Management

o Systemic: specialized nursing and medical care, fluid balance, respiratory


function, nutritional requirements, and wound care

o Ophthalmic:

o Acute: ocular surface hygiene, preservative-free artificial tear, Cycloplegics,


topical steroids (controversial), Lamellar or penetrating keratoplasty

o Chronic stage

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1. restore eyelid and forniceal anatomy and function: Epilation, cryotherapy,


argon laser treatment, electrolysis, or blepharotomy for trichiasis

2. supply tear function: artificial tear supplementation, 10% N-acetylcysteine,


tarsorrhaphy

3. restore ocular surface: Keratolimbal allograft (keratoepithelioplasty),


Topical transretinoic acid can be used to reverse conjunctival
transdifferentiation seen after ocular surface injury.

 Prognosis

o AIDS patients who develop erythema multiforme do not have a worse prognosis.
Elderly patients have a worse prognosis, and children have the best.

Toxic Conjunctivitis

 keratoconjunctivitis caused by topical atropine was described by Von Graefe in 1864

 Toxicity versus Allergy

o Toxicity implies damage to the structure of the ocular tissues, or disturbance of


function, with or without an accompanying inflammatory response. Allergic
reactions may be of the anaphylactoid (type 1) or of the delayed (type IV)
hypersensitivity type.

o Follicles are generally not seen in allergy alone, and may be a key sign suggesting
toxicity.

o Allergic conjunctivitis is often associated with a mucous discharge that is typically


thin and clear. A more purulent or mucopurulent discharge may be associated with
toxicity.

o TOXIC: oval epithelial defects located primarily in the inferonasal quadrants, with
coarse surrounding keratitis, resembling a ‘comet's impact’ crater

 Diagnostic testing

o type 1 hypersensitivity  intradermal skin test

o type IV hypersensitivity  the patch test

 Hurricane keratitis

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o postoperative corneal transplant patients as a result of the toxicity of topical


medications.

o whorl-shaped punctate keratopathy develops as early as 1 week

o related to the intrinsic pattern of corneal epithelial repair, which appears to be a


spiral or whorl-shaped epithelial slide

Superior Limbic Keratoconjunctivitis

 January 1963, Frederick Theodore

 Clinical features

1. marked inflammation of the tarsal conjunctiva of the upper lid

2. inflammation of the upper bulbar conjunctiva

3. fine punctate staining of the cornea at the upper limbus and the adjacent conjunctiva
above the limbus

4. superior limbic proliferation

5. filaments on the superior limbus or upper fourth of the cornea in about half of the
patients.

 Histopathology: The superior palpebral conjunctiva shows goblet cell hypertrophy, while
the bulbar conjunctiva, which is thickened and keratinized, shows very few goblet cells.

 Origin and Pathogenesis

o The origin of SLK has not been determined: viral, immunologic

o interesting associations: thyroid disease (hyperthyroidism, is present in patients


with SLK in at least 30%), KCS

 Treatment

o Conjunctival resection

o therapeutic soft contact lenses

o 0.5–1% silver nitrate

o botulinum toxin injection of the orbicularis

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o thermal cauterization

o topical vitamin A

o topical use of cromolyn sodium

o Supratarsal triamcinolone injection

o Liquid nitrogen cryotherapy: Brymill E tip spray (0.013-inch aperture) with a


double freeze–thaw technique is another approach described by Frederick
Fraunfelder

o N-acetylcysteine

 DD

o Theodore's SLK and CL-SLK: CL-SLK is not always bilateral and has no relationship
with thyroid disease. SLK is more commonly seen in females, while CL-SLK is not.
CL-SLK also occurs in younger patients than does SLK. While vision with SLK is
usually not decreased, it can be severely decreased in patients with CL-SLK, since
corneal involvement is greater. Corneal filaments are usually not seen with CL-SLK,
but they are frequently seen with SLK. A final distinction between the two is that
contact lens keratoconjunctivitis often improves quickly after cessation of lens
wear, whereas SLK goes on with remissions and recurrences for many years.

Ligneous Conjunctivitis
 protracted course of recurrent, membranous, conjunctival lesions, which has been
associated with a systemic plasminogen deficiency

 1847, Bouisson

 Borel in 1933, assigned the name ligneous  meaning ‘woody,’ to this disorder because of
the charateristic woodlike consistency of the membranes in severe cases

 median age of first clinical manifestation was 9.75 months

 CF

o chronic conjunctivitis

o ligneous lesion appears as a highly vascularized, raised, friable lesion.

o can be removed easily with forceps, although it tends to bleed

o pain and photophobia, almost constant discomfort

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o more severe lesions extend beyond the lid margin, giving rise to one of the worst
complications of the disorder, the cosmetic deformity

 Pathophysiology

o type I plasminogen deficiency

 Etiology

o type I plasminogen deficiency has been reported to cause any form of


pseudomembranous disease.

 Treatment

o Plasminogen substitution: Topical plasminogen preparations,

o complete excisional biopsy of all ocular ligneous lesions

o systemic and topical FFP and started on a corticosteroid and broad-spectrum


antibiotic four times daily with topical ciclosporin A 2% twice daily.

Conjunctivochalasis

 redundant conjunctiva

 Hughes in 1942

 most often located between the eyeball and the lower eyelid.

 grading of the degree of CCh was found to have a high predictive value for diagnosis of
KCS

 Epidemiology

o changes related to the aging eye

 Histopathology

o senile process related to conjunctival laxity

o abnormalities in the extracellular components: MMP-1 and MMP-3 were found to


be overexpressed in the conjunctivochalasis fibroblasts. tissue inhibitors of
metalloproteinases (TIMPs) expression remains unchanged, particularly TIMP-1 and
TIMP-2. This change in the ratio of MMPs to TIMPs may facilitate the breakdown

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of the extracellular matrix and result in the clinical changes observed in


conjunctivochalasis.

 CF:

o irritation in mild stages, marked tearing due to obstruction of the lower punctum
in the moderate stage, and ocular surface exposure in more severe stages.

 Diagnosis

o Rule out lid pathology

o LIPCOF classification

0. No persistent fold

1. Single, small fold

2. More than two folds and not higher than the tear meniscus

3. Multiple folds and higher than the tear meniscus

o Meller’s new grading system for conjunctivochalasis

 Treatment

o No treatment is recommended if the patient is asymptomatic

o medical therapy: surface lubricants, antihistamines, and topical corticosteroids

o Surgical management:

Developmental Abnormalities of Cornea

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Anomalies of Size and Shape


 organogenesis (between the fourth and sixth gestational weeks)

 period of anterior segment differentiation (between the sixth and sixteenth gestational
weeks)

 Absence of the Cornea

o always accompanied by agenesis of various other anterior segment structures.

 True cryptophthalmos, otherwise known as complete cryptophthalmos or ablepharon,


occurs when skin replaces the normal eyelid architecture and connects to the underlying
globe, leaving the cornea and part of the conjunctiva unprotected and exposed.

The term cryptophthalmos syndrome, also termed Fraser syndrome, has been used to
describe patients who meet specific criteria as outlined by Thomas.

 Pseudocryptophthalmos (total ankyloblepharon) is a related condition in which the


eyelids form but fail to separate, leaving a normal cornea and conjunctiva totally covered
by skin. Unlike its true counterpart, both lashes and brows are present with an otherwise
normal eye, and vision is restored by surgically creating a palpebral fissure.

 cornea usually reaches adult size by 2 years of age.

 newborn cornea measures approximately 10 mm in horizontal, adult 12 mm

 Megalocornea

o horizontal diameter greater than or equal to 13 mm

o XR Xq21, Xq12; nonprogressive, bilateral and symmetrical

o steeper cornea usually results in with-the-rule astigmatism and myopia

o pathognomonic biometric findings of X-linked megalocornea not present in


congenital glaucoma or other forms of megalocornea: markedly increased anterior
chamber depth, posterior lens and iris positioning, and a short vitreous length

 Microcornea

o horizontal diameter less than or equal to 10 mm in an otherwise normal-sized


globe
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o nonprogressive, unilateral or bilateral

o Male = Female

o AD, AR, Sporadic

o Flatter than normal cornea hyperopia

o rarely an isolated condition and can have many ocular and systemic anomalies
associated with it

o 20% of patients with microcornea develop glaucoma, with angle closure being most
common

 Oval cornea

o horizontal oval cornea: exaggeration of scleral encroachment in the superior and


inferior horizontal meridians. indicates the presence of some degree of
sclerocornea and has no other associated findings.

o Vertical oval cornea exists when the vertical diameter of the cornea exceeds the
horizontal diameter. a/w iris coloboma, microcornea, intrauterine keratitis,
Rieger's anomaly, and Turner's syndrome.

 Astigmatism

o with-the-rule astigmatism in the first decade of life progressing to against-the-


rule astigmatism in later years.

 Sclerocornea (cornea plana)

o cornea is flat with a curvature of less than 43 diopters (D)

o ranges from 30 to 35 D

o The embryologic explanation for sclerocornea: absence of the limbal anlage, the
structure responsible for both limbal differentiation and corneal curvature.

o Bilateral & asymmetric, may be unilateral

o AD, AR (chromosome 12), Sporadic

o Male = Female
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o Total or Peripheral

o Mx: Refraction, PK, Glaucoma Mx

 Keratoglobus

o typically develops during the first 20 years of life

o bilateral, noninflammatory, ectatic disorder in which the entire cornea becomes


thinned and takes on a globular shape, with keratometry readings as high as 60–70
D.

o strong association with Ehlers-Danlos syndrome type VI

 Congenital Anterior Staphyloma

o bulging, opaque cornea lined posteriorly with uveal tissue protrudes through the
palpebral fissure beyond the plane of the normal eyelids

o result from the abnormal migration of neural crest cells into the developing
cornea

o cornea is vulnerable to perforation in utero and subsequently undergoes dermoid


transformation to resemble the stratified squamous epithelium of skin

o unlike cryptophthalmos, the metaplastic change is limited to the cornea and does
not involve the conjunctiva or eyelids.

 Keratectasia

o congenital anterior staphyloma minus the posterior uveal lining.

ARS and PA

 Axenfeld syndrome, which is Axenfeld anomaly with glaucoma.

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 While the word ‘syndrome’ means systemic abnormalities in ‘Rieger syndrome,’ it means
glaucoma when used in ‘Axenfeld syndrome.’

 Divisions of Axenfeld-Rieger syndrome

PARR PAIS

Posterior Angle Iris stroma Systemic Glaucoma


Disease
embryotoxon abnormalities abnormalities abnormalities risk
Posterior
+ − − − −
embryotoxon
Axenfeld
+ + − − +
anomaly
Rieger
+ + + − +
anomaly
Rieger
+ + + + +
syndrome

 Axenfeld-Rieger Syndrome

Noninflammatory Ectatic Disorders

 Corneal ectasia following keratorefractive surgery

o Randleman et al. studied patients with post-LASIK ectasia and identified five main
risk factors for this complication.

1. Young age at the time of surgery

2. abnormal preoperative topography,

3. reduced residual stromal bed thickness

4. decreased preoperative cornea thickness,

5. High myopia

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 Pellucid marginal degeneration (PMD)

o Schlaeppi appropriately chose the name pellucid, meaning clear, to describe this
thinning disorder. These corneas are generally clear and avascular, with no iron
ring, infiltrate, or lipid deposition.

o bilateral, peripheral corneal ectatic disorder characterized by a band of thinning


1–2 mm in width, typically in the inferior cornea, extending from the 4 to the 8
o'clock position.

o In contrast to keratoconus, maximal corneal protrusion typically occurs just


superior to, rather than within, the area of thinning

o shift in the axis of astigmatism from against-the-rule, superiorly, to with-the-rule,


near the point of maximal protrusion.

o PMD and keratoconus can occur in the same eye

o typical crab-claw illustrates the shift in astigmatism from the superior to the
inferior cornea

o poor candidates for refractive surgery because of the potential for an undesirable
outcome and the risk that the surgical procedure might stimulate progressive
ectasia.

o present for treatment between the second and fifth decades of life with
complaints of blurred vision resulting from irregular astigmatism.

o DD:

 The findings typical of keratoconus, specifically, protrusion within the area


of corneal thinning, striae, and Fleischer's ring, are not seen in PMD.

 Terrien's marginal degeneration can cause high astigmatism in a similar


age group. However, in contrast to pellucid degeneration, this disorder has
a male predilection. It commonly affects the cornea, superiorly as well as
inferiorly, with vascularization and lipid deposition. When corneal
protrusion occurs in Terrien's degeneration, it is usually within the area of
thinning.

 Mooren's ulcer is usually unilateral and is associated with marked


inflammation and pain, an epithelial defect in the area of ulceration,
undermining of the central edge of the ulcer, and vascularization up to the
peripheral edge. Corneal changes in Mooren's ulcer are not confined to the
inferior or superior cornea.

 Idiopathic furrow degeneration, while bilateral and noninflammatory,


occurs in the elderly within a corneal arcus.

o Mx;

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 Spectacles usually fail to adequately correct the high irregular astigmatism


associated with typical cases of PMD. Large-diameter, rigid gas-permeable
contact lenses can be tried. However, because of the contour abnormality,
a stable long-term fit can be difficult to achieve. The hybrid lenses, such as
the SoftPerm lens, have been used successfully in PMD. The newer
generation of scleral lenses made from gas-permeable plastic may also be
of benefit.

 Large-diameter or eccentric penetrating keratoplasty may be necessary


to encompass the area of peripheral thinning.

 thermokeratoplasty, crescentic lamellar keratoplasty, and crescentic or


wedge excision

 Keratoglobus

o bilateral ectatic disorder that is usually nonprogressive or minimally progressive.

o generalized thinning, most marked in the periphery

o Acute hydrops occurs less frequently than in keratoconus; however, the opposite
is true about corneal perforation and rupture. Keratoglobus patients are prone to
corneal rupture after minimal trauma, even when there is no history of trauma.

o Associations:

 Unlike keratoconus, keratoglobus is not associated with atopy,


tapetoretinal degeneration, or hard contact lens wear. Keratoglobus has
been reported in association with inflammatory orbital pseudotumor,
chronic marginal blepharitis, chronic eye rubbing, and in glaucoma
following penetrating keratoplasty. Acquired keratoglobus has also been
described in association with vernal keratoconjunctivitis and
hyperthyroidism.

 no association with Down's syndrome, keratoglobus has been reported in


association with Rubinstein-Taybi syndrome, in which intellectual
impairment occurs

o Management:

 Spectacle correction is the first step

 There may be a role for a rigid gas-permeable scleral lens

 lamellar graft or epikeratoplasty

 Posterior Keratoconus

o thinning results from an increase in the curvature of the posterior cornea


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o keratoconus posticus generalis the entire posterior corneal surface has an


increased curvature and the cornea typically remains clear.

o In the localized form, keratoconus posticus circumscriptus, there may be one, or


occasionally more, central or paracentral areas of posterior excavation associated
with variable amounts of stromal scarring

o relative lack of involvement of the anterior refractive surface explains why


posterior keratoconus results in only mild to moderate reduction in visual function.

o developmental, usually nonprogressive, noninflammatory, and unilateral

o does not develop into keratoconus, despite the fact that anterior steepening can
occur in a central or paracentral affected area.

o similarities between posterior keratoconus and Peters' anomaly. However, a


difference is observed histopathologically. In Peters' anomaly the corneal
endothelium and Descemet's membrane are either absent or markedly thinned,
which is not the case in posterior keratoconus.

Keratoconus

Kerato= Horn, cornea

Conus= cone

 Keratoconus is a noninflammatory , ectatic corneal condition characterized by central or


paracentral stromal thinning , apical protrusion and irregular astigmatism

 British physician, Jhon Nottingham in 1854 did practical observations on conical cornea

 50-230 / 100000 individuals

 M=F

 Starts at puberty, over a period of 10 to 20 years the process continues until the
progression gradually stops

 Familial incidence= 65%, Autosomal dominant with variable penetrance

 Pathophysiology:

o Antioxidant deficiency

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o Proteinase and antiproteinase imbalance: up-regulation of degradative enzymes


and the down-regulation of proteinase inhibitors could result in a degradation of
the extracellular matrix of the stroma

o Apoptosis: Keratocytes from keratoconus corneas have been found to have four
times the interleukin-1 binding sites, when compared to nonkeratoconus corneas.
This may result in an increased sensitivity of the keratocytes in keratoconus to the
effects of interleukin-1. Interleukin-1 has also been shown to induce apoptosis or
controlled cell death of stromal keratocytes in vitro.

o Contact lens wear is another form of corneal microtrauma: 17.5% to 26.5%

o ectodermal disease, then associations with atopic disease and tapetoretinal


degenerations

 Pathology:

o Breaks in the epithelial layer can be associated with epithelium growing


posteriorly into Bowman's layer and collagen growing anteriorly into the
epithelium, forming Z-shaped interruptions at the level of Bowman's layer. These
Z-shaped areas are typical of keratoconus.

o Fleischer ring found at the base of the cone

o normal-sized collagen fibers; however, the number of collagen lamellae was


abnormally low. The number found within the cone was less than half (41%) the
number outside of the cone.

o Endothelial cell pleomorphism and polymegathism occur in keratoconus

 CF:

o Late teens

o Blurring of vision

o Shadowing around images

o Glare, halos, ocular irritation

o Frequent changes in spectacle number

o Contrast sensitivity measurement may, however, uncover visual dysfunction before


Snellen visual acuity loss can be measured

o Two types of cones have been described. The round or nipple-shaped cone is
smaller in diameter, while the larger oval or sagging cone may extend to the
limbus and is more prone to contact lens fitting problems.

 Signs:

o Irregular astigmatism

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o Striae occur in the posterior stroma, just anterior to Descemet's membrane.

o Red reflex - Oil droplet sign

o Scissoring reflex

o Vogt ‘s straie

o Fleischer’s ring

o Prominent corneal nerves

o Corneal topograph

o Progressive corneal thinning

o Munson’s sign

o Central corneal scarring: Factors predictive of incident corneal scarring include


corneal curvature greater than 52 diopters (D), contact lens wear, corneal
staining, and age less than 20 years.

 Investigations:

o The keratometer is an invaluable, widely available tool for measuring corneal


curvature. Inability to superimpose the central keratometric rings suggests
irregular corneal astigmatism, a hallmark of keratoconus.

o Keratoscopy or videokeratography, based on the Placido disk, can provide


qualitative contour information. In early keratoconus, a focal area of increased
corneal curvature appears as an isolated area of smaller ring spacing and
distortion. As the condition progresses, the ring spacing decreases overall and
becomes increasingly irregular

 Rabinowitz has suggested four quantitative videokeratographic indices as an aid for


screening patients for keratoconus. These indices include

1. central corneal power value greater than 47.2 D

2. inferior–superior dioptric asymmetry (I-S value) over 1.2

3. Sim-K astigmatism greater than 1.5 D

4. skewed radial axes (SRAX) greater than 21 degrees.

 KISA% index:

o Uses 4 parameters 

o keratometry; I-S value; the AST index, which quantifies the degree of regular
corneal astigmatism (simulated flat and steep keratometry values, Sim K1 and Sim
K2); and SRAX, which is an expression of irregular astigmatism.

 keratoconus-prediction index(KPI) Indices of Maeda and Klyce


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o derived from eight other quantitative videokeratographic indices.

o two simulated K values (steep and flat powers), differential sector index (DSI),
center/surround index (CSI), opposite sector index (OSI), surface asymmetry index
(SAI), analyzed area (AA), and the irregular astigmatism index (IAI).

 Amsler-Krumeich classification

• Stage 1:

Eccentric steeping

Myopia and astigmatism < 5.00 D

Mean central K readings < 48.00 D

• Stage 2:

Myopia and astigmatism from 5.00 to 8.00 D

Mean central K readings < 53.00 D

Absence of scarring

Minimum corneal thickness >400 µm

• Stage 3:

Myopia and astigmatism from 8.00 to 10.00 D

Mean central K readings >53.00 D

Absence of scarring

Minimum corneal thickness 300 to 400 µm

• Stage 4:

Refraction not measurable

Mean central K readings >55.00 D

Central corneal scarring

Minimum corneal thickness 200 µm

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 Systemic Association:

o ATOPY

 Asthma

 Atopic keratoconjunctivitis

 Hay fever

 Eczema

o CONNECTIVE TISSUE DISORDERS

 Marfan’s syndrome: An increased prevalence (38%[20] to 58%) of mitral


valve prolapse has been found in keratoconus patients

 EDS

 Osteogenesis imperfecta

o MISCELLANEOUS

 Down’s: 5.5% and 15%

 structural or biochemical changes

 habitual eye rubbing

 Turner’s syndrome

o diabetes offered a protective effect regarding keratoconus. (also smoking?? As they


cause C3R like effect)

 Ocular Associations:

o RP

o Infantile tapetoretinal degeneration (Leber's congenital amaurosis) is frequently


complicated by keratoconus and cataract.

o retinopathy of prematurity, progressive cone dystrophy, aniridia, iridoschisis, and


essential iris atrophy

o VKC: 26.8%.

o 17% in a group of patients with floppy eyelid syndrome.

 Cx:

o High Refractive errors: Intolerance to glasses

o Acute Hydrops : Rupture Descemet’s membrane Aqueous influx  Corneal


edema Sudden drop in vision / Opacity
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Management
o The management of keratoconus begins with spectacle correction.

o Once glasses fail to provide adequate visual function, contact lens fitting is
required. Contact lens wear improves visual function by creating a new anterior
refractive surface. Contact lenses do not prevent progression of corneal ectasia.
While they seem to be associated with the development of keratoconus in some
cases, this important mode of therapy should never be withheld for fear of causing
progressive disease.

 RGP: three-point touch technique, remain the mainstay of contact lens


treatment for keratoconus. apical clearance fitting technique is also
commonly used.

 Other options include soft toric lenses, standard bicurved hard lenses,
custom-back toric lenses, piggyback systems, hybrid lenses made of
combined hard lens with a soft skirt, scleral lenses, and mini-scleral lenses.

 Hybrid lenses, such as the SoftPerm lens (CIBA Vision Corp., Duluth, GA)
and the newer SynergEyes KC lens (SynergEyes, Inc., Carlsbad, CA) may be
more comfortable for patients who cannot tolerate an RGP alone.

 Mini-scleral lenses have a diameter of 14–17 mm compared to scleral


lenses with a diameter of 20–24 mm.

o Contact lens-intolerant keratoconus patients without central scarring, who have


mild or moderate disease, may be candidates for intrastromal ring segment
insertion. The ideal candidates also have low spherical equivalents and average
keratometry readings of less than 53 D.

 Ferrara rings (Ferrara Ophthalmics, Belo Horizonte, Brazil) and Intacs


(Addition Technology Inc, Des Plaines, IL, USA), commonly used ring
segments, are made of rigid polymethyl methacrylate. Ferrara rings have a
fixed inner diameter of 5.0 mm and a triangular anterior contour. Intacs
have an inner diameter of 6.8 mm, a flat anterior surface, and are available
in thicknesses of 0.25–0.45 mm, in 0.05 mm increments.

o C3R (read below as separate theory)

o While penetrating keratoplasty has traditionally been the surgery of choice,


lamellar surgery is becoming more popular for patients with mild to moderate
disease.

 The iron ring, found at the base of the cone, should be used as a reference
when planning graft size.

 Postkeratoplasty myopia can be reduced by using the same-sized donor and


host corneal buttons.

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o Lamellar Keratoplasty

 Deep anterior lamellar keratoplasty (DALK): host endothelium is preserved,


thus reducing the risk of rejection. The risk of endophthalmitis is
theoretically less because this is largely an extraocular procedure.

C3R
o Collagen cross-linking (CXL or C3-R) is the most recent addition to the surgical
armamentarium and may slow or halt the progression of keratoconus by using a photo-
oxidative treatment to increase the rigidity of the corneal stroma.

o Theo Seiler, MD, PhD, of Switzerland, was the first to suggest applying this principle to
ophthalmology, more specifically cross-linking corneal collagen fibers.

 The principal effects of cross-linking are localized to the anterior 300 µm of the
stroma.

 Riboflavin is a vitamin (vitamin B2), nontoxic and available as a drug. It has two
important functions: the absorption of the UV-irradiation and as photosensitizer
the generation of reactive oxygen species (singlet oxygen).
 molecular weight (376 g/mol)  so epithelial debridement needed
 Lambert-Beer’s-law: 400 μm-thick cornea the concentration at the endothelium
reaches a level where the absorption of the UV-light is high enough to protect
endothelium and intraocular structures
 two absorption maxima: 365 nm and 430 nm. 365 nm  higher energy, so it is used
 with an irradiance of 3 mW/cm² an optimal irradiation time of 30 minutes was
found
 damage threshold for the endothelium of 4 mW/cm2 and it gets only 0.18
mW/cm2. no risk for lens and retina.
 UVA-radiation source: UV-X (Fa. Peschke)  homogenous irradiance of 3 mW/cm²
in a distance of 5 cm within a diameter of 8 mm of the central cornea

Effect and Evidence of Cross-linking

 cross-linked cornea is stiffer by factor 1.8 than normal cornea


 cornea´s shrinking temperature is raised from 63°C to 70°C.
 Cross-linked collagen shows significantly less tendency for swelling
 The diameter of collagen lamellas increases by 12% in the anterior stroma and by 4.5% in the
posterior
 enhanced resistance against proteolytic enzymes
 Apoptosis of keratocytes in the anterior stroma is seen after cross-linking. new keratocytes
move in from the limbus.

 328.9% increase in corneal rigidity

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 2.68 D reduction in corneal power at 1 year postoperatively. Three years after the
treatment, the BCVA improved one line in 58% of 33 eyes and remained stable in 29% of eyes

 most beneficial for patients with mild progressive keratoconus

 corneal stroma is greater than 400 µm thick

Avedro KXL:

The KXL System for Accelerated Cross-linking achieves speed by increasing the UVA power
and reducing the exposure time, thereby maintaining the same energy on the eye as
standard cross-linking while reducing crosslinking time by an order of magnitude.

Avedro’s new procedures made possible with its KXL System, can restore the strength of the
cornea with a 5-minute treatment that accompanies LASIK, according to a company news
release.

“Lasik Xtra helps patients avoid the risk of ectasia after LASIK, which has become a
troublesome and unpredictable unpredictable problem,” David Muller, PhD, President and
Chief Executive Officer of Avedro, said in the news release. “In addition, our accelerated KXL
procedure offers a much more acceptable treatment for patients with keratoconus and for
those already suffering from post-LASIK ectasia.”

Other uses of C3R

 Athens Protocol

 Corneal ulcer

 LASIK Xtra

o Prophylaxis in myopic LASIK

o Hyperopic LASIK (!!.. Yes this is to prevent regression..!!)

Iridocorneal Endothelial Syndrome

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 The diagnosis of the ICE syndrome is considered when two of the three main clinical
features are present unilaterally: typical iris changes, abnormal corneal endothelium,
and PAS.

 Coincidentally, the acronym ICE also signifies commonly used names of these conditions –
Iris nevus syndrome, Chandler's syndrome, and Essential (progressive) iris atrophy.

 Etiology

o Unknown

o membrane theory of Campbell

 Earliest stage of iris and anterior chamber angle involvement. Solitary


peripheral anterior synechiae (PAS), but no pupil and iris abnormality.

 Growth and extension of abnormal membrane from posterior corneal


surface over the anterior chamber angle

 contraction of membrane on iris surface, and early stretch-induced iris


stromal atrophy in the quadrant opposite the membrane

 Diffuse anterior chamber angle and iris involvement with abnormal


membrane growth

 Essential iris atrophy

o Most common

o first presents typically in young adults, unilaterally, and in women > men

o bare eccentricity of the pupil to severe corectopia

o Iris atrophy and partial-thickness holes in the iris stroma appear on the side
opposite the pupillary eccentricity

o Glaucoma, iris atrophy, or nodules

o Specular microscopy is an invaluable tool for early or confirmatory diagnosis.


Although endothelial cell pleomorphism and a decrease in the percentage of
hexagonal cells of the contralateral eye have been described, typical morphologic
specular microscopic changes (ICE cells) are unilateral.

 Chandler's syndrome

o blurred vision or seeing colored halos around lights.

o Corneal edema was first described as occurring at a normal or slightly elevated


intraocular pressure and, because of the abnormal endothelium, is the dominating
clinical characteristic of this subtype of ICE syndrome

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o The abnormal corneal endothelium, best seen with specular reflection, has a fine
hammered silver appearance, which is finer in appearance than the guttata of
Fuchs’ endothelial dystrophy

 Cogan-Reese syndrome

o the least common of the major variants of ICE syndrome

o A hyaline membrane (‘ectopic Descemet's membrane’)

 Iris nevus syndrome

o unilateral diffuse nevus of the iris and several other signs including loss of surface
architecture of the iris resulting in a matted appearance, ectropion uvea,
heterochromia, PAS, corneal edema, and unilateral glaucoma.

 Differential Diagnosis

o Posterior polymorphous dystrophy

o Axenfeld-Rieger syndrome

 Management

o Medical treatment is generally ineffective

o glaucoma develops it may be managed initially with aqueous suppressants.


glaucoma filtering surgery is required

o corneal edema may respond to lowering intraocular pressure. Hypertonic saline


solutions and soft contact lenses may be helpful

o Cataracts may develop de novo or subsequent to glaucoma or corneal surgery.

Corneal and Conjunctival Degenerations

 Degeneration of a tissue is defined as a deterioration and decrease in function.

 Arcus senilis:

o Gerontoxon in geriatrics

o arcus juvenilis or anterior embryotoxon in the young

o lipid deposition in the peripheral cornea

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o gray to yellow arc, first in the inferior cornea then the superior cornea

o sharp peripheral border ending at the edge of Bowman's layer with a lucent zone
(lucid interval of Vogt) to the limbus

o Histopathologically, the arcus has an hourglass appearance as the opacity extends


into the corneal stroma from these two layers.

o lipid particles are similar to a type found in human atherosclerotic lesions but
accumulate in the absence of foam cells, unlike atherosclerotic lesions.

o limbal vasculature is part of a low-pressure perfusion system. The endothelium of


these blood vessels act as tight junctions but in the presence of elevated
circulating LDL may become dysfunctional. Lipid in the peripheral cornea likely
originates from LDL, it is modified LDL and apo B sparse.

o affects men more than women.

o Hyperlipoproteinemia types IIa and IIb are associated with premature corneal arcus
formation

o Rare genetic disorders of high-density lipoprotein (HDL) metabolism causing


corneal deposits include lecithin cholesterol acyltransferase (LCAT) deficiency,
fish eye disease and Tangier disease.

 Lipid degeneration

 primary lipid degeneration

o no prior history of the following: trauma, family history of similar conditions,


corneal vascularization, and no known disorders of lipid metabolism.

o due to increased vascular permeability of the limbal vessels. Alternatively, the


etiology may be an altered metabolic activity of the keratocytes

o more common in women than men, with a ratio of 70 : 30

 Secondary lipid degeneration

o associated with corneal neovascularization

 Spheroidal degeneration (climatic droplet keratopathy)

o Bietti's nodular corneal degeneration, Labrador keratopathy, climatic droplet


keratopathy, degeneratio corneae sphaerularis elaioides, corneal elastosis,
fisherman's keratitis, keratinoid corneal degeneration, and chronic actinic
keratopathy.

o Type 1 occurs bilaterally in the cornea without evidence of other ocular pathology
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o Type 2, or secondary spheroidal degeneration, occurs in the cornea in association


with other ocular pathology.

o Type 3 is the conjunctival form of the degeneration and may occur with types 1 or
2

o clear to yellow-gold spherules are seen in the subepithelium, within Bowman's, or


in the superficial corneal stroma. They measure from 0.1 to 0.4 m

o Etiology: ultraviolet radiation and microtrauma including sand, dust, wind, and
drying.

o HP: hyaline-like material are found in the corneal stroma, Bowman's layer, and
subepithelium. Bowman's layer is disrupted, and in advanced cases the epithelium
is elevated and thinned. They have a histochemical staining characteristic similar
to degenerative connective tissue, such as in pingueculae, but fail to stain for
other components found in elastotic material from pingueculae.

 Climatic proteoglycan stromal keratopathy

 Amyloid degeneration

o Primary localized

o Primary systemic

o Secondary localized

o Secondary systemic

 Salzmann's nodular degeneration

o degenerative process that follows episodes of keratitis.

o history of phlyctenular disease but was also observed after vernal


keratoconjunctivitis, trachoma, measles, scarlet fever, or interstitial keratitis

o idiopathic or in association with practically any significant corneal inflammatory


disease, especially meibomian gland dysfunction

o Lubrication can be tried for mildly symptomatic lesions. Superficial keratectomy,


by manual dissection or with phototherapeutic keratoablation, may be used for
lesions near the visual axis. For lesions extending to the mid stroma, lamellar or

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penetrating keratoplasty may be necessary. Recurrence is possible after


keratoplasty. The recurrent lesions are often not clinically similar to the original
lesion but are indistinguishable histologically.

 Corneal keloids

o after trauma or in association with chronic ocular surface inflammation

o in association with Lowe's syndrome & Rubinstein-Taybi syndrome.

o Clinically similar to SND but usually seen in a younger age group than Salzmann's
degeneration and occur more frequently in men.

o superficial keratectomy or penetrating or lamellar keratoplasty may be performed


for visually significant lesions.

 Terrien's marginal corneal degeneration

o peripheral inflammatory condition

o 20 and 40 years of age.

o M:F = 3:1

o bilateral and symmetric

o usually begins superonasally with fine punctate opacities in the anterior stroma
with a lucent area to the limbus.

o vascularization from the limbal arcades leading to the lesion differentiates it from
arcus.

o gutter similar to marginal furrow degeneration then forms between the opacity
and limbus. The stroma progressively thins, usually over many years

o Two types of Terrien's degeneration have been classified.

 The more common quiescent type is seen in older patients. These patients
may be asymptomatic for a long time because the lesion produces no pain.

 Inflammatory Terrien's degeneration usually occurs in the younger age


groups. These patients may have recurrent episodes of inflammation,
episcleritis, or scleritis. This is treated with steroids.

o against-the-rule astigmatism, which may be the presenting symptom

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o HP: fibrillar degeneration of collagen, Epithelium may be normal, thick, or


thinned; Bowman's layer is fragmented or absent. Breaks in Descemet's membrane
may be seen in thinned areas

 Limbal girdle (of Vogt)

o two types

o crescentic yellow-to-white band found in the interpalpebral limbus

 Type 1 appears as a white band that may contain holes. The central border
is relatively sharp with no extensions. It is separated from the limbus by a
narrow lucent area. Type 1 is generally thought to represent early calcific
band keratopathy.

 Type 2, however, is thought to be a true limbal girdle. This chalky band


has no holes or clear interval to the limbus. Centrally, there are irregular
linear extensions.

o Histopathologically, the lesion is subepithelial and may have overlying epithelial


atrophy. Destruction and calcification of Bowman's layer have been observed in
type 1.

 Band keratopathy

o Two forms

o Calcific band keratopathy

o deposition across the cornea at the level of Bowman's layer

o causes

1. Hypercalcemic states

2. Chronic ocular disease

3. Chemicals (eye drops and irritants)

4. Inherited diseases

5. Systemic diseases

6. Idiopathic

o sharply demarcated peripheral edge separated from the limbus by a lucent zone.
This zone is due either to the lack of Bowman's layer at the periphery or from the
buffering capacity of the limbal vessels, which prevent precipitation of calcium.

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o HP: fine basophilic granules are first seen at the level of Bowman's layer. Calcium
is deposited in the form of hydroxyapatite, a phosphate salt.

o Mx:

 When the patient becomes symptomatic, the mainstay of treatment is the


application of ethylenediaminetetraacetic acid (EDTA). Epithelial
debridement & 0.05 molar concentration on saturated cellulose sponges.

 excimer laser phototherapeutic keratectomy.

o Calcareous degeneration

o second type of calcific degeneration. Like band keratopathy, this degeneration


occurs in diseased eyes. Unlike band keratopathy, calcareous degeneration
involves the posterior stroma.

o S

 Reticular degeneration of Koby

o fine white reticulum at the level of Bowman's layer. Overlying epithelium may have
a brownish discoloration. This degeneration is most commonly reported in patients
with chronic inflammation.

 Iron lines

o most common iron line is the Hudson-Stähli line, which is located in the lower
third of the cornea

o Iron deposition in filtering bleb after glaucoma surgery was described by Ferry in
1968. It appears on the cornea just anterior to the filtering bleb. He related its
incidence to the size of the filtering bleb. Iron may be seen at the advancing edge
of a pterygium (Stocker's line) and at the base of the cone in keratoconus
(Fleischer ring).

o Histologically, iron, predominantly ferritin, is found intracellularly and


extracellularly in the basal epithelial layer of the cornea, regardless of the type of
iron line.

o The most common theory attributes the deposition to localized trauma at the site
of contour change or to a pooling of tears at this site

 Coats' white ring

o 1 mm or less in diameter

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o inferior portion of the cornea.

 Hassall-Henle bodies

o Descemet's warts are excrescences of Descemet's membrane found in the


peripheral cornea.

 Crocodile shagreen

o corneal mosaic pattern resembling cobblestone or crocodile skin is seen in the


anterior or posterior cornea.

o Histopathologically, the stroma is thrown into folds, either at Bowman's layer in


the anterior form or around Descemet's membrane in the posterior form.

 Senile furrow: Peripheral thinning is seen in the avascular zone between arcus senilis and
the limbal vascular arcades

 Cornea farinata:

o tiny opacities, found bilaterally in the posterior stroma near Descemet's


membrane.

o ‘flour dust’ appearance on retro-illumination

 Dellen:

o Fuchs’ dimples

o Dellen may last only 24 to 48 hours and are found most commonly in the temporal
peripheral cornea, usually adjacent to a paralimbal elevation.

o saucer-like depressions in the corneal surface

o Histopathologically, thinning of the corneal epithelium, Bowman's layer, and


anterior stroma is seen. Treatment with ocular lubricants or pressure patching will
accelerate the healing process.

 Pingueculae

o elevated masses on the conjunctiva, gray-white to yellow in color

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o interpalpebral zone, paralimbal, in the 3 and 9 o’clock positions.

o more often found nasally than temporally.

o HP: normal, atrophic, or hyperkeratotic conjunctival epithelium. The substantia


propria shows basophilic degeneration on hematoxylin and eosin staining. This
material stains for elastin but is not broken down by elastase. Thus it is termed
elastotic degeneration.

o damage from ultraviolet radiation, Other possible causes of pingueculae include


trauma, wind, sand, or drying

o Gaucher's disease can be associated with a pinguecula that is brownish in color.

 Concretions:

o white to yellow spots found on the palpebral conjunctiva occasionally encased in


clear cysts.

o later stages of trachoma

o chronic inflammation causes hyperplasia and invagination of the conjunctival


epithelium.

o They may be easily removed for patient comfort.

Corneal Dystrophy

 dys = wrong, difficult; trophe = nourishment

 dystrophy word was introduced in 1890 by Arthur Groenouw when he published his
classic paper describing two patients with ‘Noduli Corneae.’

 group of inherited corneal diseases that are usually bilateral, symmetric, slowly
progressive and not related to environmental or systemic factors.

o Exceptions:

1. Hereditary pattern is not present in most patients withEBMD

2. Unilateral corneal changes may be found PPCD

3. Systemic changes are found macular dystrophy, in which the level of


antigenic serum keratan sulfate correlates with the immunophenotypes of the
disease.

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 The first classification by Bücklers of corneal dystrophies described the differences


between granular, macular, and lattice dystrophy.

 The most commonly used classification system is anatomically based.

 International Committee for Classification of Corneal Dystrophies (IC3D) was created in


2005 in order to revise the corneal dystrophy nomenclature and create a current and
accurate corneal dystrophy classification system.

 four descriptive, evidential categories were created in the IC3D classification

o Category 1. A well-defined corneal dystrophy in which the gene has been mapped
and identified and specific mutations are known.

o Category 2. A well-defined corneal dystrophy that has been mapped to one or


more specific chromosomal loci, but the gene(s) remains to be identified.

o Category 3: A clinically well-defined corneal dystrophy in which the disorder has


not yet been mapped to a chromosomal locus.

o Category 4. This category is reserved for a suspected new, or previously


documented, corneal dystrophy, where the evidence for it being a distinct entity is
not yet convincing.

Anterior Corneal Dystrophies

 Meesmann's Juvenile Epithelial Dystrophy

o Least common

o mutation in corneal keratin (K3 or K12)

o seen in the first few years of life as intraepithelial microcysts or vesicles visible
only at the slit lamp.

o Vision is usually good in the first few years of life but may diminish gradually if the
cysts increase in number and cause slight irregularity of the corneal surface.

o Recurrent erosion is not common

 Epithelial Basement Membrane Dystrophy

o map-dot-fingerprint, Cogan's microcystic dystrophy

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o most common anterior corneal dystrophy and is classified as a corneal dystrophy


because these changes occur more in some families

o pathogenesis: Epithelial cells produce abnormal multilaminar basement


membrane, both in normal location and intraepithelially. As the intraepithelial
basement membrane thickens, it blocks normal migration of epithelial cells toward
the surface. Trapped epithelial cells degenerate to form intraepithelial microcysts
that slowly migrate to the surface. Abnormal basement membrane produces map
and fingerprint changes, and microcysts produce the dot pattern seen clinically.

o spontaneous recurrent corneal erosions and blurred vision. The erosions may be
mild and transient, lasting minutes, or occasionally characterized by more severe
pain.

o The treatment has been similar for recurrent corneal erosion, whether traumatic
or dystrophic.

o anterior stromal reinforcement (puncture) seems to be the best way to treat


recalcitrant recurrent erosions below the visual axis. It is effective in 80% of cases
the first time it is done

o Epithelial debridement with diamond burr polishing works best for anterior
basement membrane dystrophy in the visual axis causing either blurred vision or
recurrent erosion.

 Corneal Dystrophies of Bowman's Layer

o Küchle et al divided the anterior membrane dystrophies into two classifications:


corneal dystrophy of Bowman's layer types I (CDB-I) and II.

o Type I is synonymous with Reis–Bücklers’ original dystrophy and equivalent to what


has been called the superficial variant of granular dystrophy. It has an autosomal
dominant inheritance, recurrent corneal erosions beginning in childhood, and is
marked by early and fairly marked visual loss.

o Corneal dystrophy of Bowman's layer type II (CDB-II), which many people have
confused with the Reis–Bücklers’ dystrophy, is honeycomb-shaped and should be
known as Thiel–Behnke corneal dystrophy. Similar to CDB-I, CDB-II's inheritance is
dominant, with recurrent erosions starting early in childhood, but visual acuity is
reduced later in life than with CDB-I. The clinical appearance of these dystrophies
is similar, and differentiation can be made only with light and, particularly,
electron microscopy. Interestingly, CDB-I stains positively with Masson's stain,
whereas CDB-II is only equivocally positive to Masson's stain (honeycomb-shaped,
Thiel–Behnke dystrophy).
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o Transmission electron microscopy differentiates these two dystrophies. In CDB-I,


ultrastructural deposits of rodlike bodies are present, similar to those seen in
granular dystrophy. These changes are not seen in CDB-II. Instead, ‘curly’ fibers
appear in the region of Bowman's membrane.

o they can be managed similarly to the therapy of recurrent erosion due to epithelial
basement membrane dystrophy.

o Phototherapeutic keratectomy (PTK) with the excimer laser is now the treatment
of choice when vision is disturbed sufficiently or painful erosions occur, despite
recurrences after PTK.

Stromal Dystrophies

 Granular corneal dystrophy type 1 (classic)

o 1890 by Groenouw

o small, discrete, sharply demarcated, grayish-white opacities in the anterior central


stroma

o drop-shaped, crumb-shaped, and ring-shaped.

o the stroma between the opacities remains clear.

o As the condition advances, individual lesions increase in size and number and may
coalesce. They frequently extend into the deeper and more peripheral stroma.
However, 2–3 mm of the peripheral cornea usually remain free of deposits.

o autosomal dominant trait and appears in the first or second decade of life

o TGFBI gene-related dystrophy, 5q31 gene locus

o Histopathology

 Light microscopy demonstrates eosinophilic, rod, or trapezoidal-shaped


hyaline deposits in the stroma and beneath the epithelium.

 stain bright red with Masson's trichrome and stain weakly with periodic
acid-Schiff (PAS)

o Management

 Recurrent epithelial erosions should be managed routinely with therapeutic


contact lenses and artificial tears.
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 The traditional surgical approach has been penetrating keratoplasty, which


is uncommonly performed before the fifth decade. If the opacities are
extremely superficial, epithelial scraping, superficial keratectomy, or
lamellar keratoplasty can be performed.

o Granular dystrophy can recur in the grafts as early as 1 year after surgery,

 Granular corneal dystrophy, type 2 (granular-lattice)

o Avellino corneal dystrophy

o (1) anterior, stromal, discrete gray-white granular deposits; (2) mid to posterior
stromal lattice lesions; and (3) anterior stromal haze.

o foreign body sensation, pain, and photophobia, most likely secondary to recurring
erosion.

 Granular corneal dystrophy, type 3 (RBCD – Reis-Bücklers)

 Macular Dystrophy (MCD)

o Fehr spotted dystrophy

o corneal opacities resulting from intracellular and extracellular deposits within the
corneal stroma

o least common and the most severe

o progressive loss of vision as well as attacks of irritation and photophobia. Vision is


usually severely affected by the time the patient reaches the twenties or thirties.

o This opacification extends to the periphery and usually involves the entire
thickness of the cornea by the second decade of life.

o reduced central corneal thickness.

o slit lamp examination demonstrates a ground-glasslike haze in the central and


superficial stroma, which is best observed with oblique illumination. With
progression of the dystrophy, small, multiple, gray-white, pleomorphic opacities
with irregular borders are seen

o autosomal recessive

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o chromosome 16, Type I has no detectable antigenic keratan sulfate; type II has
normal amounts of antigenic keratan sulfate; in type IA the serum lacks detectable
antigenic keratan sulfate, but the keratocytes react with antibodies to keratan
sulfate.

o Histopathology

 accumulation of glycosaminoglycans between the stromal lamellae

 stain with Alcian blue, colloidal iron, metachromatic dyes, and PAS

 Light microscopy demonstrates degeneration of the basal epithelial cells,


and focal epithelial thinning is seen over the accumulated material.
Bowman's membrane may be irregular, thinned, or absent in some areas.
Electron microscopy shows accumulation of mucopolysaccharide within
stromal keratocytes, which are distended by numerous intracytoplasmic
vacuoles with pyknotic nuclei.

o Management

 Tinted cosmetic lenses can be used to reduce photophobia

 Recurrent erosions are treated with therapeutic contact lenses or lubricant


drops.

 Phototherapeutic keratectomy

 lamellar Keratoplasty

 penetrating keratoplasty is the surgical modality of choice

 Lattice Dystrophy

o Biber-Haab-Dimmer dystrophy

o bilateral, inherited, primary, localized corneal amyloidosis.

o ovoid or round subepithelial opacities, anterior stromal white dots, and small
refractile filamentary lines that may appear in the first decade of life

o Histopathology

 sources of the amyloid include leakage from serum, extracellular


breakdown of corneal collagen, and, most probably, localized intracellular
production

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 eosinophilic layer separating the epithelial basement membrane from


Bowman's layer is present and is composed of amyloid and collagen

 stain orange-red with Congo red, and also stain with PAS, Masson's
trichrome, and fluorochrome thioflavin T.

 When viewed with a polarizing filter, amyloid deposits demonstrate green


birefringence

o autosomal dominant mode of inheritance, and the disease results from mutations
at 5q31 gene locus

o Management

 lamellar or penetrating Keratoplasty

 recurs more frequently than does granular or macular dystrophy, and the
recurrence can appear in the graft in as few as 3 years after Keratoplasty

 Schnyder's Crystalline Dystrophy (SCD)

o Bilateral gray, disclike opacities are seen, primarily in the anterior stroma. These
opacities are often central and also may include fine polychromatic cholesterol
crystals in the anterior stroma

 Fleck Corneal Dystrophy (FCD)

 Central Cloudy Dystrophy of François (CCDF)

 Posterior Amorphous Corneal Dystrophy (PACD)

 Congenital Hereditary Stromal Dystrophy (CSCD)

 Pre-Descemet Corneal Dystrophy (PDCD)

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Descemet's Membrane and Endothelial Dystrophies

 Posterior Polymorphous Corneal Dystrophy

o bilateral asymmetrical

o asymptomatic to progressive

o second or third decade of life

o abnormalities in PPCD occur at the level of Descemet's membrane and endothelium


and can be divided into three patterns:

1. vesicle-like lesions: 0.10 to 1.00 mm, sharply demarcated large round


areas that contain lighter thick ridges or cell aggregates

2. band lesions: typically horizontal, have parallel scalloped edges, and do


not taper toward the ends

3. diffuse opacities: either small, macular, gray-white lesions or larger


sinuous geographic lesions at the level of Descemet's membrane

o hallmark of PPCD is the vesicular lesion

o Corneal edema occurs infrequently and ranges from minimal stromal thickening to
bullous keratopathy

o PAS are also a characteristic feature of PPCD and an important prognostic indicator

o Angle closure is thought to result from endothelial cell migration across the
trabecular meshwork onto the iris, forming synechiae. The mechanism of open
angle glaucoma has been suggested to be compression of the trabecular meshwork
secondary to a high iris insertion.

o DD: ICE syndrome

 share many clinical features, including iridocorneal adhesions, glassy


membranes over the angle and anterior surface of the iris, iris atrophy,
corectopia, increased intraocular pressure, and corneal edema.

o Mx:

 Risk factors for severe disease included the presence of iridocorneal


adhesions and increased intraocular pressure. Only 27% of patients had
iridocorneal adhesions, yet 57% of patients with iridocorneal adhesions
required corneal transplantation. Similarly, only 14% of patients in this

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series had increased intraocular pressure, yet 62% of patients with


increased intraocular pressure required corneal transplantation.

o HP:

 epithelium and stroma: chronic edema, subepithelial fibrosis, and band


keratopathy

 Descemet's membrane and the endothelium: thickening of Descemet


membrane with rare foci of bilayered large endothelial cells, to 3–4 layered
broad patches of flattened endothelial cells and irregular thickness of
Descemet's membrane with focal absences

 ABZ: Normal, thinner in early onset

 PNBZ: Absent or minimal, Changes to a thick PCL-like layer with scant BM*

 Fuchs’ Endothelial Corneal Dystrophy

o slowly progressive disease with initial onset in the fifth through seventh decades in
life.

o 50% autosomal dominant, variable penetrance

o Females are predisposed to Fuchs’ dystrophy and develop corneal guttae 2.5
times more frequently than males, progressing to corneal edema 5.7 times more
often than males.

o CF:

 The first stage is asymptomatic. Slit-lamp examination discloses central


corneal guttae, but vision and corneal thickness are normal. Guttae,
irregularly scattered excrescences in the posterior cornea, are often
associated with fine pigment dusting

 In this second stage, patients have painless decreased vision, especially


upon awakening. Vision may improve as the day progresses as evaporation
promotes corneal deturgescence. Glare and haloes may be noted. Stromal
edema occurs in the setting of corneal guttae, most typically in the fifth
decade of life

 Epithelial edema characterizes the third stage. Initially, fine epithelial


microcysts are noted. The epithelial surface is roughened, with an irregular
surface texture. Vision invariably deteriorates during this stage and
marked fluctuations in vision are common. Occasionally, erosive symptoms
are the presenting complaint. Large intraepithelial and subepithelial bullae
may rupture, resulting in severe eye pain and rendering the patient
susceptible to infection.

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 In the fourth stage, growth of avascular subepithelial connective tissue


occurs, causing reduced vision from scarring. The cornea is opaque and
compact. Pain is decreased, but vision is severely reduced to the hand
motions level. Corneal sensation is decreased or absent. With time,
peripheral corneal vascularization may occur.

o Differential diagnosis

 gutta formation without corneal edema has been observed in interstitial


keratitis

 gutta: macular dystrophy and posterior polymorphous dystrophy.

 Corneal pseudoguttae: transient, representing edema of the endothelial


cells, and disappear with resolution of the underlying condition can be
seen after trauma, intraocular inflammation, infection, toxins, and
thermokeratoplasty

 Central herpetic disciform keratitis: keratic precipitates (KP)

 Chandler's syndrome: unilateral

o medical management:

 topical hypertonic saline solutions

 dehydration of the cornea by a blow dryer in the morning or throughout the


day

 lowering the intraocular pressure may reduce the hydrostatic pressure,


which acts to push fluid into the cornea and thereby decrease corneal
edema.

 Bandage lenses may be helpful in the treatment of recurrent erosion caused


by epithelial bullae. a loosely fit, high-water-content soft contact lens,
e.g., Kontur lens, may be used to reduce the irritation and pain

o Surgical Mx:

 cell count of less than 1000 should raise concern about the possibility of
corneal decompensation with intraocular surgery.

 corneal thickness of over 640 microns (µm) increases the risk of corneal
decompensation with cataract surgery

 central corneal thickness exceeds the mid-peripheral thickness, this may


be a indication of clinically significant corneal thickening.

 endothelial transplantation

 optical PK/ Triple Sx


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 CCT < 600 microns, ECD > 1000  cataract surgery f/by DSAEK-OPK

o HP:

 LM: increase in cellular size and irregularity of shape, DM thickens 2-3


times

 EM: normal ABZ of type 7 collagen, PNBZ is of type 4 collagen. Besides a


thin or absent PNBZ, the most typical finding in FECD is an abnormal
posterior collagenous layer (PCL) which is responsible for most of the
thickness.

 Thinning of the endothelium over the enlarging guttate bodies may result in
complete baring of these bodies as the disease progresses: like those in
peripheral Hassal-Henle warts

o Genetics:

 many patients have no known inheritance pattern

 one family traced for  single locus at 13p

 Congenital Hereditary Endothelial Dystrophy

o rare corneal dystrophy except in Saudi Arabia and south India

o bilateral, symmetric, noninflammatory corneal clouding without other anterior


segment abnormalities that is usually evident at birth or within the early postnatal
period

o Differential diagnosis

 Mucopolysaccharidoses: clouding is not present at birth, typically


developing within the first few years, urinalysis or corneal biopsy will
usually identify the abnormal metabolic

 congenital glaucoma: ncreased IOP, often an increase in corneal diameter,


Haab's striae, and, in severe disease, buphthalmos.

 Transient corneal edema can occur in congenital rubella, but, in contrast


to CHED, there is episcleral injection, typically a nuclear cataract,
increased intraocular pressure, posterior synechiae, miosis, and
chorioretinopathy.

 Syphilitic interstitial keratitis also produces an inflamed eye with corneal


clouding, deep stromal vascularization, and iris atrophy, but it rarely occurs
within the first year of life

 Dystrophies at birth-natal age groups: CHED, PPCD and CHSD.


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 CHED 1 (AD)

o Photophobia and tearing

o corneal clouding is not present at birth, developing late in the first year

o chromosome 20p11

 CHED 2 (AR)

o gray-blue, ground-glass haziness of the corneal stroma noted within the first week
to 6 months

o fine nystagmus

o chromosome 20p13-12

o Harboyan syndrome (CHED 2 and perceptive deafness (CDPD)) is an autosomal


recessive disease mapped at overlapping loci 20p13. Novel SLC4A11 mutations
have been found in seven families.

o prognosis for graft clarity and visual rehabilitation is dependent upon the age of
onset

o HP:

 corneal showed alterations secondary to chronic corneal edema, appearing


thin or atrophic with hydropic changes of the basal epithelium

 stroma was generally thickened to two to three times

 Descemet's membrane was usually observed to be thickened.

 The endothelial cells were absent, markedly reduced in number, or showed


evidence of significant degeneration

o EM:

 normal 110 nm ABZ of approximately 3 µm thickness, but an abnormal,


poorly demarcated PNBZ merging into, or mixed with, a PCL.

 X-Linked Endothelial Corneal Dystrophy (XECD)

PUK

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 From DOS article

Corneal Infections

Herpes Simplex Keratitis


 HSV-1 usually involves the oropharynx and HSV-2 usually involves the genital area

 ocular disease is caused by type 1 rather than type 2, with the exception of herpetic
keratitis in neonates in which 75% is caused by HSV-2

 icosahedral-shaped capsid surrounds the core, which contains the double-stranded


deoxyribonucleic acid (DNA) and associated phosphoproteins of the viral chromatin.

 HSV binds to one or more cellular receptors, heparin sulfate probably being one of them

 Epidemiology

o Humans are the only natural reservoir

o primary infection manifests clinically in only 1–6% of people infected with the virus

o high male:female ratio (1.67:1) in patients more than 40 years of age. In younger
patients, no difference was observed.

 Pathogenesis

o After peripheral entry into the host and primary infection with viral replication
within an end organ, HSV travels in a retrograde fashion to various ganglia
including the trigeminal, cervical, and sympathetic gangliae, and possibly the brain
stem.

o Latently infected neurons have not been found to produce infectious virus.
However, a region of the viral genome that is retained within the host cell nucleus
during latency is responsible for RNA transcripts termed latency-associated
transcripts (LATS).

o the trigeminal ganglion is the most common source of recurrent HSV infection.

o Systemic antibodies have no known role in the development of recurrent disease


despite their role in the host response to active primary and recurrent infection

o activation of recurrent HSV ocular disease:

 Sunlight, trauma (including surgery), heat, abnormal body temperature,


menstruation, other infectious diseases, and emotional stress,
Prostaglandin F2 alpha analog and prostamide glaucoma medications
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latanoprost and bimatoprost have also been implicated in ocular or even


periocular HSV

 CD8+ T-cell inhibition of HSV-1 reactivation show viral inactivation via the
use of lytic granules degrading precursors to viral gene expression. These
CD8+ T cells maintain latency without causing neuronal apoptosis

o Immune defense mechanisms

 Congenital and neonatal ocular herpes

o HSV-2 accounts for 80%

o periocular skin lesions, conjunctivitis, epithelial keratitis, stromal keratitis, and


cataracts.

o maternal IgG to HSV may cross the placenta, it does not appear to be sufficient to
prevent ocular disease completely.

o The use of antibody titers for diagnosis is not useful because of pre-existing
maternal antibody and the delayed production of IgM.

 Primary ocular herpes

o By the age of 5 years, nearly 60% of the population has been infected with HSV.
Latent infection  viral carrier state.

o Only 6% of infected actually develop clinical manifestations, which typically affect


the perioral region rather than the eye.

o Can present as acute follicular conjunctivitis, keratoconjunctivitis, preauricular


adenopathy, and periocular and eyelid skin vesicles

 Recurrent ocular herpes

o Liesegang's review: 36% at 5 years and 63% at 20 years

o HEDS study: 18%

 Blepharitis

o vesicular lesion involving a focal area of the eyelid with surrounding erythema

o ulceration and crusting and heals without a scar unless secondarily infected.

 Conjunctivitis

o follicular conjunctivitis, self-limiting


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o may develop follicular conjunctivitis. In many patients, this conjunctivitis is self-


limiting

o may constitute up to 23% of cases of acute conjunctivitis

 Keratitis

o Recurrent HSV keratitis is typically a unilateral disease. Bilateral herpetic keratitis


occurs in approximately 3% of patients with ocular HSV.

o Infectious epithelial keratitis (Cornea vesicles, Dendritic ulcer, Geographic ulcer,


Marginal ulcer)

 photophobia, pain, and a thin, watery discharge; DOV if central

 branching, linear lesion with terminal bulbs and swollen epithelial borders
that contain live virus

 true ulcer in that it extends through the basement membrane.

 Fluorescein staining with negative stain of terminal bulbs, rose Bengal is


toxic to HSV and will decrease the yield of the culture.

 HSV dendritic epitheliopathy: not ulcerated and simply represents healing


epithelium after the infection.

 An enlarged dendritic ulcer that is no longer linear is referred to as a


geographic ulcer. (22% of all epithelial)

 marginal ulcer: proximity the limbus, quickly infiltrated with white blood
cells, more symptomatic because of the intense inflammation

 four recognized sequelae

1. complete resolution

2. infectious epithelial keratitis

3. stromal scarring: ‘ghost scarring’ or ‘footprints’ of HSV keratitis.

4. stromal disease (25%)  Necrotizing keratitis represents true viral infection


of the stroma, whereas immune stromal keratitis is mediated by antibody–
complement reactions to viral antigen.

o Neurotrophic keratopathy

 arises from impaired corneal innervation in combination with decreased


tear secretion.

 irregularity of the corneal surface and lack of the normal corneal luster.

 oval in shape with smooth borders, in direct contrast to the geographic


ulcer, which is irregular in shape with scalloped borders

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o Stromal disease

 2% of initial episodes, 20–48% of recurrent ocular HSV

 2 cases where stroma is involved primarily. Necrotizing stromal keratitis


occurs from direct viral invasion of the stroma, whereas immune stromal
keratitis is the result of an immune reaction within the stroma.

o Necrotizing stromal keratitis

 necrosis, ulceration, and dense infiltration of the stroma with an overlying


epithelial defect.

 Risk factor: use of topical corticosteroids without antiviral coverage

o Immune stromal (interstitial) keratitis

 20% of patients with ocular HSV

 due to retained viral antigen within the stroma. This antigen triggers an
antigen-antibody-complement (AAC) cascade that results in intrastromal
inflammation.

 stromal inflammation with overlying epithelium almost always intact

 often accompanied by anterior chamber inflammation, ciliary flush, and


significant discomfort.

 immune ring: AAC precipitate similar to a Wessely ring

 stromal neovascularization: sectoral, with a single frond of vessels, to


complete, involving all quadrants of the cornea. Ghost vessels, in and of
themselves, do not cause decreased vision or increased risk of penetrating
keratoplasty rejection.

o Endotheliitis

 corneal stromal edema without stromal infiltrate

 keratic precipitates (KP), overlying stromal and epithelial edema, and iritis.

 three forms of HSV endotheliitis are disciform, diffuse, and linear

 Disciform endotheliitis: MC, ocular discomfort, Limbal injection, disc-


shaped area of stromal edema,

 Diffuse endotheliitis: rare,

 Linear endotheliitis:

o Iridocyclitis

 most commonly accompanies immune stromal keratitis or endotheliitis,


but, as previously stated, it may occur as the only inflammatory finding.
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 Diagnosis:

o ophthalmic examination

o viral culture: within several days of the onset and may require up to 1 week of
incubation

o Cytologic examination of specimens stained with Giemsa or Wright stains

o Immunologic tests

o Polymerase chain reaction (PCR)

 Management:

o 4 valuable insights of HEDS

1. Oral antiviral prophylaxis reduces recurrences of epithelial and of stromal


keratitis.

2. Use of topical corticosteroids is of benefit in stromal keratitis.

3. Use of oral acyclovir may be of help in iridocyclitis.

4. Prophylactic oral acyclovir helps prevent recurrences of herpetic keratitis,


particularly stromal with a history of recurrence.

Acanthamoeba Keratitis
 free-living protozoan that is ubiquitous in nature

 found commonly in water, soil, air, cooling towers, heating, ventilating, and air conditioning
(HVAC) systems, and sewage systems.

 Unlike disseminated Acanthamoeba infection, corneal disease is not associated with


immunosuppression.

 three morphologic groups: group 1,2,3

o major human pathogens belong to Group II

o Twelve lineages referred to as T1-T12

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o MC: A Polyphaga, A Castellani

o Stages: trophozoite & cyst

o Trophozoite – Mobile

o Cyst - stable & highly resistant form

 Pathogenesis
o Exposure to contact lens - 70-85%
o Corneal trauma.
o Natural immunity exists.
o Host response by acute inflammatory cells especially around cyst & necrotic organisms.
Contaminated contact lens solution + Microtrauma to Epithelium by contact lens
o acanthamoeba infection by trophozoite
 Clinical features
 Presentation: Blurred vision with acute pain disproportionate to signs.
 Signs:
 Early
o Epithelial irregularity & infiltration pseudodendrite or raised epithelial ridges
o Radial keratoneuritis
o Stromal infiltration, satellite lesion, disciform lesion, ring infiltrate
o Conjunctival follicles.
o Preauricular nodes.
 Late
o Stromal opacification
o Scleritis
o Descematocele formation
 Diagnosis
o Gram & Giemsa stain
o Calcofluor white stain - stains wall of cyst.
o acridine orange.
o Immunofluorescent antibody stain.
o PAS & methenamine silver.
o Confocal microscope - confirmatory pear shaped cyst & irregular trophozoite
o Phase contrast Microscope
o PCR and Corneal Biopsy
o Transported in: Page saline with sample of contact lens saline & case.-Ideal.
o Alternative media is buffered charcoal yeast extract agar-Lower efficacy (72%)
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o E-coli on non nutrient agar (1.5%) at 25 and 37 degree C, May require up to 14 days to
grow - Create track by eating E Coli.
 Differential diagnosis
o Diagnosis By Exclusion
o Herpetic keratitis - no systemic association
o Fungal
 Treatment
 Biguanides-Cationic Antiseptics - inhibits membrane function
o Chlorhexidine, Solution, 0.02%
o Polyhexamethylene, Solution, 0.02% (PHMB)-BAQUACIL
 Aromatic Diamidines - inhibits DNA synthesis
o Propamidine isethionate, Solution, 0.1% (BROLENE)
o Pentamidine isehionate, Solution 0.1% (PENTAM )
 Aminoglycoside - inhibits protein synthesis
o Neomycin Solution, 1.75 mg/ml Ointment 3.5 mg/g
 Azoles - destroys cell wall
o Clotrimazole, suspension, 1%
o Fluconazole, solution, 0.2%
o Ketoconazole, oil solution, 5%
o Miconazole, solution, 1%
o Initially - hrly x 48 hrs.
 Corticosteroid - reduces inflammation. Very Cautious use (While continuining anti-amoebic agents):
Prevents encystment of Trophozoite in vitro and may therefore enhance effectiveness of Topical
treatment. Topical steroids have shown to prolong effective treatment and used in specific
conditions like Limbitis,Scleritis and uveitis
 Course & outcome
 Majority eradicated by medical therapy.
 Treatment of Complications
o Scleritis:-consider immunosuppressant with steroids/ cyclosporine.
o Corneal Scaring:- Two Types Therapeutic or Penetrating Keratoplasty

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Bacterial Keratitis (lecture notes)

Fungal Keratitis (lecture notes)

 6-20% worldwide

 49% india

 65% in 21-50 years

 M:F= 1.5:1

 Season: monsoon, early winter

 Risk factors:

o Ocular

 Trauma: vegetative matter

 Chronic inflammation

 CL wear

 Topical antibiotics and steroids

 Prior ocular surgery (LASIK, PK, Cataract)

o Systemic

 NIDDM, HIV, Leprosy

 Classification of fungi

o Filamentous septate

 Non-pigmented

 Fusarium solani

 Aspergillus fumigatous, flaus, niger

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 Acremonium

 Paecilomyces

 Pigmented

 Curvelaria

 Alternaria

 Cladosporium

 Helminthosporum (diechslera)

o Filamentous non-septate: rhizopus

o Yeasts: candida albicans, tropicalis

 Symptoms

o Indolent, FB sensations

o Increasing pain

o Diminution of vision

 Signs

o Dry rough texture

o Feathery margins

o Abscesses

o Satellite lesion

o Endothelial plaques

o Fixed hypopyon

 Specific signs

o Demataceous fungi: brown pigmentation

o Fusarium: severe sourse, deep extension, perforation

o Aspergillus: indolent course

o Yeast: collar button configuration

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 Laboratory diagnosis

o Smears: DEEP SCRAPING

 10% KOH sensitivity 91-99%

 Gram stain sensitivity 45-73%

 Lactophenol cotton blue sensitivity 45-73%

 Grocott’s methenamine silver sensitivity 80-90%

o Culture

 Sabouraud dextrose agar (without cycloheximide)

 Positive culture 52-68%

 Initial growth occurs within 72 hours

 Wait at least 7 days before culture negative report

o Newer diagnostic modalities

 PCR: 74% within 4 hours

 Confocal microscopy

 Fungal keratitis sensitivity 94% and specificity 84%

 Acanthamoeba keratitis sensitivity 100% and specificity 84%

 Antifungal drugs

o Polyenes: natamycin, nystatin, amphotericin B

o Azoles: fluconazole, itraconazole, voriconazole, posaconazole, ravuconazole

o Fluorinated pyrimidines: flucytosine

o Echinocandins: caspofungin, micafungin

 Topical antifungals

o 5% natamycin hourly – daytime, 2 hourly bedtime  2 hourly daytime, taper in 4-7


days

o If worsening  add 0.15% amphotericin or 2% fluconazole for candida

o Therapy for 3-4 weeks

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o Limitations

 Commertially available preparations less

 Poor ocular penetrations

 Poor bioavailability

 Toxicity

o Topical voriconazole 1%: powder for parenteral use, alternaria and scedosporium
keratitis, inhibits CYP450 dependent 14-sterol demethylase, FUNGISTATIC

 Systemic antifungals

o Indications

 Large ulcers

 Severe deep keratitis

 Scleritis

 Post-PK

 endophthalmitis

o drugs

 ketoconazole 200 BD

 fluconazole 200 BD

 itraconazole 100 BD

 voriconazole 200 BD

 LFT should be done every 2 weekly

 Targeted drug delivery

o Injections

 Intracameral

 Non responsive to medical therapy

 Thick hypopyon

 Endothelial exudates

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 Deep anterior chamber exudates

 Amphotericin 5-7.5 ug/0.1ml/5%D

 Voriconazole 50-100 ug/0.1ml

 Intracorneal/ intrastromal

 Deep mycotic keratitis

 Non perforated corneal ulcer

 Non responsive to conventional topical+ systemic anti-fungal therapy


for 4 weeks

 Remember flow chart of management. (read it)

Viral Keratitis (Lecture notes)


 Herpetic Eye Disease: HSV, HZV

 Non herpetic eye disease: adenoviral

 Primary ocular herpes

o Confined to epithelium

o Blepharoconjunctivitis

o Preauricular LAP

 Recurrent ocular herpes

o Infections:

 Epithelial: dendritic, geographical

 Stromal: necrotizing, immune  most devastating, heavy infiltration, deep


vascularization, corneal thinning, perforation

 Endothelial: disciform, linear, diffuse

o Neurotrophic keratopathy

o Herpetic marginal ulceration: peripheral corneal ulceration, underlying anterior


stromal infiltrate, adjacent limbal congestion

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Herpes Zoster Eye Disease

 Acute phase:

o punctate epithelial keratitis

o micrdendritic ulcers

o nummular keratitis

o disciform keratitis

 chronic phase

o mucus plaque keratitis

o neurotrophic keratitis

o nummular keratitis

o disciform keratitis

 Laboratory Diagnosis

o Giemsa staining sensitivity 57% and specificity 85%

o PCR specificity 70%

o Viral culture 70%

o Immunological tests

 Topical antivirals

o Acyclovir 3% ointment

o Vidarabine 3% ointment

o Trifluothymidine 1% solution

o Idoxuridine 1%

 Topical steroids: for stromal component

 Systemic acyclovir

o Recurrent stromal-epithelial keratitis

o Immunocompromised patients

o HSV keratitis in a corneal graft

o 400 mg 5 times a day for HSV, 800 mg 5 times a day for VZV
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 Metaherpetic keratitis

o Medical

 Withdraw epitheliotoxic drugs

 Intensive lubricants

 Cycloplegics

 Steroids

o Surgical

 Conjunctical flap

 AMG

 Glue for small perforation

 Patch graft

 Tectonic graft

 Adenoviral keratitis

o EKC

o 8,19,37

o 10% transmission ot household contacts

o Severe follicular kerato conjunctivitis

o Hemorrhagic conjunctivitis

o Acute stage

 Cold compresses

 Lubricants

 Prophylactic antibiotics

o Nummular opacity

 Topical steroids: 6 weeks

 Topical cyclosporine

 Lubricants
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Akanthamoeba Keratitis (lecture notes)

 1% of all infectious keratitis

 Risk factors

o 85% CL users

o Home made saline

o Contaminants/ swimming pool

o Trauma

o Vegerable matter

o Orthokeratology

 CF

o Unilateral

o Severe pain due to keratoneuritis

o Immunocompetent patients

o Fails to respond to antibacterial, antiviral or antifungal treatment

 Signs

o Epithelial irregularities: punctate, linear, pseudodendritiform, haze 25-50%

o Patchy stromal infiltrate 5-50%

o Radial pretineural infiltrate (pathognomonic)

o Ring infiltrates 19-90%

o Satellite lesion, stromal thinning, lysis, perforation

o Absence of corneal neovascularization

o Slow progression, period of remission

o Days to months

o Scleritis 11-40% (immunological response)


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 Diagnosis

o Microbiology

 Corneal scrapings, CL, case, solution

 Confocal

 Corneal biopsy

o Cysts: polygonal and double walled appearance on calcoflour white 0.1%

o Culture: non nutrient agar with e.coli/aeromonas/klebsiella, blood agar, chocolate


agar

 Treatment

o Biguanide: PHMB 0.02%, chlorhexidine 0.02%

o Diamidine: propamidine 0.1%, hexamidine 0.1%

 Taper till 6 months

o Miconazole and clotirmazole 1-2%

Stages of Corneal Ulcer

 Stage of infiltration

o Infiltration of PMNL/Lymphocytes into the epithelium and stroma

 Stage of progression

o Necrosis and sloughing of the necrotic material

o Surrounding area is packed with leucocytes. Wall of the ulcer projects due to
edema and infiltration of cells

o Zone of infiltration extends beyond and underneath the ulcer margin

o Ciliary congestion

o Involvement of iris and ciliary body (due to absorption of toxin)–causing


iritis/cyclitis

o Hypopyon formation

 Stage of regression

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o Induced by immunodefence mechanism and treatment

o Line of demarcation develops around the ulcer area

o Necrotic material is sloughed off and the ulcer bed enlarges.

o As the surrounding infiltration and swelling disappears, the floor and edges become
smooth and transparent.

o Superficial vessels grow in from the limbus near ulcer, to restore the loss of
substance and supply antibody.

 Stage of cicatrization

o Vascularisation of ulcer

o Regeneration of collagen and formation of fibrous tissue (causes corneal opacity)

Pterygium
 An Elastotic Degenerative condition of conjunctiva with a wing like encroachment of
conjunctiva on to the Cornea.

 Pathogenesis –

o Environmental causes- UV exposure, dust heat , wind exposure

o peri-equatorial ‘pterygium belt’ latitudes 37° north and south of the equator.

o Heredity:

 Loss of heterozygosity (17q,9p) and microsatellite instability-- Spandidoras


(1997), Detorakis et al(1998)

 p53 mutation--Tan et al (1997)-- pterygium is not a degeneration but a


growth abnormality.

o Coroneo Effect -Nasal segment of cornea gets highest UV exposure effect

o Limbal Stem cell defect with Fibroblast Activation: conjuctivalisation,


inflammation and vascularisation

o HSV & HPV --Spandidoras et al (1994)--HSV in 45% of pterygia, Dushku et al( 1999)
ruled out HPV. Gallagher et al( 2001) –HPV may play a role in recurrence

 Classification

o Primary Pterygium

o Recurrent Pterygium

o Atrophic Pterygium: Older pts, thin translucent body with thin vessels
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o Pogressive Pterygium: Thick fleshy growth seen in Younger pts

 Grading

o Size

 1: just touching cornea

 2: midway between 1 & 3

 3: upto pupil margin

o Tan Grading:

 T1 (atrophic) denotes a pterygium in which episcleral vessels underlying the


body of the pterygium are unobscured and clearly distinguished

 Pterygia in which the episcleral vessel details are indistinctly seen or


partially obscured are categorized as grade T2 (intermediate)

 Grade T3 (fleshy) denotes a thick pterygium in which episcleral vessels


underlying the body of the pterygium are totally obscured by fibrovascular
tissue

 Clinical features

o Males:female-2:1,

o young -20-40yrs and elderly,

o incidence proportional to proximity to equator.

o diminution of vision-astigmatism, usually with the rule, can be against / oblique/


irregular, late stages dv due to encroachment into pupillary area

o intermittent episodes of inflammation

o cosmesis

o diplopia-- symblepheron formation (more common in recurrent cases)

 Medical Management

o Symptomatic Grade 1 and 2 pterygium

o protection from sunlight

o Eye drops – Tear substitutes, Decongestants

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o Local injections – anti VEGFs, Steroid

 Surgical Management

Indications-

 Symptomatic patients: recurrent irritation, redness and watering

 Visual need: covering visual axis or threatening visual axis, causing irregular
astigmatism, Grade 2 and 3 Pterygium

 Cosmetic

 Therapeutic: suspected associated neoplastic degeneration, motility restriction

four main groups

1. Bare sclera excision

o 1948, D’Ombrain

o high recurrence rates ranging from 24% to 89%

2. Excision with conjunctival closure/transposition

o high recurrence rates of 37% /29%

3. Excision with antimitotic adjunctive therapies

o Beta irradiation: Strontium-90, recurrence rate – 10%

o Mitomycin C: the postoperative use of topical mitomycin C as eyedrops, and the


intraoperative application of surgical sponges soaked in MMC, recurrence rate – 0
to 38%

4. Ocular surface transplantation techniques.

o Conjunctival autograft transplantation

o Variations of conventional conjunctival autografting

o Conjunctival rotational autograft

o Annular conjunctival autograft

o Cultivated conjunctival transplantation

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o Conjunctival limbal autograft transplantation

o Amniotic membrane transplantation.

 Adjuvants – to reduce recurrence

Mitomycin C- For recurrent pterygia

Intra op or post op

Uncommonly used

Late Scleral necrosis & melt

Thiotepa – used post op

Beta radiation with Strontium 90

Excimer Laser in PTK mode – for corneal smoothening

 Complications.

o Graft contration

o Graft edema

o Graft necrosis

o Granuloma formation

o Excessive cautery- scleral necrosis

o Infection

o Recurrence

o Corneal scaring

o Ocular motility restriction

o Surgical induced Necrotising Scleritis (SINS)

 Pterygium Recurrence Rate---Alp et al 2002

MMC: Intra OP: 3.33-42.7 /Post OP:0-54.5


Beta radiation: 0.5-33

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Excimer PTK: 4.5-91


AMG: 3.8-37.5
CAG: 2.6-39
LCAT: 0-14.6
Simple Excision: 29.2 -89

 Recurrent pterygium

o surgical trauma-excess cautery, excess tenonectomy, post op inflammation and


infection, incomplete removal .

o Mean recurrence time – Hirst et al (1994)

1st recurrence – 123 days, 2nd – 97 days, 3rd – 67 days.

Avisar et al (2001) – 91% recurrence in 1 year

 A true pterygium must be differentiated from a pseudopterygium, which may occur after
trauma. Pseudopterygium has been reported secondary to inflammatory corneal disease. A
probe may be passed at the limbus under a pseudopterygium. Further distinction can
be made, since pseudopterygia may be found anywhere on the cornea and are usually
found obliquely, whereas true pterygia are horizontal in the 3 or 9 o’clock positions.

Corneal Complications of Intraocular Surgery

1. Epithelial: Abrasion, Edema, Filaments, Toxic keratopathy

2. Thermal burns: Cautery, Phacoemulsification probe

3. Infection: Bacterial, Fungal, Herpes simplex keratitis

4. Descemet's membrane: Tear, Detachment

5. Endothelial injury: Aphakic bullous keratopathy, Pseudophakic bullous keratopathy,


Brown-McLean syndrome, Phakic bullous keratopathy, TASS

Descemet's membrane Detachment

 Risk factors for Descemet's membrane detachment include blunt knife entry, oblique
insertion of instruments, entry of instruments or viscoelastics into a false plane above
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Descemet's membrane, or history of ocular conditions disrupting Descemet's membrane


such as congenital glaucoma, birth forceps injury, keratoconus, and Terrien's marginal
degeneration.

 can spontaneously reattach with medical treatment alone, with a mean resolution time
of 10 weeks.

 With large detachments or slow resolution, descemetopexy with air, sulfur hexafluoride
(SF6), perfluoropropane 14% (C3F8) gas injections, sodium hyaluronate or through-and-
through corneal mattress sutures may help

 Bullous keratopathy or corneal scarring may occur, requiring endothelial or penetrating


keratoplasty in 7–8% of cases

Aphakic/Psudophakic bullous keratopathy

Imbibition pressure = IOP - Swelling pressure

 Incidence:

o ICCE with IOL: 0-0.8%

o Complicated Cataract Surgery: 0-11.3%

o Iris clip lens: 9%

o ECCE with ACIOL: 15%

o ECCE/Phaco with PCIOL: 0.1% to 0.47%

PBK with different IOL

PCIOL: 0.06%

ACIOL: 1.2%

Iris-clip lens: 1.5%

 Histopathology:

o attenuation and loss of corneal endothelial cells

o epithelial bullae and stromal edema

o thickening of the posterior collagenous layer of Descemet's membrane


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o decrease in stromal keratocytes

o Subepithelial and retrocorneal fibrous proliferation

o epithelial basement membrane has decreased amounts of fibronectin, laminin,


and collagen type IV, which function as adhesive proteins leading to epithelial
bullae

o accumulation of antiadhesive proteins, such as tenascin-C and thrombospondin-1

 Pathogenesis:

o 12% reduction of the central corneal endothelial cell density in eyes having
intracapsular cataract extraction

o 9% central endothelial cell loss at 1 year after phacoemulsification and posterior


chamber lens insertion, with 11.5% loss at 3 years, followed by only 0.3% per year
greater loss than in control eyes.

o Bates model predicts decompensation of the cornea at 542cells/mm2 and a time


to decompensation of almost 40 years for uncomplicated cases.

 Causes of ABK and PBK

1. Pre-existing endothelial disease


a) Fuchs' dystrophy, cornea guttata
b) Pseudoexfoliation
c) Trauma
d) Angle-closure glaucoma

2. Intraoperative factors
a) IOL-to-cornea touch
b) Irrigating solutions
c) Instrumentation
d) Sterilization technique: AbTox Plazlyte, a sterilization technique that can degrade brass
to copper and zinc on cannulated surgical instruments, resulted in irreversible endothelial
cell destruction
e) Ultrasound damage
f) Vitreous loss, nuclear loss
g) Drug toxicity
h) Intracameral anesthesia
i) Descemet's membrane detachment

3. Postoperative factors
a) Long-term cell loss

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b) Vitreous-to-endothelial touch
c) IOL dislocation – touch
d) Flat anterior chamber
e) Peripheral anterior synechiae
f) Pseudophakodonesis
g) Inflammation
h) Toxic materials

 Treatment:

o Anterior stromal puncture may help reduce tearing and pain, and improve vision
through regression of epithelial bullae and epithelial edema in patients with early
corneal edema

o Annular keratotomy has also been reported with good success for patients with
pain

o Endokeratoplasty has become the treatment of choice over conventional


penetrating keratoplasty for patients with diseased endothelium.

o Conjunctival flap: In 1958, Gundersen introduced the technique of using


conjunctiva alone without use of tenon's capsule to cover the cornea.

o AMG with basement membrane surface up in all cases. The side of BM could be
distinguished from stromal side by touch with sponge. The former was not sticky,
while the later was & could be caught by the sponge.

o Cautenisation of Bowman's membrane

o Diamond burr polishing of basement membrane

o Phototherapeutic keratectomy for bullous keratopathy

 Superficial PTK showed improvement in 62% cases

 Intermediate PTK showed improvement in 40% cases

 Deep PTK: Mean ablation performed was of 206 um, 66% showed
improvement

 preterminal neural plexus of cornea is located just deep to Bowman's


membrane. Hence moderately deep ablation would have superior effect on
decreasing the pain; by ablation of neural plexus.

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Brown-McLean syndrome

 unusual form of peripheral corneal edema occurring long after cataract surgery

 edema extends 2–3 mm centrally from the limbus and up to 360 degrees, although the
superior limbus may remain clear

 central corneal endothelium may have decreased cell density but rarely becomes
edematous

TASS
 sterile postoperative inflammatory reaction most likely caused by a noninfectious agent
that gains entry into the anterior segment at the time of surgery and results in toxic
damage to intraocular lenses.

 12 to 48 hours after anterior segment surgery

 hallmark of this inflammation, which distinguishes it from infectious endophthalmitis is


Gram stain and culture negativity

 blurred vision (60%), anterior segment inflammation (49%), classically with limbus-to-
limbus diffuse corneal edema and cell deposition.

Mechanical Injury

 perform a complete examination and not to become distracted by the injury itself

 errors are rarely made by commission; rather, errors of omission are the rule.

 Abrading Injuries:

o Epithelial abrasions:

 If Bowman's membrane has not been disturbed, the surface will heal
without scarring. If Bowman's membrane is removed, or the corneal stroma
is involved, corneal scarring of some degree will result.

 quite symptomatic, often out of proportion to the degree of visible injury.


The exception to this rule is found in patients with ultraviolet keratitis
(welder's ‘burn’) or contact lens overwear.
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 pain, photophobia, foreign body sensation, and tearing

 cycloplegic agent, topical antibiotics, and application of a tight patch/ BCL.

 NSAIDs for pain control, did not result in a delay in healing.

 Most corneal abrasions heal spontaneously without difficulty in 24 to 48


hours

o Stromal abrasions

 occur in the setting of a tangential blow with an abrasive or sharp object.

 abrasion without a flap, the therapeutic options depend on the amount of


tissue remaining.

 If a corneal flap is present, the therapeutic goal becomes stabilization of


the remaining tissue in its proper anatomic location.

 major complications seen in these patients is keratorefractive alteration,


which can be difficult to correct.

 Blunt Trauma

o Contusion injuries: result from direct impact and may involve tissue bruising and
fractures.

o Concussion injuries, on the other hand, arise from the rapid acceleration,
deceleration, or oscillation of tissues as a result of the impact and energy transfer
to the surrounding tissues

o Diffuse endotheliopathy: eyes with angle recession <180 degrees had a 12%
decrease in endothelial cell density compared to the fellow uninjured eye. Eyes
with greater than 180 degrees of recession had a 21.2% decrease compared to their
fellow eyes.

o Endothelial rings

o Stromal injuries and fractures

o Obstetric injuries

 Injuries Caused by Radiant Energy

o UV Radiation

o Infrared Radiation

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 Thermal Burns

 Foreign Body Injuries:

o Second to corneal abrasions, corneal foreign bodies are the most common form of
ophthalmic trauma.

o Sclerotic scatter may highlight transparent intrastromal foreign material, whereas


retroillumination from the iris or fundus will help delineate discontinuities in the
stroma.

o In most cases of superficial foreign bodies, a tuberculin syringe with an attached


27- or 30-gauge needle is an effective instrument for removal.

o Rusting begins almost immediately after the object is embedded, and a ring may
begin to form as early as 3 hours after injury

 Stings

o Bee and wasp stings

o Jellyfish stings

Chemical Injuries of the Eye


 A strong acid or base can be thought of as being more or almost completely dissociated
into cations (+) and anions (−) in solution. And they have ph towards extremes of limits.

 In biologic systems, alkaline agents saponify the lipids of cell membranes, causing both
rapid and deep penetration. Acids, on the other hand, precipitate and denature
proteins somewhat limiting further penetration. Alkalis penetrate lipid layers more
readily and rapidly; however, acids bind proteins, limiting penetration but potentially
increasing the local duration of exposure to the anion. Acid anions with higher binding
potentials can cause damage at higher pH than anions with lower binding potentials.

 An amphoteric substance is loosely related to buffers in that it is capable of acting like


either an acid or a base, and as such, it can neutralize both acids and bases. Two products
have been introduced taking advantage of this phenomenon: Diphoterine, and
Hexafluorine, both developed by Prevor Laboratories in France. Diphoterine is an
amphoteric, hypertonic, polyvalent compound for use in ocular and skin decontaminations
of about 600 chemicals, including acids, alkalis, reducers, oxidizers, alkylating agents,
and radionucleotides. Additionally, the binding reaction is not exothermic. Hexafluorine is

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its counterpart for ocular and dermal exposures to hydrofluoric acid as well as fluorides in
acidic environments.

Acid Injury
 acids are components in rust removal products, pool cleaners, and car batteries

 Most serious is hydrofluoric acid & MC is sulfuric acid. (Survey)

 Traditionally, acid injuries have been considered less destructive to the eye than alkali
injuries.

 Collagen shrinkage immediately raises the intraocular pressure, and the effect persists
for at least 3 hours through the elaboration of prostaglandins, possibly from the presence
of H+ ions in the aqueous. Additionally, the stroma liberates ascorbic acid (vitamin C).
In severe acid injuries, ascorbate levels in the aqueous plummet after 24 hours, probably
due to either breakdown of the blood–aqueous barrier or damage to the active transport
mechanism of the ciliary body. Ascorbate is an essential element in the elaboration of
collagen, and its loss can lead to stromal ulceration.

 mucopolysaccharides, which are initially unharmed by acid, are either liberated from
damaged tissue or destroyed, contributing to decreased tear breakup time, punctate
staining (PEE), or slow-healing epithelial defects.

 Epithelial breakdown can result in stromal edema, especially in the first 24–36 hours;
however, as long as the endothelium is undamaged, stromal hydration largely normalizes
upon reepithelialization.

 Hughes Classification and prognosis in acid injuries of the eye (ESCLator) ( for
Chronic Injury)

1 Vision
Epithelial Stromal
Conjunctival Limbal impairment,
Grade opacity, edema, Recovery
involvement ischemia 2 scarring,
defect opacity
3 vessels
None to Erythema,
Opacified 1, 2, 3 none
(I) Mild minimal, opacification, None Rapid
white to little
none chemosis
1 mild, 2
Opacification,
faint
Opacified Mild to chemosis,
(II) None to Epithelial healing likely anterior scar
white,common moderate, petechia or
Moderate minimal within 10 days possible, 3
at 24–36 hours none subconjunctival
little
hemorrhage
tendency
Moderate 1 moderate
Entire Epithelial healing
to severe, Opacification, to severe, 2
(III) epithelium possible in weeks to
mild hemorrhages, ≤1/3 moderate
Severe opacified months, ulcers/
opacity necrosis anterior
white perforation possible
obscures scar, 3

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1 Vision
Epithelial Stromal
Conjunctival Limbal impairment,
Grade opacity, edema, Recovery
involvement ischemia 2 scarring,
defect opacity
3 vessels
iris details peripheral
usual

1, 2, 3
Opacified Protracted (months–
extensive,
(IV) Very white (if Marked, Necrosis may years), sloughing of
>1/3 like severe
severe present) and severe be extensive stroma possible with
alkali
sloughs rapidly ulceration/perforation
injuries

 Treatment

 copious and continuous irrigation of clean water or other nontoxic irrigant: low osmotic
washes such as tap water or high buffer capacity agents such as diphoterine or Cederroth
Eye Wash Solution should be considered for use as initial rinsing agents.

 never use a base to neutralize an acid because it can magnify the injury.

 irrigating lens should be inserted into the fornices while the solution is flowing.

 checking the fornices for particulate matter by double inversion of the lids and sweeping
them with moist, sterile cotton swabs

 end point, a pH check of the tears 5 to 10 minutes following irrigation might be useful,
and if the pH is less than 7, irrigation should continue.

 Following irrigation, a more thorough ophthalmologic examination should ensue, including


vision, external and slit lamp examinations, epithelial and limbal involvement, stromal
edema, and intraocular pressure.

 broad-spectrum topical antibiotic to guard against infection in the face of an epithelial


defect

 Moderately long-acting cycloplegic agents

 topical or oral anti-glaucoma agents

 Topical NSAIDs drugs should be used cautiously due to the possibility of corneal melting
in conjunction with epithelial defects

 significant inflammation and/or secondary iritis may benefit from cautious use of topical
steroids in the first 7 to 10 days; however, the use of steroids beyond this time may
increase corneal ulcerations or perforations.

 Systemic ascorbic acid (vitamin C) has been shown in an animal study to reduce the rate
of corneal ulceration in acid injuries.
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 AMT is being utilized in both acute and chronic chemical

 LSCD occurs most frequently in high-grade chemical injuries with extensive perilimbal
ischemia.

 limbal stem cell transplants range from conjunctival limbal autografts (CLAU), living
related and cadaveric donors, to ex vivo culture expanded limbal epithelium.

 (DALK) with limbal stem cell transplantation with or without AMT

 limbus-to-limbus penetrating grafts.

Alkali Injuries of the Eye

 Nonperforating ocular injuries of this type result in destruction of cellular components,


denaturation and degradation of collagenous tissues, and release of inflammatory
mediators by alkaline hydrolysis of a broad range of intracellular and extracellular
proteins, invading cells, and basal epithelial cells.

 The hydroxyl ion (OH) saponifies the fatty acid components of cell membranes, resulting
in cell disrupttion and death, while the cation is responsible for the penetration of the
specific aIkali. Cations react with carboxyl COOH group of stromal collagen and GAGs.

 with the carboxyl groups (COOH) of stromal collaThe


type of alkali causing eye injury can be
ammonia, lye, potassium hydroxide, magnesium hydroxide, or lime. Most serious is
ammonia/ lye & MC is Lime. (Survey)

 The pain, lacrimation, and blepharospasm following an ocular alkali injury result from
direct injury of free nerve endings located in the epithelium of the cornea, conjunctiva,
and eyelids.

 a wave of hydroxyl ions rapidly penetrates the eye, causing saponification of cellular
membranes with massive cell death and partial hydrolysis of corneal glycosaminoglycans
and collagen.

 spiking rise in the intraocular pressure, lasting about 10 minutes, caused primarily by
shrinkage of the collagenous envelope of the eye. A more prolonged rise in pressure
quickly follows, secondary to prostaglandin release.

 Repair:

o loss of epithelial adhesion might result from accelerated degradation of fibrinogen


by plasminogen activator, a substance probably secreted in excessive amounts by
the basal epithelial cells in the alkali-injured eye.

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o Healing of the corneal stroma: (1) degradation and removal of necrotic debris, and
(2) replacement of portions of the fixed cells, collagenous matrix, and
glycosaminoglycans.

o Moderate injuries probably cause some endothelial cell death but mostly interfere
with the pump mechanism, leading to a variable degree of reversible corneal
edema. Severe injuries will destroy endothelium, which leads to severe corneal
thickening.

 Classification of Alkali Injuries:

Roper Hall classification (for Chronic)

Grade I: There is no corneal opacity or limbal ischemia and the prognosis is excellent.

Grade II: The cornea is hazy with visible iris details, there is ischemia of less than one-
third of the limbus and the prognosis is good.

Grade III: There is sufficient stromal haze to obscure iris details, ischemia of one third to
one half of the limbus and the prognosis is guarded.

Grade IV: The cornea is opaque with no view of iris or pupil, there is ischemia of more
than one-half of limbus and the prognosis is poor. A new classification has been proposed
by Dua et al that take into account the extent of limbal involvement in clock hours and
the percentage of conjunctival involvement. Dua et al stressed the inadequacy of the
currently followed RoperHall classification that is reflected in the inconsistencies of
success rates reported in literature. This is particularly true for grade IV burns (50-100%
limbal ischemia) which are equated with poor prognosis.

Dua’s classification

Grade Prognosis Limbal Conj. Analogue Involvement Involvement Scale


I Very good 0 clock hours 0% 0/0%

II Good =3 clock hours = 30% .1-3/1-29.9%

III Good >3-6 clock hours >30-50% 3.1-6/31-50%

IV Good -guarded >6-9 clock hours >50-75% 6.1-9/51-75%

V Guarded-poor >9-<12 clock hours >75-100% 9.1-11.9/75-99.9%

VI Very poor Total limbus Total conj.inv. 12/100%

 Treatment:

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McCulley’s 4 stages:

Immediate, Acute 0-7 days, early repair 7-21 days, late repair after 21 days.

 Immediate

 Thorough washing of eye with saline or water for at least 30 min

 Assessment of injury with history and examination

 Acute

 Topical steroids 2 hourly inhibits PMN proliferation and function

 Topical sodium citrate 10% 2 hourly inhibits PMN degranulation by Ca chelation

 Tetracycline 1% ointment QID inhibits collagenase enzyme by chelating with Zn.

 Oral sodium ascorbate 500mg QID promotes collagen synthesis

 Topical sodium ascorbate 20% 2 hourly promotes collagen synthesis

 Tear substitutes 2 hourly promotes epithelial healing

 Cycloplegics TDS or BD relieves pain

 Topical/oral antiglaucoma therapy, if needed

 Conjunctival/tenons advancement for grade-IV. Improves vascularization

 Intermediate stage

 Review of patient

 Rapidly taper steroids after 10 days

 Continue topical and oral medication

 Look for stromal ulceration

 Prevent symblepharon formation

 Look for re-epithelialisation

 Sequelae

 Symblepharon formation

 Limbal stem cell deficiency

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 immediate irrigation at the scene of the accident with clear water and subsequently the
emergency room for 1 to 2 hours with isotonic buffered saline.

 Reformation of the aqueous humor with buffered phosphate solution lowered the pH by
an additional 1.5 pH units. It is premature to suggest that all severe alkali injuries should
undergo paracentesis.

 Diphoterine (Prevor) is a proprietary amphoteric compound which has been much


heralded as a universal emergency irrigant for eyes injured with acidic or alkaline
compounds.

 sticky paste of lime: EDTA 0.01 M

 intraocular pressure rise after alkali injury can usually be treated by topical alpha- or
beta-blockers and topical and/or systemically administered carbonic anhydrase inhibitors

 Limbal stem cell ischemia is looked for and graded by the newer classification.

Grade-I Involves little or no loss of limbal stem cells and presents with little or no evidence of
ischemia

Grad-II Involves subtotal loss of limbal stem cells and presents with ischemia of less than one
half of the limbus.

Grade-III Involves total loss of limbal stem cells with preservation of proximal conjunctival
epithelium and presents with ischemia of one half the entire limbus.

Grade-IV Involves total limbal stem cell loss as well as loss of proximal conjunctival
epithelium and extensive damage to entire anterior segment.

 The severity of injury will show the following healing patterns.

Grade-I Healed cornea with normal epithelium

Grade-II Epithelial defect, smaller in size

Grade-III No epithelization, inflammation

Grade-IV Sterile corneal ulcer + conjunctival defect, inflammations

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Autologous Serum Eyedrops

Serum is the fluid component of full blood that remains after clotting.
plasma is obtained when clotting is prevented by mixing a full blood donation with an
anticoagulant and removing all corpuscular elements by centrifugation

persistent epithelial defects or severe dry eyes, OSR, RES, SLK


first evaluated in 1984 by Fox

Rationale:
1. vitamin A, epitheliotrophic and neurotrophic growth factors, immunoglobulins and
fibronectin
2. lacks antigenicity
3. without preservatives and hence toxicity due to additives is not an issue.

Production Process (CCDS)

1. Clotting phase: 2 h at room temperature


2. Centrifugation: 15-min centrifugation at 3,000 g results in good separation of
serum and blood clot, without inducing haemolysis
3. Dilution: 20%, 33%, 50% or 100%, BSS rather than saline should be used
4. Storage: drops can be refrigerated or stored frozen. 3months if stored at –20 °C
and for 1month if stored at 4 °C.

Umbilical Chord Serum: prepared like autologous serum (5 min centrifugation at 1,500 rpm),
diluted to a 20% concentration in 0.9% saline and used as an alternative treatment for
promoting corneal epithelial wound healing.

Keratoplasty

Sir Benjamin Rycroft in his Doyne lecture divided keratoplasty evolution into four periods:

ITCAR
1. Inspiration (1789–1824)
2. Trials and Frustration (1825–1872)
3. Conviction (1873–1905)
4. Achievement (1906–1965)
5. Refinement and Innovation (1966-present) (added by others later)

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 Von Hippel favored lamellar transplantation, performing the first successful human
corneal transplant in 1886, in which a full-thickness rabbit cornea was placed into a
human recipient corneal lamellar bed.

 first documented successful corneal penetrating transplant performed by Eduard Konrad


Zirm in 1906

 Franz Reisinger, who first described the term ‘keratoplasty’

 work of Ramon Castroviejo that had the most profound influence on modern-day
keratoplasty.

 first eye bank by R. Townley Paton in 1945

 Max Fine led to the recognition that keratoplasty could be successfully performed for the
treatment of aphakic bullous keratopathy

 immunologic discoveries of A. Edward Maumenee and the simultaneous introduction of


topical corticosteroids

 PLK

o 1998, Melles el al. described the technique of PLK just like DLEK

o Terry and Ousley developed new instrumentation and performed a similar


procedure in the United States, calling it DLEK.

o 2004, Melles DSEK

o Gorovoy advocated the use of a microkeratome DSAEK

o Melles et al. described a technique, currently known as DMEK

 ALK

o 1985, Archila deep lamellar dissection by injecting 1 cc of air

o 1994, Sugita and Kondo removed the anterior stromal tissue by standard
lamellar dissection, followed by hydrodelineation with saline through a 27-gauge
cannula

o 1998, Morris et al. modified the technique Sugita utilized by adding a viscoelastic
after hydrodelineation

o Anwar and Teichmann's description of the ‘Big Bubble Technique for DALK’ in
2002

o Vajpayee Double Bubble Technique for DALK

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Decision-Making in Keratoplasty
 EBAA statistics from 2009 revealed that 45% of all keratoplasty procedures performed in
the United States were partial-thickness corneal grafts.

 Ocular surface reconstruction procedures

1. Dry eye states

2. Neurotrophic states

3. Limbal stem cell deficiency states

They include, but are not limited to punctal occlusion, tarsorrhaphy, superficial
keratectomy, amniotic membrane transplantation, and limbal stem cell transplantation.

 ALK:

o anterior 85–95% of the cornea, definitely sparing Descemet's membrane and


endothelium

1. Corneal ectasias (keratoconus, keratoglobus, pellucid marginal degeneration)

2. Stromal dystrophies (granular, lattice, macular, and others)

3. Scars from previous infections (bacterial, fungal, viral, parasitic, atypical)

o Lamellar keratectomy (LK)

1. Manual peeling technique

2. Microkeratome-assisted keratectomy

3. Excimer laser phototherapeutic keratectomy

4. Femtosecond laser-assisted keratectomy

o Tectonic, reconstructive, and excisional anterior lamellar Keratoplasty

o Automated lamellar therapeutic Keratoplasty (ALTK)

 conditions affecting the anterior one-half to two-thirds of the cornea and


usually sparing the surface.

o Deep anterior lamellar Keratoplasty (DALK)

 takes advantage of the potential space between Descemet's membrane and


the stroma to cleave the entire host stroma off Descemet's membrane

o Femtosecond laser-assisted lamellar Keratoplasty (FALK)

 PLK

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1. Posterior corneal dystrophies (Fuchs’, nonguttate endothelial dystrophy,


posterior polymorphous)

2. Aphakic and pseudophakic corneal edema and bullous keratopathy

3. Iridocorneal endothelial syndrome (ICE)

4. Other causes of endothelial dysfunction (trauma, foreign body, age, etc.)

o Advantages

1. Rapid visual rehabilitation

2. No suture-related complications

3. Decreased incidence of allograft rejection

4. Intact globe, resistant to traumatic wound dehiscence

5. Predictable corneal toricity, minimal topographic change

6. Predictable, small hyperopic refractive shift (1.0–1.5 diopters)

o transplanted tissue usually measures 100–200 µm in thickness and includes the


donor endothelium, Descemet's membrane, and a lamella of posterior stroma.
Thinner donor tissue is associated with a lower incidence of graft dislocation
(<1%) and rapid clearing of vision.

o most endothelial cell loss from the donor appears to take place during the
insertion of the graft into the recipient's anterior chamber, various injectors,
cartridges, and inserters have been developed to ameliorate this problem. One
example is the Neusidl Corneal Inserter (NCI)

 PK

1. Combined endothelial and stromal disease (Fuchs’ dystrophy with corneal ectasia
or macular stromal dystrophy)

2. Severe corneal opacification and inability to ascertain the status of the


endothelium by history or examination

3. Keratoconus after hydrops with tears in Descemet’s membrane; successful deep


anterior lamellar keratoplasty is unlikely

4. Other causes of corneal opacification and lack of familiarity with selective


keratoplasty techniques

o Conventional PK

o Femtosecond Assisted PK

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 Permanent keratoprosthesis surgery

1. Eyes with multiple graft failures

2. Stem cell deficiency states (aniridia, etc.)

3. Corneas with four-quadrant deep stromal vascularization

Penetrating Keratoplasty

 Patient Selection:

o Age: advantages of advancing age is that the immune system is less likely to mount a
graft-destroying rejection

o Mild to moderate mentally challenged individuals sometimes greatly benefit

o Ocular surface disease is a leading cause of corneal transplant failure. Dry eye,
neurotrophic, or exposure keratitis patients often benefit from topical ciclosporin,
punctal occlusion, and tarsorrhaphy.

o Preoperative glaucoma is a risk factor for graft failure, with a relative risk factor of
2.5.

 Preoperative Preparations

o Infection control

o Intraocular pressure control

o Lens management

o Donor corneal tissue management

 allow approximately 60 minutes of warming time

 donor rim fungal culture is associated with endophthalmitis in the


recipient in 3%

 donor rim bacterial culture is associated with recipient endophthalmitis in


1%

o Anticipate suprachoroidal hemorrhage


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 0.45% to 1.08% of cases

 0.56% with general anesthetic and 4.3% with local anesthetic.

 risk factors include older age, glaucoma, previous vitrectomy, tachycardia,


systemic hypertension, arteriosclerosis, anticoagulant therapy, and prior
suprachoroidal hemorrhage

 Phakic Penetrating Keratoplasty

Goals

1. obtain good wound alignment with minimal astigmatism

2. avoid endothelial cell damage.

 lid speculum

 scleral fixation ring: potential scaffold to maintain scleral support, exerting its influence
once the eye is opened if scleral rigidity is insufficient. Another option is to proceed
without a fixation ring or sutures, to avoid associated globe distortion and astigmatism.

 Marking of host cornea: donor graft is usually centered on the host cornea or over the
pupillary axis

 donor tissue trephine is routinely sized 0.25 mm larger than the host trephine
because, using current techniques, donor corneal tissue cut with a trephine from the
endothelial surface measures approximately 0.25 mm less in diameter than host corneal
tissue cut with the same diameter trephine from the epithelial surface. Keratoconus
patients also may benefit from using same-diameter trephines for both donor and host
tissue, which in effect undersizes the donor button and helps reduce postoperative
myopia.

 Trephination of donor cornea: endothelial side facing up using a sharp disposable blade in
a guillotine punch block apparatus

 Trephination of host cornea:

 Placement of viscoelastic material in the anterior chamber

 Placement of the donor corneal tissue in the host bed

 Placement of four interrupted radial 10/0 nylon cardinal sutures:

o Suture depth is approximately 90% to prevent wound gape

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o The second suture, placed 180° away at 6 o’clock, is the most critical in terms of
tissue alignment and subsequent astigmatism.

 Complete suturing

o the most prevalent suturing error in corneal transplantation surgery is tying too
tightly.

 Readjustment of sutures to minimize astigmatism: An inexpensive plastic ring


(Karickhoff keratoscope, DORC keratoscope, or the like) or even the round end of a
safety pin can be used effectively for this purpose.

 Administering medications: Subconjunctival dexamethasone, 4 mg; subconjunctival


gentamicin, 20 mg; and subconjunctival cefazolin, 25 mg, or another suitable antibiotic
are injected.

Femtosecond Laser-assisted Penetrating Keratoplasty

 creation of a more structurally stable and predictable wound configuration with the
objectives of faster recovery of vision and higher optical quality compared to conventional
blade trephination.

 The first femtosecond laser platform to accomplish the full-thickness corneal cuts for PKP
was the Intralase™ (IntraLase Femtosecond Laser, AMO, Irvine, CA)

 A second femtosecond laser platform, FEMTEC (20/10 Perfect Vision, Heidelberg,


Germany) has also subsequently created stable full-thickness PKP wounds and
demonstrates short-term visual results analogous to other femtosecond laser-assisted PKP
studies.

 Intralase enabled keratoplasty (IEK)

 The two most popular patterns remain the ‘top-hat’ and ‘zig-zag’ incisions.

 ‘zig-zag’ incision may prove to be the most biomechanically sound incision pattern.

Keratoplasty Suturing Techniques

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 Castroviejo's original suturing technique utilized a continuous silk suture coursing back
and forth in multiple passes across the external surface of a square graft, using the suture
to support the graft in place against the intraocular pressure.

 After four cardinal sutures, a diamond-shaped pattern of corneal striae will appear in
the donor cornea. At this point, the wound approximation should be symmetric in all four
quadrants.

1. Interrupted sutures (IS)

 standard means of keratoplasty wound closure.

 10-0 nylon using a 160-degree single-curve 6-mm needle

 A 2-1-1 closure facilitates burial of the knot, but adequate suture tension is more
difficult to establish than with a 3-1-1 knot. Slipknots (1-1-1-1) allow for
intraoperative adjustment.

 Eight sutures, in general, is the minimal number required to keep the wound
watertight, and 16 sutures is the average number for a complete interrupted suture
wound closure

 A total of 24 or 32 interrupted sutures may be necessary in pediatric grafts,


keratoconus patients, same-size donor–host grafts, or large-diameter grafts.

 Knots can be buried in the host tissue so that when the suture is removed there is
less tension on the graft–host junction, reducing the chance of dehiscence should the
sutures be removed during the early stages of wound healing. Alternatively, the knots
can be buried in the donor tissue to help reduce inflammation and vascularization
since the knot is farther from the limbal vessels.

2. Combined continuous and interrupted sutures (CCIS)

 With a continuous suture in place the interrupted suture may be removed for
astigmatism control earlier than if interrupted sutures were used alone.

 2 interrupted 10-0 nylon sutures and a continuous 12-bite 10-0 or 11-0 nylon running
suture

 should not be used if there is vascularization or infectious keratitis or any other need
for total suture removal in some portions of the wound before others

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3. Single continuous suture (SCS)

 technically more unforgiving than interrupted sutures, because one irregular bite can
impair the integrity of the closure and once passed cannot be removed without
removing the entire suture

 ease of placement, the ease with which the suture can be removed at a later date,
and the potential for suture adjustment intra- and postoperatively to reduce
astigmatism.

 Antitorque suturing is not necessary for continuous sutures with 12 or more bites.

Antitorque suture: radial overlying sutures and antitorque intrastromal suture bites. The
overlying radial sutures produce minimal suture torque and induce astigmatism.

Torque suture: radial intrastromal sutures and overlying torquing suture bites. These
torquing suture bites rotate the graft and induce astigmatism.

4. Double continuous suture (DCS)

 benefits of a single continuous suture with the added safety of a second suture
should one suture break or need to be removed early.

 requires more expertise than a single continous suture, because both continuous
sutures must have regular and symmetric bites to close the wound without disturbing
the wound.

 Suture Adjustment

o Topographical analysis using keratometry, photokeratoscopy, or


videokeratography, individually or in combination, is helpful in planning suture
adjustment

 Suture removal

o if corneal astigmatism is satisfactory with sutures in place, sutures should remain


until there is some indication for removal, such as graft rejection, scarring,
vascularization, patient discomfort, suture breakage, infection, or decreased
vision (residual astigmatism). Leaving sutures in place as long as possible
maintains topography, if acceptable, and decreases the risk of dehiscence.

o All the dehiscences occurred within 2 weeks of suture removal, which was
perfomed between 14 and 42 months postoperatively.

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o Single interrupted sutures

 A tight suture, or any suture felt to be distorting the corneal topography,


can be removed as early as 6–8 weeks postoperatively in a well-constructed
keratoplasty with 16 interrupted sutures. However, adjacent sutures should
generally not be removed for 6 months postoperatively.

o Combined continuous and interrupted sutures

 One to three weeks later, the patient's corneal topography is remeasured to


assess changes induced by suture removal and to determine whether
removal of additional sutures is indicated.

 The average astigmatism is 4 diopters after all sutures are removed,


using most suturing techniques.

o Single continuous suture

 adjustment of the single continuous suture can change corneal topography


and still support the wound suture

 McNeill first described adjustment of a single continuous suture to reduce


postkeratoplasty astigmatism in 1988

 The suture is advanced from the flat meridian toward the tight
meridian to equally distribute suture tension around the wound.

o Double continuous suture

 adjusted the deeper, tighter 10-0 nylon suture to alter corneal topography
and reduce astigmatism, and left the shallower suture in place as a safety
net

Intraoperative Complications of Penetrating Keratoplasty

 Scleral perforation with fixation sutures: Flieringa rings, the McNeill-Goldman


blepharostat

 Improper trephination

o power of the lens must be adjusted to account for 2 to 3 diopters of induced


hypertropia

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o eccentric placement of the trephine can result in large amounts of postoperative


astigmatism.

 Damaged donor button

 Retained Descemet's membrane: The iris architecture should be inspected carefully, and
the iris should be gently picked up and identified with forcep

 Iris–lens damage

 Torn posterior capsule

 Vitreous loss with pseudophakic bullous keratopathy and posterior chamber intraocular
lenses

 Anterior chamber hemorrhage

 Expulsive choroidal hemorrhage: 0.47% to 3.3%

Postoperative Management

Immediate postoperative care (first 24 hours)

 Antibiotics should be given preoperatively, intraoperatively, and postoperatively

 Oral fluoroquinolone administration may also be considered in high-risk cases


(ciprofloxacin has highest ocular penetration among all fluoroquinolones)

 Prophylactic Antiglaucoma

 A pressure patch and Fox shield

 Systemic steroids are commonly administered in high-risk keratoplasty in the early


postoperative period, usually at a dose of 1 mg/kg per day over the first 5 to 7 days.
Acyclovir in a prophylactic dose of 400 mg twice daily or valacyclovir 500 mg daily is
given perioperatively in cases with previous known herpetic involvement, especially
previous stromal keratitis.

 Azathioprine at a dose of 1–2 mg/kg/day and ciclosporin A orally have been used as an
adjuncts to oral and topical steroids in high-risk cases but the side-effects profile has
limited their widespread use. Tacrolimus at a dose of 0.16 mg/kg per day has been
shown to be effective in prevention of rejection with less systemic impact.

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Early postoperative care (1 to 7 days)

 should be examined in the first 36 hours following surgery

 presence of concomitant external eye and eyelid disease including blepharitis,


lagophthalmos, spastic entropion, and trichiasis.

 without topical fluorescein to assess the surgical wound, level of corneal edema, anterior
chamber reaction, and overall status of the anterior segment

 fluorescein allows for a better evaluation of the status of the corneal epithelium, wetting
of the ocular surface, and tension on the suture material

 The intraocular pressure may be measured in more regular corneas by applanation.

 Treatment of early intraocular pressure elevations involves the use of topical beta-
blockers followed by carbonic anhydrase inhibitors and brimonidine.

Postoperative care (1 to 12 weeks)

 period of greatest change and highest risk for the corneal graft.

 Topical antibiotics should generally be discontinued once the epithelium is intact.


Continuing long-term topical antibiotic therapy selects out more resistant organisms, but
does not act significantly to prevent infection in the absence of other problems such as
persistent epithelial defects, suture removal, exposure, trauma, or wound leaks.

 Persistent elevated anterior chamber flare may be associated with higher incidence of
rejection.

 Epithelial rejection lines begin at the graft periphery and migrate towards the center of
the graft with time. They are seen as hazy elevations in the epithelium and may stain with
either fluorescein or rose Bengal. These lines are usually seen in a relatively quiet or
mildly inflamed eye. They are seen at a median of approximately 3 months following
surgery and may occur in up to 14% of corneal transplants.

 Signs of stromal rejection are seen as a haze or infiltrate spreading from the graft
periphery towards the center of the donor cornea. These are associated with findings of
endothelial rejection, and are frequently accompanied by stromal vascularization. The
classic finding of endothelial rejection is a rather sharply demarcated line (Khodadoust
line) that is seen as contiguous keratic precipitates.

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 Epithelial downgrowth, occurring 1 to 12 weeks after penetrating keratoplasty or suture


manipulation, may also appear as an advancing line with signs of inflammation.

 In the absence of complications, topical steroids should be tapered during the first 6
months following penetrating keratoplasty.

 An assessment of intraocular pressure should be done on each postoperative visit.

 Macular edema is often suspected when the visual function does not match the surgeon's
estimation of the anterior segment in the postoperative period.

Postoperative care (after 3 months)

 average postoperative astigmatism was in the 4 to 6 diopter range

 Contact lens correction is generally indicated for convenience when the other eye
requires contact lenses, in cases of high toricity and anisometropia, and in aphakia.

 Higher oxygen permeability (Dk value) lenses with base curves flatter than the flattest K-
reading are generally used.

 Corneal sensitivity may take years to return to normal in the corneal graft, and this may
be a significant factor in the development and late recognition of microbial keratitis from
contact lens wear or suture erosion.

 Significant iatrogenic complications may be induced by the chronic long-term


administration of topical steroids in the postkeratoplasty patient.

Postoperative care in infants and children

 intense inflammatory reaction in the anterior segment following Keratoplasty

 Epithelial and stromal healing is very rapid in children, resulting in early suture
loosening, exposure, secondary vascularization, and subsequent rejection. Infants and
young children may need to be examined every 2 days until the sutures are removed,
usually in a few weeks following surgery.

Early Postoperative Complications

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 Wound Leaks and Wound Displacement: Pupillary block or choroidal detachment can also
cause a shallow or flat anterior chamber, but a coexistent wound leak must be ruled out.
Seidel's test is useful for detecting an area of leakage and may be positive even in the
presence of a flat anterior chamber. If nonsurgical attempts fail to seal the leak after 24
to 48 hours, surgical repair is recommended.

 Persistent Epithelial Defects: reepithelialization and the maintenance of an intact


epithelium is critical for postoperative wound healing, improved visual acuity, graft
transparency, graft survival, and protection of the stroma against infection and melting.

The postoperative prevention and treatment of epithelial defects may include the use of a
permanent or temporary tarsorrhaphy, pressure patching, a bandage soft contact
lens, a collagen shield, or an amniotic membrane transplant. Using nonpreserved
artificial tears and limiting medication toxicity to the epithelium are essential. Once an
epithelial defect is present, it must be treated aggressively. If the defect persists for
more than 1 week, it will heal more slowly. The risks of stromal scarring and ulceration
increase significantly with defects present longer than 3 weeks.

The possibility of active herpes virus infection must always be considered when an
epithelial defect does not respond to treatment. Surgical incision of the trigeminal nerve
has been shown to reactivate latent herpes simplex virus in humans.

 Filamentary Keratitis: abnormal collections of mucus and epithelial cells on the corneal
surface. Patients with minimal symptoms should be treated with hypotonic artificial
tears because more mucoid solutions may contribute to the formation of filaments. In
patients with severe symptoms, the filaments should be carefully removed with a forceps
followed by treatment with hypotonic tears and/or topical acetylcysteine, which has a
mucolytic action. Punctal occlusion can also be beneficial, and in severe cases a soft
bandage contact lens may be indicated.

 Suture-related Complications:

o Suture exposure:

o Suture-related infection:

o Suture-related immune infiltrates:

Suture-related immune infiltrate: Multiple, Usually occurs on the host side of


the graft–host interface, No overlying epithelial defect

Infectious suture abscess: Solitary, May occur on the graft or host side of the
graft–host interface, Associated with an overlying epithelial defect

o Kaye dots: discrete white dots in the donor corneal epithelium in a 1–2-mm region
central to the graft sutures. found primarily in the depressed zone central to the

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swollen donor cornea edge. Their formation may be a non-specific response of


the epithelium to an area of tissue angulation. Disappears within 30 days.

 Elevated Intraocular Pressure:

o pneumotonometer or an electronic tonometer

o Tight suturing, long suture bites, larger trephine sizes, a smaller recipient total
corneal diameter, same-size donor–host trephination, and increased recipient
peripheral corneal thickness were shown to result in greater iridocorneal angle
compression and elevated intraocular pressure.

o retained viscoelastic, intraocular inflammation, anterior synechia causing angle


closure, and pupillary block.

o topical beta-blocker, topical alpha-2 receptor agonists, and/or an oral carbonic


anhydrase inhibitor may be considered at the conclusion of surgery. Prostaglandin
analogs and miotic agents should be avoided since they may worsen anterior
segment inflammation.

 Postoperative Inflammation: uncontrolled inflammation may lead to the formation of


intraocular fibrin due to breakdown of the blood–aqueous barrier. Fibrin can serve as a
scaffold for the formation of strands or membranes, leading to the development of
pupillary block and glaucoma or direct damage to the endothelial cells.

o intense hourly topical corticosteroids & Mydriatics.

o Intraocular TPA -25 micrograms.

 Anterior Synechia Formation:

 Pupillary Block:

 Choroidal Detachment and Choroidal Hemorrhage:

 Hyphema:

 Fixed Dilated Pupil: The development of a fixed, dilated pupil following penetrating
keratoplasty for keratoconus has been observed as part of a syndrome associated with iris
atrophy, scattered pigment on the lens capsule and corneal endothelium, and secondary
glaucoma with posterior synechia: Urrets Zavalia Syndrome

 Postoperative Infection:

o The incidence of endophthalmitis after penetrating keratoplasty ranges from


0.2% to 0.77%.

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 Primary Donor Failure: irreversible edema of the corneal graft in the immediate
postoperative period. It is due to inadequate endothelial cell function of an unhealthy
donor endothelium, inadequate tissue preservation, or surgical trauma.

Postkeratoplasty Astigmatism

1. Host factors: Peripheral corneal thinning or Ectasia, Scleral Ectasia, Scarring, Aphakia,
Wound healing, Wound edge profile, Epithelial healing, Shape, Postoperative melting

2. Donor factors: Diameter, Intrinsic astigmatism, Edge profile, Shape

3. Surgical factors: Suture tension, Suture length, Suture depth, Suture radiality, Intraocular
pressure, Suture technique, Intraocular lens implantation, Timing of suture removal,
Surgeon experience, Trephine tilt, Scleral ring placement

 Large-diameter penetrating keratoplasties (LDPKs), defined as grafts that are 8.75 mm


or larger

4. Donor–host interaction: Override/underride, Wound healing, Postoperative trauma

 Relaxing incisions

o can be placed in the graft–host junction or in the graft itself.

o A relaxing incision placed in the graft is termed ‘astigmatic keratotomy (AK)’.

o The term ‘arcuate keratotomy’ describes the creation of one or more arc-shaped
relaxing incisions in the corneal stroma or graft–host interface.

o Relaxing incisions in the graft–host junction are of the arcuate variety and
astigmatic keratotomy incisions can be of the arcuate or straight (transverse)
variety. Relaxing incisions and astigmatic keratotomy incisions are associated with
a coupling effect. Coupling is defined as the simultaneous flattening of the steep
meridian in which the incision is placed and the steepening of the flat meridian 90
degrees away from the incision. When the coupling ratio (the amount of
flattening in the meridian of the incision divided by the induced steepening in the
opposite meridian) is 1.0, the spherical equivalent remains unchanged. When
there is a positive coupling ratio (>1.0), a hyperopic shift occurs. When there is a
negative coupling ratio (<1.0), a myopic shift occurs

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 If the relaxing incisions themselves cannot correct the astigmatism, compression sutures
may be placed across the graft–host interface 90 degrees away from the relaxing incisions

 Wedge resections involve the excision of a wedge of corneal tissue in order to reduce
post-PKP astigmatism.

 LASIK has been introduced as another attempt to surgically correct post-PKP


astigmatism.

 Photorefractive keratectomy

Corneal Allograft Rejection

 allograft rejection is a form of delayed hypersensitivity.

 Studies Streilein and associates, have raised the possibility that anterior chamber
associated immune deviation (ACAID) phenomena contribute to graft survival and that
allograft rejection represents a breakdown in the protection afforded the graft by ACAID.

 Risk Factors

o young recipient age (less than 40 years) (CCTS)

o large-diameter corneal grafts (nearby limbal vasculature, Langerhans cells in


periphery)

o prior graft failure, particularly due to rejection (8% in one, 40% in two)

o pre-existing inflammation

 Clinical Features

o circumcorneal (ciliary) flush

o Anterior chamber flare indicates elevated levels of protein in the aqueous humor

o cellular infiltration of the cornea as discrete subepithelial infiltrates: an early sign


of rejection

o Epithelial rejection 10%, earlier in the postoperative period (1 to 13 months)

o Isolated stromal rejection: uncommon but can be seen as stromal infiltrates and
neovascularization. In very aggressive episodes of graft rejection the stroma can
become necrotic during severe or prolonged bouts of rejection.

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o Endothelial rejection is the most common of the three types, with reported rates
of from 8% to 37% of cases undergoing rejection. Endothelial keratic precipitates
occur as scattered lesions or as a linearly oriented wave of leukocytes migrating
from the peripheral cornea toward the center. Referred to as the Khodadoust
line: hallmark of corneal allograft rejection, but it is not a sine qua non for
rejection. In patients who have received posterior lamellar donor tissue (DSAEK)
cellular keratic precipitates occur only on the transplanted endothelial layer.
Often, there is associated edema of the stroma overlying the area that has been
traversed by the advancing keratic precipitates.

o Edema of the graft

o Corneal thickness usually stabilizes by the third postoperative month, and if the
corneal thickness is greater than 0.59 mm at the sixth postoperative month
there is a greater risk of ultimate graft failure.

o elevated intraocular pressure can be a sign of rejection

 DD

o Recurrence of herpes simplex keratouveitis is the most difficult condition to


differentiate from corneal allograft rejection: typical dendriform epithelial lesion,
endothelial keratic precipitates in herpetic inflammation are not confined to the
graft but involve as well the peripheral host endothelium.

o epithelial downgrowth: inflammation is not a prominent part, not respond to


steroid therapy.

o low-grade corneal infection: candida

 Mx:

o Corticosteroid therapy by topical, periocular, or systemic administration is the


treatment of choice for acute corneal allograft rejection reaction.

 CCTS: higher-frequency postoperative topical steroids, close follow-up of


the patient, and the aggressive treatment of suspected or diagnosed
rejection reaction (including the use of hourly topical prednisolone acetate
for mild reactions plus intravenous methylprednisolone pulse therapy [3–
5 mg/kg IV push] followed by 5 days of oral prednisone [1 mg/kg/day] for
severe reactions)

o immunosuppressive agents such as ciclosporin, tacrolimus, and mycophenolate


mofetil

o biologic methods: intracameral administration of anti-T-lymphocyte monoclonal


antibodies.
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Infections after Penetrating Keratoplasty

 Microbial Keratitis

o 1.76% to 12.1%, most within first year

o three general categories

1. contaminated donor button

2. intraoperative contamination

3. recurrence of host infection.

o Streptococcus pneumoniae (27%) and Staphylococcus aureus (20%) followed by


Gram-negative organisms (20%) and fungal organisms (13%)

o Topical corticosteroids should be stopped in the presence of an acute graft


infection. Only when the organism has been identified and the infection brought
under control should the clinician consider restarting corticosteroid therapy.

o Preferably, the epithelium should be intact before corticosteroids are


reintroduced.

o Graft decompensation was documented in 13–57% of eyes.

 Suture Abscess

o infiltrate in either the donor or recipient cornea which is in direct contact with, or
adjacent to, suture material

o 2–3.3% of penetrating keratoplasties after an average of 21.5–30.8 months

o S. epidermidis, S. pneumoniae, and S. aureus, although cases of Gram-negative


infection

o DD: A sterile suture infiltrate occurs with an exaggerated inflammatory response


usually within the first few weeks after surgery. In this situation there are usually
multiple lesions typically on the host cornea, and the overlying epithelium is
intact.

o careful removal of the offending suture followed by corneal scrapings for smears,
cultures, and sensitivities

 Infectious Crystalline Keratopathy


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o 1983, as a noninflammatory, intrastromal bacterial colonization of a corneal graft

o crystalline branching opacities in the anterior or midstroma due to


intralamellar aggregates of Gram-positive cocci occurring several months following
penetrating keratoplasty and after the long-term use of topical corticosteroids.

o most commonly reported causative organism in ICK is Streptococcus viridans.

o Bacteria are thought to gain access to the corneal stroma via epithelial ingrowth
into a suture track or by direct access through an epithelial defect.

o Scrapings or corneal biopsy

o fortified topical antibiotic drops given in an intensive dosing regimen. Antibiotic


coverage for S. viridans includes topical penicillin G 333 000 units/mL, cefazolin
33–50 mg/mL, or vancomycin 33–50 mg/mL.

o use of Nd:YAG laser to disrupt the protective glycocalyx matrix surrounding the
organisms causing ICK

 Endophthalmitis

o Incidence: 0.08% to 0.77%.

o immediate postoperative period (within 72 hours)

 Contaminated donor tissue or corneal storage media

 Prolonged storage of corneal tissue for more than 5 days

 Preoperative warming of corneal tissue to room temperature for 1 hour


prior to transplantation

 50% had positive donor rim cultures out of which, in 97% cases
organism maching cultures

 Additional risk factors for postoperative endophthalmitis include


intraoperative communication with the vitreous, placement of an
intraocular lens with polypropylene haptics, and a history of drug allergy.

o late postoperative period (months to years)

 secondary to an acquired infection. Ulcerative keratitis within the graft or


at the graft–host interface may progress to perforation and subsequent
endophthalmitis. Concurrent endophthalmitis and ICK from the same
organism has been reported 3 months after penetrating keratoplasty.

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o overall rate of donor rim culture positivity was 14%, with the predominant
organism being S. epidermidis (39%)

o 75% bacterial in origin, whereas fungi are implicated in another 20%

o CF:

 pain

 marked inflammation with or without hypopyon

 diminished or poor red reflex.

 wound dehiscence may also be present

o aspiration of aqueous humor as well as vitreous sampling

o Diagnostic vitrectomy or vitreous aspiration

o Mx:

 Intraocular injection of vancomycin 1 mg in 0.1 mL and ceftazidime


2.25 mg in 0.1 mL should be carried out after a diagnostic or therapeutic
Vitrectomy

 for fungal endophthalmitis is very high, intravitreal injection of


amphotericin B 0.005 mg in 0.1 mL should be performed.

 intravitreal dexamethasone may help in the early reduction of


inflammation in exogenous bacterial Endophthalmitis

 broad-spectrum fortified topical antibiotics should be administered with an


intensive dosing regimen of at least every hour around the clock.

o only 3% of all eyes with endophthalmitis after penetrating keratoplasty had a visual
acuity of 20/40 or better. Acuity of 20/50 to 20/200 was achieved in 17% of cases.
An additional 17% of eyes had acuity ranging from 20/300 to hand motions.

 Herpetic Keratitis after Keratoplasty

o HSV keratitis: relatively infrequent indication for penetrating Keratoplasty 


4.2%.

o recurrent herpetic dendritic keratitis in 10–25% of patients during the first year of
follow-up and in 9–21.6% during 2 to 5 years of follow-up

o in case of recurrence or without prophylaxis: 15–28% of patients having


recurrences in the first year and 18–45% during the second through fifth years.

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 Transmission of Unusual Infections

o Rabies

 Total 8 cases till now- death within 7 weeks

o Creutzfeldt-Jakob disease

 1-2 cases

o Hepatitis virus

 2 cases

o Human immunodeficiency virus

 No cases

Retrocorneal Membranes

 epithelial downgrowth: epithelialization that extends into the anterior chamber

epithelial ingrowth: epithelialization under the LASIK flap.

 Epithelial Downgrowth

o 0.6% of all traumatic and surgical perforations

o 0.27% after PK

o Cataract extraction remains the most frequent cause

o Pathogenesis:

 delayed closure or dehiscence of the surgical wound, often with a


fistula or inadvertent bleb and incarceration of tissue in the surgical
margin.

o dull aching pain, photophobia, and blurred vision. Clinical examination reveals
a hypotonous, normal, or elevated intraocular pressure, and the incision site
may contain incarcerated tissue, a conjunctival bleb, or a fistula.

o argon laser photocoagulation and specular microscopy are often sufficient for
diagnosis when combined with the clinical picture

o The argon laser settings of 0.1–0.2 s, 100–500 µm spot size, and 100–
500 mW are used to outline the extent of epithelial invasion over the iris. The

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involved areas turn white when the laser energy is applied as opposed to an
inapparent burn to the normal iris. The specular microscope can also confirm
the diagnosis if the leading edge of the epithelium can be visualized by
focusing just posterior to the endothelium.

o Confocal microscopy has been shown to aid in the diagnosis of epithelial


downgrowth.

o glaucoma is the most common presenting sign and a common pathway for
eventual enucleation.

o Mx:

 Radiation was the treatment of choice from 1930 to the 1960

 Maumenee's eradication technique:

 Naumann and Rummelt ‘s block excision:

 endoscopic photocoagulation

 Fibrous Ingrowth

o fibrous proliferation and invasion of the tissues surrounding the surgical site

o distinct from epithelial downgrowth, less likely to result in enucleation

o Penetrating keratoplasty is the most recognized source

o 50-60% of failed Keratoplasty

o Pathogenesis:

 Subepithelial connective tissue and corneal stromal fibroblasts


participate in normal traumatic and surgical wound healing, and an
exuberant response leading to fibrous ingrowth can be easily imagined.

o translucent membrane on the posterior surface of the cornea near the wound.
The edges may be frayed or irregular, and, unlike epithelial downgrowth, the
stroma of the membrane may be vascular

o no ancillary diagnostic tests have been useful to confirm

o medical management of inflammation, glaucoma, or corneal edema is


sufficient, and the fibrous proliferation matures into a quiescent scar and can
even fade considerably

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 DD:

o Beveled corneal incisions

o Peripheral corneal edema

o pigmented membrane can appear on the posterior surface of the cornea as a


result of proliferation of iris stromal melanocytdes from trauma or surgery.

Glaucoma after Penetrating Keratoplasty

 most devastating complication after penetrating Keratoplasty

 practical definition of PKP glaucoma is an IOP > 21 mmHg after penetrating keratoplasty,
with or without associated visual field loss or optic nerve changes, necessitating the
addition of medications to reduce the intraocular pressure.

 PKP glaucoma treatment escalation definition: Treatment escalation was either surgical or
medical; in the case of medical escalation, only sustained increases in medication burden
compared to baseline were included; treatment to deal with brief IOP spikes in the early
postoperative period was excluded from analysis.

 Incidence: IOP > 25 mmHg occurred in 37% of phakic eyes, 88% of aphakic eyes, and 100%
of eyes undergoing combined cataract extraction with penetrating Keratoplasty

 Risk factors:

o Preexisting glaucoma

o Aphakia

o Anterior segment inflammation

o Corneal diagnosis

o Intraocular lens removal

o Vitrectomy

o Postkeratoplasty/extracapsular cataract extraction/intraocular lens

 The Pre-Keratoplasty Evaluation

o Tonometry and a careful pupillary examination

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o ASOCT

o UBM

o afferent pupillary defect is an ominous clinical sign

o Visual fields are frequently unreliable in the patient with cloudy media

o flash VEP was the single best predictor of postoperative vision

 Clinical Presentation

o most important is its detection

o astigmatism and alterations in corneal thickness can influence the accuracy of


applanation measurement techniques, with thinner corneas under-reading
‘true’ IOP

o pneumotonometer, Tono-Pen and the dynamic contour tonometer all provide


reasonable results in PKP eyes.

 glaucoma is a risk factor for corneal graft failure, whether it is preexisting or develops
after penetrating keratoplasty.

o graft survival probabilities using Kaplan–Meier analysis were 82% at 1 year and
66% at 2 years, versus 93% at 1 year and 87% at 2 years

o high IOP causes damage to endothelial cells.

o BAK found in most glaucoma medications

 Causes of glaucoma after penetrating Keratoplasty

o Preexisting glaucoma: Primary, Secondary

o Secondary angle-closure glaucoma

o Trabecular meshwork collapse (aphakia): Six factors were found to be related


to iridocorneal angle compression: (1) diameter of the host cornea, (2) size of
the recipient bed, (3) length of the suture bites, (4) tightness of the sutures,
(5) thickness of the recipient cornea, and (6) size of the donor button relative
to the size of the recipient bed.

o Postoperative glaucoma: Pupillary block, Iritis, Hemorrhage, Lens induced,


Steroid response, Malignant, Viscoelastic induced

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 Medical management

o use of aqueous suppressants preoperatively and close monitoring

o Miotics are generally ineffective and contraindicated in the early postoperative


period.

o Topical CAIs: reports of corneal decompensation

o prostaglandin analogue: CME

 Surgical management when medical therapy fails

o Laser iridoplasty and trabeculoplasty

o Filtering surgery

o Glaucoma Drainage Devices

 corneal graft failure in eyes with GDD: immune, mechanical

o Cyclodestructive Procedures

Pediatric Penetrating Keratoplasty

 Special problems:

o Preoperative problems

1. Complete preoperative evaluation of the corneal pathology is usually not possible.

2. Need for specialized investigations such as ultrabiomicroscopic examination.

3. IOP evaluation usually not accurate in opaque corneas.

4. Patient should be evaluated for systemic associations in cases of congenital


corneal opacities.

o Intraoperative problems

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1. Small size of the palpebral fissure reduces the working space available for
manipulations.

2. Excessive lowering of the intraocular pressure is to be avoided as severe hypotony


prevents optimal trephination of the recipient cornea.

3. Caution is to be exercised while performing the scleral fixation due to the higher
risk of perforation as the sclera is thinner in pediatric eyes.

4. Use of Flieringa rings with unequal placement of fixation sutures may also result
in increased distortion resulting in difficulty while suturing.

5. Need for performing associated procedures such as lensectomy, anterior


vitrectomy, glaucoma procedures, and so on, is high.

6. Increased positive pressure of vitreous with forward shift of lens–iris diaphragm


due to the low scleral rigidity and increased elasticity of pediatric eyes.

7. Increased difficulty in suturing and cheese wiring due to the thin peripheral
corneal tissue in certain cases.

o Postoperative Problems:

1. need for frequent examinations under anesthesia for postoperative follow-up


evaluations

2. frequent loosening of sutures necessitating replacement/early removal

3. increased risk of rejection and infections

4. Difficulties with repeated refractive error assessments, and reversal of


amblyopia.

5. Even with increased anatomic success of pediatric corneal grafts, visual


rehabilitation remains a concern.

 prevalence of congenital corneal opacities is approximately 3/100,000. With congenital glaucoma


included this rises to 6/100,000

 most common primary cause of congenital corneal abnormalities in the developed nations is Peter's
anomaly (40.3%), followed by sclerocornea (18.1%), dermoid (15.3%), congenital glaucoma (6.9%),
microphthalmia (4.2%), birth trauma, and metabolic disease (2.8%).

 Indications:

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1. Congenital:

a. CHED

b. Non CHED with Glaucoma: Congenital glaucoma, peter’s, anterior segment


dysgenesis

c. Non CHED without Glaucoma: Sclerocornea, dermoid, birth trauma, metabolic


dz, keloid, aniridia

2. Acquired, nontraumatic: Herpes simplex keratitis, Bacterial keratitis, Stevens–Johnson


syndrome, Keratoconus, Neurotrophic keratitis, Interstitial keratitis, Fungal keratitis,
Exposure keratopathy

3. Acquired, traumatic: Corneal or corneoscleral laceration, Blood stain, Nonpenetrating


injury with scar

 clear grafts in 80% of pediatric patients at 1 year and 67% at 2 years. excellent prognosis
for graft survival in eyes with CHED and a fair prognosis for graft survival in eyes with non-
CHED congenital opacities and acquired opacities.

 Reasons for graft failure:

o Allograft rejection

o Primary graft failure

o Graft decompensation

o Infection

o Corneal ulcer

o Glaucoma

o Trauma

o Phthisis bulbi

 Complications of pediatric Keratoplasty:

o Allograft rejection: 22 to 44%, lower reversal rate, CsA 2% QID  OD in 3 months

o Graft infection: 10 – 50%

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o Persistent epithelial defects (PED): poor graft host junction apposition and faulty suturing,
early suture loosening, drug toxicity, tear, and surface abnormalities

o Corneal ulcer

o Cataract: 2%

o Glaucoma: 5 – 9%

o Retinal detachment: 3-5%

o Endophthalmitis: 2%

o Wound leak or dehiscence: 2 – 10%

o Expulsive choroidal hemorrhage: 2-3%

o Inadvertent lens loss

o Phthisis bulbi: 4-13%

Outcomes

1. Congenital:

a. CHED (25% to 90%)

b. Non CHED with Glaucoma: Congenital glaucoma (50% or less), peter’s (62%),
anterior segment dysgenesis

c. Non CHED without Glaucoma: Sclerocornea (70% in eyes with sclerocornea and
83% for partial sclerocornea), dermoid, birth trauma, metabolic dz, keloid,
aniridia

2. Acquired, nontraumatic: Herpes simplex keratitis, Bacterial keratitis, Stevens–Johnson


syndrome, Keratoconus, Neurotrophic keratitis, Interstitial keratitis, Fungal keratitis,
Exposure keratopathy

3. Acquired, traumatic: ( 55-100%)Corneal or corneoscleral laceration, Blood stain,


Nonpenetrating injury with scar

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Large-Diameter Corneal Grafts

 1951 Castroviejo: large-diameter penetrating keratoplasty, or sclerokeratoplasty,

 Two types

o Total penetrating Keratoplasty: sclerokeratoplasty

o Large-diameter lamellar grafts: Malbran procedure  advanced keratoconus

 Indications

o uncontrolled Pseudomonas corneal ulcers, keratomycoses, and other severe


necrotizing corneal

o chronic progressive peripheral corneal ulceration, corneal melting (as in some


cases of Mooren's ulcer), rheumatoid keratolysis, or descemetocele formation

o large-diameter lamellar graft: pellucid marginal degeneration, advanced or


eccentric keratoconus, and keratoglobus

 topical and systemic antirejection medications must be administered postoperatively.

PK in Herpes Simplex Disease

 Stromal keratitis is the leading cause of permanent corneal transparency loss

 penetrating corneal graft survival for herpetic eye disease/scar is 86% at 1 year,
dropping to 75% at 5 years, and to 59% at 10 years postoperatively

 A recurrence-free or inflammation-free interval for transplantation of such cases has not


been determined yet, but it is considered as a period of at least 6 months.

 Preoperative Measures

o Control of inflammation

o Vascularization

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o Corneal sensation: Reduced corneal sensation may cause reduced epithelial growth
and differentiation with consequent development of epithelial defects

o Antiviral prophylaxis: Oral antiviral agents inhibit viral replication at the


trigeminal ganglion, avoiding recurrence of ocular disease. Topical antivirals do
not have the capability of arresting viral replication in the central nervous system
but, if the recurrence appears, they may locally inhibit viral replication.

o Uveitis, glaucoma, and recurrent graft rejection episodes – all of which damage the
corneal endothelium – are common after PKP for herpetic keratitis.

 Operative Technique

o Graft size

o Perforated eyes

o Suture: interrupted

o 'Triple procedure’

o Anterior lamellar Keratoplasty

o Femtosecond laser

o Boston keratoprosthesis

 Postoperative Management

o Use of corticosteroids

o Suture removal

o Persistent epithelial defects: 33% and 44%, Herpetic keratitis must be in the
differential diagnosis of early- and late-onset postkeratoplasty epithelial defects
with or without a history of previous infections.

o Recurrence of HSV keratitis: 6% and 44%. 23% of corneal grafts performed for
herpes simplex keratitis that develop a recurrence may undergo an episode of
rejection.

o The allograft rejection: 29% and 46%

o Herpes simplex virus in corneas for transplantation

o Secondary graft failure

o Glaucoma

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o Wound dehiscence

o Secondary infections

High-Risk Penetrating Keratoplasty

 ‘transplantation antigens,’ fall into two categories: major and minor

o The genes that encode the major transplantation antigens in humans are located
within the major histocompatibility complex (MHC) and individually are called
human leukocyte antigen (HLA).

 Class I antigens are transmembrane glycoproteins designated HLA-A, HLA-


B, and HLA-C. They are expressed on most nucleated cells.

 Class II antigens are encoded by HLA-D genes and include HLA-DP, DQ, and
DR antigens. Class II antigens are found on specific immunocompetent
antigen-presenting cells (APCs) of the lymphoreticular system.

o Minor transplantation antigens are encoded by genes outside the MHC at


numerous loci spread throughout the genome. They are only available for
detection if processed and presented on the surface by class I or II MHC molecules
of the host. ABO blood group antigens, which differ from most classic minor
antigens because they are highly glycosylated. In the cornea, ABO antigens are
expressed by epithelial cells, and are upregulated during graft rejection.

 CCTS Risk factors

1. Corneal stromal vascularization >= 2 quadrants, deep, 7% per quadrant

2. Prior graft loss, especially from allograft rejection: Rejection rates in patients with
comparably vascularized recipient beds are approximately 40% after the first graft,
68% after the second graft, and 80% after the third graft.

3. Increased graft diameter and eccentric grafts: but in recent study  smaller ??
independent ??

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4. Anterior synechiae: three or four quadrants of iris synechiae

5. Previous intraocular surgery

6. Herpes simplex keratitis

7. History of anterior segment inflammatory disease

8. Ocular surface disease

9. Young age, especially infants and children

 Management:

o Controlling ocular inflammation

o Rehabilitating the ocular surface

o Tissue matching: HLA is conflicting, ABO has some definitive role

o Surgical technique

o Postoperative considerations: Teaching each patient the symptoms of rejection


facilitates its early recognition. A useful acronym is RSVP, which stands for
redness, sensitivity to light, visual loss, and pain.

o Immunosuppression

 Corticosteroids: large systemic doses prednisone (1 mg/kg) around the


time of surgery, which can then tapered on an individualized schedule
within 2 months. A typical regimen involves prednisolone acetate 1% every
2 hours for the first few weeks with a gradual decrease over the next
several months.

 Calcineurin inhibitors

 Ciclosporin A: It inhibits the transcription of many factors necessary


for T-cell activation, most prominently IL-2. Topical & Systemic

 Tacrolimus

 Antimetabolites

 Azathioprine

 Mycophenolate mofetil

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 Rapamycin

 Monoclonal antibodies

 Daclizumab (Zenapax) and basiliximab (Simulect)

 Campath-1H is a ‘humanized’ monoclonal antibody

Anterior Lamellar Keratoplasty

 Indications

o Tectonic: to restore normal corneal thickness by using tailor-made lamellar corneal


patches to match the defect on the patient (lesion-fit keratoplasty)
1. Descemetocele
2. Pellucid marginal degeneration
3. Advanced Terrien's marginal degeneration
4. Sterile Mooren's ulcer and other forms of peripheral corneal melts related to
autoimmune disorders (as in rheumatoid arthritis and Wegener's granulomatosis).

o Optical: to enhance vision:


1. Ectatic disorders: keratoconus, keratoglobus, keratotorus (Schlappi’s pellucid
marginal degeneration)
2. Scars:
3. Dystrophies: epithelial, Bowman's membrane, stromal dystrophies
4. Degenerations:
5. Post refractive surgery complications:
6. Advanced recurrent pterygium involving central cornea
7. Special circumstances:

o Therapeutic: Resistant corneal infections, Dermoids and some tumors, Inflammatory


mass, Perforations

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o Cosmetic: Corneal opacity

 Contraindications

o endothelium is unhealthy

o big-bubble technique is contraindicated if there is a pre-existing break in the


Descemet's membrane (post hydrops) or there are deep scars (however small)
involving the Descemet's membrane

 benefits of anterior lamellar Keratoplasty

1. Extra ocular surgery:


2. No risk of endothelial graft rejection:
3. No need for long term steroid prophylaxis:
4. Rapid functional recovery of vision:
5. No interface haze: in DALK
6. Very good BSCVA.
7. No significant endothelial cell loss:
8. Lesser postoperative glaucoma:
9. Less astigmatism then penetrating keratoplasty:
10. Penetrating Keratoplasty can be done if recurrences.
11. Better long-term graft survival
12. No late failures
13. Easier follow-up
14. A lower-quality donor cornea can be used
15. Allows larger grafts when needed without risking rejection

 Techniques can be grouped into: (4)

1. Stroma to Stroma (manual, microkeratome, and laser-assisted)

2. DM to DM

3. DM to Stroma (2 & 3 can develop subgraft clefts, pseudochambers, or folds in


donor Descemet's membrane; hence this type of interface is not recommended)

4. Stroma to DM (only manually)

Two main categories

1. pre-Descemet's membrane procedures


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2. Descemet's membrane procedures,

 Techniques

o Layer-by-layer dissection
o Stromal delamination
o Automated therapeutic lamellar Keratoplasty
o Intrastromal dissection
o Cleavage separation
o Donor preparation

 Additional Equipment for DALK

o Pachymeter

o Slit lamp microscope

o Blunt-tipped scissors and spatula

 Intraoperative Complications

o Perforations and ruptures of Descemet's membrane: Most common complication

 Postoperative Complications

o Pseudoanterior chambers, or double anterior chambers

o Pupillary block and fixed dilated pupil (Urrets-Zavalia syndrome)

o Sclerocorneal inflammation: Postkeratoplasty atopic sclerokeratitis (PKAS) is a rare


form of acute inflammation of the ocular surface associated with suture loosening
and melting of the graft.

o Suture-related complications

o Interface infection

 Outcomes of ALK:

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o Visual Outcomes: no statistically significant difference in best corrected visual


acuity (BCVA) from 6 months postoperatively through to 5 years postoperatively in
DALK vs PK in KC.

o Graft Survival: endothelial cell count 12 months to 2 years postoperatively was


significantly greater following DALK than PK

o Suture Management: in PK early removal of sutures can result in unpredictable


refractive changes, graft movement, and instability.

o Resistance to Trauma: DALK must theoretically be stronger than a cornea which


has undergone PK.

o Surgical Planning: no risk of endothelial rejection and there may be a reduced risk
of suture-related events and full-thickness wound dehiscence.

Endothelial Keratoplasty

Indications

1. Endothelial dystrophy: Fuchs', posterior polymorphous,

2. Bullous keratopathy: pseudophakic, aphakic

3. Endothelial failure: from trauma, previous surgery, angle closure, tubes

4. Iridocorneal endothelial (ICE) syndrome

5. Failed penetrating Keratoplasty (if acceptable refractive result was achieved)

Contraindications

1. Stromal opacity or scarring that limits visual potential

2. Keratoconus, ectasia

3. Hypotony/pre-phthisical eye

Assessment of anterior chamber space and specialized techniques advised in eyes with:

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1. Anterior synechiae

2. Glaucoma tubes

3. Iris abnormalities

4. Anterior chamber intraocular lens

 Benefits

1. maintenance of the structural integrity of the eye

2. more rapid visual recovery

3. minimal change in refractive spherical equivalent.

 Patient Selection

o Age: There is certainly no upper age limit for the procedure. 2-90 years

o Duration of corneal edema:

 some eyes can achieve 20/20 vision within a week of EK.

 longstanding corneal edema: remodeling by keratocytes appears to progress


from the periphery inward, with the central area over the pupil clearing
last.

o Lens Considerations

 generally preferable to perform cataract surgery before the transplant,


either as a staged or combined procedure

 Removal of the crystalline lens first also creates more room in the anterior
chamber

 opportunity to preserve accomodation by leaving an eye phakic after EK


must be weighed against the additional risk and cost of subsequent cataract
surgery.

 Challenging Eyes

o Failed penetrating grafts: EK graft that is 1 mm larger in diameter than the


failed PK, avoid stripping Descemet's membrane and endothelium from the failed
PK
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o Glaucoma tubes:

o Shallow anterior chambers: Performing a peripheral iridectomy, use of


microforceps

o ACIOLs: to be replaced by SFIOLs

o Iris abnormalities, aniridia and aphakia: generally avoid stripping the recipient
Descemet's membrane, pull-through technique helps ensure that the graft is
secured at all times

 Donor Preparation

 Issues to Consider

o General: Preparation immediately before surgery or ‘pre-cut tissue.’

o Uniform thickness: donor of approximately 180 µm  much easier handling and


unfolding of the tissue

o Diameter: 3 mm less than the smallest diameter of the recipient cornea, larger
EK are more difficult to unfold

o Shape: meniscus shape is produced by most microkeratomes and femtosecond


laser  thinner in the center than at the edges 1.5 diopter (D) hyperopic shift

o Stromal bed consistency: smooth stromal bed surface is desired for improved
Snellen vision.

o Scleral rim size: 16–18 mm total diameter

o Endothelial cell count: 2000–3000 cells/mm2

o Donor age: 2-75 years

o Preservation to cutting to surgery time: death due to implantation time longer


than 165 hours as well as a cut to implantation time of less than 94 hours is
acceptable

 Methods-4

o Manual dissection: PLK & DLEK

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 Securing donor rim onto the artificial anterior chamber. Trephination of the
donor rim with a 9.0-mm Hessberg-Barron vacuum trephine. Manual
dissection of the anterior stroma with 0.12 forceps and a crescent knife is
started at the keratectomy edge. After removal of the anterior cap, the
residual stromal bed is smooth and ready for final resection.

o Automated microkeratome dissection: smoother but bed profile is often of a


meniscus shape, which has been associated with postoperative hyperopic shift.

 Donor disc secured into position with the anterior ring lock. Microkeratome
track is placed on top of the anterior ring lock. The applanation lens is used
to verify adequate vacuum. (<< refers to the circular gauge within the
applanation cone; < refers to actual corneal applanation reflex; when
within the circular gauge, the vacuum is considered to be adequate.) The
cornea is moistened with BSS and the microkeratome pass is made.
Microkeratome has produced a free anterior cap and a smooth residual bed.
The donor is placed endothelial-side up onto a Barron vacuum trephine,
while the trephine diameter is confirmed with calipers. After trephination
with a 9.0-mm trephine blade, the donor is ready for insertion.

o Femtosecond laser dissection:

 The donor rim is placed onto an artificial anterior chamber and centered
with the femtosecond laser applanation cone. A spiral ablation pattern is
started centrally. The ablation extends to the 9.0-mm zone, while the side
cut is visible. A 15-degree hinge is located at the 6 o’clock position. The
anterior flap is lifted with a flap elevator. The residual bed is evaluated
and has surface irregularity that corresponds to the spiral ablation pattern,
an inherent weakness of the IntraLase.

 many promising applications such as customized EK lenticules with a smooth


central zone (i.e. to improve Snellen vision) and a roughened peripheral
zone (i.e. to facilitate adhesion), it is very expensive compared to other
methods.

o Submerged cornea using backgrounds away (SCUBA) technique: addresses the


challenges of handling and visualizing a thin EK donor which consists of just
Descemet's membrane and the endothelium (i.e. 20 µm thickness) DMEK

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 After securing the donor rim to a Barron vacuum trephine and stabilization
with 0.12 forceps, a closed tying forceps are used to scroll the peripheral
Descemet's membrane. The donor endothelium is stained with trypan blue.
Under submersion with either BSS or Optisol GS, the Descemet's/endothelial
layer is gently peeled with tying forceps to begin the process. At this point,
the process is two-thirds complete, with an intact Descemet's endothelial
layer. After removal, the tissue usually scrolls with the endothelium facing
outward. It is placed into trypan blue to allow visualization after insertion.

 Surgical Techniques

o Barraquer first proposed selective replacement of the corneal endothelium for


treatment of corneal edema in 1950

o Donor Tissue Preparation:

 avoid an eccentric cut of the posterior corneal tissue

 potential priming effect on donor endothelium from glutathione and/or


glucose in BSS Plus, thereby maximizing the endothelial pump function of
the donor endothelium, allowing for better adherence when presoaking
prepared donor tissue.

o Intraoperative Techniques:

 The horizontal and vertical diameters of the eye

 centration point is determined on the recipient cornea followed by marking


the epithelium

 Wound creation

 one to three paracentesis incisions, Marking the noncutting edge


blade prior to paracentesis, as peripheral as possible to minimize
graft touch or graft dislocation with cannula

 anterior chamber maintainer

 incision into the anterior chamber is typically created using a


diamond or metal keratome, 3 mm and later enlarged to 5 m,
scleral, limbal, or clear cornea

 Recipient preparation

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 reverse Sinskey hook or similar device is typically used to


underline or score the endothelium/DM 1–2 mm inside the
previously made epithelial trephine mark

 Once the circular zone of recipient tissue has been removed, it can
be unfolded on the corneal epithelium for careful inspection to
detect any potential retained fragments left inside the eye.

 Techniques to Improve Donor Adherence

o ‘vent incisions’ as described by Price and Price

o Vent incisions + surface massage with a specially designed roller or a long cannula

 Donor Insertion Techniques

o endothelium should be coated with viscoelastic to minimize future endothelial


trauma with avoidance of any gentian violet touch to the corneal tissue directly, as
it is endothelial toxic.

o compression forceps such as Kelman-McPherson forceps.

o noncompression forceps (Irrigation must be in the ‘off’ position)

o A trifold technique or ‘burrito’ fold has also been described for tissue insertion
with forceps through a 3-mm incision.

o A shovel may also be used as an insertion device

o suture pull-through insertion technique

o Injectors like The Busin glide

 Donor Apposition Techniques

o Two to four sutures are typically required to close a 5-mm wound

o Once sutures are placed, the tissue is unfolded unless a pull-through or inserter
technique was used, in which case the tissue is already in proper orientation with
endothelium down and stroma side up.

o BSS or air may be irrigated through the paracentesis or wound between the fold of
the tissue to complete the unfolding process

o The pressure must be high after air insertion to ensure tissue apposition, as the
inability to achieve a high pressure at this point of the surgery is the single most
important risk factor for dislocation.

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o pressure is maintained for at least 10 minutes, an air–fluid exchange can be


performed to reduce the risk of pupillary block from an anterior chamber full of
air.

o Phenylephrine should be avoided as it may increase graft dislocation in a similar


manner as it increases flap slippage with LASIK.

 Early Postoperative Management

o shield is typically placed after topical cycloplegic, antibiotic, and antiinflammatory


drops

o supine position 6-24 hours

 DMEK

o idea of DMEK was first introduced by Melles in 1998, the first successful report of
DMEK did not occur until 2006

o advantage:

 avoidance of expensive mechanical microkeratomes, femtosecond lasers,


and an artificial anterior chamber.

 avoidance of a recipient stroma–donor stroma interface as in DSEK, quicker


visual acuity recovery and better final visual acuities

o A SCUBA technique (submerged cornea using backgrounds away) has been


described for donor tissue preparation by Geibel

o It is important to not leave extra endothelium/DM within the 9-mm trephine mark,
unlike with DSEK, as recipient–donor overlap is a risk factor for dislocation with
DMEK.

 EK & Glaucoma

o risk factors for increased corneal endothelial damage,


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 whether from carbonic anhydrase inhibitor toxicity to the endothelium

 intraocular pressure (IOP)-induced endothelial damage

 shallow angles with increased risk of peripheral iris synechiae and resulting
iris–cornea touch

 endothelial trauma from trabeculectomy or a glaucoma drainage device


(GDD)

o main difficulty: ability to maintain an air bubble after air insertion, as both types
of fistula immediately shunt air from the anterior chamber

 EK & Phacoemulsification

o cataract surgery is performed prior to the EK procedure to avoid exposing the


donor to unnecessary ultrasound energy and other potentially traumatic insults
related to the cataract removal

o paracentesis in the triple procedure should be more vertical than the standard

o While EK has minimal effects on postoperative keratometry, it does affect the


postoperative corneal power. hyperopic shifts between 0.75 and 1.5 diopters.

o Intraoperative Issues

 Small vertical paracenteses

 mark all paracentesis blades with gentian violet

 use a cohesive viscoelastic for all aspects of the surgery

 adequate incision size is important to minimize endothelial trauma: 4-5 mm

 To minimize the tendency for this anterior displacement, it is helpful to


make sure that the capsulorhexis is smaller than the IOL optic.

o Postoperative Results

 refractive spherical equivalent was within 1 diopter of emmetropia in 73%


of eyes

 postoperative refractive results had a mean shift of +1.46 diopters from the
targeted outcome

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 Intraoperative Complications

o Damaged donor tissue: small scleral rim, during insertion

o Eccentric trephination: increase the risk of graft detachment,

o Thin donor tissue: tend to fold over on itself, prismatic optical effect that an
uneven graft

o Retained Descemet's membrane: prevent proper attachment of the DSAEK graft,


with subsequent graft detachment

o Air management: keep the patient in a strict supine position or the use of higher
buoyancy gases

o Others complications: Expulsive choroidal hemorrhage, Anterior chamber


hemorrhage, Lens damage

 Postoperative Complications

o Donor dislocation: most common complication  reported upto 23-35% ,with


newer techniques its <1%

o Primary graft failure: any graft that fails to clear within the first 2 weeks after
the DSEK surgery. donor cornea should have at least 2000 cells/mm2. 2% to 45% in
the literature.

o Secondary graft failure is the term used when the donor endothelial tissue is
detached from the recipient stromal cornea, therefore preventing the cornea from
clearing.

o Graft rejection: presence of anterior chamber cells with or without keratic


precipitates and concomitant corneal edema. 2.2% to 14%.

o Pupillary block glaucoma: may lead to formation of PAS. high intraocular


pressure, peripheral anterior synechiae, iridocorneal adhesions, and a shallow AC.

o Endothelial cell loss: 31% to 50% at the 6-month postoperative examination.

o Refractive change: hyperopic refractive shift

o Interface deposits and epithelial ingrowth:

o Retinal complications: Suprachoroidal hemorrhage, RD, CME

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 The speed of visual recovery after DSAEK is generally superior to that of traditional PK,
with many patients recovering excellent uncorrected and corrected vision in a matter of
weeks rather than months or years.

Management of Corneal Perforations

Etiology

o Infectious (bacterial, fungal, viral [herpes simplex, herpes zoster])

o Inflammatory (collagen vascular disease, acne rosacea, atopic disease, Wegener's


granulomatosis, Mooren's [idiopathic] ulcer)

o Trauma (chemical, thermal, ultraviolet [UV], penetrating)

o Xerosis (idiopathic, Sjögren's syndrome, Stevens-Johnson syndrome, ocular cicatricial


pemphigoid, vitamin A deficiency)

o Exposure (seventh nerve palsy, thyroid-related ophthalmopathy, ectropion, floppy


eyelid syndrome)

o Neurotrophic (postviral, tumor, trauma, postsurgical [cataract extraction, penetrating


keratoplasty])

o Degeneration/ectasia (Terrien's marginal degeneration, keratoconus, keratoglobus,


pellucid marginal degeneration)

o Surgical (cataract extraction, LASIK, PRK, epithelial sparing PRK, pterygium excision
with mitomycin-C, glaucoma filtering/shunt surgery)

o Toxic/keratolytic (topical NSAIDs, topical antibiotics [gatifloxacin], topical


corticosteroids, silicone oil)

 Know difference between terms

1. Corneal Ulcer

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2. Descemetocele

3. Perforation

 Symptoms

o Pain

o Decreased visual acuity

o Increased ‘tearing’

 Signs

o Shallow or flat anterior chamber (perforation)

o Positive Seidel test (perforation)

o Uveal tissue to the posterior cornea or frank prolapse (perforation)

o Hypotony (perforation)

o Central clear zone (often bulging) within area of infiltrate or thinning (descemetocele)

o Radiating folds in Descemet's membrane emanating from the base of the ulceration
(descemetocele)

 Treatment

o Tissue adhesives

 Cyanoacrylate glue: 1960, Webster, small, relatively central perforations 1–


2 mm or less,

 2-octyl-cyanoacrylate: DERMABOND

 Iso-Dent: DENTAL GLUE

 Human Fibrin Glue

 Commercial superglue ??: methyl-2-cyanoacrylate

o Penetrating keratoplasty

 Larger perforations not amenable to repair using tissue adhesive or tissue


adhesive failures

o Patch graft
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 lesions that are too large to use tissue adhesive but small enough to obviate
the need for a full-sized penetrating

o Amniotic membrane transplantation

 multilayed procedure

o Medical management

 Prevention of Corneal Perforation

o Bandage soft contact lens

o Conjunctival flap

o Tarsorrhaphy

o Amniotic membrane transplantation

o Miscellaneous: simple pressure patching, aggressive lubrication, punctal occlusion, and


the use of topical ciclosporin

Therapeutic Lamellar Keratoplasty


 Optical Indications

o Reis-Bücklers' dystrophy, spheroidal degeneration (Labrador keratopathy), and


superficial leukomas

 Tectonic Indications

o Peripheral noninflammatory corneal thinning disorders: PMD, TMD

o Peripheral inflammatory corneal disease

o Central thinning and Ectasia

Therapeutic Keratoplasty

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 primary purpose is either to restore the structural integrity of the eye (tectonic
keratoplasty) or to resolve an infectious or inflammatory keratitis that is refractory to
conventional medical therapy.

 Indications

o Infections

o persistent epithelial defects and sterile melts

 Postoperative Management

o Eradicate all remnants of infection, and prevent reinfection.

o Promote reepithelialization of the cornea and wound healing.

o Control inflammation with corticosteroids.

o patient's intraocular pressure should be followed carefully. Glaucoma is seen in


approximately 50% of optical penetrating keratoplasties.

 Prognosis

o clear therapeutic grafts in 73% of bacterial corneal ulcers, 60% of fungal corneal
ulcers, 50% of Acanthamoeba corneal ulcers, and 36% of herpes ulcerations with
inflammation.

Surgical Management of Superficial Corneal and Conjunctival Disease

Molluscum Contagiosum
 completely excised with a blade or cautery

 can be treated with cryotherapy

 simply curetting the central umbilication and making the lesion bleed

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Superior Limbic Keratoconjunctivitis


 patients should undergo thyroid testing

 Medical treatments: artificial tears, antihistamine and mast cell stabilizer drops,
ciclosporin drops, nonsteroidal antiinflammatory drops, steroid drops, autologous serum,
and steroid injection.

 Surgical treatments: punctal occlusion to silver nitrate solution cautery, cryotherapy,


thermal cautery, suture stabilization, and conjunctival recession or resection, with or
without amniotic membrane grafting.

Conjunctivochalasis
 An ellipse of excess conjunctiva is marked and removed with Westcott forceps.

Recurrent Corneal Erosions


 Two most common underlying conditions:

1. previous corneal trauma

2. corneal dystrophy (typically anterior basement membrane dystrophy [ABMD]).

 ointment lubrication

 BSCL

 ASP

 Epithelial debridement alone, or combined with a diamond burr (DB) polishing procedure
or with excimer laser phototherapeutic keratectomy (PTK)

Band Keratopathy
 simple observation in asymptomatic cases to lubricating drops, gels, and ointments for
irregular corneal surfaces to removal of the calcium in more advances cases.

 chelation with disodium ethylenediamine tetraacetic acid (EDTA), not calcium EDTA.

 2-3% solution.

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Partial Limbal Stem Cell Deficiency


Phototherapeutic Keratectomy

 FDA approval:

o PRK: 1995

o PTK: 1995

o LASIK: 1998

 Advantage

o Precision: 0.25 µm of tissue, or about 1/2000 of the corneal thickness.

o shape of the laser spots can be adjusted

o allows the surgeon to remove superficial corneal abnormalities

 disadvantage

o does not discriminate between abnormal and normal tissue

 FDA-approved indications for PTK

(1) superficial corneal dystrophies (including granular, lattice, and Reis-Bücklers dystrophies),

(2) epithelial basement membrane dystrophy and irregular corneal surfaces (e.g. secondary to
Salzmann's nodular degeneration, keratoconus nodules or other irregular surfaces), and

(3) corneal scars and opacities (e.g. due to trauma, surgery, infection, and degeneration)

 Contraindications

o immunocompromised host, uncontrolled ocular disease such as uveitis, blepharitis


or dry eyes, and any condition thought to adversely affect corneal healing.

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 laser should not remove greater than one-third of the corneal thickness and should leave
at least 250 µm of tissue after the procedure.

 Side Effects and Complications

o Pain

o Poor epithelial healing

o Haze/scar

o Infection

o Induced hyperopia (common)

o Induced myopia

o Induced regular and irregular astigmatism

o Decreased uncorrected and best-corrected vision

o Recurrence of herpes simplex virus infection

o Recurrence of the condition (especially stromal dystrophies, Salzmann's nodular


degeneration, keratoconus nodules)

o Graft rejection/failure

Conjunctival Flaps

 1958, Gundersen

 Indications

o Persistent corneal epithelial defect

o Unresponsive ulcerative microbial keratitis

o Corneal thinning and perforation

o Corneal limbal disease

o Scleral necrosis

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o Glaucoma surgery complications

o Surface preparation for a cosmetic scleral shell

 Disadvantages

o vision may be significantly decreased in cases where the flap covers the visual axis

o prevents monitoring of disease progression by making direct visualization

o limited assessment of the intraocular pressure

o compromises the donor site should the patient need a trabeculectomy in the future

 Types

o Total conjunctival flap

 thin, bipedicle, bridge flap described by Gundersen

o Bipedicle bridge flap

o Single pedicle flap

o Advancement flap

 Complications

 Intraoperative complications

o Buttonhole formation

o Dissection of an inadequate flap

o Excessive hemorrhage

 Postoperative complications

o Retraction of the flap

o Ptosis

o Cystic flap

o Opacification and vascularization

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Iris Reconstruction Surgery

 Iris Suture Techniques: McCannel's technique and its modification

o The sliding knot intracameral suture: Siepser

o Pupil cerclage procedure

o Iridodialysis Repair

 Iris Relaxing Incisions

 Scissors Sculpting

 Vitrector Sculpting

 Iris Prostheses

o Large-incision, rigid diaphragm devices: Morcher GMBH, PMMA

o Rigid small-incision devices: multipiece ‘IPS’ prosthesis, Morcher 50 Series in the


bag prosthesis

o Flexible small-incision iris prostheses: Custom Flex,

Keratoprosthesis

 Guillaume Pellier de Quengsy in 1789, who first proposed that an artificial cornea could
be implanted in place of a natural cornea opacified by disease or infection: Father of
Keratoprosthesis

 Nussbaum– First human KPro (1855)

 Candidates for keratoprosthesis implantation can be classified into three main prognostic
groups. In increasing order of success, these groups are:

Bilateral blindness in severe cases of

1. autoimmune-related corneal opacity and ulceration (SJS & OCP)

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2. chemical injury

3. corneal allograft failure (nonautoimmune).

 Contraindications

o Children ( less than 17 years)

o No PL/ Phthisis/ Advanced glaucoma/ RD

o Failure to grasp gravity of surgical program/ mentally unstable

o Refusal to commit to long term follow up

o The “happily blind”

o Unreasonable expectations of outcome

o Cosmesis

 Types of keratoprosthesis

PERMANENT

o Intralamellar

o Penetrating

 Anterior

 Posterior : Choyce

o Perforating

 Anterior fixation: Cordona, Ceramic, Dohlman

 Posterior fixation: Nut and Bolt type

 Intralamellar fixation: Osteo Odonto Keratoprosthesis,


chondrokeratoprosthesis, onychokeratoprosthesis

TEMPORARY

o Disposable: Eckardt, Aachen keratoprosthesis

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o Multiple use: Landers Foulk type2, Landers widefield, Venu

 Designs and Materials

Optical cylinder

Polymethyl methacrylate (PMMA) – most commonly used material

Glass, Ceramic, Quartz, Silicon

Supporting flange

Biological Skirts

o Tooth root & alveolar bone (OOKP– Strampelli)

o Bone (Temprano)

o Cartilage (Casey)

Synthetic Skirts

o PMMA (Choyce, Boston KPro)

o Dacron (Pintucci KPro)

o Polycarbonate (Champagne cork KPro)

o Hydroxy-apatite (Leon-Barraquer KPro)

o Hydrogel (AlphaCor KPro)

o Polyurethane (Seoul KPro)

o Expanded PTFE (Legeais KPro)

 three devices are most widely used.

1. OOKP:

o first used in Italy by Strampelli in the 1960s and later modified by Falcinelli.

o PMMA optical cylinder into an excised monoradicular tooth root, and is


implanted in two stages in conjunction with a mucous membrane graft.

o retention rate of 66–85% at 10–18 years from implantation.


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o most invasive and technically difficult of the keratoprosthesis techniques and the
one associated with the worst cosmesis, and would not be considered for any
patient with functional vision in the other eye.

2. AlphaCor artificial cornea:

o developed by Chirila and coworkers in Australia

o nonporous transparent optic of poly-2-hydroxyethyl methacrylate (pHEMA) and


peripheral porous skirt of the same material to allow infiltration with tissue
stromal cells and blood vessels.

o also requires two surgeries

o device is hydrophilic, a healthy tear film is essential to prevent tissue melting.

o The most common indication for the AlphaCor is corneal allograft rejection.

o reportedly contraindicated in herpes simplex keratitis and autoimmune disorders,


and can become opaque with specific combinations of topical medications.

3. Boston keratoprosthesis:

o formerly known as the Dohlman-Doane keratoprosthesis, was developed at the


Massachusetts Eye & Ear Infirmary and the Schepens Eye Research Institute

o The type I device consists of two plates sandwiched around a donor corneal
allograft or the patient's own cornea. Implantation is performed in one stage, and
is technically similar to standard corneal transplantation. A soft contact lens is
used indefinitely to prevent corneal desiccation and thus minimize the risk of
corneal melts.

o When conjunctival cicatrix is significant or the patient has severe keratinizing dry
eye, it is preferable to implant the type II device, which has an anterior
extension of the lens to allow implantation through the surgically closed
eyelid.

o most commonly used in the world

o Common indications include corneal allograft rejection, opacity when accompanied


by extensive corneal neovascularization making allograft success unlikely, opacity
with limbal stem cell deficiency syndromes including but not limited to aniridia,
and chemical injury.

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o Common complications specific to the Boston keratoprosthesis design include


retroprosthetic membrane formation, sterile vitritis, and worsening of glaucoma.

 Cardona device remains a paradigm in keratoprosthesis design

 Pintucci and coworkers developed a biointegrated keratoprosthesis with a PMMA optical


cylinder and a porous Dacron mesh haptic, similar to that of Girard

 the Worst ‘champagne cork’ keratoprosthesis has been implanted in a large number of
cases, particularly in India.

 Boston Keratoprosthesis Type 1

o Boston KPro comes packaged with the following components: anterior front part
(optic), posterior back plate (small or large size by surgeon choice), titanium
locking ring, 3.0-mm dermatologic punch, white plastic hollow pin, double-sided
adhesive tape, and a contact lens.

o The Keratoprosthesis Unit (KPro plus donor graft carrier) is typically assembled
prior to addressing the patient's cornea.

 AlphaCor

o totally different skill set as the device is placed intrastromally and often utilizes a
full conjunctival (Gunderson) flap.

o soft, flexible prosthesis with a peripheral opaque skirt and a clear central portion

o have an advantage in not requiring a donor cornea.

1. half-thickness limbus-to-limbus stromal dissection

2. central 3.0-mm trephination is completed through the cornea stromal bed.

3. Conjunctiva is used to cover the implanted AlphaCor.

 OOKP (Osteo-odonto-keratoprosthesis)

o integrates biologically an inert plastic- PMMA optical cylinder in a lamina fashioned


from the patient's own tooth and its surrounding alveolar bone. The device is
covered by a tough buccal mucous membrane or rarely by other biological
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membranes including lid skin. This allows it to withstand the hostile environment
of a keratinized, dry eye with lower rates of extrusion compared with KPros
supported by nonbiological material.

o Stage 1a surgery involves harvesting a full-thickness buccal mucous membrane


graft and suturing this in place on the recipient eye.

o In stage 1b, the preselected donor tooth is harvested from the mouth with its
root and surrounding alveolar bone. This is used to prepare the osteo-odonto-
lamina. The bone surrounding the tooth is shaped with a diamond-dusted flywheel
and a hole is drilled through dentine to receive the anterior part of the PMMA
optical cylinder, which is cemented into place. The osteo-odonto-lamina is
implanted deep to the orbicularis oculi muscle of the lower lid in the fellow
eye. This remains in place for 2–4 months during which time the bone is invested
with soft tissues.

o Stage 2 surgery is carried out after an interval of 2–4 months. The lamina is
retrieved from its submuscular location, inspected, and excess soft tissues
trimmed ready for implantation onto the eye. The dentine side which faces the
cornea requires thorough soft tissue removal to avoid ingrowth into the eye. A
Flieringa ring suture is used to support the eye. The cornea is trephined. The iris is
removed with forceps and lens extraction by ECCE or ICCE is carried out. Posterior
capsulotomy and anterior vitrectomy are then performed. The lamina is sutured to
the cornea with the posterior part of the optical cylinder traversing the corneal
opening.

 Auro KPro

o Auro K pro design is similar to Boston Keratoprosthesis

o made of clinical grade PMMA

o 3 parts: the front plate, the back plate & Lock ring

o For the eye that is pseudophakic and therefore, approximately emmetropic, and
where the IOL is left in place at surgery, a single standard power (45 D) is
manufactured

o For aphakic eyes of different axial lengths, however, devices with varying degrees
of power are made to allow a match to the patient’s need as closely as possible.

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Postoperative Management of Keratoprosthesis

 All Boston Type I keratoprosthesis surgery patients require postoperative antibiotics,


steroids, and, if possible, a bandage contact lens.

o Antibiotics

o Corticosteroids

o Glaucoma management

o Soft contact lens: decreases the evaporative forces on the ocular surface, and
creates a moist chamber around the neck of the keratoprosthesis, maintaining
hydration and viability of the carrier donor tissue. Kontur lens, 16.0 mm in
diameter and 9.8 mm base curve with no power.

 AlphaCor™ artificial cornea is very similar to that of the Boston Type I keratoprosthesis
with two notable differences:

o There is no role for a bandage contact lens over the AlphaCor™ device.

o AlphaCor™ researchers have documented the usefulness of topical


medroxyprogesterone 1% suspension postoperatively. Its anticollagenase properties
may decrease the incidence of melt/extrusion.

 As for the osteo-odonto-keratoprosthesis, it is essentially an all-or-none proposition. If and


when it is successfully performed, there is very little postoperative care required other
than a short course of systemic antibiotics, systemic steroids for the management of
chronic or recurrent inflammation, and oral carbonic anhydrase inhibitors, as needed, for
intraocular pressure control.

 Complications and Management

 Retroprosthetic membrane:

o most common complication

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o increasing the topical steroids or placing a peribulbar injection of triamcinolone


(20–40 mg).

o early membranectomy with the YAG laser is indicated to avoid thickening of the
membrane

 Loss of the soft contact lens:

 Sterile vitritis

 Elevated intraocular pressure

 Endophthalmitis

 Retinal detachment

 Corneal melts and keratoprosthesis extrusion

Ocular Surface Transplantation

 Eyes do not have natural protective layer skin. But have multifactorial system which his
system includes the eyelids and eyelashes, the tear film, and the ocular surface, which is
made up of the conjunctiva and the corneal epithelium.

Limbal Stem Cell Deficiency

 Limbal stem cells

 Stem cells:
– Undifferentiated
– Long lived
– Slow cycling
– Clonogenic
– Asymmetric division
– Potency: usually pluripotent or multipotent
– Plasticity: transdifferentiation
– Niche: SC microenvironment

 SC progeny:
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– ‘Transient cells’
– Transient amplifying cells – basal epithelium
– Postmitotic cells – wing cells
– Terminally differentiated cells –superficial squamous cells

 epithelial cells of the limbus and central cornea

Limbus: CK 5/14+ve, CK 3/12–ve, CK 19+ve, P63+ve, CX 43–ve, Vimentin+ve

Central Cornea: CK 5/14 -ve, CK 3/12+ve, CK 19-ve, P63-ve, CX 43+ve, Vimentin-ve

 The current evidence of the limbal location of corneal stem cells (Corneal Surgery
BrightBill)

lacks the corneal epithelial differentiation associated keratin pair keratin 3 (K3) and keratin
12 (K12)
higher proliferative potential. limbal basal epithelium contains slowcycling cells identifi ed as
the ‘label-retaining cells’.
Abnormal corneal wound healing with conjunctivalization, vascularization, and chronic infl
ammation occurs when the limbal epithelium is partially or completely removed.
relative preponderance of limbal neoplasms and the scarcity of corneal epithelial tumors,
assuming that neoplasms arise mainly from relatively ‘undifferentiated cells’
corneal epithelium can be maintained by cellular proliferation originating from limbal stem
cells without contribution of the adjacent conjunctiva.

 These are undifferentiated electron dense basal cells present at the limbus

 Contains minimal cytoplasm and organelles

 Surface markers are - K19,Integrin ß1, Enolase α (lacks K3)

 The hallmark of limbal stem cell deficiency is ‘conjunctivalisation’ of the cornea and the
most significant clinical manifestation is a persistent corneal epithelial defect

Symptoms: decreased vision, photophobia, tearing, blepharospasm, and recurrent episodes of


pain (epithelial breakdown), as well as a history of chronic inflammation with redness

Signs

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– Mild  severe

– Loss of limbal anatomy

– Conjunctival epithelial ingress onto cornea – stippled fluorescein staining

– Columnar keratopathy

– Unstable tear film over affected area

– Frank conjunctivalisation

– Corneal vascularisation – superficial and deep

– Fibrovascular pannus covering corneal surface

– Persistent epithelial defect

– Stromal melting

– Perforation, scarring, calcification

– Keratinisation

Classification

 Congenital

o Aniridia: most common cause of congenital limbal stem cell deficiency

o 1 in 64K-96K

o iris deformities foveal hypoplasia, optic nerve hypoplasia, nystagmus,


glaucoma, and cataract.

o Aniridic keratopathy occurs in 90% of patients with aniridia

o Dominantly inherited keratitis

o Ectodermal dysplasia

o dyshidrotic ectodermal dysplasia

o keratitis–ichthyosis–deafness (KID) syndrome  keratodermatous


ectodermal dysplasia (KED)

o Multiple endocrine deficiency

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 Acquired

o Chemical injury

o Thermal burns

o Ultraviolet /ionising radiation

o Autoimmune Disorders:

o Steven-Johnson syndrome

o OCP

o Contact lens induced keratopathy

o Iatrogenic limbal stem cell deficiency

o prior surgery involving the corneoscleral limbus

o Chronic use of topical medications, including pilocarpine, beta-blockers,


antibiotics, and corticosteroids

 Holland staging system

o system based on the status of the limbal stem cells and conjunctiva

Limbal
Normal conjunctiva Previously inflamed Inflamed conjunctiva
stem cells
(stage a) conjunctiva (stage b) (stage c)
lost (%)
History of chemical or Mild SJS, OCP, recent
<50 (stage Iatrogenic, CIN,
thermal injury (stage chemical injury (stage
I) contact lens (stage Ia)
Ib) Ic)
Aniridia, severe History of severe Severe SJS, OCP, recent
>50 (stage
contact lens, and chemical or thermal chemical or thermal
II)
iatrogenic (stage IIa) injury (stage IIb) injury (stage IIc)

 Diagnosis

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o Based on

o Clinical examination

o Presence of conjunctivalization

o Disappearance of palisades of Vogt

o Confirmed by

o Impression cytology: Make a definite diagnosis by showing


conjunctivalization by the presence of conjunctival goblet cells

o Biopsy – multilayered epithelium, intraepithelial lymphocytes, vessels

o Vimentin and CK 19 positive cells in central cornea (normally present in


peripheral cornea and limbus)

Treatment algorithm

General principles:

– Manage underlying factors, e.g., chronic inflammation, contact lens wear, topical
medications

– Topical lubrication

– All associated problems, e.g., raised pressure, conjunctival adhesions, lid malpositions,
should be addressed before undertaking ocular surface reconstruction

– Limbal transplants do not perform well in dry eyes

In acute limbus injury:

– If partial, i.e. some limbus is surviving – allow corneal epithelialisation to occur from limbus
derived cells – SSCE

– If total:

a) Allow conjunctival epithelium to grow onto cornea

b) Transplant sheet of ex vivo expanded limbal epithelial cells

c) Avoid use of autologous or living related donor tissue until acute inflammation is well under
control

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In established cases:

– Treat eye lid problems, glaucoma and conjunctival adhesions first

– Partial or total

– Partial:

a) Visual axis not involved: symptomatic, lubricants of SSCE

b) Visual axis involved: SSCE

c) Dense fibrovascular pannus: sector limbal transplant

Total:

a) Unilateral: auto-limbal transplant

b) Ex vivo expansion of autologous limbal cells

c) Bilateral: allo-limbal transplant

d) Ex vivo expansion of cells (living related, living non-related, cadaver)

e) Amniotic membrane and autologous serum drops as adjuncts

f) Allo-transplants require systemic immunosuppression

 Surgical Mx: (OSD & LSCD)

o Sequential Sector Conjunctival Epitheliectomy (SSCE)

o removal of the conjunctivalised epithelium In cases with partial, mild to


moderate conjunctivalisation of the cornea,without significant
fibrovascular pannus

o advantage of not overstressing the small remaining sector of limbal


‘stem’ cells.

o Conjunctival Limbal Autograft (CLAU)

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o Unilateral limbal deficiency , partial stem cell loss,

o Concurrent conjunctival inflammation

o No risk of rejection

o Living Related Conjunctival Limbal Allograft (lr-CLAL)

o Bilateral limbal stem cell loss: cicatricial pemphigoid (OCP), Stevens–


Johnson syndrome (SJS), and atopic keratoconjunctivitis

o Large risk of transplant rejection

o Keratolimbal Allograft (KLAL)

o disease entities that primarily affect the limbus with no or minimal


involvement of the conjunctiva: Aniridia

o Combined Conjunctival Limbal and Keratolimbal Allograft (C-KLAL)

o Cadaveric Stem Cell Allograft

o Fresh Tissue

o Age: < 40 years

o Good Quality Donor Material

o Risk of transplant rejection

o Annular Corneo-scleral Allograft

o Prompt re-epithelization

o Minimal vascularization (mechanical barrier)

o Less risk of graft rejection

o Large diameter LK

o Advantages

 Removes superficial stromal opacities

 Tectonic function

 Smooth surface

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 Less astigmatism

o Disadvantage

 More risk of allograft rejection

 Ex Vivo Tissue Engineered Procedures

o Ex Vivo Cultivated Limbal Transplantation

o Ex Vivo Stem Cell Allografts

o Ex Vivo Cultivated Conjunctival Transplantation

o Ex Vivo Cultivated Mucosal Transplantation

o Limbal Stem Cell Culture

o This technique expands limbal epithelial progenitor cells from a small


biopsy using a 3T3 fibroblast feeder layer or amniotic membrane.

o Immunostaining techniques : resultant phenotype of HLEC grown on


amniotic membrane retains a limbal origin, is predominantly basal
epithelial cells, and remains undifferentiated

o Taking the Biopsy

o Avoid or eliminate the conjunctiva

o as small as 1–2mm2 and 100 mm in depth.

o Superior limbus if possible so as to include immature cells

o The obtained tissue is placed with Ham’s F12 medium


containing 50 mg/ml gentamicin and 1.25 mg/ml amphotericin B
until it is processed
o exposed for 5min to Dispase II (1.2 U/ml in Mg2+ and Ca2+ free
Hank’s balanced salt solution, HBSS)
o cultured in DMEM medium, which is a 1:1 mixture of DMEM and
Ham’s F12 medium
o plated onto the basement-membrane side of the amniotic
membrane, placed in the center
o maintained for 2–3 weeks, by which time the epithelial cells
have grown and spread to form a cell layer that covers an area
2–3 cm in diameter

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 Amniotic Membrane Transplantation (AMT)

 Failure of LSCT

o Early Failure

o Rejection: acute rejection occurs in about 10–20% of cases and is most


common in the first 1 to 12 months

o Adnexal abnormalities

o Inflammation

o Dry eye

o Late Failure

o Sectoral conjunctivalization

o Stem cell exhaustion

o Late rejection

Algorithm for an approach to treat patients with severe OSD

a. Management of glaucoma

b. Correction of eyelid and eyelash abnormalities

c. Suppression of inflammation

d. Ocular surface transplantation

i. Conjunctival limbal autograft (CLAU) for unilateral disease

ii. Keratolimbal allograft (KLAL) for bilateral limbal deficiency with


minimal to moderate conjunctival disease

iii. Living related conjunctival limbal allograft (lr-CLAL) for bilateral limbal
deficiency with moderate to severe conjunctival disease

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iv. Combined conjunctival–keratolimbal allograft (C-KLAL) for bilateral


limbal deficiency with severe conjunctival disease

e. Keratoplasty

i. Lamellar (LK) for patients with stromal opacification with normal


endothelium

ii. Penetrating (PK) for patients with stromal opacification with loss of
endothelial function

iii. Keratoprosthesis (K-Pro) for patients with good fornices but are not good
keratoplasty candidates.

Amniotic membrane Transplantation

first documented ophthalmologic application: 1940’s, in the treatment of ocular burns

five layers from within outward:


1. A single layer of highly metabolically active, columnar to cuboidal epithelium
2. A thin basement membrane
3. A compact layer made of reticular fibres virtually devoid of cells
4. A loose network of reticulum containing fibroblasts, called the fibroblast layer
5. A spongy layer of wavy bundles of reticulum bathed in mucin,which forms the
interface with the chorion

mechanisms of action

1. promotes epithelialization
2. inhibits scarring
3. inhibits vascularization
4. reduces inflammation
5. provides a substrate for cell growth (The most uncontroversial mechanism of
action)
6. antimicrobial effects
7. as a biological bandage

Composition

Enzymes: prostaglandin synthesis  phospholipases, prostaglandin synthase and cyclo-


oxygenase

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prostaglandin-inactivating  Prostaglandin dehydrogenase


Cytokines: anti-inflammatory cytokines  IL-1Ra and IL-10
Pro-inflammatory  IL- 6 & 8
Growth Factors: EGF, TGFa, KGF, HGF, bFGF, TGF-b1, and -b2
MMP & TIMPs:

 Processing and Preservation


o Now not used  lyophilisation, air drying, glutaraldehyde and
polytetrafluoroethylene treatment and irradiation
o Now used  freezing is the commonest mode
 Solutions
o DMSO in phosphate buffered saline
o Eagle’s minimum essential medium (MEM) & glycerol

 Graft: When the membrane was used with the intention of it becoming incorporated into
the recipients tissue
 Patch: when the intention was for it to come away or be removed at a certain point
following surgery

 primarily as a graft or a patch with four objectives:


1. establish epithelial cover in an area where none existed
2. to prevent corneal perforation in eyes at risk due to stromal melting
3. to limit scarring where the clinical likelihood was high or where scarring
(symblepharon/adhesions) previously existed
4. to limit inflammation and neovascularisation.

 success: when the membrane served the purpose that was intended
 partial success: when the membrane did not serve the purpose that was intended but the
objective was achieved
 failure: when the objective was not achieved even though the purpose may have been
achieved

Must remember following chart:

AM layer Constituents Biological properties


Growth factors* Maintains undifferentiated epithelial phenotype
Epithelium
Cytokines when culturing limbal stem cells
Basal
Collagen IV/VII Improves epithelial cell migration
lamina
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AM layer Constituents Biological properties


Laminin 1/5 Strengthens adhesions on basal cells
Fibronectin[†] Induces epithelial differentiation (including
goblet cells in conjunctiva)
Prevents apoptosis
Suppresses corneal myofibroblasts, limbal
TGF-beta
and normal and pathological conjunctival
Anti-inflammatory fibroblasts proliferation and differentiation –
Stromal and antiangiogenic inhibits cicatrization
matrix proteins
Traps inflammatory cells from other tissues,
Protease-inhibition inducing rapid apoptosis
factors
Inhibits inflammation and neovascularization

 Methods

o Graft (epithelial-side up):

o Patch (epithelial-side down):

o Combined approach:

Prokera
 Prokera is a medical devise designed by Dr Tseng where AM has been clipped into a dual, concave,
polycarbonate ring set, acting as a biologic bandage. It can be inserted
much like a contact lens without needing any sutures or glue.

 Prokera is a conformer type device made of amniotic membrane with a rigid frame so that
it can be inserted into the conjunctival sac. It affords both cover to the surface and also
keeps the bulbar and palpebral conjunctival surfaces apart. I have not used Prokera
directly (its cost is prohibitive) but was effectively using a home made similar device even
before Prokera was introduced: I place a sheet of 2 x 2 inches amniotic membrane over
the surface of the eye and tuck the membrane into the superior, inferior, medial and
lateral fornices of the conjunctival sac, with a squint hook or similar blunt instrument. I
then take a plastic conformer shell of the desired size and insert it in the conjunctival sac
such that a layer of the membrane is beneath it and the folded surface, above it. In
patients who are bed ridden for example patients in acute stage of Stevens Johnson
syndrome in the intensive care unit, that is all that is required. The membrane can be
changed every other day or so.
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 In ambulatory patients, after inserting the membrane and conformer in the eye, I
approximate the membrane covering the anterior surface of the plastic conformer shell
and suture the edges together. I then trim off the excess membrane. It effectively
becomes a conformer shell wrapped in membrane. It can stay in situ up to a week and
even can be removed for examination of the eye and reinserted.

Refractive Surgery

 Decision Making

o three major challenges: to select the right patient, to select the right procedure,
and to achieve the right outcome

o Preoperative subjective questionnaires, such as the Dell Vision Questionnaire,


have two values: (1) to assess the patient's attitudes and expectations –
documenting them in the clinical record, and (2) to assess postoperative
outcomes by using the same or a related questionnaire.

o Patient age: previously 18–21 years. Now 14 years

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o Refractive error: 0.50 D to 10 D of myopia and 4 D of hyperopia, Astigmatism up


to 5 D

o Corneal thickness: adequate residual stromal bed thickness of 300 µm. A residual
thickness of 250 µm is a customary target. Abnormally thick corneas (greater than
620 µm) raise suspicion of endothelial dysfunction and warrant endothelial
specular microscopy.

o Corneal topography: characteristics of early keratoconus or PMD, FF-KC should


not receive LASIK, because they may be predisposed to further steepening
(ectasia) after surgery.

o Keratometry: postoperative minimum value of 38 D and a maximum value of 50 D


set the limits after surgery.

o Pupil size: very large pupils under mesopic conditions – 7.5 to 8 mm – seem at
greater risk of optical aberrations.

o Thin-flap LASIK:

 100–110 µm flaps, also referred to as sub-Bowman's keratomileusis

 more safely with regard to ectasia and corneal hypoesthesia

o Surface Ablation

 photorefractive keratectomy (PRK): epithelium is removed manually or with


an excimer laser (transepithelial PRK). PRK is especially effective in
patients with recurrent corneal erosion and epithelial basement membrane
degeneration

 epi-LASIK: not used

 laser assisted subepithelial keratomileusis (LASEK): no advantage in


replacing the epithelium, since that delays recovery, does not reduce
postoperative pain, and requires the healing epithelium to subsequently
remove the epithelial flap.

o Conductive Keratoplasty

 Lans in the 1880s.

 can steepen the central cornea approximately 1 to 1.5 D

 treating residual astigmatism after previous surgery and for creating


monovision in presbyopes
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o Arcuate Transverse Keratotomy

 oldest corneal refractive surgery procedure

 partial-thickness incisions are placed perpendicular to the steep corneal


meridian to induce flattening and a coupled effect of steepening 90 degrees
away. Also called astigmatic keratotomy, the most frequent indication for
the technique is astigmatism correction at the time of cataract surgery with
limbal relaxing incisions.

 The closer the incision is to the center of the cornea, the greater the
effect.

 generally effective technique to treat 1–4 D of astigmatism.

o Phakic Intraocular Lenses:

1. the Verisyse anterior chamber iris fixated phakic IOL (Ophtec, Boca Raton,
FL, USA),

2. the Visian posterior chamber plate ICL (STARR Surgical Company, Monrovia,
CA),

3. the Alcon (Alcon Laboratories, Fort Worth, TX) anterior chamber angle
fixated ‘acrysof’ design.

 treatment of myopia and astigmatism

 cell counts of approximately 2400 cells/mm2

 minimum anterior chamber depth of 3.2 mm

o Intraocular Lens after Phacoemulsification

 IOL implantation is refractive surgery.

 Toric IOLs may be used to treat up to 2.50D of astigmatism.

o Retreatments and Sequential Procedures

 10–20% will require a second treatment

 Bioptics: the combination of an intraocular lens with the refractive


outcome modified by excimer laser cornea sx

 CK

 Intacs intracorneal ring segments

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 corneal cross-linking

o Treatment of Presbyopia

 Simple monovision for presbyopia – myopia for near vision in the non
dominant eye and full distance correction in the dominant eye

 presbyLASIK

Patient Evaluation and Selection

 complete ocular history: patients with a history of ocular herpes simplex virus (HSV),
strabismus, diplopia, previous refractive surgery, dry eye, or contact lens intolerance,
Previous radial keratotomy (progressive hyperopic shift)

 Examination

o Visual acuity

o Refraction

o Contrast sensitivity

o Keratometery

o Computed topography

o Pupil examination: patients with pupils >6.5 mm will often have increased scores
for total higher-order aberrations both pre- and postoperatively

o Slit lamp examination

o Fundus examination

o Tonometry

o Pachymetry

o Endothelial cell evaluation

o Anterior chamber depth

o Dry eye testing

o Monovision testing

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o Ocular dominance determination

o Wavefront testing: unit of measure in wavefront testing is the root mean square
(RMS) in microns (µm)

 lower-order aberration  defocus (MC)

 higher-order aberrations  spherical aberration and coma

wavefront-optimized versus a wavefront-guided treatment:

wavefront-optimized treatment, the laser treatment is designed to minimize the


increase in spherical aberration which commonly occurs in myopic conventional
ablation

wavefront-guided treatments virtually always provide superior visual results


compared to conventional treatment on other platforms, such as the VISX laser.

 Informed Consent: geometrically greater need as it being elective procedure

Topographic Analysis

 True topography implies knowledge of the exact contour or shape.

 The term ‘videokeratoscope’ more accurately describes the technology of these


instruments.

o Orbscan combines optical sectioning with Placido reflection

o Pentacam and Galilei utilize Scheimpflug imaging to measure the corneal surface.

 ‘form fruste’ keratoconus

 Displaced apex syndrome

Incisional Corneal Surgery

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 Dutch ophthalmologist: Lans

Radial Keratotomy

 obsolete procedure

 -1.00 to -4.00 D of myopia

 does not involve removal of tissue

 PERK study: Prospective Evaluation of Radial Keratotomy

o -2.00 to -8.75 D (mean: - 3.875 D)

o 8 radial incisions were used for all patients

o 53% of the 435 study patients had 20/20 or better uncorrected visual acuity (UeVA)
and 85% were 20/40 or better.

o most important finding in the 10-year PERK study was the continuing long-term
instability of the procedure. A hyperopic shift of 1.00 D or greater was found in
43% of eyes between 6 months and 10 years postoperatively. There was an
association between length of the incision and hyperopic shift, particularly if the
incisions extended into the limbus.

 not only the curvature of the central cornea but also its overall topography, creating a
multifocal cornea  flatter in the center and steeper in the periphery.

 2 phenomena of postoperative refractive instability-

o diurnal fluctuation of vision

o progressive flattening effect of surgery

Incisional Correction of Astigmatism

Coupling:

When one meridian is flattened from an astigmatic incision, an amount of steepening occurs
in the meridian 90' away. This phenomenon is known as coupling. When the coupling ratio
(the amount of flattening in the meridian of the incision divided by the induced steepening in

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the opposite meridia n) is 1.0, the spherical equivalent remains unchanged. When there is a
positive coupling ratio (greater than 1.0), a hyperopic shift occurs.

Arcuate Keratotomy

 arcuate incisions of approximately 95% depth are made in the steep meridians of the
midperipheral cornea at the 7-mm optical zone

Limbal Relaxing Incisions

 LRIs are incisions set at approximately 600u depth, or 50u less than the thinnest
pachymetry at the limbus, and placed just anterior to the limbus

Onlays and Inlays

Keratophakia
 plus-powered lens is placed intrastromally to increase the curvature of the anterior
cornea for the correction of hyperopia and presbyopia.

 The lenticule can be prepared either from donor cornea (homoplastic) or synthetic
material (alloplastic).

o Homoplastic Corneal Inlays

 obsolete

 aphakia and hyperopia of up to 20 D

o Alloplastic Corneal Inlays

 ability to be mass-produced in a wide range of sizes and powers that can be


measured and verified

 AcuFocus, ReVision Optics, and Presbia

 The Kamra Inlay (AcuFocus Corneal Inlay): for the treatment of presbyopia.

 ultrathin (5 um), biocompatible polymer that is microperforated to


allow improved near vision and perhaps nutrient flow.
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 The 3.8-mm diameter inlay has a central aperture of 1.6 mm.

 In the nondominant eye, a corneal flap that is 200 flm thick is


created, and the inlay is placed on the stromal bed, centered on the
pupil. Although the inlay has no refractive power, the goal of the
device is to have the central aperture function as a pinhole to
increase depth of focus and improve near vision without changing
distance vision.

Epikeratoplasty
 also called epikeratophakia

 obsolete

 suturing a preformed lenticule of human donor corneal tissue directly onto the Bowman
layer of the host cornea

ICRS
 Intrastromal Corneal Ring Segments

 treat low amounts of myopia by displacing the lamellar bundles and shortening the
corneal arc length

 placed in the midperipheral corneal stroma

 thicker the segment, the greater the flattening

 Intacs

o 2 segments of 150' of arc

o fixed outer diameter of 8.10 mm

o 0.210, 0.250, 0.275,0.300,0.325,0.350,0.400 and 0.450 mm thickness

o approximately 68%-70% stromal depth

 Ferrara rings

o smaller optical zone

o more of a flattening effect

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o not FDA approved

 Advantage: potentially REVERSIBLE

 Patient Selection

o 21 years or older

o with documented stability of refract ion, as demonstrated by a change of <0.50 D


for at least 12 months prior to the preoperative examination

o with 1.00 D of astigmatism or less

 Indication

o low levels of myopia (- 1.00 to - 3.00 D spherical equivalent)

o KC

o KC+PMD?

o Ectasia After LASIK

 contraindication

o patients with collagen vascular, autoimmune, or immunodeficiency diseases

o pregnant or nursing women

o the presence of ocular conditions (such as recurrent corneal erosion syndrome, or


corneal dystrophy) that may predispose the patient to future complications

 In cases of peripheral KC, single segment can be applied. When a Single segment is
placed, it flattens the adjacent cornea but causes steepening of the cornea 180 away-the
"bean bag effect" (when one sits on a bean bag, the bag flat tens in one area and pops up
in another area).

 Complications

o anterior chamber perforation

o microbial keratitis

o implant extrusion

o shallow ring segment placement

o corneal thinning over lntacs

o reduced corneal sensitivity (5 .5%)


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o induced astigmatism between 1 and 2 D (3.7%)

o deep neovascularization at the incision site ( 1.2%)

o persistent epithelial defect (0.2%)

o iritis/uveitis (0.2%)

o Visual symptom

 difficulty with night vision (4.8%)

 blurred vision (2.9%)

 diplopia (1.6%)

 glare (1.3%)

 halos (1.3%)

 fluctuating distance vision (1.0%)

 fluctuating near vision (0.3%)

 photophobia (0.3%)

Orthokeratology

 corneal refractive therapy CRT

 overnight use of rigid gaspermeable contact lenses to temporarily reduce myopia.

 The contact lens is fitted at a base curve flatter than the corneal curvature

 Paragon CRT: FDA approved rigid contact lens

Photoablation

Two broad groups:

1. Surface Ablation:
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 Photorefractive keratectomy (PRK), laser subepithelial keratomileusis (LASEK),


and epipolis LASIK (epiLASIK)

 Bowman layer is exposed either by debriding the epithelium through various


methods or by loosening and moving, but ultimately preserving, the epithelium

2. LASIK

 Laser in situ keratomileusis

 excimer laser ablation is performed under a lamellar flap that is created with
either a mechanical microkeratome or femtosecond laser

Wavefront-Optimized and Wavefront-Guided Ablations

 WGA

o the treatment is aimed to correct the pre-operative HOAs

o profiles that are customized for individual patients.

o WGA are Good.

 WOA

o the treatment attempts to reduce HOAs generated during surgery.

o profile corrects expected HOAs for an average eye, and those that are anticipated
as a result of the surgery. This means that an eye with higher than normal HOAs,
will end up with near equally high HOAs after treatment in WOA.

Potential Contraindictions

o Connective tissue disease

o Dry-eye syndrome

o Stromal/ endothelial dystrophies

o Previous herpes infection

o Pregnant or nursing mother

o Ectatic corneas

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 Patients with EBMD are better candidates for surface ablation than for LASIK because
surface ablation may be therapeutic, reducing epithelial irregularity and improving
postoperative quality of vision while enhancing epithelial adhesion

 steeper than 48.00 D are more likely to have thin flaps or frank buttonholes (central
perforation of the flap) with mechanical microkeratomes. Corneas flatter than 40.00 D
are more likely to have smaller-diameter flaps and are at increased risk for creation of a
free cap due to transection of the hinge with mechanical microkeratomes.

 formula is used to calculate residual stromal bed thickness (RSBT): Central corneal
thickness - thickness of flap - depth of ablation = RSBT

PRK-Photorefractive Keratectomy

 PRK was the first widely accepted surgical procedure to ablate corneal tissue

 1980s, PRK using the 193 nm argon fluoride excimer laser

 up to −10 D of myopia and +4 D of hyperopia

 PRK Epithelial Removal

o Mechanical:

1. scraping using a Paton spatula, scalpel blade, Desmarres blade, or blunt no. 67 blade,

2. motorized brush such as that described by Pallikaris or the Amoils Epithelial Scrubber

o Chemical: 18–20% ethanol, 20 seconds

 Laser

o Excimer laser: Broad-beam lasers & scanning laser

 Postoperative Management

o broad-spectrum antibiotic

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o topical NSAID

o topical steroids

 Complications

 Intraoperative

o Eccentric ablations and decentrations

 Postoperative Complications

o Epithelial problems

o Dry eyes

o Corneal infiltrates and infectious keratitis

o Central islands

o Irregular astigmatism

o Undercorrection

o Overcorrection

o Haze, scarring

o Regression

LASEK
 In the LASEK variant of surface ablation, the goal is to preserve the patient's epithelium.

 Instead of debriding and discarding the epithelium or ablating the epithelium with the
excimer laser, the surgeon loosens the epithelium with 20% alcohol for 20 seconds and
folds back an intact sheet of epithelium

Epi-LASIK
 largely supplanted LASEK because there is no alcohol damage to the epithelium.

 In epi-LASIK, an epithelial flap is fashioned with a microkeratome fitted with a modified


dull blade and a thin applanation plate that mechanically separates the epithelium. In this

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manner, epiLASIK preserves more viable epitheli al cells, may improve results compared
with LASEK

LASIK

History

 Jose I. Barraquer, Bogota, Colombia  father of lamellar corneal refractive surgery

o 1949: keratomileusis  keras (‘horn,’ here applied to the cornea) and mileusis
(carving or chiseling).

o myopic keratomileusis (MKM)  freeze myopic keratomileusis, or F-MKM.

o Keratophakia

 Kaufman and Werblin: Epikeratophakia

 Ruiz: automated lamellar keratoplasty (ALK), and the keratome was named the automatic
corneal shaper (ACS)

 Barraquer–Krumeich–Swinger (BKS) refractive system and its refined microkeratome (the


BKS 1000)

 Srinivasan, an IBM researcher: ablative photodecomposition with argon fluoride 193

 Trokel and L’Esperance: photorefractive keratectomy (PRK)

 1989, Peyman: erbium:YAG laser to ablate rabbit corneal stroma using infrared (thermal)
rather than ultraviolet energy

 1990, Pallikaris: laser in situ keratomileusis

 1999, the Summit Excimer Laser (Summit Technologies, Waltham, MA) was the first laser
to be approved by the FDA for use in LASIK.

Suction Ring

 The suction ring has 2 functions:

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o to adhere to the globe, providing a stable platform for the microkeratome cutting
head

o to raise the lOP to a high level, which stabilizes the cornea.

Microkeratomes

 Five major types of microkeratome exist:

1. nondisposable horizontal motor

2. nondisposable vertical moto

3. disposable

4. Waterjet

5. picosecond or femtosecond laser microkeratomes

Femtosecond laser

 creates flaps by performing a lamellar dissection within the stroma.

 several extra steps

o suction ring is centered over pupil and suction is applied

o docking procedure

o applanation lens is then centered over the suction ring

o femtosecond laser treatment applied

 Advantages of FEMTO

o Less increase in lOP required

o More control over flap diameter

o Size and thickness of flap less dependent on corneal contour

o Centration easier to control

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o Epithelial defects on flap are rare

o Less risk of free cap and buttonhole

o More reliable flap thickness

o Hemorrhage from limbal vessels less likely

o Ability to re-treat immediately if incomplete femtosecond laser ablation

 Disadvantages

o Longer suction time

o More flap manipulation

o Opaque bubble layer may interfere with excimer ablation

o Bubbles in the anterior chamber may interfere with tracking and registration

o Increased overall treatment time

o Difficulty lifting flap >6 months

o Increased risk of diffuse lamellar keratitis

o Increased cost

o Need to acquire new skills

o Delayed photosensitivity or good acuity plus photosensitivity (GAPP), which may


require prolonged topical corticosteroid therapy

 Application of laser Treatment

o Tracking

o Centration

o Ablation

 Refractive Outcomes

o For Myopia: mild to moderate

 90% achieved 20/20

 ~100% achieved 20/40

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o For Hyperopia

 46%-59% of eyes had postoperative UCVA of20/20 or better, 92%-96% had


UCVA of 20/40 or better, and 84%-91 % were within 1.00 D of emmetropia

Complications

Surface Ablation and LASIK

 Overcorrection

 Undercorrection

 Central Islands: steepening of at least 1.00 D with a diameter of 1 mm compared with the
paracentral flattened area.

 Optical Aberrations:

o glare, ghost linages, and halos

o Night-vision complaints are often caused by spherical aberration

 Decentered Ablation: Centration is even more critical for hyperopic than myopic

 Corticosteroid-Induced Complications

 Endothelial Effects

 Dry Eye and Corneal Sensation

 Infectious Keratitis

Complications Unique to Surface Ablation

 Persistent Epithelial Defects

 Sterile Infiltrates

 Corneal Haze

o Early: within 6 months

o Late: after 6 months

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Complications Unique to LASIK

 Microkeratome Complications

o Buttonhole, free cap, decentration

o Perforation

o Epithelial Sloughing or Defects

o Striae

 Macrostria

 Microstria

o Flap subluxation has been reported to occur in up to 1.4%

o Traumatic Flap Dislocation

o Diffuse Lamellar Keratitis

 "sands of the Sahara" (SOS),

 can range from asymptomatic interface haze near the edge of the flap to
marked diffuse haze under the center of the flap with diminished BCVA.

1. Peripheral faint white blood cells; granular appearance

2. Central scattered white blood cells; granular appearance

3. Central dense white blood cells in visual axis

4. Permanent scarring or stromal melting

o Pressure-Induced Stromal Keratitis PISK

o Epithelial Ingrowth

o Interface Debris

o Ectasia

Disturbances Related to Femtosecond Laser LASIK Flaps

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 Good acuity, postoperative photophobia GAPP

 Rainbow glare

Collagen Shrinkage
 Lanz: dutch medical student

 Terrian: cautery to correct astigmatism

 Gasset and Kaufmann: thermokeratoplasty, 1975

Laser Thermokeratoplasty
 1990s: holmium:yttrium-aluminum-garnet (Ho:YAG) laser  FDA approved

 noncontact Sunrise Hyperion system was approved by the FDA in 2000.

Conductive Keratoplasty
 2002, the FDA approved the ViewPoint CK system

 Radiofrequency waves

 presbyopic patient with an endpoint of -1.00 to -2.00 D

 The number and location of spots determine the amount of refractive change, with an
increasing number of spots and rings used for higher amounts of hyperopia.

C3R
(Read more details from KC topic.)

All FemtoSecond Sx

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FLEX
 Femtosecond lenticule extraction or FLEx

 Femtosecond laser creates two cuts, a refractive and a nonrefractive as a single step. The
first cut is made at the bottom of the refractive lenticle while the second one at its roof.
Once the cuts are made, flap is lifted and refractive lenticule is removed. The flap is
reposited in usual manner. It is important to make manipulation at correct plane between
flap & lenticule and separate lenticule edge.

SMILE
 small incision lenticular extraction

 less invasive where by the entire lenticule can be extracted through a small incision
without lifting up the flap.

INTRACOR
 done on TECHNOLAS Femtosecond work station.

 It applies energy inside the cornea without bringing it to the surface

 no incision of epithelium, endothelium or Bowman’s or Descemet’s membrane and thus


ensure better healing with minimal risk of infection.

 The pulses are placed on concentric intrastromal circles centered about visual axis and
extended at least up to 100 microns from the surface. The concentric patterns of cut
fibers shift the centre of cornea slightly anteriorly and create a hyperprolate shape. At
present myopia up -3D and astigmatism up to 2D have been tried. However the results are
not very accurate. Also its role in presbyopia has been emphasized as it causes a
biomechanical change in cornea that shifts centre slightly forward creating a pattern of
hypersphericity thus allowing some near vision while retaining distance vision.

Intraocular Surgery

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Phakic IOLs
(Read more from Lens.)

Bioptics

 term suggested by Zaldivar in the late 1990s

 PCPIOL implantation followed at a later time by LASIK to treat patients with extreme
myopia and/or residual astigmatism

 Term adjustable refractive surgery (ARS), is also used

Refractive Lens Exchange


 considered only if alternative refractive procedures are not feasible

 may be preferable to a PIOL in the presence of a lens opacity that is presently visually
insignificant but that may soon progress and cause visual loss

 Risk of intraocular surgery present

225
i notes
Ophthalmology PG Exam Notes
1st Edition

GLAUCOMA
Dhaval Patel
MD (AIIMS)
I notes
(Ophthalmology PG Exam Notes)

Dhaval Patel MD (AIIMS)


drdpatel87@gmail.com

by inotesforPG.blogspot.com
1st edition, February 2014

This is a compilation effort from my preparation notes and other sources, thus
any contributions or comments are welcomed in the effort to improve this book.
Therefore, feel free to e‐mail me at
drdpatel87@gmail.com
I notes

(Ophthalmology PG Exam Notes)

Thank you GOD

This manual is collection of the notes I made, found in books or internet while
studying for the Final MD exams for ophthalmology.

I have segregated topics just like book chapters to find them back easily. Though these all
might be far less then other preparation notes available, I am proud of what I have made
and I feel nice to present them to my upcoming ophthalmology friends.

Good luck!

-Dhaval Patel MD
drdpatel87@gmail.com
February 2014
I notes GLAUCOMA Dhaval Patel MD

Glaucoma

History ....................................................................................................... 4

Anatomy & Physiology ..................................................................................... 5

Genetics of Glaucoma ..................................................................................... 9

Intraocular pressure....................................................................................... 10

Gonioscopy ................................................................................................. 20

Visual Field ................................................................................................. 23

Optic nerve ................................................................................................. 43

Primary angle-closure glaucoma ........................................................................ 56

Secondary angle-closure glaucoma ..................................................................... 63

Aqueous Misdirection Syndrome (Malignant Glaucoma).............................................. 70

Primary open angle glaucoma ........................................................................... 71

Glaucoma suspect ......................................................................................... 73

Ocular hypertension....................................................................................... 74

Normal Tension Glaucoma ............................................................................... 75

Combined and Mixed Glaucoma ......................................................................... 77

Secondary open angle glaucoma ........................................................................ 78

Developmental and childhood glaucoma ..............................................................104

Medical management of Glaucoma ....................................................................112

Laser therapy for Glaucoma ............................................................................132

Surgical Management of Glaucoma ....................................................................141

Misc Q ......................................................................................................169

1
I notes GLAUCOMA Dhaval Patel MD

History Visual field Doppler Ocular


Anatomy & Physiology interpretation Coherence
Development of ALGORITHMS Tomography
Anterior Chamber How to Read Primary angle-closure
Trabecular meshwork Glaucoma Progression glaucoma
Ciliary Body Analysis Mechanisms
Aqueous Humor Visual Field Index 1. pupillary block
Dynamics Newer Perimetry glaucoma
Mechanism of Glaucoma Techniques Demographic risk
Genetics of Glaucoma Short Wave factors
Intraocular pressure Automated Perimetry Ocular risk factors
Applanation Instruments Frequency Doubling and mechanisms
Goldmann tonometer Perimetry (FDP 2. Plateau Iris
Perkins tonometer Matrix) Plateau iris
Draeger tonometer High-Pass Resolution configuration
MacKay-Marg Perimetry (HPRP) Plateau iris syndrome
tonometer Flicker Perimetry Pseudoplateau iris
Tono-Pen™ Motion Perimetry 3. phacomorphic
Pneumotonometer Multifocal mechanism
Non-contact Electroretinography Q: Acute Angle Closure
tonometer Optic nerve Secondary angle-closure
Ocular Response Factors influencing glaucoma
Analyzer™ ONH circulation Phacomorphic
The Ocuton™ Clinical evaluation Glaucoma
tonometer Optic nerve imaging Neovascular Glaucoma
Maklakow tonometer Stereophotography ICE Syndrome
Indentation instruments Confocal scanning Aqueous Misdirection
Schiøtz tonometer laser ophthalmoscopy Syndrome (Malignant
Electronic Schiotz (CSLO) Glaucoma)
tonometer Optical coherence Primary open angle
Impact–rebound tomography (OCT) glaucoma
tonometer Scanning laser Glaucoma suspect
Transpalpebral polarimetry Ocular hypertension
tonometry Retinal Thickness Normal Tension Glaucoma
Dynamic contour Analyzer Combined and Mixed
tonometry Posterior Pole Glaucoma
Continuous monitoring Asymmetry Analyser Secondary open angle
of IOP Blood Flow in Glaucoma glaucoma
Factors influencing Scanning Laser Pigmentary glaucoma
intraocular pressure Ophthalmoscope Exfoliation syndrome
Corneal Hysteresis Angiography Steroid Induced
Target IOP Color Doppler Imaging Glaucoma
Gonioscopy Measurement of Lens-induced glaucoma
Methods Ocular Pulsation Phacolytic Glaucoma/
Grading of chamber Confocal Scanning Lens Protein
angle Laser Doppler Glaucoma
Visual Field Flowmetry Lens-Particle
Techniques Spectral Retinal Glaucoma
Oximetry
2
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Phacoanaphylaxis - Hyperosmotic agents Implantable Collagen


Lens-Associated Preservative Free Matrix
Uveitis Drops Glaucoma Drainage
Glaucoma after Neuroprotection in Devices
cataract surgery Glaucoma Ex-Press Mini
Glaucoma after Laser therapy for Glaucoma Shunt
Vitrectomy Glaucoma Complications:
Glaucoma with uveitis Tissue effects of laser Non-penetrating
Fuchs’ Heterochromic Thermal effects glaucoma surgeries
Iridocyclitis (photocoagulation, Deep sclerectomy
Glaucomatocyclitic photovaporization) Schlem's Canal-based
Crisis Photodisruption Surgery
Traumatic Glaucoma Photoablation Newer Surgical
Hyphema Photochemical modalities
Angle Recession/ Laser treatment for Small incision
Glaucoma internal flow block trabeculectomy (SIT)
Cyclodialysis Cleft Laser peripheral Intrastromal
Elevated episcleral iridotomy Holomium Laser
venous pressure Laser iridoplasty Keratostomy:
Carotid-Cavernous (gonioplasty) Glaucoma surgery
Fistula Lasers in malignant using Fugo blade
Sturge-Weber glaucoma E-PTFE Membrane
syndrome Laser treatment for Implant for refractory
Idiopathic Elevated outflow obstruction glaucomas
Episcleral Venous Argon Laser Retinectomy for
Pressure trabeculoplasty intractable glaucoma
Developmental and Selective laser Surgical Mx Cataract &
childhood glaucoma trabeculoplasty Glaucoma
Primary congenital Contraindications
glaucoma Complications Complications &
Glaucoma Associated Excimer laser Management
with Congenital trabeculostomy ELT Gene Therapy in
Anomalies Laser sclerostomy Glaucoma
Aniridia Cyclodestructive Misc Q
Axenfeld's Anomaly Procedures Glaucoma in Marfans
Rieger's Anomaly Surgical Management of Weinreb’s 5 R
Peter's Anomaly Glaucoma True Exfoliation
Neurofibromatosis External Filtration Syndrome
Medical management of Surgery Glaucoma versus red
Glaucoma Guarded Filtration disease
Target pressure Procedure Pregnancy and
Adrenergic agonists Surgical Technique Glaucoma
Adrenergic Antimetabolites UBM Study of Anterior
antagonists READ -- Releasable Segment Changes
Prostaglandins Sutures After
Carbonic anhydrase Filtering Bleb Phacoemulsification
inhibitors Full-Thickness
Cholinergics Filtration Procedures

3
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History

 The term glaucoma originally meant cataract and distinction between glaucoma and
cataract was not understood till 1705. “glaukos” means “watery blue” or gray color which
is actually appearance of typical cataract.

 “The scientific history of glaucoma began the day on which cataracts were put in their
correct place” (Albert Terson, 1867–1935, French ophthalmologist).

 The correct anatomic location of cataracts is credited to Pierre Brisseau (1631–1717) in


1707.

 Elevation of intraocular pressure as a sign of glaucoma was first mentioned in Breviary


(1622) by Richard Banister (1570–1626, English ophthalmologist).

 Discovery of the ophthalmoscope in 1851 by Hermann von Helmholtz (1821–1894, German


ophthalmologist) and its subsequent use by Edward Jaeger (1818–1884) led to the belief
that the optic nerve was also involved.

 Cupping of the optic nerve as a sign of glaucoma was confirmed by anatomist Heinrich
Muller in the late 1850s.

 Von Graefe is credited as having first described contraction of the visual field and
paracentral defects in glaucoma in 1856.

 Sir William Mackenzie (I835) was the first to describe raised intraocular pressure (IOP) in
glaucoma.

 Following the introduction of the ophthalmoscope, the presence of glaucomatous cupping


was soon recognized (Jacobson, I853; Jaeger, I854; von Graefe, 1854; Weber, 1855; and
others) and was confirmed histopathologically by Muller (1856).

 Mackenzie (1854) also described flattened and atrophic nerves in glaucomatous eyes.

 Nerve fibre bundle defects were first described by Landesberg (1869) and later by
Bjerrum (1889).

 Cavernous degeneration of the optic nerve in glaucoma was noted by Schnabel (1892).

 Jonas's ISNT rule:

4
I notes GLAUCOMA Dhaval Patel MD

modern definition: a pathologic condition in which there is a progressive loss of ganglion cell
axons causing visual field damage that is related to IOP.

On a molecular level, glaucoma of diverse aetiology is linked by the presence of endothelial


leucocyte adhesion molecule-1 (ELAM-1), which indicates activation of a stress response in
trabecular meshwork cells.

Anatomy & Physiology

Development of Anterior Chamber


The anterior chamber structures are derived from the mesenchyme and the ectoderm.

The chronological development is:

5-6 weeks: Cells of neural tissue origin migrate anteriorly.

6-8 weeks: Three waves of mesenchyme migrate anteriorly.

Wave 1: Forming the corneal endothelium.

Wave 2: Forms the iris stroma

Wave 3: forms the keratocytes.

3-4 months: Angle defined, trabecular meshwork develops, and aqueous production begins

5-7 months: Differentiation and perforation of trabecular meshwork enables it to


communicate with the anterior chamber

Birth : Iris and ciliary body are aligned with the scleral spur

1 year : angle recess develops

Trabecular meshwork

5
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The trabecular meshwork is functionally classified into:

1. Anterior non filtering portion

2. Posterior filtering portion.

The ultrastructure of the trabecular meshwork shows the following divisions:

1. Uveal meshwork

2. Corneoscleral meshwork

3. Juxtacanalicular meshwork

 The trabecular meshwork comprises of sheets of connective tisue lined by endothelium


and fenestrated with pores of size ranging from 75 to 5 um

 The extra cellular matrix comprises of endogenous metalloproteinases which are


responsible for ECM turnover and maintenance of aqueous outflow

 The juxtacanalicular layer offers maximal resistance to aqueous outflow.

Ciliary Body
The ciliary body is composed of:

 Bilayered epithelium.

 Ciliary vasculature.

 Ciliary muscles

The two layers of the epithelium are:

o Outer pigmented epithelium

6
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o Inner non pigmented epithelium

The twin layers show the presence of three types of intercellular junctions:

o Desmosomes: maintain cell adhesion

o Gap junctions: inter cellular transfer of solutes occur.

o Tight junctions: form the blood aqueous barrier. They play an important role in
the formation of aqueous humor

 The ciliary body derives its blood supply from the major arterial circle formed by:

o Long posterior ciliary arteries

o Anterior ciliary arteries

The capillaries of the ciliary circulation are highly fenestrated and form the site for
ultrafiltration

The ciliary body comprises of three types of muscle fibres:

o Longitudinal

o Circular

o Radial

The longitudinal muscle fibers terminate in three types of tendons:

Type A - Terminates in the cornea

Type B – Terminates in the sclera

Type C - Terminates in the trabecular meshwork

Aqueous Humor Dynamics

 Goldmann equation [P0 = (F/C) + Pv], P represents the IOP, F is the rate of aqueous
formation, and C is the facility of outflow, which roughly corresponds to the inverse of the
total resistance to outflow.

7
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 uveoscleral outflow is relatively insensitive to changes in pressure

 so Goldmann equation can be modified as: P = (F - U)/C + Pv, where P represents the IOP,
F is the rate of aqueous formation, U is the rate of aqueous outflow through the pressure
insensitive uveoscleral pathway, and C is the outflow facility. Each of these parameters
can be measured except U which must be calculated from IOP and the remaining
variables.

 outflow facility is typically between 0.23 and 0.33 µL/min/mm Hg

 mean aqueous humor production rate is typically found to range from 2.2 to 3.1 µL per
minute.

 Episcleral venous pressure is currently the most difficult parameter to measure in aqueous
humor dynamics. (episcleral venomanometer)

 FORMATION:

1. Ultrafiltration: Involves entry of plasma constituents into ciliary stroma

2. Active secretion: Involves secretion of Na and bicarbonate ions

3. Diffusion: Involves movement of fluid oxygen and glucose across the gradient

• Aqueous humor outflow:

1. Trabecular pathway: TM  SC  CC  Episcleral vein  ciliary circulation

2. Uveoscleral pathway: loose tissue between fibres of long ciliary muscles  flow
through suprachoroidal space  trans-scleral emmisory vein

3. Posterior pathway

Mechanism of Glaucoma

 the mechanical theory:

o 1858, Müller

o proposed that the elevated IOP led to direct compression and death of the neurons

8
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 the vascular theory:

o von Jaeger, 1858

o suggested that a vascular abnormality was the underlying cause of the optic
atrophy

 Schnabel cavernous atrophy:

o 1892, Schnabel

o atrophy of neural elements created empty spaces, which pulled the nerve head
posteriorly

Genetics of Glaucoma

 1.8% of the Indian population is blind and 0.15% suffers from glaucoma (Balasurbramanian
et al.)

 glaucoma affects 15 million Indians and around 25 million are at risk

 1938, Barkan: deep-chamber and shallow- chamber glaucoma

 Primary open-angle glaucoma

o 11 genetic loci designated GLC1A to GLC1K

o The first gene identified from GLC1A is myocilin (MYOC)

• chromosomal region 1q23-24

• codes for a protein that was initially named trabecular meshwork inducible
glucocorticoid response protein (TIGR)  now myocilin

o second gene for POAG was identified from GLC1E as optineurin

• chromosome 10p15-p14

9
I notes GLAUCOMA Dhaval Patel MD

• interacts with different proteins that are involved in apoptosis,


inflammation, and vasoconstriction.

o The third gene for POAG was recently characterized as the WD repeat domain 36
(WDR36)

• uniquely involved in T-cell activation and highly coregulated with


interleukin 2

o NTF4 gene on chromosome 19q13.3.

 Primary angle-closure glaucoma

o presence of MYOC mutations in a few individuals

o CYP1B1 gene is located on chromosome 2 at position 2p21. CYP1B1 is a member of


cytochrome P450 superfamily

 Congenital glaucoma

o Primary congenital glaucoma

• 22.2% of congenital glaucomas

• anomaly of trabecular meshwork and anterior chamber angle

• autosomal recessive

• 3 genes loci: GLC3A to GLC3C

• 2p21 (GLC3A), for which the responsible gene is CYP1B1, 1p36 (GLC3B) and
14q24 (GLC3C), for which the genes are not yet identified.

• familial in 10 to 40% and bilateral in 80%

Intraocular pressure

 Direct: manometric technique (needle insertion in AC, most accurate but invasive  not
used)

10
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 Indirect: Tonometric, eye’s response to an applied force

o Palpation  digital pressure (only gross alterations of IOP)

o Tonometry

 Applanation: force necessary to flatten a small, standard area of the cornea

 Indentation: amount of deformation or indentation of the globe in response


to a standard weight applied to the cornea.

 contour matching

 transpalpebral phosphene induction

 indentation/rebound

 intraocular implantation of pressure sensors.

Classification

A. Contact tonometers (instruments that touch the eye):


1. Static instruments

a) Applanation tonometers -flatten a portion of the cornea

Constant area:

i. Goldmann

ii. Hand-held versions of Goldmann's instrument: Perkins and Drager tonometers

iii. Pneumatonometry

iv. Mackay – Marg

Constant force- Maklakoff: a highly displacement tonometer, requires a supine subject

b) Indentation tonometers - indent the cornea with a shape other than a flat surface
Schiotz - a highly displacement tonometer that nearly doubles IOP during
measurement.

2. Dynamic instruments

a) Ballistic tonometers
-Impact acceleration

11
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-Impact duration: Pascal Dynamic Contour Tonometry (DCT): digital tonometer


that uses the principle of contour matching instead of applanation to measure
lOP. Theoretically this tonometer can measure lOP independent of CCT or
corneal biomechanics

-Rebound velocity- iCare rebound tonometer

b) Vibration tonometer - Krakau - a low displacement tonometer

B. Noncontact tonometry (NCT)

Nidek NT 4000 - synchronizes air discharge with the cardiac cycle.

Topcon NT- discharges air automatically when the corneal dome is in focus and
discharges only the amount air needed to applanate the cornea (older units discharged
a fixed amount of air each time).

Applanation Instruments

Goldmann tonometer
 constant-area applanation: 3.06 mm (because Theoretically, average corneal rigidity and
the capillary attraction of the tear meniscus cancel each other out when the flattened
area has the 3.06 mm diameter contact surface of the Goldmann prism)

 force necessary to flatten (or applanate) an area of the cornea

 Imbert–Fick principle, which states that for an ideal, dry, thin-walled sphere, the
pressure (P) inside the sphere equals the force (F) necessary to flatten its surface divided
by the area (A) of flattening (i.e. P = F/A).

 displaces only about 0.5 uL of aqueous humor, which raises IOP by about 3%

 Because the volume displaced is so small, ocular rigidity, or the ‘stretchability’ of the
globe, has little effect on the pressure readings.

 When the inner margins of the two semicircles are aligned in a smooth S curve at the
midpoint of their pulsations, the proper degree of applanation has been achieved

 Disposable tonometer tip designed to fit over Goldmann prism  Tonosafe, acrylic better
than silicone

 Tension knob is set at 1 g. If the knob is set at 0, the prism head may vibrate when it
touches the eye and damage the corneal epithelium. The 1 g position is used before each
12
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measurement. As a rule, it is more accurate to measure IOP by increasing rather than


decreasing the force of applanation.

 more than 3 D of corneal astigmatism elliptical mires, prism should be rotated to about
45° from the long axis of the ellipse – that is, the prism graduation corresponding to the
least curved meridian of the cornea should be set at the red mark on the prism holder

FLAT AXIS AT RED MARK

 fluorescein rings should be approximately 0.25–0.3 mm in thickness – or about one-tenth


the diameter of the flattened area.

Potential errors of applanation tonometry


 Thin cornea
 Thick cornea
 Astigmatism >3 diopters
 Inadequate fluorescein
 Too much fluorescein
 Irregular cornea
 Tonometer out of calibration
 Elevating the eyes >15°
 Repeated tonometry
 Pressing on the eyelids or globe
 Squeezing of the eyelids
 Observer bias (expectations and even numbers)
 Wide pulse pressure. It is normal for there to be a small oscillation in IOP in time with the
rhythm of ocular perfusion. If this ‘pulse pressure’ is substantial, the mid-point is taken as
the reading.

Perkins tonometer
 The Perkins tonometer is similar to the Goldmann tonometer, except that it is portable
and counterbalanced, so it can be used in any position.

Draeger tonometer
 similar to the Goldmann and Perkins tonometers, except that it uses a different biprism

MacKay-Marg tonometer
 movable plunger 1.5 mm in diameter, that protrudes slightly from a surrounding footplate
or sleeve. The movements of the plunger are measured by a transducer and recorded on a
paper strip.

13
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 tonometer measures IOP over a brief interval, so several readings should be averaged to
reduce the effects of the cardiac and respiratory cycles.

 tip of the instrument is covered with a plastic film to prevent transfer of infection

Tono-Pen™
 small portable applanation tonometer that works on the same principle as the MacKay-
Marg tonometer

 community health fairs, on ward rounds

 depends on an electronic end point  more accurate

 disposable latex cover

Pneumotonometer
 OBF pneumotonometer (Ocular Blood Flow OBF)

 sensing device that consists of a gas chamber covered by a polymeric silicone diaphragm

 As the diaphragm touches the cornea, the gas vent is reduced in size, and the pressure in
the chamber rises

 Some properties that are more like an indentation tonometer

 scarred, irregular, or edematous corneas

Non-contact tonometer
 applanates the cornea by a jet of air, so there is no direct contact between

 When an area of the cornea 3.6 mm in diameter is flattened, the light reflected to the
photocell is at a maximum.

 useful for screening programs, non-medical person can operate, no TA

Ocular Response Analyzer™


 Reichert Ophthalmic Instruments, Depew, NY, USA

14
I notes GLAUCOMA Dhaval Patel MD

 air puff tonometer that directs the air jet against the cornea and measures not one but
two pressures at which applanation occurs

 when the air jet flattens the cornea as the cornea is bent inward and as the air jet lessens
in force and the cornea recovers. The first is the resting intraocular pressure.

 The difference between the first and the second applanation pressure is called corneal
hysteresis and is a measure of the viscous dampening and, hence, the biomechanical
properties of the cornea

The Ocuton™ tonometer


 hand-held tonometer that works on the applanation

 very light probe, for home tonometry

Maklakow tonometer
 differs from the other applanation instruments in that a known force is applied to the eye, and the area
of applanation is measured – a technique known as constant-force rather than constant-area
applanation
 The instrument consists of a wire holder into which a flat-bottom weight, ranging from 5 to 15 g, is
inserted.

Indentation instruments
 known weight is placed on the cornea, and the IOP is estimated by measuring the
deformation or indentation of the globe.

Schiøtz tonometer
 metal plunger that slides through a hole in a concave metal footplate.

 The plunger supports a hammer device connected to a needle that crosses a scale. The
plunger, hammer, and needle weigh 5.5 g. This can be increased to 7.5, 10, or 15 g by
the addition of appropriate weights.

 lower the IOP, the higher the scale reading. Each scale unit represents a 0.05 mm
protrusion of the plunger

 portable, sturdy, relatively inexpensive, and easy to operate.

Friedenwald nomogram

15
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 An important concern is that placing the heavy tonometer (total weight at least 16.5 g) on
the eye raises IOP. This ocular rigidity is not taken into account.

Electronic Schiotz tonometer


 continuous recording of IOP that is used for tonography.

Impact–rebound tonometer
 updated version of an indentation tonometer

 very light, disposable, sterile probe is propelled forward into the cornea by a solenoid;
the time taken for the probe to return to its resting position and the characteristics of the
rebound motion are indicative of the IOP

 comparable to the Goldmann in both normal and post-keratoplasty human eyes.

Transpalpebral tonometry
1. TGDc-01 (Envision Ophthalmic Instruments, Livonia, Michigan, USA) was developed in
Russia  weight falling within the instrument onto the closed eyelid and the amount
of indentation it causes.

2. DIATON TONOMETER: IOP through the Eyelid

3. Proview (Bausch & Lomb, Rochester, NY, USA)  pressure on the eyelid required to
induce these phosphenes is proportional to the intraocular pressure.

Dynamic contour tonometry


 Kanngiesser

 Principle: by surrounding and matching the contour of a sphere (or a portion thereof), the
pressure on the outside equals the pressure on the inside.

 Measures transcorneal pressure with minimal deformation of the cornea. This principle
measures pressure instead of force.

 concave pressure-sensing tip (10.5 mm radius of curvature) is slightly flatter than that of
the average human cornea.

 The 1.7-mm piezoresistive pressure sensor at the center of the concavity measures the
intraocular pressure at the cornea 100 times per second with less than 1 g of appositional
force.
16
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 Requires measuring periods of 4–5 s and is difficult in the incompliant patient or in


nystagmus.

 dynamic contour tonometer (DCT) (Pascal™, Zeimer, Zurich, Switzerland)

 not affected by pachymetry, previous refractive surgery

 measures IOP in real time, the actual measurement, like the IOP, is pulsed

 less dependent than applanation tonometry on central corneal thickness, corneal


curvature, astigmatism, anterior chamber depth, and axial length.

 It is possible to measure both the diastolic and the systolic intraocular pressures and
determine the difference between the two, that is, the ocular pulse amplitude. Ocular
pulse amplitude is an indirect measure of choroidal perfusion and may have a role in the
pathophysiology of glaucoma.

Continuous monitoring of IOP


 Contact lens or suction cups

 Sonic resonance of the eye

 Infrared spectroscopy

 Miniature pressure sensor

 Sensimed Triggerfish (uses a sensor which is a soft hydrophilic single use contact lens,
containing passive and active strain gauges embedded in the silicone to monitor
fluctuations in diameter of the corneo-scleral junction)

Factors influencing intraocular pressure


Demographic

Age: Mean IOP increases with increasing age


Sex: Higher IOP in women Effect more marked after age 40 years
Race: Higher IOP among blacks
Heredity: IOP inherited

Systemic

17

http://architebooks.com
I notes GLAUCOMA Dhaval Patel MD

Diurnal variation: Most people have a diurnal pattern of IOP Quite variable in some
individuals
Seasonal variation: Higher IOP in winter months
Blood pressure: IOP increases with increasing blood pressure
Obesity: Higher IOP in obese people
Posture: IOP increases from sitting to inverted position Greater effect below horizontal
Exercise: Strenuous exercise lowers IOP transiently Long-term training has a lesser effect
Neural: Cholinergic and adrenergic input alters IOP
Hormones: Corticosteroids raise IOP; diabetes associated with increased IOP
Drugs: Multiple drugs alter IOP

Ocular
Refractive error: Myopic individuals have higher IOP
Eye movements: IOP increases if eye moves against resistance
Eyelid closure: IOP increases with forcible closure
Inflammation: IOP decreases unless aqueous humor outflow affected more than inflow
Surgery: IOP generally decreases unless aqueous humor outflow affected more than inflow

Corneal Hysteresis
 Corneal hysteresis is a measurement of the viscoelastic properties of the cornea. It can
be likened to the spring effect of the cornea.

 Corneal elasticity is affected by corneal thickness, collagen composition, hydration, and


extracellular matrix.

 Corneal hysteresis appears to have a greater effect on measured IOP than on CCT or
corneal radius of curvature.

 Corneal hysteresis is measured by the ocular response analyzer.

 Low CH may underestimate IOP and high CH may overestimate IOP.

 Average normal CH is around 12.5 mmHg.

 Normal children have CH values similar to normal adults.

 Decreased CH values are associated with glaucoma.

 Glaucoma patients with lower CH values have greater progressive visual field worsening.

 The dynamic contour tonometer (DCT) is least affected by corneal biomechanics of all
instruments used to estimate IOP.

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Target IOP

 The discussion till now indicates that past efforts to lower intraocular pressure in the
‘normal’ range of 21 mm Hg or lower may be inadequate and that “control” really means
an intraocular pressure of less than 15 mm or 16 mm of Hg especially in advanced
glaucoma.

 Target pressure may be defined as a pressure, rather a range of intraocular pressure


levels within which the progression of glaucoma and visual field loss will be delayed or
halted. The goal should be to lower the intraocular pressure to a level that is ‘safe’ for
that particular eye. Because individuals vary in their susceptibility to IOP independent
damage, there is no ‘Safe’ intraocular pressure that can be guaranteed to prevent further
glaucomatous damage. The optic nerve that has already been damaged appears to be
more susceptible to pressure mediated injury, so patients with advanced glaucomatous
neuropathy may require very low target pressure to halt the disease.

 In determining the appropriate target pressure for an individual, the ophthalmologist must
take into account several major factors, the IOP level at which the nerve damage
occurred (damaging IOP), the extent and rate of progression of glaucomatous damage, if
known; the presence of other risk factors for glaucoma; and the patient’s age, expected
life span, and medical history.

 Specific IOP ranges may be recommended as a starting point. The AAO guidelines suggest:

o For patients with mild damage (optic disc cupping but no visual field loss), the
initial target pressure should be 20-30% below baseline.

o For patients with advanced damage, the target pressure range may be a reduction
of 40% or more from baseline.

o For patients with NTG, a 30% reduction is recommended.

 A target intraocular pressure that is appropriate when you first see a patient may not be a
safe pressure 10 years later when he/she may have developed systemic hypertension,
diabetes or some other condition, that may affect the person’s susceptibility to
glaucomatous progression. The clinician should always revaluate each glaucoma patient at
regular intervals to determine if the target intraocular pressure originally selected is still
valid.

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Gonioscopy

 Optical principles

o total internal reflection: angle of the anterior chamber cannot be visualized


directly

o refractive index of a goniolens is similar to that of the cornea, it eliminates total


internal reflection by replacing the tear film-air interface with a new tear film-
goniolens interface.

 Two important parameters of anterior chamber depth & angle width.

 When the angle formed between the iris and the surface of the trabecular meshwork is
between 20° and 45°, the eye is said to have a wide angle (= scleral spur visible).
Angles smaller than 20° are termed narrow angles (= scleral spur not visible).

Interpretation

 Pupil

 Iris:

1. Contour: flat, concave, convex

2. Site of iris insertion: apparent and actual

3. the angulation between the iris insertion and the slope of the inner cornea in the
angle, in approximate steps of 10°.

Last, abnormalities such as neovascularization, hypoplasia, atrophy, and polycoria should


be noted.

 Ciliary Body:

 Iris process and PAS

 Scleral Spur

 Schwalbe’s line, pigmented Sampaolesi’s line

 Trabecular meshwork and trabecular pigment band

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 The angle recess represents the posterior dipping of the iris as it inserts into the ciliary
body.

 any blood vessel that crosses the scleral spur onto the trabecular meshwork is abnormal.

In most eyes the inferior quadrant is widest, the lateral quadrants narrower, and the
superior narrowest. In eyes with narrow angles, the temporal quadrant may be
narrowest.

Methods
Direct method: Koeppe lens, Medical workshop, Barkan, Swan-Jacob

allows the observer to look directly at the angle

1.5x magnification

Barkan hand illuminator or fiber optic light source also used along with microscope having
1.6x objective lenses and 10x ocular lenses  24x magnification of trabecular area

Indirect method: Goldmann and Zeiss lenses


mirrors by which the angle is examined with reflected light
ight and magnification of the slit lamp and corneal microscope.

The mirrored arrangement of both of these types of lenses causes the observed image of the
angle to be reversed but not crossed.

Indentation (compression) gonioscopy: Zeiss, Posner, Suzzman


tear-coupled indirect (e.g., Zeiss) contact lens, the physician can observe the effects on
angle width.

Grading of chamber angle


 Scheie  like Shaffer but in reverse order

 Shaffer:

o 0 – 0,

o S – no obvious iridocorneal contact but no angle structures can be identified,

o 1 –10,
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o 2 –20,

o 3 -25-35,

o 4 – 35-45,

 Spaeth

 three-dimensional information in coded form

 indirect goniolenses (e.g., Zeiss four mirror) that allow for indentation

1. the site of insertion of the iris root in the eyewall

A = Anterior to trabecular meshwork (i.e., Schwalbe’s line)


B = Behind Schwalbe’s line (i.e., at level of trabecular meshwork)
C = Centered at the level of the scleral spur
D = Deep to the scleral spur (i.e., anterior ciliary body)
E = Extremely deep in the ciliary body.

2. width or geometric angle of the iris insertion

like Shaffer: 10-40

3. the contour of the peripheral iris near the angle

initially 3 contours

s = ‘steep’ or convexly configured (e.g., plateau iris)


r = ‘regular’ or flat (the most common contour seen)
q = ‘quixotic’ or ‘queer’ for deeply concave (e.g., pigment dispersion syndrome).

Now 4 contours

b = ‘bows 1 to 4 plus’ (usually indicative of optically-appearing closure, altering with indentation)


p = ‘plateau’ (comparable to older ‘s’ designation)
f = ‘f lat approach’: the commonest iris appearance (comparable to the older ‘r’ designation)
c = ‘concave’ as in posteriorly bowed iris (comparable to the older ‘q’ designation).

4. intensity of the trabecular pigmentation

trabecular meshwork pigmentation (TMP) is labeled from 1 to 4: minimal or no pigment is graded 1,


and dense pigment deposition is indicated as grade 4, with lesser degrees between.

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5. presence or absence of abnormalities such as mid-iris bowing, peripheral


synechiae, and so on.

 RPC

Grade 0 Closed

Grade 1 dipping of light

Grade 2 Schwalbe’s line visible

Grade 3 anterior trabecular meshwork

Grade 4 posterior TM scleral spur

Grade 5 ciliary body band visible

Grade 6 root of iris visible

 van Herick estimate of angle width

Grade 4 angle Anterior chamber depth = Corneal thickness

Grade 3 angle Anterior chamber depth = 1⁄4 to 1⁄2 corneal thickness

Grade 2 angle Anterior chamber depth = 1⁄4 corneal thickness

Grade 1 angle Anterior chamber depth = Less than 1⁄4 corneal thickness

Slit angle Anterior chamber depth = Slit-like (extremely shallow)

Closed angle absent peripheral anterior chamber

Visual Field

 normal visual field: an island of vision in a sea of darkness Traquair

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 60° superiorly and nasally, 75° inferiorly, and 100° temporally

 Visual field testing is usually done in the photopic (light-adapted) or mesopic (partially
light-adapted) state

 Visual acuity  resolving power of the retina

 Static visual field  tests differential light sensitivity

 Central field: within 30 degrees

 Peripheral field: 30 degrees to far periphery

 Bjerrum’s area (arcuate area): within the central 25°, extending from the blind spot and arcing above
or below fixation in a broadening path to end at the horizontal raphe nasal to fixation.

 Kinetic perimetry: stimulus location is moved.

 Static perimetry: stimulus intensity is varied

 Isopter: an area outlined by a given stimulus in kinetic perimetry

 Threshold: At a given retinal point, the intensity of a stimulus that is perceived 50% of the times it is
presented.

 Short-term fluctuation: variability within a field during the time of its measurement.
 Long-term fluctuation: variability between two visual fields performed sequentially on
the same eye that cannot be attributed to pathologic change.

 Candela per square meter (cd/m2). The international unit of luminance.


 Apostilb. 0.1 millilambert = 3.183 cd/m2.
 Log unit. Logarithm base 10 of the luminance in apostilbs.
 Decibel. One-tenth of the log unit.

Kinetic perimetry

1. Confrontation

2. tangent screen

3. Goldmann perimeter.

 non-seeing periphery and moved at approximately 2° per second toward fixation

 15° intervals around 360° of the visual field

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Static perimetry

 full-threshold testing: each point in the visual field is evaluated by positioning the stimulus at a test
point and varying the intensity until the threshold for that particular retinal location is defined

 Slopes and scotomas are shown better by static than by kinetic perimetry.

 automated achromatic static visual field (AASVF) testing is the gold standard for the
evaluation of optic nerve function.

 There are many makers of AASVF machines, among them are Humphrey (Allergan, Irvine,
CA), Octopus, and Dicon

 modifications:

o threshold-related testing: Each retinal location has a statistically determined ‘normal’


sensitivity range

o zone testing: normal, relative defect, or absolute defect.

o algorithms that use less precise bracketing to estimate the threshold: Swedish Interactive
Testing Algorithm (SITA) program in HFA

o Noisefield perimetry = white-noise perimetry = campimetry: TV sceen – normal abnormal areas

o Optokinetic perimetry:

Combined static and kinetic perimetry

 uses the speed of kinetic perimetry and the sensitivity of static testing

 With manual perimetry, a threshold stimulus is chosen for testing the central field. This stimulus is
chosen by a variety of methods, but commonly it is the weakest stimulus visible at the point either 15°
above or 15° below the horizontal meridian 25° temporal to fixation.

Reasons for Computerized Perimetry

1. Reproducible testing conditions.

2. Data-storage capability:

3. More sensitive testing: Many researchers claim static perimetry to be superior to kinetic.

4. Easy operation and menu driven software make automated perimetry easy to learn and to use.

 STATPAC analysis: HFA STATistical PACkage

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Techniques
 Mean sensitivity of the visual field decreases approximately 0.58–1.0 dB per decade

 If the patient generates fixation losses more than 20–30% of the time, the test can be considered only an
approximation of the true visual field

 learning curve

 pupillary diameter of less than 3 mm can cause generalized depression of the visual field

 Humphrey, Goldmann, and more recent Octopus perimeters use 31.5 apostilbs of background
illumination.

 Temporal summation, the ability of the visual apparatus to accumulate information over time, can
influence visual field testing for stimulus exposure times less than 0.5 seconds

Patient variables

Age

Fixation

Reliability

Ocular variables

Pupil size

Media clarity

Refractive correction

Testing variables

Technician

Background illumination

Stimulus size and intensity

Stimulus exposure time

Area tested

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• The 30-2 program is better for recognizing change along horizontal and vertical meridians
such as those that occur in patients with glaucoma and neurologic deficits.

 Fixation Target

1. Central—Yellow light in the center of the bowl


2. Small diamond —It is located below the central target and should be used if the patient cannot see the
central fixation light (e.g: macular degeneration). The patient should look in the center of the diamond
formed by the four lights.
3. Large diamond—It is located below the central target and is used for patient with central scotoma who
cannot see either central fixation light or small diamond.
4. Bottom LED—Some tests have points in the superior visual field that require a lower fixation light
than the central target. The target used is the bottom LED of the large diamond. When testing with the
superior 64 or superior 36 screening speciality tests, the bottom LED is the default fixation target. It is
automatically illuminated at the beginning of a test.

Size of the stimulus: The standard size of the stimulus is size III for all routine tests. But in situations
like advanced glaucoma, the test will be conducted with size V to know the status of macular split.

Visual field interpretation

 Generalized or localized defects

 In an absolute scotoma, the brightest stimulus of the machine is not perceived. In a relative scotoma,
the brightest stimulus is visible, but dimmer stimuli are not.

 In glaucoma:

29% of their patients had paracentral scotomas

20% had nasal steps

18% had simple arcuate defects as the predominant diagnostic field abnormality

 HFA vs OCTOPUS

o MD : Octopus  mean defect, Humphrey  Mean Deviation

o Humphrey: PSD Pattern Standard Deviation; Octopus: loss variance

o important thing to remember is that in both instruments has reverse off


nomenclature.
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Glaucomatous visual field defects

 Generalized depression

 Irregularity of the visual field

 Nasal step or depression: nasal portion of the visual field is often affected early in
glaucoma, and defects may persist until the last stages of the disease. The horizontal
raphe is the anatomic basis for this appearance.

 Temporal step or depression: more commonly found as a component of late-stage


disease

 Enlargement of the blind spot: nonspecific, The normal blind spot is about 7° vertically
and 5.5° horizontally, with sharp borders.

 Seidel’s scotoma: If the blind spot enlarges in an arcuate manner.

 Isolated paracentral scotomata: 20% of glaucomatous visual fields

 Arcuate defects (nerve fiber bundle defects): begins at the blind spot, arcs around
fixation, and ends at the horizontal nasal raphe, classicaly known as Bjerrum’s defect

 Central and temporal islands: end stage field, only the Papillomacular bundle and some
nasal fibers left.

 Temporal Wedge:

 split fixation: only fibers from half of the papillomacular bundle remain, these patients
more susceptible to central vision loss at surgery

Clover leaf pattern that can accompany fatigue (Four primary pointsaround fixation are
checked and confirmed)

nerve fiber bundle associated visual field defects

Chorioretinitis
Myopic retinal degeneration
Refractive scotomata
Trauma
Retinal laser damage glaucoma
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Optic nerve ischemia


Optic nerve compressive lesions
Optic neuritis
Drusen of optic nerve head

Esterman disability rating: binocular assessment used by government and industry is described more
fully in the AMA Guides to the Evaluation of Impairment and the Physicians’ Desk Reference for
Ophthalmology.

Reliability indexes

False-positive responses occur when the patient indicates that he or she has seen a stimulus
when one was not presented. This is usually a reaction to random noise generated by the
perimeter. <20-30%

False-negative responses occur when the patient fails to respond to a stimulus that is at least
as bright or brighter than one that he or she had previously recognized in that position. <20-
30%

Fixation reliability: <20-33%


1. Heijl-Krakau technique: blind spot may be stimulated periodically
2. technician can offer a subjective assessment of the patient’s fixation
3. computer may stop the test if a video or infrared fixation monitor indicates that the
eye has shifted

Short-term fluctuation: the intra-test variation, result of checking several loci in the visual field
twice. Deviation should exceed about 5 dB to be considered abnormal.

Long-term fluctuation: the inter-test variation,

Global indexes
1. Mean sensitivity
2. Mean deviation or defect
3. Standard deviation or variance (PSD/ LV)
4. Corrected SD (CPSD/ CLV)

ALGORITHMS
 First described by Lynn in 1968.

 1st Generation-Threshold determination simply by altering stimulus intensities from infra-


or supra luminal until threshold was crossed

 2nd Generation-Staircase methods (Standard Full Threshold Testing Algorithm)

o Predetermined rules for stimulus sequences, Step wise, Number of reversals


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o Used in Humphrey Field Analyzer

o White, size III stimulus

 3rd Generation

o FASTPAC

 Introduced in 1991,it changes stimulus intensity in 3 dB steps

 When sequences crosses threshold (i.e. either from seeing to nonseeing or


vice versa) ,testing stops without reversing direction in smaller steps

 More vulnerable to pt. response because it defines threshold only on the


basis of single crossing of threshold

o Swedish Interactive Threshold Algorithm (SITA) (SITA Standard/ SITA Fast)

 Test starts by measuring thresholds at 4 primary points, one each


quadrant,12.7 degrees from point of fixation

 Conventional up-down staircases using 4-2 step sizes is used in these 4


points

 Threshold values at these points are used to calculate threshold values in


adjacent points

 Testing stops if the confidence in a threshold value at a point is


(compared to a predetermined value)

 If confidence is low another staircase is initiated

 The SITA stragegy does not determine Short term Fluctuation.

 SITA uses information gained throughout the program to determine the


threshold strategy for adjacent points. SITA measures the response time
of each patient and uses the information to set the pace of the test.

o Types-

 30-2-Central 30 deg with tested points 6 deg apart( offset 3 deg from both
horizontal and vertical axes)-total 76 locations

 24-2-Central 24 deg with grid spacing same like 30-2 i.e. 6 deg total 54
locations

 10-2-68 locations spaced on a 2 deg within 10 deg of fixation

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 MACULA TEST: it tests a square grid of 16 points 2 degrees apart centred


around the point of fixation. It is used to monitor the central field in
advanced glaucoma

 60-2/60-4

 120 point test

 Nasal Step Pattern

 Throughout the test 3 types of catch trials performed-

1. Fixation loss

2. False +ve response

3. False –ve response

 WEBER’S LAW: When the threshold visibility is a matter of contrast alone then the threshold sensitivity is a constant
expressed as the ratio between the stimulus and background intensity. This constant is termed as the Weber’s fraction.

Thus if Weber’s law is operating any change in the background intensity is reflected in the stimulus intensity maintaining a
constant threshold sensitivity. Hence variables like pupillary size do not affect the threshold sensitivity.

 TEMPORAL SUMMATION: The visibility of a stimulus varies directly with the duration upto a critical period of 0.3 s

 SPATIAL SUMMATION: If the intensity of a stimulus remains the same then its visibility varies directly with the size.

How to Read

Zones - Independent of normative data and STATPAC analysis

Zone 1: Patient data / test data


Zone 2: Reliability indices / foveal threshold
Zone 3: Raw data
Zone 4: Gray scale

Zones- Dependent on normative data and STATPAC analysis

Zone 5: Total deviation numerical plot,


Zone 6: Total deviation probability plot
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Zone 7: Pattern deviation numerical plot,


Zone 8: Pattern deviation probability plot
Zone 9: Global indices—Mean Deviation Index in dB value and with its P value. Pattern
Standard Deviation (PSD) in dB value and with its P value, Corrected Pattern Standard
Deviation (CPSD) in dB value and with its P value. Short-term Fluctuation (SF) in dB value.
Zone 10: Glaucoma hemifield test :
a. Out side normal limits
b. Border line
c. Abnormally low sensitivity,
d. Abnormally high sensitivity,
e. Within normal limits.

 How to decide Eye??  The blind spot is to the left side of mid line so this is a print of a
left eye.

 In 24-2 pattern, the outermost ring is omitted from the test except the two nasal points
(because they are MC involved), the will reduce tested locations from 76 locations in the
30-2 test to 54 locations in the 24-2 test, thus reducing the number of tested locations by
29%.

 Reliability indices include fixation loss, false positive and false negative: should be <33%

 short term fluctuation less than 2.5 means a test of good accuracy

 blind spot: at temporal side of point of fixation, having a size of 5 X 7 and its centre is
located 12.5 from point of fixation and slightly below the horizontal line.

 Fixation loss is the number of times a patient responds to a target placed in the blind
spot.

 False positive error: is the number of times a patient responds to the audible click of the
perimeter's shutter when no target is presented.

o Typical areas of white scotomas

o Trigger happy patients

o Remember, this can show abnormality in pattern deviation, but pure localized
defects should also appear exactly on the total deviation area.

 False negative error: is the number of times a patient fails to respond to a suprathreshold
target placed in a seeing area of the visual field.

o Clover leaf pattern

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o Fields should not be considered unreliable solely upon a false negative response
rate, particularly if there is a great deal of pathology. In patients with advanced
glaucomatous optic nerve damage we may get more than 50% false response which
can be attributed in small shifts in fixation.

 Gray Scale (Halftone): used to explain to the patient, only points are actually tested (54 -
76 points), and at the same time 2000 symbolic representations are used to draw the gray
scale.

 Total Deviation: the difference between the measured threshold of each individual test
location & the age corrected normal value for that location.

 Visual field thresholds decline with age at a rate of 0.5-1.0 dB per decade.

 Generalized depression is seen in cases of cataracts and miosis.

 Pattern deviation is derived from the total deviation via adjustment of the measured
thresholds upward or downward by an amount which reflects any generalized change in
the threshold of the least-damaged portion.

 The graphic probability plots of total deviation or pattern deviation: how frequently a
value at a particular test location is found in the normal population.

 Global indices:

o Mean Deviation (MD):

 average departure of each test location from the age-corrected normal


value.

 severity of damage is considered mild if the value of MD is below 6,


moderate if the value is between 6-12 and severe if the value is more
than 12

o Pattern Standard Deviation (PSD):

 measure of focal visual loss

 higher PSD suggests greater localized field damage, In advanced glaucoma,


PSD can actually decrease because damage is no longer focal

 SD calculated for the differences of each test location of that patient and
that of the normal of the same age.

 Remember that MD points toward the height of the field while PSD
indicates the shape of the field

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o Corrected Pattern Standard Deviation (CPSD): deviation from normal reference


hill after adjusting for short term fluctuation

o Short Term Fluctuation (SF): Variability of the threshold for test location when
determined within the same session. 1.5 db in young and 2.5 db in old.

 Long term fluctuation: variability present between the tests.

 Glaucoma Hemifield Test (GHT) evaluates five zones in the superior field and compares
these zones to their mirror image zones in the inferior field.

1. Outside normal limits

2. Borderline

3. Generalized reduction in sensitivity

4. Abnormally high sensitivity

5. Within normal

 GAZE TRACKER:

o Present in the newer machines.

o Follows the patient’s cornea and records the movements.

o More spikes and taller spikes indicate greater deviation. Downward spikes
represent the situation when fixation was unrecordable.

Anderson’s Criteria

1. 3 or more contiguous, non edge points in an expected location of the field that have
p<5% on the PD plot, one of which must have p<1% in 30-2.

2. GHT outside normal limits.

3. CPSD values seen in < 5% of population.

Glaucoma Progression Analysis

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 Procedures used for progression

o Clinical judgment.

o Defect classification systems.

o Trend analyses

o Event analyses.

 analytic method in a suite of progression evaluation techniques called guided progression


analysis

 based on the visual field endpoint from the Early Manifest Glaucoma Trial (EMGT)

 identifies each point as stable, deteriorating, or improving

 possible progression: When three test points are significantly progressing (p < 0.05) in the
same location over two consecutive tests

 Likely progression: when three test points are significantly progressing in three
consecutive tests.

 can be used in following all glaucoma patients and glaucoma suspects.

Visual Field Index


 component of the GPA suite

 each point on the pattern deviation map is scored as a percent.

 normal sensitivity are given a score of 100% and points with absolute defects are given a
score of 0%.

 Points with depressed sensitivity (p < 0.05) receive a score calculated by a formula that
includes total deviation and age-corrected normal threshold.

 The center of the visual field is then weighted more highly.

 resulting percentage is displayed on a graph

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Newer Perimetry Techniques

Why??

 To identify glaucomatous damage prior to conventional white-on-white perimetry

 Because traditional Automated Perimetry will not reveal a scotoma until 25-40 % of nerve
fibers are damaged

 Motion attributes of vision are involved early in glaucoma and not picked up by
conventional perimetry

Techniques

 Short wave automated perimetry (S.W.A.P)

 High pass resolution perimetry (H.P.R.P)

 Frequency doubling perimetry (F.D.P)

 Flicker perimetry

 Motion perimetry

 Detection and resolution perimetry

Retinal Ganglion Cell Types

1. Parvocellular (80%):

-smaller diameter axons

-slower conduction

-sensitivity to higher spatial freq(details)

-projection to parvocellular layer

-concentrated in the central fields

2. Magnocellular (15%):

-larger diameter axons

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-faster conduction

-sensitivity to higher temporal freq (ficker, motion)

-projection to magnocellular layer

-found throughout the retina

3. Koniocellular (5%):

-5% of cells project to the koniocellular interlaminar layer of the L.G.B.

-involved in the blue-yellow opponent information

Short Wave Automated Perimetry


 Developed by Stiles

 Also called Blue on yellow perimetry

 Software incorporated into Humphrey’s Field Analyser II (30-2, 24-2 programs)

 now available using the SITA strategy (SITA-SWAP), which reduces testing time.

 Intense yellow background with blue stimulus

 The Principle:

o Concept of reduced redundancy

o Stimulate one color-vision mechanism

o Large blue target stimulate short wave sensitive mechanism

o Isolate the short–wave sensitive pathways

 Stimulus Goldman size V, blue light (440 nm), 200 ms duration

 Background- 100 cd/m2 intensity yellow light (500-700 nm)

 Instrumentation and software same as W-W-perimetry

 Advantages

o Detect glaucomatous visual field loss prior to conventional white-on-white (W-W)


perimetry (3-5 yrs in advance)

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o Predict future visual feid defects for standard W-W

o More rapid glaucomatous progression seen, earlier

o Correlate well with early optic nerve head changes

o SWAP shown more extensive visual field loss than W-W perimetry in optic neuritis
and in diabetic macula oedema( blue cones are more susceptible to damage in
diabetes)

o SWAP pathway deficits precede luminance pathway deficits in age-related


maculopathy, central serous choroidopathy and retinitis pigmentosa.

 Disadvantages:

o Affected by absorption of short wavelength stimuli by the aging lens

o Influenced by macular pigment absorption causing a depression in the foveal peak

o Takes approx 15% longer than W-W perimetry , 30-2 using the Full Threshold
strategy and approx 17% with the FASTPAC strategy

o Between-subject normal variability is greater for SWAP than for conventional


perimetry

Frequency Doubling Perimetry (FDP Matrix)


 Portable small tabletop unit

 Principle

o M-cell neuron sub-set comprising a third to a half of the M-cell neurons (called
"non-linear" My-cells) are first involved in glaucoma, basis for frequency doubling
testing (25%)

o When a low spatial frequency sinusoidal grating with alternating wide light and
dark bars undergoes high temporal-frequency counterphase flicker, (i.e., the black
bands reverse to become white and the white bands reverse to become become
black in rapid sequence) gratings appear twice as many light/dark bars (spatial
frequency appears doubled) called the “frequency doubling illusion”

o Non-linear M-cell neurons transmit signals related to this illusion. These neurons
are the first involved in glaucoma, tests presenting alternate grating stimuli
attempt to identify neuron loss earlier

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 greater than 90% sensitivity and specificity when compared to the HFA standard
achromatic perimetry as the gold standard

 FDT perimetry tolerates up to 6 D of refractive error

 Not affected by external room illumination

 Not affected by variations in the pupil size, the pupil diameter should be greater than 2
mm

 Instructions to the patient are also quite simple: look at a black dot in the center of the
screen and press a button any time a grating pattern is seen

 A 10-degree square pattern is presented at 17 different locations within the central 20 *


20 degrees visual field

 Test options include a screening field (Screening C-20-1) in which 5-degree gratings with
three contrast levels are show at 17 locations in the central 20 degree field

 abnormal when

o Any defect in the central five locations

o Two mild or moderate defects in the outer 12 squares

o One severe defect in the outer 12 squares

o Screening test time greater than 90 seconds per eye

 Advantages:

o Short test duration( 4-5 min for full threshold)

o quick, inexpensive, easily administered, and highly sensitive and specific.

o Not affected by blur upto 6 D

o Not affected by pupil size

o Minimal training required

 Limitations:

o Fewer spots with larger area (19 spots, each subtending 10 degrees of visual arc, in
the N-30 glaucoma testing program)

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High-Pass Resolution Perimetry (HPRP)

 Principle

o Ring-shaped stimuli are presented on a computer screen

o The inner and outer borders of the ring are darker, and the area between is
lighter, than the background. the average contrast of the stimulus is identical to
that of the background, and is maintained at a constant level while stimulus size is
altered

o The computer-generated stimuli are "high pass filtered"; that is, all low spatial
frequency information is removed. This technique forms a stimulus type known as
the "vanishing optotype"

o The thresholds for the detection of an object as present and for recognition of
what it is become simultaneous-if the target cannot be recognized, it will not even
be seen

o Stimulus design is thus chosen because it corresponds to center-surround


arrangement of retinal ganglions receptive field

 Test available in Ophthimus (High Tech Vision)

 14 target sizes in 1 db steps are available

 Parameters obtained are Global deviation, Local deviation, neural capacity index, etc

 The Ophthimus provides global indices and statistical analyses conceptually similar to
those produced by the Humphrey. In addition, the Ophthimus provides, as a unique
parameter, the estimated neural capacity

 Ophthimus provides a printout that includes the ring target sizes seen graphically as well
as data about the overall deviation and fluctuation of the responses

 Subject reliability is also assessed

 Central 30 degrees visual field is examined, 50 locations tested

 Adapts automatically to the patient´s reaction time as well to responses to fixation


control tests and "blank" and "catch" targets

 Advantages

o Quicker examination (5 min duration)

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o Excellent test-retest reliability

o Earlier detection of progression

o Continuous feedback helps to improve concentration

o Early detection and monitoring of glaucomatous damage

o Useful for neurophthalmologic conditions

 Disadvantages

o Limited commercial distribution and representation

o Requires near correction of 6D greater than patients distance correction , special


trial lens needed

o Use of ring targets makes it difficult to show the linear nature of defects such as a
hemianopia that respects the vertical midline or a nerve fiber layer defect that
splits fixation

o The exact location and dimensions of the blind spot are not delineated, this is
rarely a significant problem

Flicker Perimetry
 Detection of rapidly flickering stimuli depends on the magnocellular mechanisms( M-cells)

 Tyler suggested that deficits in flicker sensitivity (for high temporal freq) was lost early in
glaucoma and ocular hypertensives

 Three different methods are employed for flicker perimetry

 Employs light emitting diodes

 Uniform background of 50 cd

 Stimuli are briefly flickered, patient is asked to respond if flicker detected

 Temporal frequency of flicker is varied to determine highest rate at which it is detected


(CFF, critical flicker fusion)

 Advantages:

o Normal aging appear later than in HFA

o More resistant to optical degradation (from Blur, cataract, etc)

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 Disadvantages:

o Still experimental

o Lack of standardization

o Not too patient- friendly

Motion Perimetry
 Principle:

o M-cells and large neurons may be damaged early in glaucoma leading to


degradation in motion perception

o Involves detection of direction of motion of small dot / line stimulus

o Detects the min displacement required to detect movement (Motion displacement


thresholds are found elevated in pt at risk of glaucoma with normal visual fields)

 Another technique for motion perimetry uses random pattern of light and dark dots, ‘snow
pattern’, this portion is than moved in a particular direction, pt detects the direction of
movement

 Minimum percentage of dots (coherence) needed to detect the direction is determined

 The central 21 degrees of the visual field are tested

 To complete a test takes 3-8 minutes

 Moving stimuli are vertical bars as described in detail by Fitzke et al

 Test randomly examines 16 locations with one displacement distance (amplitude) and then
the procedure is repeated five times

 Motion sensitivity score are based on the percentage of response from a total of
84 movements over 14 locations (excluding two close points to the blind spot)

Multifocal Electroretinography
 objectively establishes the loss of retinal function

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 focal responses are obtained from a large number of retinal patches, and topographic
maps of dysfunctional areas are derived.

 All focal areas are independently and concurrently stimulated as the ERG signal is derived
from the cornea by means of a contact lens electrode.

 103 hexagonal patches displayed on a video monitor stimulate the central 50 degrees of
the patient's visual field

 focal stimulation consists of pseudorandomly presented flashes.

Optic nerve

 optic nerve head is defined as the distal portion of the optic nerve that is directly
susceptible to intraocular pressure (IOP) elevation.

 average disc area: 2.56 mm2 (different studies)

 diameter: mean of 1.88 mm vertically and 1.77 mm horizontally

 diameter of the nerve expands to approximately 3 mm just behind the sclera, where the
neurons acquire a myelin

Three major alterations of glaucomatous damage are

1. thinning of the retinal NFL

2. posterior excavation and enlargement of the central cup

3. posterior outward rotation of the lamina cribrosa with cupping.

ONH vasculature

1. Surface layer: arteriolar branches of the central retinal artery

2. Prelaminar region: Peripapillary choroidal vessels

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3. Laminar region : Arterial circle of Zinn-Haller/ SPCA

4. Retro laminar region: contributions from the retinal and ciliary circulation

 circle of Zinn-Haller: Medial and lateral perioptic nerve short posterior ciliary arteries
anastomose to form an elliptical arterial circle around the optic nerve, only in 75%

 Supportive structures of the optic nerve head:

o internal limiting membrane of Elschnig: continuous with the internal limiting


membrane of the retina

o central meniscus of Kuhnt: central thickening of the internal limiting membrane

o intermediary tissue of Kuhnt: separates the nerve from the retina (muller cells)

o border tissue of Jacoby: separates the nerve from the choroid

o border tissue of Elschnig: rim of connective tissue occasionally extends between


the choroid and optic nerve tissues, especially temporally

o lamina cribrosa

o meningeal sheaths: posterior to globe

Factors influencing ONH circulation

 The blood flow depends upon three parameters: (1) vascular resistance (2) blood pressure,
and (3) IOP.

 To calculate the ONH blood flow, the following formula is used: BF= PP/ R

 Perfusion Pressure PP= MABP – IOP [MABP= DBP + 1/3(SBP-CBP)]

 Vascular Resistance

o Autoregulation of blood flow is to maintain a relatively constant blood flow,


capillary pressure and nutrient supply in spite of changes in perfusion pressure.
Evidences show that blood flow in both the retina and ONH is autoregulated by
neural, endothelial and myogenic mechanisms.

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o Vascular endothelial vasoactive agents play an important role in modulating the


local vascular tone. The vascular endothelial cells release various known
endothelial vasoactive agents, which include prostanoids, nitric oxide, endothelins,
angiotensins, oxygen free radicals, smooth muscle cell hyperpolarization,
thromboxane A2 and other agents.

 Retinal circulation has autoregulation while choroidal circulation has neural control.

Clinical evaluation

 increasing evidence that alterations in the ONH are the earliest signs of primary open-
angle glaucoma (POAG), and that visual field studies are more useful later in the disease
process

 Slit-lamp funduscopy

 Monocular examination direct ophthalmoscope

 Photographs of the ONH

 clinician’s disc drawings

 Disc Damage Likelihood Scale (DDLS) [Spaeth and co-workers]

o radial width of the neuroretinal rim measured at its thinnest point. The unit of
measurement is the rim/disk ratio,

o average size 1.5-2.0 mm2

 Armaly back in 1970 introduced the idea of cup disc ratios (CDR).

Optic disc changes in glaucoma

Intrapapillary disc changes

8: two aspects of the optic disc (its size and shape); two aspects of the NRR (its size and
shape); three aspects of the optic cup (its size and configuration, and the cup:disc ratio); and
the relative position of the central retinal
vascular trunk.

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1. Optic disc size: 2.1–2.8 mm2, smallest 5° aperture

2. Optic disc shape: only correlates with the extent of corneal astigmatism

3. Neuroretinal rim size:

4. Neuroretinal rim shape: characteristic vertical oval shape of the optic disc and the
horizontal oval shape of the optic cup. Neuroretinal rim loss manifests earliest in the
inferotemporal and superotemporal regions, followed by the temporal sector, and
lastly the nasal rim.
5. Optic cup size:
6. Optic cup configuration and depth
7. Cup:disc ratios: vertical cup:disc ratio increases faster than the horizontal ratio
Quigley found up to 40% of some nerves’ axonal mass could be lost without having any
recognizable field defect on Goldmann perimetry.
8. Position of central retinal vessels and branches

Peripapillary disc changes

4: optic disc splinter hemorrhages; changes in the RNFL; variations in the diameter of retinal
arterioles; and patterns of peripapillary choroidal atrophy (PPCA).
1. Optic disc hemorrhage
2. Nerve fiber layer defects: Hoyt and co-workers, visible loss of optic nerve axons from
any form of optic atrophy.
3. Diameter of retinal arterioles: Diffuse narrowing of the retinal vessels
4. Peripapillary choroidal atrophy:
a. more peripherally zone alpha is characterized by irregular
hypopigmentation/hyperpigmentation. It suggests superficial retinal pigment
epithelial changes.

b. Zone beta is located closer to the optic disc border and is usually more
distinctive because of its visible sclera and visible large choroidal vessels. It
chorioretinal atrophy. When both zones are present, zone beta is always
internal.

Subtypes of glaucoma by optic nerve head appearance

1. High myope

2. Focal normal pressure (focal ischemic)

3. Age-related atrophic POAG (senile sclerotic)

4. Juvenile OAG

5. POAG (generalized enlargement)

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Specific subtypes of glaucomatous damage

(A) Type 1 – focal ischaemic; (B) type 2 – myopic; (C) type 3 – senile sclerotic; (D) type 4 –
concentrically enlarging

 The Disc Damage Likelihood Scale (DDLS)

o way to describe quantitatively and simply the changes that occur in the Optic
Nerve Head (ONH) (the disc).

o It is used to quantify the health of the optic disc, specifically as it relates to


glaucoma.

o two characteristics of the disc: (1) the width of the neuroretinal rim and (2) the
size of the optic disc. The DDLS scale goes from 1 to 10, 1 being the most normal
and 10 the most pathologic.

o First, one measures the size of the optic disc and classifies the disc as small,
average, large, or very large. Small is less than 1.5 mm in height, average between
1.5 and 2.0 mm in height, large between 2 and 3 mm in height, and very large
greater than 3 mm

o Next, one looks for where the neuroretinal rim is the narrowest. (“thin” is the
wrong word) The narrowest rim would be 0 and the widest rim possible would be
.5.

o Discs with DDLS of 6 or more are never normal.

Optic nerve imaging

 structural glaucomatous changes which usually precede functional deterioration (visual


field loss)

 Pre-perimetric diagnosis

 Progression

1. confocal scanning laser ophthalmoscopy (CSLO)HRT; ONH

2. optical coherence tomography OCT: ONH, RNFL, Macula

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3. scanning laser polarimetry (SLP)  GDX; RNFL

Stereophotography

 most widely used imaging technique and is considered the gold standard for
documentation of glaucomatous optic neuropathy (GON)

 two photographs in sequence

o manually repositioning the camera

o using a sliding carriage adapter (Allen separator)

o by taking two photographs simultaneously with two cameras that utilize the
indirect ophthalmoscopic principle (Donaldson stereoscopic fundus camera)

o a twin-prism separator can be used

 digital stereochronoscopy

 Advantage

o ability to document parameters that cannot be quantified  disc hemorrhages,


peripapillary atrophy, and pallor

 Disadvantage

o interpretation remains subjective

o increased variability and limited usefulness over time

o media opacities, such as cataracts, or a poorly focused photograph can inhibit


optimal analysis

Confocal scanning laser ophthalmoscopy (CSLO)


 In 1980, R. H. Webb; created a laser light source device to illuminate the fundus and
produce an image of it on a television monitor---Flying Spot TV ophthalmoscope. It was
later termed as scanning laser ophthalmoscope (SLO)

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To improve the contrast and resolution of the SLO, the confocal mode is used. Confocality
of the system is achieved by placing a pinhole in front of the detector, which is conjugate
to the laser focus.

 Heidelberg retina tomography has three generations: HRT (1991), HRT II (1999) and HRT
3.

 three-dimensional images of the optic disc

 principle:

o spot illumination and spot detection

o diode laser is aimed through a pinhole onto the retina. The light reflected passes
through a second pinhole into a detector, which transfers the maximum intensity
of light at a given point to create an image

o The instantaneous volume of tissue from which reflected light is accepted by the
confocal aperture is called a voxel, and the smaller the aperture, the smaller the
voxel and the higher the resolution of the image.

 670 micron diode laser

 bi-dimensional image (15 x 15 degrees); total of 64 sections, each done with 1/16 mm of
depth

 optical section is composed of 384 x 384 points

 transverse resolution is 10 microns and the axial resolution is 300 microns.

 3 sets of scans done  data are combined to produce a pseudo-three-dimensional image


of the nerve head

 image is taken  Optic nerve disc delineation by operator  ‘best-fit’ ellipse

 The reference plane is located 50 microns posterior to the mean height along a 6° arc of
the contour line at the temporal inferior sector.

 Data based on OHTS

 Classification of the eye is done with Moorefield’s regression analysis in HRT or other
discriminating method in HRT II, or with neural network analysis in HRT 3.

 printout formats currently available: initial report, follow-up report and OU report

Components of the HRT report

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1. Patient data

2. Topography image: red indicates the cup, green and blue indicate neuroretinal rim
tissue. Blue indicates sloping rim.

3. Reflectance image: it is overlaid with Moorfields analysis

4. Retinal surface height variation graph: retinal height along the contour line and of the
thickness of the nerve fiber layer. double-hump  superior and inferior nerve fiber layer

5. Vertical and horizontal interactive analysis: disc steepness, presence of sloping,

6. Stereometric analysis: 14 nerve parameters in HRT II

7. Moorfields regression analysis (MRA):

red x: below the 99.9% prediction interval


yellow checkmark: between the 95% and 99.9%
green checkmark: within the 95%

8. Glaucoma probability score (GPS): in HRT 3

Evaluating scan quality: Image quality is expressed by a "topography standard deviation (TSD)" value.
do not analyzing scans with a SD value greater than 40.

Strengths:
 rapid and simple operation
 specificity from 75% to 95% and sensitivity from 51% to 97%.

Limitations:
 contour line drawn by the operator.
 overestimate rim area in small optic nerves and to underestimate rim area in large nerves

Change analysis with HRT


1. Trend analysis
2. topographic change analysis (TCA): automatically done at 3rd scan

Top five Parameters in HRT II: Rim area, Rim volume, Cup shape measure, Height variation
contour, Mean RNFL Thickness

HRT 3:
 larger ethnicity-specific normative database.

 reduces technician dependence by producing automated results of the contour line as


described by Swindale et al
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Optical coherence tomography (OCT)

 Carl Zeiss, 1991


 ONH, RNFL and macula
 Principle: intensity and echo time delay of back-scattered and back-reflected light
from the scanned tissues
 super luminescent 810 or 850 nm diode laser
 best axial resolution: 3–4 microns
 OCT 1, OCT 2, OCT 3 or Stratus OCT, and OCT 4/ Spectral domain & OCT fourier domain
 1.73 mm radius circle

Peripapillary scan
3.4 mm circular scan
thickness values are provided for the four quadrants

Macular scan
six linear scans in a spoke pattern configuration.
The linear scans are spaced 30° apart

ONH scan
‘star’ or ‘spoke’ pattern scan, 4 mm

Components of the oct report

1. RNFL thickness average analysis:

Characteristic double hump appearance

2. Macular analysis

3. Optic nerve head analysis

Quality assessment

1. Peripapillary circular scan centration

2. Signal strength value: not lower than 5

3. Homogeneity of the RNFL scan

4. OCT algorithm

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Strengths:
 most versatile
 best axial resolution
 the only technology capable of imaging the RNFL, macula and ONH.

 GCC of Macula: The higher speed and resolution of FD-OCT improved the repeatability of
macular imaging compared with standard TD-OCT. Ganglion cell mapping and pattern
analysis improved diagnostic power. The improved diagnostic power of macular GCC
imaging is on par with, and complementary to, peripapillary NFL imaging. Macular
imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for
tracking glaucoma progression.

 sensitivity ranging from 61% to -84% and specificity from 85% to 100%.

Limitations:
 its normative database
 transverse resolution
 originated from one set of scans and not a series (three) of sets of scans as in HRT
 not yet developed robust programs for the longitudinal evaluation of glaucomatous
progression

Scanning laser polarimetry

 GDX

 Latest: GDX VCC  GDX variable corneal compensator

 measure peripapillary RNFL thickness

 principle of birefringence: In the retina, the parallel arrangement of the microtubules in


retinal ganglion cell axons causes a change in the polarization of light passing through
them. The change in the polarization of light is called retardation, which can be
quantified by a built-in ellipsometer. The retardation value is proportionate to the
thickness of the RNFL.

 2.8 mm and 3.2 mm diameter circle, 0.4 mm band

 diode laser 780 nm

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 VCC: to account for the variable corneal birefringence in patients, it uses the
birefringence of Henle’s layer in the macula as a control for measurement of corneal
birefringence

 ECC: enhanced corneal compensator

Components of the GDX report

1. Patient data and quality score: ideal quality score is from 7 to 10


2. Fundus image: reflectance image of the posterior pole 20 x 20 degrees
3. RNFL thickness map
4. TSNIT graph
5. TSNIT symmetry graph
6. TSNIT comparison graph and serial analysis graph
7. Deviation from normal map:
8. TSNIT parameters
9. Nerve fiber indicator (NFI): proprietary value, origin not published, [range 1 (normal)
to 100 (glaucoma)]
 <30: low likelihood of glaucoma
 30–50: glaucoma suspect
 >50: high likelihood of glaucoma.

Strengths

 rapid and simple imaging of peripapillary RNFL

 sensitivity ranging from 80% to 92% and specificity from 66% to 98%

 Progression in the GDx is documented using guided progression analysis

limitations

 only provide RNFL data

 Corneal surgery will induce error

 Macular pathology is likely to impede GDX scanning

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Retinal Thickness Analyzer

 RTA; Talia Technology, Mevaseret Zion, Israel

 computes macular thickness and displays 2D-3D images

 green, 540-nm HeNe laser slit beam to image the retina.

 Nine scans with nine separate fixation targets are taken. The compositions of these scans
cover the central 20 degrees (measuring 6 × 6 mm) of the fundus.

 highest concentrations of retinal ganglion cells reside in the macula, and retinal ganglion
cells are significantly thicker than their axons (which comprise the NFL), macular
thickness may be a good measure of glaucoma.

 RTA and OCT may both be used for macular thickness assessment.

 Limitations

o requires a 5-mm pupil size and is limited by eyes with numerous floaters or
significant media opacity.

o more sensitive to nuclear sclerotic cataract

Posterior Pole Asymmetry Analyser


 Latest in sprectalis.

 Macular vulnerability area.

 Looks like corneal topography colour maps..!!

 Considered to be most most most sensitive..!!

Blood Flow in Glaucoma

 other than IOP, Vascular risk factors, including systemic blood pressure, ocular perfusion
pressure, disc hemorrhage, and migraine, have been linked to glaucoma.

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Scanning Laser Ophthalmoscope Angiography


 replacing the incandescent light source with a low-power argon laser beam to achieve
better penetration through lens and corneal opacities

 Laser frequency according to FA or ICG

 measurements such as arteriovenous passage time (AVP) and mean dye velocity.

 Fluorescein SLO Angiography

o Evaluation of retinal hemodynamics

o AVP allows localization of measurements to a specific retinal quadrant

o Mean dye velocity: evaluates the average speed of blood flowing through large
retinal vessels

o mean transit time (MTT): measures the amount of time that blood spends in the
retinal vasculature

 Indocyanine Green SLO Angiography

o Evaluation of choroidal hemodynamics

o Two areas adjacent to the optic disk and four areas surrounding the macula, each
25 × 25 pixels, are selected

o Area dilution analysis: measures the brightness of these six areas and determines
the time required to reach predefined levels of brightness (10% and 63%)

Color Doppler Imaging


 retrobulbar vessels, specifically the ophthalmic, central retinal, and posterior ciliary
arteries.

 B-scan with superimposed color representation of blood flow velocity

 velocity data are graphed against time, and the peak and trough are identified as the
peak systolic (PSV) and end diastolic (EDV) velocities.

 Pourcelot's resistive index (RI) is a measure of downstream resistance that is derived


from the PSV and EDV.

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Measurement of Ocular Pulsation


 modified pneumotonometer or a dynamic contour tonometer is used to assess pulsatile
ocular blood flow (POBF)

 POBF device provides real-time measurement of IOP approximately 200 times per second

Confocal Scanning Laser Doppler Flowmetry


 Heidelberg retinal flowmeter (HRF) is a commonly utilized confocal scanning LDF device

 790-nm laser to scan each pixel within the targeted area of the retina.

Spectral Retinal Oximetry


 measurement of the oxygen saturation of hemoglobin in retinal vessels

Doppler Ocular Coherence Tomography

Primary angle-closure glaucoma

 congestive/non-congestive and compensated/uncompensated.

 acute, subacute, and chronic

 International Society of Geography and Epidemiology of Ophthalmology (ISGEO)


Terminology

 facilitates meaningful comparison

 addresses both the prognosis for progression, and the stage-appropriate need for treatment.

o PAC disease relies on three simple categories: IOP measurement, gonioscopy, and disc
and visual field evaluation.

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1. PAC suspect:

o greater than 270° of irido-trabecular contact

o absence of PAS

o normal IOP, disc, VF

2. PAC

o greater than 270° of irido-trabecular contact

o PAS

o Increased/ normal IOP

o normal disc, VF

 PACG

o greater than 270° of irido-trabecular contact

o PAS

o Increased IOP

o abnormal disc, VF

Mechanisms

RECENT TRENDS: Angle closure is characterized by iris apposition to the trabecular


meshwork. The mechanisms of this anatomic abnormality can be categorized at four
structural levels:

1. The pupillary margin (e.g., pupillary block)

2. The ciliary body (e.g., plateau iris and iridociliary cysts)

3. The lens (e.g., phacomorphic glaucoma)

4. Posterior to the lens (e.g., malignant glaucoma)

1. pupillary block glaucoma


2. plateau iris: configuration and syndrome (ciliary body anomalies)
3. phacomorphic glaucoma (lens-induced obstruction)

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1. pupillary block glaucoma

Demographic risk factors


Age: greatest frequency in the sixth and seventh decades

Gender: 2–3 times more commonly in women

Heredity: sporadic, AD, AR

Refractive error: much higher in individuals with hyperopic eyes


Miscellaneous factors: winter, low levels of illumination, increased cloudiness, changeable weather, and
low sunspot activity

Ocular risk factors and mechanisms


 Shallow anterior chamber both centrally & peripherally

 Decreased anterior chamber volume

 Short axial length of the globe

 Small corneal diameter

 Increased posterior corneal curvature

 Decreased corneal height.

 Anterior position of the lens with respect to the ciliary body

 Increased curvature of the anterior lens surface

 Increased thickness of the lens

 More anterior insertion of the iris into the ciliary body, giving a narrower approach to the angle
recess, and possible anomalies of iris histology.

 Thinning of the ciliary body is reportedly associated with anterior movement of the lens, increased
lens thickness and decreased anterior chamber depth.

 It is estimated that central anterior chamber depth decreases 0.01 mm/year

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2. Plateau Iris
 Barkan: 20% of eyes with ‘noncongestive’ forms of angle-closure glaucoma were atypical
in that they had normal central anterior chamber depths, little bombé, and minimal
pupillary block

 Shaffer and Chandler: plateau iris

 Wand: plateau iris configuration and plateau iris syndrome

Plateau iris configuration


 narrow angles or angle closure in an eye with a ‘normal’ central anterior chamber depth
on slit-lamp examination, and a flat iris plane from pupil to periphery
 Tornquist: plateau, on gonioscopy, iris appears flat from the pupillary margin to the
periphery
 double hump or S-sign: peripherally elevated roll of iris
o best seen in Koeppe gonioscopy, where the forwardly positioned ciliary processes
prevent the peripheral iris from falling backward in the supine
o on–off indentation maneuver of compression gonioscopy at the slit lamp

 In many cases, plateau iris configuration is accompanied by some degree of pupillary


block, which exacerbates the problem. Therefore, it is often not possible on clinical
grounds to differentiate between a pupillary block PAC and a plateau iris configuration
embarrassing the angle until after an iridotomy has been performed. In conditions
precipitated by pupillary block, iridotomy will cause the iris to fall back and the
peripheral chamber to deepen; whereas in plateau iris, the peripheral angle remains
unchanged
 Mydriasis if required: one drop of 0.5% tropicamide or 2.5% phenylephrine. Always reverse
with dipiperazole.

Plateau iris syndrome


 angle closure in the presence of plateau iris configuration following a patent iridotomy
 angle closure occurs because the ciliary processes are rotated forward (UBM is the
mainstay Dx)
 Lowe and Ritch: incomplete form of PIS  iris is not as far forward as in the complete
syndrome;
 diagnosis is usually not made until after a successful iridotomy; at that point, little
significant opening of the chamber angle and elevated IOP (especially after pharmacologic
dilation) may signal its presence
 differential diagnosis
o extensive PAS due to any cause
o imperforate or occluded iridotomy
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o multiple cysts of the iris or ciliary body


o ciliary block glaucoma (aqueous misdirection or malignant glaucoma)
 treatment
o laser iridotomy
o peripheral iridoplasty: ALPI is useful to open appositionally closed angle. Typical
treatment includes approximately 20 to 30 spots of argon laser placed in the far
periphery over 360 degrees. Filtration surgery may ultimately become necessary in
some patients.
o miotic agents can be tried to minimize pupillary dilation

Pseudoplateau iris

 Primary cysts of the iris and ciliary body

3. phacomorphic mechanism

 abnormal lens either compromises the lens–iris channel (pupillary block) or mechanically
pushes the peripheral iris forward into the angle structures.

 age-related cataract or rapidly with a traumatic, swollen cataract.

 The definitive treatment for this condition is cataract extraction.

 Angle-closure glaucoma from a swollen lens

o idiosyncratic response to a variety of systemic medications: sulfonamide drugs and their


derivatives, the carbonic anhydrase inhibitors, thiazide diuretics, tetracycline,
prochlorperazine, spironolactone, phenformin, acetylsalicylic acid, and the anticonvulsant
topiramate (Topamax)

o blurred vision at distance, and are noted to have acquired bilateral myopia, with shallow
anterior chambers and angle closure

 CF

o unilateral blurring and ocular pain to extreme ocular or periocular pain, headache,
nausea, vomiting, and diaphoresis.

o Acute attacks may be precipitated by pharmacological mydriasis, dim illumination,


stress, or prolonged near work.
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o conjunctival injection, corneal epithelial edema, mid-dilated pupil, a shallow


anterior chamber

o intraocular pressure may be as high as 70

o Glaukomflecken: flecks of anterior subcapsular opacities.

 Treatment

o Topical beta-blocker, cholinergic agent, and carbonic anhydrase inhibitor, and


systemic acetazolamide (i.v. 250 to 500 mg

o osmotic agent (e.g., i.v. mannitol 1 to 2 g per kg over 45 minutes)

o argon laser peripheral iridoplasty (ALPI) can be applied from 180 degrees to 360
degrees

o Once the corneal edema has cleared, a laser peripheral iridotomy (LPI) can be
performed to prevent recurrent attack.

o LPI of the fellow eye

Q: Acute Angle Closure

 Precipitating factors: Emotional stress, near work in dim lit conditions, watching a movie
in a dark theater, acute hyperglycemia, pharmacological dilation, general anesthesia, and
rarely ciliary body tumors/cysts, trauma, uveal melanoma and secondaries to the eye, can
precipitate an acute angle closure attack.

 Drug induced angle closure glaucoma : Drugs like topiamate (antiepileptic) and paroxetine
(antidepressant) can induce bilateral angle closure attacks probably due to cilio retinal
effusion.

 Symptoms : Blurred vision with haloes around lights, severe pain in eyes with redness and
frontal headache on the affected side, nausea vomiting and rarely palpitations with
abdominal cramps. In some patients the attack may be associated with minimal pain and
no congestion.

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 Signs : Elevated IOP > 45mmHg, corneal edema, shallow or flat anterior chamber, circum
ciliary congestion, pupil is mid dilated with reduced or no reactivity. Fundus shows disc
edema, with venous congestion and splinter hemorrhages or it may be a normal disc or
may show glaucomatous excavation. There may be some inflammation and rarely a
hypopyon if the attack is long standing.

 Differential diagnosis

o Phacomorphic glaucoma

o Neovascular Glaucoma

o Glaucomatocyclitic Crisis:

o Acute anterior uveitis:

 Management

o Mannitol is used as 20% solution. It acts over ½ - 1hour (5-7 ml/kg body wt)

 actions via osmoreceptors in the brain and the local actions of shrinking the
vitreous and pulling back the iris – lens diaphragm.

o syrup glycerol used as 50% solution. Lime juice is added to make it palatable.

o intravenous acetazolamide should be considered if available. Oral acetazolomide 500 mg is


given followed by three times a day

o pilocarpine drop installation

o Special Maneuvers

 compression gonioscopy

 alternative is to indent the central cornea with cotton tipped applicator

 Argon laser iridoplasty

o Definitive Management

 Iridotomy

 prophylactic iridotomy in the fellow eye

 Trabeculectomy

 surgical iridectomy

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Secondary angle-closure glaucoma

Narrowing of the angle due to Pulling

Contracture of membranes in:

• Neovascular glaucoma

• ICE syndrome

• Posterior polymorphous dystrophy

• Penetrating and non-penetrating trauma.

Narrowing of the angle due to pushing

With Pupillary Block

• Phacomorphic glaucoma

• Ectopia lentis

• Posterior synechiae due to uveitis.

Without Pupillary Block

• Ciliary block glaucoma

• Phacomorphic glaucoma

• Ectopia lentis

• Intraocular tumours like malignant melanoma/ retinoblastoma

• Anterior rotation of the ciliaty body following scleral buckling/PRP.

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Phacomorphic Glaucoma
 angle closure secondary to a mature or hypermature lens

 Pathophysiology

o crowding of the anterior segment structures pupillary block may cause high IOP.
Later, the growing size of the lens presses forward on the iris in the periphery,
blocking off outflow through the trabecular meshwork.

o Mapstone hypothesis of pupillary block.

 only 57% of 49 patients with phacomorphic glaucoma attained visual acuity of 6/12 or
better

 CF

o pupil may be mid-dilated with or without iris bombé, and gonioscopy reveals angle
closure.

 Mx

o Medical therapy to suppress aqueous formation

o NO MIOTICS

o Iridotomy may open up the angle, lower the IOP, and allow the eye to quiet before
cataract removal

o definitive treatment for phacomorphic glaucoma is removal of the intumescent


lens

Neovascular Glaucoma

 Neovascular glaucoma (NVG), is a type of secondary glaucoma which results due to growth
of new blood vessels on the iris and the anterior chamber angle. It is one of the most
intractable types of secondary glaucoma, and if not recognized and managed early, can
rapidly lead to vision loss.

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 Pathogenesis:

 In 97% of cases the cause for the development of new blood vessels in the anterior
segment, is underlying retinal ischemia. Only in 3% of cases, other causes like chronic
anterior segment inflammation, can contribute to the new vessel development.

o Ischemia

o Release of angiogenesis factors ( PRE RUBEOSIS STAGE)

( FGF, VEGF, angiogenin, TGF, interferon, tumor necrosis factor-a, and platelet
derived growth factor)

o New blood vessels on the iris and angle ( RUBEOSIS IRIDIS/PRE GLAUCOMA STAGE)

o open angle but occlusion of aqueous outflow( NVG-OAG)

o fibrosis with NV, closed angle, Ectropion uveae( NVG-ACG)

Underlying retinal causes for NVG:

 Vascular disorders

o Central retinal vein occlusion: The most common cause for NVI. The overall
incidence of NVI in all CRVO cases is 12% to 30%. NVI also more commonly occurs in
the ischemic type of CRVO. One thirds of CRVO cases are ischemic, and of them
two thirds develop NVG. NVG usually develops after three months of the vein
occlusion.

o Diabetic retinopathy: one third of patients with NVI have Diabetic retinopathy.
More common in aphakic eyes, and pseduophakic eye with posterior capsule
opening.

o Central retinal artery occlusion

o Branch retinal vein occlusion

o Carotid occlusive disease

o Ocular ischemic syndrome (OIS) encompasses the ocular signs and symptoms that
result from chronic vascular insufficiency. Severe atherosclerotic disease of
unilateral or bilateral internal carotid arteries, or, at the bifurcation of the

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common carotid arteries, results in OIS. 5% of severe carotid artery stenosis cases
present with OIS.

 Ocular disease

o Uveitis

o Retinal detachment

o Persistent hyperplastic vitreous

 Surgery and radiation therapy

o Retinal detachment surgery

o Vitrectomy

o Radiation

 Trauma

 Neoplastic diseases

o Retinoblastoma*

o Melanoma of the choroid

 Clinical findings:

Symptoms: In the early stages of NVG, where NVI and or NVA are present but IOP is not
raised, the patient does not have any symptoms. Once the IOP is increased, symptoms
attributable to the raised IOP, and its sequelae are seen. The patient may have pain, and
redness in the involved eye, accompanied by a decrease in vision. Corneal epithelial and
stromal edema if present can give rise to photophobia and watering, in the affected eye.

Signs: Undilated anterior segment examination under high magnification can help detect fine
NVI at the pupillary border. This should be compulsorily done in all cases of CRVO, PDR, and
when other systemic or ocular diseases which can cause NVI are present.

Gonioscopy in the affected eye in crvo can reveal presence of NVA. Gonioscopy should also be
done in all cases of PDR, to detect fine NVA if present. NVA can be distinguished from normal
angle vessels by the fact that these are fine and cross the Trabecular meshwork, unlike
normal angle vessels which do not cross the scleral spur.

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In advanced cases, synechial closure of the angle, may be present, with none of the angle
structures being seen.

Ectropion uveae may be seen as a result of the contraction of the fibro vascular membrane ,
which pulls the iris pigment epithelium, anteriorly.

Pupillary reaction may be sluggish and a RAPD may be seen in eye with coexistent retinal
pathology, or if extensive glaucomatous disc damage has occurred.

Dilated retinal exam in all cases with NVI/NVA is mandatory as the underlying cause can be
detected, in most cases by fundus examination.

In advanced stages of NVG, IOP is raised, and secondary to the raised IOP, one may see
corneal stromal, and epithelial edema. Visual acuity is grossly reduced.

Anterior segment flare may be present, because of the compromised blood ocular barrier, due
to the presence of NVI.

Pupil is fixed in the mid dilated position, with Ectropion uveae, and does not react to light.

Hyphaema may also be seen due to bleeding into the Anterior chamber due to the NVI.

Investigations:

- Fundus fluorescein angiogram- to assess retinal ischaemia

- Electroretinogram – to assess for retinal ischemia. The electroretinogram measures a


mass electrical response of the retina, allowing for assessment of the retinal periphery, which
cannot be seen with fluorescein angiography.

- Iris angiography- in cases of doubtful NVI, to confirm the diagnosis

- B scan ultrasound- if view of retina not possible due to media opacity/ corneal edema.

Systemic:

- FBS and PPBS- to r/o Diabetes Mellitus.


- Carotid Doppler in case OIS is suspected- NVG in absence of either PDR, or CRVO.

Differential Diagnosis:

1) Fuchs Heterochromic Cyclitis.


2) Acute Angle closure Glaucoma.
3) Other Inflammatory Glaucomas.

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The management of NVG, is two pronged.

- Management of the underlying condition which led to development of NVI/NVA- e.g-


CRVO, PDR, OIS, etc.
- Management of the NVG per se- IOP and Pain management.
Management of the underlying condition is crucial to effectively control IOP, and preserve
vision in NVG.

Pan Retinal Photocoagulation:

Ablation of retinal tissue is known to cause a decrease in the release of angiogenesis factors,
and leads to regression of NVI/ NVA. If done early in the natural history of the disease, before
synechial closure develops, PRP itself can help in reduction of IOP. The presence of extensive
synechiae will warrant additional medical/ surgical methods to control the IOP.

In some instances where media is hazy, PRP may still be performed with the use of an indirect
ophthalmoscopic delivery system. When adequate PRP (1200–1600 laser spots) is not
achievable, other modalities should be considered, including panretinal cryotherapy and
transscleral diode laser retinopexy.

Management of the IOP:

Medical management of raised IOP in cases of NVG, involve use of

- Topical antiglaucoma medications- Beta blockers- Timolol maleate 0.5%, or Betaxolol


0.5% bd, or Brimonidine, or Dorzolamide eye drops.
- Prostaglandin analogues and Pilocarpine are contraindicated in the setting of NVG,
as they tend to further compromise the blood ocular barrier, and are not effective in
NVG to bring down IOP
- Systemic antiglaucoma medications- Acetazolamide 250 mg upto qid, and use of Oral
Glycerol, or Intravenous Mannitol can help in decreasing IOP, and clearing up the
cornea to enable pan retinal photocoagulation.
- Atropine 1% bd, can stabilize the blood ocular barrier, and decreases pain associated
with NVG.
- Topical steroids can also help stabilize the blood ocular barrier, and reduce pain.
Initial medical management helps control IOP, and enables performing PRP.

In case of raised IOP despite adequate PRP/ other retinal ablation, the treatment options are
as follows:

- Supplemental medical management with topical anti glaucoma medications.


- If uncontrolled despite this,( maximal medical management)
o Trabeculectomy with Mitomycin- C
o Implantation of Glaucoma Drainage devices- Ahmed Glaucoma Valve, Molteno
Valve, Baerveldt valve etc.
o Cyclodestruction:
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 Cyclocryotherapy.
 Trans scleral cyclo photocoagulation.
 Endoscopic cyclophotocoagulation.

Anti VEGF treatment with various Intravitreal drugs e.g: Bevacizumab, Pegatanib, VEGF
trap, Ranibizumab can cause regression of NVI/ NVA. The use of these anti angiogenic
agents, is to obtain a therapeutic window, in which one can perform PRP, or other forms of
retinal ablation.

ICE Syndrome
 Classically unilateral (if bilateral, first think of Reiger’s syndrome with late
presentation)

 middle-aged women

 Pathophysiology

o The corneal endothelium grows abnormally over the anterior chamber angle
covering the iris, which gives the iris the characteristic findings.

o Initially, the anterior chamber angle is open but occluded.

o Over time, the endothelial membrane contracts, secondarily closing the angle and
distorting the pupil and iris.

 CF

o usually asymptomatic in the early stages

o decreased vision in one eye and irregular appearance of the iris

o fine, beaten-metal appearance in the endothelial layer unilaterally

o Essential iris atrophy—MC, there are areas of thinning and a displaced and
distorted pupil as the endothelial membrane contracts, pulling on the iris.

o Chandler's syndrome—the iris changes are nearly identical to those of essential


iris atrophy, but there is a greater degree of corneal edema, and the corneal
findings are more apparent.

o Cogan–Reese syndrome: Iris Nevus—the iris has a flattened appearance with small
nodules of normal iris tissue poking through holes in the endothelial layer, giving
the appearance of a mushroom patch.
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o broad and irregular peripheral anterior synechiae occluding some or all of the
angles may be seen.

o glaucomatous optic nerve cupping as the intraocular pressure rises.

 Mx

o medical management is not adequate

o trabeculectomy with an antifibrotic agent, a glaucoma drainage implant device,


and cyclodestructive procedures.

o Corneal transplantation

Aqueous Misdirection Syndrome (Malignant Glaucoma)


 usually occurs following penetrating surgery of the eye

 1951, Chandler: 4% incidence after glaucoma surgery, now decreased

 Pathophysiology

o intervention in the eye changes the direction of aqueous humor flow  aqueous
goes into the vitreous  increased IOP and flat AC

 CF

o blurry vision, pain, Increased IOP

o shallow AC, NO IRIS BOMBE

o bleb is usually low with no evidence of wound leak.

o Corneal edema

o The hallmark of the disease is that there are no choroidals.

o UBM shows flattening of the ciliary body processes

 Management

o medically with topical cycloplegics and aqueous suppressants

o key component to resolving the attack is disruption of the anterior hyaloid face by
lasers or PPV

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Primary open angle glaucoma

 chronic, progressive, anterior optic neuropathy that is accompanied by a characteristic


cupping and atrophy of the optic disc, visual field loss, open angles, and no obvious
causative ocular or systemic conditions.
 60–70% of the cases seen in the United States.
 Prevalence: 0.5–1% of the population
 Incidence: 1.2% in the 40–49 age group to 4.2% in those over 70
 Genetics
o Mutations at 15 loci in the human genome have so far been identified as associated
with POAG and are designated primary open angle glaucoma-1A (GLC1A) to GLC1O.

o Four susceptible genes have been identified: the MYOC gene (chromosome 1q21-
q31), coding for the glycoprotein myocilin that is found in the trabecular meshwork
and other ocular tissues, the OPTN gene on chromosome 10p, which codes for
optineurin, the WDR36 gene on chromosome 5q22, and the NTF4 gene on
chromosome 19q13.3. Among them MYOC is the most frequently mutated gene in
POAG

 Variables

o Intraocular pressure

o Age

o Gender: males had a higher prevalence

o Race: more prevalent in blacks than in whites

o Socioeconomic factors

o Refractive error: Myopia has been associated with POAG

o Corneal thickness: thin cornea is a risk factor for conversion from ocular hypertension
to open-angle glaucoma

o Heredity:

 If a parent has POAG, the risk of the child developing POAG is 4%

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 But if a sibling has POAG, the chance of the other sibling developing POAG is
10%

o Systemic factors: diabetes mellitus (Blue Mountains Eye Study in Australia, the
Rotterdam Study, and the Beaver Dam Eye Study in Wisconsin.)

 Pathophysiology

 Diminished aqueous humor outflow facility

o An obstruction of the trabecular meshwork by foreign material


o A loss of trabecular endothelial cells
o A reduction in pore density and size in the inner wall endothelium of Schlemm’s
canal.
o A loss of giant vacuoles in the inner wall endothelium of Schlemm’s canal.
o A loss of normal phagocytic activity.
o Disturbance of neurologic feedback mechanisms

 Altered corticosteroid metabolism

 Dysfunctional adrenergic control

 Abnormal immunologic processes

 Oxidative damage

 Other toxic influences: TGF beta2

 Optic nerve cupping and atrophy

 The final common pathway in all the primary open-angle glaucomas is the death,
sometimes by necrosis, but usually by apoptosis, of the retinal ganglion cells.

 Symptoms
o notices a scotoma when performing a monocular visual task
o corneal edema, halo vision, and discomfort
o Marcus Gunn’s sign
o The angles are open in patients with POAG

 DD
o Exfoliative syndrome
o pigmentary dispersion

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o trauma
o anterior segment inflammation
o subacute or chronic angle closure
o elevated episcleral venous pressure
o Axenfeld’s and Rieger’s syndromes
o Corticosteroid administration.

Glaucoma suspect
 on the basis of family history of the disease (8 times higher risk)

 a suspicious-appearing optic disc (a large cup-to-disc ratio, slight asymmetry of the cups, slight
irregularity of the rim, questionable nerve fiber layer dropout)

 an elevated IOP.

 Definition of a Glaucoma Suspect

Open angle by gonioscopy and one of the following in at least one eye:

o IOP consistently >21 mm Hg by applanation tonometry


o Appearance of the optic disc or retinal nerve fiber layer suggestive of glaucomatous
damage
o Diffuse or focal narrowing or sloping of the disc rim
o Diffuse or localized abnormalities of the nerve fiber layer, especially at superior and
inferior poles
o Disc hemorrhage
o Asymmetric appearance of the disc or rim between fellow eyes (e.g., cup-to-disc ratio
difference > 0.2), suggesting loss of neural tissue
o Visual fields suspicious for early glaucomatous damage

 High-Risk Glaucoma Suspects

High-risk glaucoma suspects include patients who have one or more of the following:

o IOP consistently >30 mm Hg


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o Thin central corneal thickness (dependent on ethnicity)


o Vertical cup-to-disc ratio >0.7
o Older age
o Abnormal visual field, e.g., increased pattern standard deviation on Humphrey Visual
Field test
o Presence of exfoliation or pigment dispersion syndrome
o Disc hemorrhage
o Family history of glaucoma or known genetic predisposition
o Fellow eye of patient with severe unilateral glaucoma (excluding secondary unilateral
glaucoma)
o Additional ocular (e.g., suspicious disc appearance, myopia, low optic nerve perfusion
pressure, steroid responder) or systemic risk factors that might increase the likelihood
of developing glaucomatous nerve damage (e.g., African ancestry, sleep apnea,
diabetes mellitus, hypertension, cardiovascular disease, hypothyroidism, myopia,
migraine headache, vasospasm)

Ocular hypertension

 Individuals with IOPs of 21 mmHg (the statistical upper end of the ‘normal’ range) or
greater

 normal visual fields

 normal optic discs

 open angles

 absence of any ocular or systemic disorders contributing to the elevated IOPs

 4–10% of the population over age 40


 0.5–1% of ocular hypertensive patients per year develop visual field loss as detected by
kinetic perimetry

Risk factors in ocular hypertension

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Prospectively proven risk factors


 Thin corneas (<535 microns)
 Elevated intraocular pressures
 Increasing age
 Vertical cupping of the optic nerve (>0.6)
 Increased pattern standard deviation on threshold perimetry
 Abnormalities in the optic nerve with the scanning laser ophthalmoscope
 Pseudoexfoliation

Pfizer Corporation (STARR II Risk Calculator)

 Management:

o 9.5% cumulative risk of developing POAG after 5 years; treatment (which aimed to
reduce IOP by 20% or more and to reach 24 mmHg or less) reduced this to 4.4%.

o Drug choice is the same as for POAG, although a less aggressive pressure-lowering
approach is frequently taken

Normal Tension Glaucoma

 CF

o IOP consistently equal to or less than 21 mmHg.

o Signs of optic nerve damage in a characteristic glaucomatous pattern.

o An open anterior chamber angle.

o Visual field loss as damage progresses, consistent in pattern with the nerve
appearance.

o No features of secondary glaucoma or a non-glaucomatous cause for the


neuropathy.

 Risk factors

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o Older age

o Female

o Japan > Europe

o Family History of POAG

o Lower CCT

o Abnormal vasoregulation

o Systemic hypotension

o Obstructive sleep apnoea syndrome

o Autoantibody levels

 DD

I. Glaucoma
A. Elevated intraocular pressure (IOP) not detected
1. Undetected wide diurnal variation
2. Low scleral rigidity
3. Systemic medication that may mask elevated IOP (e.g., recent B-blocker treatment)
4. Past systemic medication that may have elevated IOP
5. Elevation of IOP in supine position only
B. Glaucoma in remission
1. Past corticosteroid administration
2. Pigmentary glaucoma
3. Associated with past uveitis or trauma
4. Glaucomatocyclitic crisis
5. Burned-out primary open-angle glaucoma

II. Optic nerve damage


A. Congenital optic nerve conditions45
1. Pits
2. Colobomas
3. Tilted discs
B. Ischemic optic neuropathy
1. Arteritic
2. Non-arteritic
C. Compressed lesions
1. Tumors
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2. Aneurysms
3. Cysts
4. Chiasmatic arachnoiditis
D. Optic nerve drusen
E. Demyelinating conditions
F. Inflammatory diseases
G. Hereditary optic atrophy
H. Toxic drugs or chemicals

III. Ocular disorders


A. Myopia
B. Retinal degeneration
C. Myelinated nerve fibers
D. Branch vascular occlusions
E. Choroidal nevus or melanoma
F. Choroidal rupture
G. Retinoschisis
H. Chorioretinal disease

IV. Systemic vascular conditions


A. Anemia
B. Carotid artery obstruction
C. Acute blood loss
D. Arrhythmia
E. Hypotensive episodes

V. Miscellanenous
A. Hysteria
B. Artifact of visual field testing

Combined and Mixed Glaucoma

 Combined mechanism glaucoma refers to situations in which both open-angle and angle-
closure components are present. Most commonly, angle-closure glaucoma is treated
successfully with iridotomy, eliminating all appositional closure, and IOP still remains
elevated, with or without the presence of PAS of any extent.

 Mixed mechanism glaucoma refers to the term to describe an eye with angle-closure due
to more than one contributory mechanism. When pupillary block is eliminated by
iridotomy and the angle opens to a greater degree than before the iridotomy, an
appositional closure remains on the basis of plateau iris, phacomorphic glaucoma, or
malignant glaucoma, a mixed mechanism may be present.

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 In RP Centre what is followed is different than this, and I don’t find reference for it. What is followed in RPC
is mixed mechanism is when one primary and one secondary mechanism of glaucoma co-exist whereas
combined mechanism is when both primary mechanisms of glaucoma i.e. POAG and PACG co-exists.

Secondary open angle glaucoma

 Secondary open-angle glaucoma can be subdivided on the basis of the site of aqueous
outflow obstruction as follows:

 Pre-trabecular glaucoma
• Fibrovascular membrane in neovascular glaucoma
• Epithelial ingrowth
• Fibrous downgrowth
• Proliferation of the endothelium
• Posterior polymorphous dystrophy
• Penetrating and non-penetrating trauma
• Inflammatory membrane

 Trabecular glaucoma
Clogging of the trabecular meshwork
• RBC's in Haemorrhagic/ ghost cell/ sickled cell glaucoma
• Macrophages in hemolytic/phacolytic/melanomalytic glaucoma
• Neoplastic cells in primal)' ocular tumours/juvenile xanthogranuloma
• Pigment particles in pigmentary glaucoma/ exfoliation syndrome/malignant
• Protein in uveitis/lens induced glaucoma
• Viscoelastic agents.

Alterations of the trabecular meshwork


• Steroid induced glaucoma
• Uveitis
• Scleritis
• Alkali burns
• Trauma
• Intraocular foreign body

 Post-trabecular glaucoma

• Collapse of the Schlemm's canal


• Elevated episcleral venous pressure
- Carotid cavernous fistula
- Cavernous sinus thrombosis
- Retrobulbar tumours
- Thyroid ophthalmopathy
- SVC obstruction
- Mediastinal tumours
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- Sturge Weber syndrome

Pigmentary glaucoma

Pigment dispersion syndrome (PDS): no Glaucoma

 1.0–2.5%

 young adults

 male > female

 most often in white

 strong association between pigmentary glaucoma and myopia

 significant linkage between the disease phenotype and genetic markers located on 7q35-
36.

 Pathophysiology: release of pigment particles from the pigment epithelium of the iris.
These particles are carried by the aqueous humor convection currents and then deposited
on a variety of tissues in the anterior segment of the eye, including the corneal
endothelium, trabecular meshwork, anterior iris surface, zonules, and lens.

o Campbell’s Mechanical Theory: concave shape of the peripheral iris allows it to rub
against the zonules, causing pigment release and dispersion.

o Anderson’s Genetic Predisposition Theory: conditions resulted from mutations in


genes encoding melanosomal proteins. They postulate that pigment production and
mutant melanosomal protein genes may contribute to human pigmentary
glaucoma.

 Jarring exercise, strenuous physical activity, or rarely dilation may lead to dramatically
increased pigment dispersion, a so-called pigment storm, leading to sudden elevations of
IOP.

 CF

o spokelike, midperipheral transillumination iris defects

o very deep anterior chambers

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o concave appearance of the peripheral iris, and mild iridodonesis

o Krukenberg’s Spindle: deposition of pigment on the corneal endothelium.


(extracellular as well as intracellular pigment granules phago-cytized by the
corneal endothelium)

o Sampaolesi’s line: pigment line anterior to Schwalbe’s line

o Zentmayer’s ring or Scheie’s stripe: Pigment deposition on the zonules, posterior


lens surface and anterior iris surface

o Resembles POAG in IOP, ON, VF changes

o Pigment release and marked IOP elevation after exercise can be blocked by
topical pilocarpine therapy

o UBM of patient with PDS, showing backward-bowing peripheral iris in contact with
lens surface

 differential diagnosis

o normal eyes with aging


o POAG
o Uveitis
o cysts of the iris and ciliary body
o pigmented intraocular tumors
o previous surgery (including laser surgery)
o trauma
o angle-closure glaucoma
o amyloidosis
o diabetes mellitus
o herpes zoster
o megalocornea
o radiation
o siderosis and hemosiderosis
 Management

o Like POAG: medical therapy to argon laser trabeculoplasty (ALT) to filtering


surgery.

o Miotic agents reduce IOP in pigmentary glaucoma and are theoretically appealing
because they increase pupillary block and lift the peripheral iris from the zonules.
However, cholinergic drugs are generally poorly tolerated by these young patients

o Thymoxamine, an A-adrenergic antagonist, might be useful in this situation


because it constricts the pupil without inducing a myopic shift in refraction

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o Laser peripheral iridotomy also may reduce pigment shedding, because it allows
the posteriorly bowed iris to move anteriorly as any built-up fluid pressure in the
anterior chamber is then normalized with the posterior chamber (relief of so-called
reverse pupillary block). This may help prevent glaucoma in individuals at higher
risk but have not yet developed uncontrolled pressure.

o ALT: done with relatively low energy settings

Exfoliation syndrome

 1917, Lindberg: inherited microfibrillopathy

 previously or classically known as pseudoexfoliation syndrome

 40% of patients with exfoliation syndrome may have associated glaucoma.

 ranges in prevalence from near 0 in Eskimos to near 30% in people in Scandinavian


countries.

 prevalence: Framingham study: 0.6% in patients younger than 65 years of age, 2.6% in
patients 65–74 years of age and 5.0% in patients 75–85 years of age.

 Syndrome: Female> Male

 Glaucoma: Female = Male

 The cumulative risk of glaucoma in eyes with PXF is 5% at 5 years and 15% at 10 years.

 Pathogenesis

o Genetics: polymorphism in exon 1 of the LOXL1 gene, chromosome 15q22 


extracellular matrix formation and stability: LOXL1 is one of a family of lysyl
oxidase enzymes essential for the formation of elastin fibers. It has an important
role in modifying tropoelastin, the basic building block of elastin, and catalyzing
process for monomers to cross-link and form elastin.

o exfoliation material: random 10 to 12 nm fibrils, arranged in a fibrillogranular


matrix and occasionally coiled as spirals

o affects the rigidity of the lamina cribrosa

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o increased inhibitors of MMPs

 CF

o Target Sign: classic pattern on the anterior lens surface consisting of a central
translucent disc surrounded by a clear zone, which in turn is surrounded by a
granular grey-white ring with scalloped edges

o Dandruff-like flakes of exfoliation material are deposited on the corneal


endothelium, trabecular meshwork, anterior and posterior iris, pupillary margin,
zonules, and ciliary processes as well as the anterior hyaloid face in aphakic eyes.

o Peripupillary iris has an irregular, moth-eaten pattern of transillumination

o Sampaolesi’s line: An accumulation of pigment may also be seen along the


Schwalbe line

o Most eyes with exfoliative glaucoma have an open-angle mechanism, although


acute angle-closure glaucoma also occurs in a small number of cases

o Systemic Associations: material has also been demonstrated in tissues throughout


the body of patients with the exfoliation syndrome, including lung, heart, liver,
gallbladder, skin, kidney, and cerebral meninges, Alzheimer Disease

 Management

o Medical therapy is relatively less effective

o ALT has maximum benefit

o Filtering surgery has a high rate of success

Steroid Induced Glaucoma

 Epidemiology

 bimodal distribution: Children less than 6 years of age and older people, usually more
than 70 years

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 Steroid Responders
 4-6% of patients may demonstrate a rise of IOP more than 30mmHg after 4 weeks
application of potent topical corticosteroids-these are the patients at maximum risk
 A third of the population have a moderate elevation of IOP (22-30mm Hg)
 Non responders have virtually no change in IOP
 Open angle glaucoma patients have a higher rate of steroid response than the general
population
 Diabetics, myopes, eyes with angle recession, patients with collagen vascular disease have
a higher rate of steroid responsiveness
 Other factors like potency, duration and dose of the steroid also influence the rise in IOP.
 Topical administration, periocular and systemic administration are the ones most
commonly implicated.
 Onset of IOP elevation can occur within days, weeks, months or even years of
administration. With topical corticosteroids it typically occurs over 2-6 weeks
 Lelorier et al., noted that high doses of inhaled corticosteroids (defined as > 1500µg
flunisolide or > 1600µg of beclomethasone, budesonide or triamcinolone) was associated
with a significantly increased risk of ocular hypertension or open-angle glaucoma.
 The odds ratio was 1.44 after 3 months of corticosteroid use.
 Use of lower doses of inhaled steroids or use of nasal corticosteroids was not associated
with a rise in intraocular pressure

 Pathogenesis:
o increased deposition of extracellular material in the trabecular beams, fingerprint
like deposits in the uveal meshwork and fibrillar deposits in the juxtacanalicular
tissue of the TM
o TM cell function: inhibition of proliferation, migration and phagocytosis.
o TM cell extracellular matrix: increased deposition of ECM material in TM.
Increased expression of fibronectin, laminin, collagen and elastin. Decreased
expression of t-PA and MMPs.
o TM Cell morphology: activation of TM cells (increased endoplasmic reticulum,
Golgi complexes, and secretory vesicles), increased biosynthesis
o heritability of the steroid response and its relation to glaucoma: expression of the
protein myocilin (previously known as TIGR and GLC1A) in cultured TM cells is
greatly enhanced by treatment with glucocorticoids.

 Pathophysiology (read STEROID mnemonic from Ophthalmonics)

1. Stabilization of lysosomal membranes and leading to accumulation of polymerized


glycosaminoglycans( GAG).
2. Alteration of the composition of the extracellular matrix through which aqueous flows
(such as the proteoglycans or glycosaminoglycans), thereby increasing resistance to
outflow (Biological edema).
3. Increased expression of collagen, elastin, laminin and fibronectin within the trabecular
meshwork, as a result of which there is increased trabecular meshwork resistance.
4. Inhibition of phagocytosis by endothelial cells lining the trabecular meshwork thereby
leading to accumulation of debris in the trabecular meshwork.
5. Decreased expression of extracellular proteinases including fibrinolytic enzymes,
stromolysin, matrix metalloproteinases.
6. Steroids increase the expression of TIGR gene and decrease the MMP.
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7. Inhibition of the production of outflow-enhancing PGs (such as PGF2α).

 Relative risks of various steroids


o The risk generally parallels the potency
o The most potent include betamethasone, dexamethasone and prednisolone
o Some steroids like rimexolone, loteprednol etabonate and fluorometholone have
less tendency to raise IOP but are also less potent
o Different preparations of the same corticosteroid may have different
antiinflammatory effects with similar IOP raising tendency e.g., 0.1%
dexamethasone phosphate and acetate
o Topical NSAIDS have little tendency to raise IOP
o IVTA: 50% of cases starting at 1-2 months > 30 mmHg
o PST: > 5 mm Hg

 TYPE OF RESPONDER (Armaly-Backer)

o LOW: <20mmHg (58%)

o INTERMEDIATE: 20-31mmHg (36%)

o HIGH: >31mmHg (6%)

INCIDENCE OF STEROID RESPONSIVENESS


RESPONDERS HIGH(%) INTERMEDIATE(%) NONRESPONDER(%)
General Population 5 35 60
POAG 90 10 0
Siblings Of POAG 30 50 20
Offsprings Of POAG 25 70 5

 Risk factors

1. Patients with primary open angle glaucoma. About 30% of the glaucoma suspects and
90% of patients with POAG might have an ocular hypertensive response to a 4 week
course of topical Dexamethasone 0.1%.

2. First degree relatives of POAG patients.

3. Children below 10 years

4. High myopia

5. Diabetes Mellitus

6. Connective Tissue Disorders (Rheumatoid Arthritis)


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7. Eyes with Traumatic Angle Recession

8. Pigment Dispersion Syndrome

9. Endogenous Hypercortisolism.

 Steroid formulation and glaucoma

Topical ocular Oral and intravenous Skin preparations


preparation steroids(equivalent
doses in mg)
High potent Prednisolone Acetate Betamethasone –3 Clobetasole
1% Dexamethasone-3 propionate
Dexamethasone 0.1% Betamethasone
Betamethasone 0.1% Dipropionate
Intermediate Prednisolone Sodium Triamcinolone-12 Diflucortolone
Phosphate 0.5% Methylprednisolone-15 Valerate
Prednisolone-15 Mometasone furoate
Flucinolone
acetonide
Low potent Fluoromethalone 0.1% Hydrocortisone -60 Hydrocortisone
Loteprednol Etabonate

 Duration and dose of steroids


Route Average dose Average Time
taken for IOP rise
Oral 25 mg hydrocortisone/ day 1 year
50 mg prednisolone/day 2-15 months
Inhalational 1500 µg flunisolide 3 months
1600µg beclomethasone, budesonide,
triamcinalone
200 µg fluticasone 1 year
Pulse steroids 140mg repeated 4 weekly 6 months
Dermatological Betamethasone cream (0.1%) 3 months
Topical QID dose of a potent steroid 2-6 weeks
IVTA 4mg of triamcinolone acetonide 4-8 weeks
PST 40 mg of triamcinolone acetonide 5-9 weeks

 Differential diagnosis
1. POAG
2. Uveitic glaucoma
3. Glaucomatocyclytic crisis
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4. Normal tension glaucoma


5. Primary juvenile open angle glaucoma

 Management

o stop the responsible steroid preparation

o switch to lower potency steroids like phosphate forms of prednisolone and


dexamethasone, rimexolone, loteprednol etabonate, flurometholone, medrysone

o substituting with non steroidal anti inflammatory drugs like diclofenac, ketorolac,
bromfenac,nepafenac that act as cyclooxygenase inhibitors and reduce
inflammation.

o steroid sparing drugs are the immunosuppressants like tacrolimus ointment/


cyclosporin for vernal keratoconjunctivitis or methotrexate for systemic condition
or uveitis

o Selective Laser Trabeculoplasty or argon laser trabeculoplasty can be considered

o medical and laser therapy fails  surgery (esp in Age< 20 years, Higher base line
IOP, Greater glaucomatous optic neuropathy)

o Anecortave acetate (AA): potent inhibition of blood vessel growth but with no
evidence of glucocorticoid receptor mediated bioactivity

Lens-induced glaucoma

1. Phacomorphic glaucoma: a swollen lens causes increased pupillary block and secondary
angle closure.

2. Phacotopic Glaucoma: a dislocated lens causes increased pupillary block and secondary
angle closure.

3. Phacolytic glaucoma: lens protein leaks from an intact cataract and obstructs the
trabecular meshwork.

4. Lens-particle glaucoma: lens material liberated by trauma or surgery obstructs the outflow
channels.

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5. Phacoanaphylaxis: sensitization to lens protein produces granulomatous inflammation and


occasionally secondary glaucoma.

Phacolytic Glaucoma/ Lens Protein Glaucoma

 Protein composition of the lens is altered to components with heavier molecular weight. If
these soluble molecules leak through micro leaks what grossly appears to be an intact
capsule, they can obstruct the trabecular meshwork, also macrophages engulf the lens
protein and may further obstruct the outflow channels.

 Pathophysiology

o heavy-molecular-weight (HMW) proteins (greater than 150 × 106 Da) obstruct


trabecular meshwork outflow, causing a rise in IOP.

 CF

o acute onset of monocular pain, redness, and perhaps a further decrease in vision

o intense flare, may be yellow

o white particles on the anterior lens surface and in the aqueous; these particles are
thought to be cellular aggregates or clumps of insoluble lens protein

 Aqueous humor is examined by phase-contrast microscopy or Millipore filtration and


staining.

 Mx

o IOP and inflammation control

o Cataract extraction is the definitive treatment

Lens-Particle Glaucoma
 Disruption of the lens capsule by penetrating trauma or surgery

 glaucoma has its onset a few days after the precipitating event.

 Pathophysiology

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o Lens particles obstructing the trabecular meshwork

o Inflammatory cells

o Peripheral anterior synechiae and angle closure related to the inflammation

o Pupillary block from posterior synechiae

 CF

o Elevated IOP can cause corneal edema, and inflammation can be marked, as
evidenced by flare and cell.

o Hypopyon

Phacoanaphylaxis -Lens-Associated Uveitis


 when patients become sensitized to their own lens protein

 after penetrating trauma or extracapsular cataract extraction

 Pathophysiology

o alteration in immune tolerance to lens proteins

o indolent bacteria such as Propionibacterium acnes that are found in lens material
or that bacteria instigate a loss of immune tolerance in the eye.

o autoimmune theory (yet to be proven)

o zonal granulomatous inflammation with three populations of cell types

 Zone 1—Neutrophils closely surround and infiltrate the lens.

 Zone 2—A secondary zone of monocytes, macrophages, epithelioid cells,


and giant cells surround the neutrophils.

 Zone 3—A nonspecific mononuclear cell infiltrate forms the outer zone of
inflammation.

 CF

o low-grade anterior segment inflammation

o Panuveitis with a hypopyon

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o associated with hypotony rather than with elevated IOP, although high IOP can
occur

Glaucoma after cataract surgery


 A transient rise in IOP has been reported in 33% to almost 100%

 Mechanism of IOP rise

1. Inflammation with the release of active substances, including prostaglandins and the
formation of secondary aqueous humor
2. A watertight wound closure with multiple fine sutures limiting the ‘safety valve’ leak
of aqueous humor.
3. Deformation of the limbal area, reducing trabecular outflow
4. Obstruction of the trabecular meshwork by pigment, blood, lens particles,
inflammatory cells, and viscoelastic substances

I. Open-angle glaucoma

A. Early onset (within first postoperative week)

1. Pre-existing chronic open-angle glaucoma


2. alpha-Chymotrypsin-induced glaucoma
3. Hyphema/debris
4. Viscoelastic material
5. Idiopathic pressure elevation

B. Intermediate onset (after first postoperative week)

1. Pre-existing chronic open-angle glaucoma


2. Vitreous in the anterior chamber
3. Hyphema
4. Inflammation
5. Lens particle glaucoma
6. Corticosteroid-induced glaucoma
7. Ghost-cell glaucoma

C. Late onset (more than 2 months postoperatively)

1. Pre-existing chronic open-angle glaucoma


2. Ghost-cell glaucoma
3. Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy
4. Vitreous in the anterior chamber
5. Late-occurring hemorrhage

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6. Chronic inflammation

II. Angle-closure glaucoma

A. With pupillary block

1. Anterior hyaloid face


2. Posterior lens capsule
3. Intraocular lens
4. Posterior synechiae
5. Silicone oil

B. Aqueous misdirection (malignant glaucoma)

C. Without pupillary block

1. Pre-existing angle-closure glaucoma


2. Inflammation/hyphema
3. Prolonged anterior chamber shallowing
4. Iris incarceration in cataract incision
5. Intraocular lens haptics
6. Neovascular glaucoma
7. Epithelial ingrowth
8. Fibrous ingrowth
9. Endothelial proliferation
10. Proliferation of iris melanocytes across the trabecular meshwork

Glaucoma after Vitrectomy

 Pre-existing glaucoma
o Angle recession
o Ghost cell
o Primary open-angle glaucoma
o Pigmentary glaucoma
 Associated with intraocular hemorrhage
o Hyphema
o Ghost cell
o Hemolytic
o Hemosiderosis
 Related to lens material
o Phacolytic
o Lens particle

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o Phacoanaphylactic
 Neovascular
 Inflammatory
 Corticosteroid induced
 Intraocular gas or liquid
o Air
o Viscoelastic substances
o Perfluorocarbons
o Silicone
o Band/ buckle

Glaucoma with uveitis

 Aka inflammatory glaucoma, uveitic glaucoma, or glaucoma secondary to uveitis

 In patients with uveitis and no demonstrable “glaucomatous” optic nerve damage or


“glaucomatous” visual field defects:  uveitis-induced ocular hypertension, ocular
hypertension secondary to uveitis

 Epidemiology

o Uveitis may account for 5% to 10% of legal blindness

o 25% of all patients with uveitis will develop increased intraocular pressure

o more common in cases of granulomatous

 Pathophysiology

 Open Angle Mechanisms


 Abnormal Aqueous Secretion
 Aqueous Humor Proteins
 Inflammatory Cells
 Prostaglandins
 Trabeculitis
 Steroid-induced Ocular Hypertension
 Closed-Angle Mechanisms
 Peripheral Anterior Synechiae
 Posterior Synechiae
 Forward Rotation of the Ciliary Body
 Uveal effusion
 neovascularization

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 Management

o Control of uveitis

o beta-blockers, carbonic anhydrase inhibitors, adrenergic agents, and hyperosmotic


agents

o miotic agents and prostaglandin-like agents are generally avoided

o pupillary block: YAG PI (multiple PI might be needed, in 4 quadrant PI- inferior PI


should be done first)

o Goniosynechialysis

o Trabeculodialysis

o trabeculectomy with and without the use of antimetabolites: success rate 62-81%

o tube shunt procedures such as the Ahmed, Baerveldt, and Molteno implants

o Nonpenetrating glaucoma surgery

o Ciliary body destructive procedures

Fuchs’ Heterochromic Iridocyclitis

 chronic but relatively mild form of anterior uveitis associated with cataract and glaucoma
 90% of the cases are unilateral
 1.2% to 3.2% of all uveitis cases
 third and fourth decades
 male = female
 CF
o minimal cell and flare
o fine round or stellate keratic precipitates
o fine filaments on the endothelium between the keratic precipitates
o a patchy loss of the iris pigment epithelium
o hypochromia
o grey-white nodules on the anterior iris
o a few opacities in the anterior vitreous
o chorioretinal scars that resemble toxoplasmosis.
o Heterochromia in 25-70%
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o Gonioscopy reveals fine vessels that bridge the angle and


o can bleed with minimal trauma, such as paracentesis – AMSLER’S SIGN
o Increased IOP has been reported in 13–59%
o Despite the chronicity of the intraocular inflammation in these patients, peripheral
anterior synechiae and posterior synechiae almost never form
o Cataract formation has been reported in more than 80%
o

 Etiology
o Rubella virus and antibodies against rubella virus ??

 DD
o herpetic uveitis, the Posner–Schlossman syndrome, sarcoidosis, syphilis, and, in
those cases with posterior pole lesions, toxoplasmosis.

 Mx
o Cataract
o Glaucoma Medical management

Glaucomatocyclitic Crisis

 Posner-Schlossman syndrome
 first described in 1929, it carries the eponym of Posner and Schlossman who reported the
syndrome in 1948
 young to middle-aged adult
 CF
o recurrent episodes of mild anterior uveitis and marked elevations of IOP.
o Unilateral >> bilateral
o slight discomfort, slight blurring of vision, or halo vision.
o 0.4% of all uveitis
o mild ciliary flush
o a dilated or sluggishly reactive pupil
o If pressure is significantly elevated, the pupil may be slightly dilated; however,
peripheral anterior synechiae and posterior synechiae do not occur.
o corneal epithelial edema
o IOP in the range of 40–60 mmHg
o decreased outflow facility
o open angle
o faint flare
o 1–20 fine keratic precipitates.

 Etiology
o cytomegalovirus or herpes simplex virus (HSV) in at least some cases
o increased prostaglandins  breakdown of BAB

 DD
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o Fuchs' heterochromic iridocyclitis, herpes simplex or zoster uveitis, sarcoidosis,


HLA-B27–associated anterior uveitis, and idiopathic anterior uveitis.

 Mx
o self-limited ocular hypertension that resolves spontaneously regardless of
treatment.
o topical corticosteroids to control the anterior uveitis.
o Mydriatic and cycloplegic agents are not commonly needed as ciliary muscle spasm
is uncommon and synechiae rarely form
o Glaucoma:
 Miotics and argon laser trabeculoplasty are generally not effect

Traumatic Glaucoma

Hyphema

 Blood in AC can be either due to Blunt or Penetrating injury, in blunt trauma there is
antero-posterior compression and equatorial expansion leading to damage to ciliary body
and TM. There are shearing forces acting on the angle structures and the ciliary body
leading to damage to the anterior face of ciliary body and damage to major arterial circle
causing the hyphema, Penetrating injury leads to hyphema by damaging the blood vessels
and due to hypotony.

 Certain conditions lead to HYPHEMA even in MINOR TRAUMA – Rubeosis iridis, juvenile
xanthogranuloma, iris melanoma, iris leiomyosarcoma, myotonic dystrophy , vascular iris
tufts blood dyscrasias.

 Hyphema resorption occurs by anterior surface of the iris and TM. Uncomplicated
hyphemas are cleared within 1 week.

 Grading

grade 1: < 1/3th of AC

grade 2: 1/3oth -1/2 of AC

grade 3 > ½ of AC

grade 4: total or eight ball hyphema.

 Complications of Hyphema

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o Increased IOP: various causes of high iop in hyphema are:

o occlusion of trabecular meshwork by clot, inflammatory cells, erythrocytic debris.

o pupillary block due collar button shaped clot.

o Peripharal anterior synechiae: PAS are formed if hyphema pesists for more than a
week .

o Optic atrophy : optic atrophy in hyphema can occur because of high IOP , contusion
to the optic nerve, secondary to damage to short posterior ciliary arteries. Risk of
optic atrophy increases when th IOP is > 50 mmHg for 5 days or 35 mmHg or more
for 7 days. Patients with sickle cell disease have optic atrophy even at normal or
slightly raised IOP.

o Corneal blood staining: Factors which influence corneal blood staining include:
rebleeding, prolongd clot duration, sustained increase in IOP and corneal
endothelial dysfunction. Two main risk factors of corneal blood staining include
IOP>25mmHg and >6 days duration.

o Accommodative impairment

 Earliest sign of corneal blood staining is a straw coloured discoloration of deep stroma,
presence of tiny yellow granules in posterior 1/3rd of the cornea.

 In sunlight the haemoglobin gets converted in to porphyrins, which toxic to the corneal
endothelium therefore patching might have a role in management of hyphema.

 Corneal blood staining can cause decreased visual acquity and depriviation amblyopia in
children.

 Secondary haemorrhage: rebleed occurs because of clot retraction on and after day 4.
signs of rebleed incude increase in size of hyphema, layer of free RBCs over previous clot,
change of colour from dark red to bright red.

 Chances of rebleed are more with black race and children

 Medical Management:

o Anti fibrinolytic agents: epsilon amina caproic acid( EACA) and Tranexamic acid are
used to prevent rebleed in cases of hyphema

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 EACA( amicar ) binds to lysine molecules in the clot via lysine binding site
and inhibits fibrin clot digestion. Its dose is 100mg/kg every 4 hours to a
maximum dose of 30g/day by mouth for 5 days.

 Side effects include nausea, vomiting, diarrhea, postural hypotention,


pruritis, muscle cramps, rash, nasal stuffiness, arrhythmia, confusional
state. Rhabdomyolysis and myoglobinuria are rare. Contraindications
include drug allergy, active intravascular clotting, history of thrombosis
hematuria, renal failure and hemophilia.

 Tranexamic acid also has similar mechanism. Side effects are lesser as
compared to amicar The results of various studies indicate that both amicar
and tranexamic acid have beneficial effect on rate of secondary
haemorrhage but none of them had improved the final visual outcome.

o Corticosteroids: by stabilizing the blood-ocular barrier and by directly inhibiting


fibrinolysis corticosteroids decrease the incidence of secondary
haemorrhage.predinislone in dase of 40mg/day or 0.6 mg/kg in children is
effective in reducing the incidence of rebleed statistical analysis indicates that
coticosteroids decreased the incidence of rebleeding without having any effect on
the longterm visual outcome.

o Studies advocate use of mydriatics as they relieve ciliary spasm and prevents
formation of PAS. Aspirin should not be given in cases of hyphema

 Outpatient management:

can be considered in following Cases (Walton et al):

o no associated injury

o hyphema< ½ of AC volume

o satisfactory IOP

o no blood dyscrasia

o safe home environment

o good patient compliance

o good follow up (no time delay at presentation)

 Indications for surgical management

irrigation, vitrectomy, trabeculectomy-walton et al:

o microscopic corneal blood staining


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o Risk of optic atrophy/ CRAO

o sickle cell disease/trait, IOP avg >25 mmHg> 24 hours or spikes repeatedly >
30mmHg

o IOP >60mmHg for 2 days OR 50mmHg for >4 days

o presence of pre-existing glaucomatous optic atrophy and “unacceptable” IOP.

o Risk of corneal blood staining( e.g 4 days after the onset of glaucoma, > ½ - total
hyphema with IOP > 25mmHg > 6 days

o Risk of synechiae formation ( e.g > 50% hyphema for > 8 days.

Angle Recession/ Glaucoma


 COLLINS was the first person to describe angle recession due to blunt trauma in 1892.
Wolf and Zimmerman in 1962 linked angle recession to development of Glaucoma. tear in
the ciliary body between the longitudinal and circular muscle layers.

 Angle recession occurs in 20-94% cases of eye trauma. Studies indicate that incidence of
glaucoma in angle recession ranges from 7-9%.

 Clinically, there is abnormal widening of the ciliary body band on gonioscopy

 blunt or penetrating trauma to the anterior segment

 risk of developing glaucoma: proportional to the extent of ciliary body damage, with an
incidence as high as 10% in eyes with greater than 180 degrees of damage.

 50% of these patients will develop elevated pressures in the contralateral eye.

 Pathophysiology

o Pathologically angle recession is a separation between the circular and the


longitudinal fibers of the ciliary body, longitudinal muscles remain attached to the
scleral spur. There might be associated cyclodialysis, iridodialysis, damage to the
lens manifested as cataract, subluxation ,dislocation , hyphema. Later the inner
layer of ciliary body atrophies leading to broadand fusiform ciliary band
appearance on gonioscopy.

o Impaired outflow may occur as the result of direct damage to the trabecular
meshwork

o as the result of a Descemet-like endothelial proliferation over the trabecular


meshwork.
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 CF

o Grading is done according to Howard’s Classification as Grade I (shallow), grade II


(moderate), grade III (deep)

o pain, photophobia, and decreased vision as the result of elevated intraocular


pressure

o evidence of previous trauma: Corneal scarring or blood staining, cataract,


phacodonesis, iris sphincter tears, or tears at the iris root (iridodialysis)

o Gonioscopy demonstrates an irregular widening of the ciliary body band

o Choroidal ruptures, retinal detachments, or vitreous hemorrhage may be present.

 Treatment

o Bilateral simultaneous gonioscopy is a very effective way detecting even the subtle
changes in the angle.

o angle recession on gonioscopy following trauma need to be followed indefinitely


for the development of glaucoma

o Medical

 aqueous suppressants, Hyperosmotics

 Miotics often make angle recession worse, because they decrease


uveoscleral outflow in eyes that rely on uveoscleral outflow for intraocular
pressure control.

 Laser trabeculoplasty has limited success in eyes with angle recession.

o A guarded filtration procedure or implantation of a glaucoma drainage device is


often required to control intraocular pressure in these patients.

Cyclodialysis Cleft
 term was first used by Heine in 1905

 separation of the meriodinal ciliary muscle fibers from its attachment to the scleral spur
and ciliary body band

 Hypotony

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o direct communication between drainage of aqueous from the anterior chamber to


the suprachoroidal space.

o decreased aqueous humor production due to diminished blood supply to the ciliary
body.

 Etiology

o traumatic, caused by contusion injuries, or iatrogenic, caused by anterior segment


surgeries, like extracapsular cataract surgery, phacoemulsification, etc.

o Occasionally, there can be traumatic cyclodialysis cleft that remains dormant and
is later potentially opened during anterior segment surgery leading to
postoperative hypotony

 CF

o corneal folds, shallow AC, cataract formation, optic disk edema, hypotonous
maculopathy, choroidal effusion, retinal striae and choroidal folds resulting in
severe visual loss. The magnitude of hypotony is not proportionate to the size of
the cleft

 Dx

o deep angle recess with a gap between the sclera and the ciliary body band.

o Surgical gonioscopy with chamber deepening with OVDs is a useful method in cases
of shallow AC that precludes proper angle visualization.

o UBM is a contact procedure used to identify and localize the cleft when direct
visualization is difficult. The UBM transducer tip emits high frequency pulses and
detects the reflection from the ocular tissue interfaces giving a detailed
representation of the anterior chamber, angle and the ciliary body. It can
accurately diagnose and delineate the cyclodialysis cleft.

o AS-OCT is a noncontact procedure. The technique is accurate and reproducible


allowing the visualization of the angle in great detail. It has a higher resolution
than UBM.

 Mx

o Spontaneous closure of cyclodialysis rarely occurs in smaller clefts

o Medical therapy is the first line management in all the cases. It consists of topical
cycloplegics (atropine sulphate 1%) twice daily for 6 to 8 weeks

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o Laser photocoagulation can be delivered via transcorneal , transscleral route or by


endophotocoagulator probe. It may be effective in small clefts.

o Transconjunctival cyclocryopexy is another noninvasive procedure to achieve


adhesion between the choroids and the sclera.

o Transscleral ciliochoroidal diathermy after creating a partial thickness scleral flap.

o Surgical management is effective in moderate-to-large sized clefts.

o Direct cycloplexy

o Cataract surgery with PCIOL in sulcus

o Cataract Surgery with CTR

Elevated episcleral venous pressure

 episcleral venous pressure is raised 1 mmHg, IOP increases approximately 0.8 mmHg
 concept of pseudofacility ??  pressure-related reduction in aqueous humor formation
 signs
o chemosis
o proptosis
o orbital bruit
o pulsating exophthalmos
o episcleral veins are dilated, tortuous, and have a corkscrew appearance

 can be confused with conjunctivitis, episcleritis, scleritis, and general orbital inflammation.

Etiology of elevated episcleral venous pressure

I. Obstruction of venous drainage

A. Episcleral
1. Chemical burns
2. Radiation
B. Orbital
1. Retrobulbar tumors
2. Thyroid eye disease
3. Pseudotumor
4. Phlebitis
C. Cavernous sinus thrombosis
D. Jugular vein obstruction
E. Superior vena cava obstruction
F. Pulmonary venous obstruction

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II. Arteriovenous fistulas

A. Orbital
B. Intracranial
1. Carotid-cavernous fistula
2. Dural fistula
3. Venous varix
4. Sturge-Weber syndrome

III. Idiopathic

Carotid-Cavernous Fistula

 Classification

o direct CCF in which highly pressurized blood from the carotid artery is directly
shunted into the venous CS: HIGH FLOW  trauma

o indirect CCF, which develops as a result of communication between smaller, low-


pressure arterial branches and veins of the CS: LOW FLOW  congenitally, during
pregnancy, or spontaneously in post-menopausal women.

 Pathophysiology

o CCFs alter ocular hemodynamics in a way whereby the high-flow, high-pressure


profile of the carotid artery is transmitted to orbital and ocular structures

o classic clinical triad

 Unilateral exophthalmos: pulsatile

 Ocular or cephalic bruit

 Injection and chemosis of the conjunctiva

 CF

o Direct: headaches, diplopia, epistaxis, and visual loss

o Indirect: ocular redness and swelling, loss of Visual acuity and color vision

o arterialized and tortuous, corkscrew conjunctival vessels

o IOP is often elevated and wide mires


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 Mx

o Orbital imaging with CT or MRI

o Carotid angiography

o endovascular embolization using balloons or detachable coils or stenting for both


types of fistulas

o indirect CCFs: spontaneous regression can occur

o Filtration surgery is to be avoided in eyes with CCFs if at all possible.

Sturge-Weber syndrome
 encephalotrigeminal angiomatosis

 triad of neuropsychiatric, dermatological, and ophthalmological manifestations

 often referred to as the “fourth phacomatosis” but unlike the other phacomatoses, it has
no known inheritance pattern.

 neurocutaneous disorder with angiomas involving the leptomeninges (leptomeningeal


angiomas [LAs]) and skin of the face, typically in the ophthalmic (V1) and maxillary (V2)
distributions of the trigeminal nerve. The cutaneous angioma is called a port-wine stain
(PWS).

 Roach Scale for classification

Type I - Both facial and leptomeningeal angiomas; may have glaucoma

Type II - Facial angioma alone (no CNS involvement); may have glaucoma

Type III - Isolated LA; usually no glaucoma

 Pathophysiology

o During development there is an abnormal vascular plexus adjacent to the neural


tube during development. This vascular nexus fails to regress and is dragged to
various surface ectodermal and neuroectodermal locations during development.
These loci of aberrant vascular tissue contribute to the clinical manifestations in
SWS.

 CF

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o The facial hemangioma “port wine stain” is usually unilateral but may be bilateral.
These skin lesions do not necessarily respect a strict dermatomal distribution

o Conjunctival, episcleral, and choroidal hemangiomas are also common


abnormalities. Diffuse uveal involvement has been termed the “tomato-catsup”
fundus.

o Glaucoma more often occurs when the ipsilateral facial hemangioma involves the
lids and conjunctiva.

o 30% to 70% of individuals with SWS develop glaucoma, with 60% of cases reported
at birth or in infancy and 40% reported in adolescence or young adulthood

o The glaucoma that occurs in infancy looks and behaves like glaucoma associated
with isolated trabeculodysgenesis and responds well to goniotomy.

o The glaucoma that appears later in life is probably related to elevated episcleral
venous pressure from arteriovenous fistulas.

o serous retinal detachment from large choroidal vascular malformations and


homonymous hemianopsia.

 Mx

o Pulsed dye laser photocoagulation: for cosmetic effects of cutaneous port wine
lesions

o older children medical therapy should be attempted first. However, if this is not
successful, trabeculectomy should be considered in > 3years

o prophylactic posterior sclerotomy is often recommended to prevent perioperative


choroidal hemorrhage in SWS ??

o Filtering surgery has an increased risk of choroidal hemorrhage, resulting in


shallowing or flattening of the anterior chamber related to the diminution of the
intraocular pressure at the moment of surgery. This probably occurs when the
intraocular pressure level falls below that of arterial blood pressure and results in
effusion of choroidal fluid into surrounding tissues

o Cyclodesctruction and glaucoma drainage device implantation

Idiopathic Elevated Episcleral Venous Pressure

 IEEVP is a diagnosis of exclusion.


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 CF

o dilated, tortuous episcleral vessels with onset occurring subacutely typically in the
third or fourth decade of life.

o UL/ BL/ Asymmetric

o blood in Schlemm's canal which is a generalized sign of elevated episcleral venous


pressure

Developmental and childhood glaucoma

 childhood glaucomas

 Congenital glaucoma, in which the developmental abnormality of the anterior chamber


angle is not associated with other ocular or systemic anomalies

 Developmental glaucomas with associated anomalies, in which ocular or systemic


anomalies are present

 Secondary glaucomas of childhood, in which other ocular pathologies are the cause of the
impairment of the aqueous outflow

Shaffer-Weiss Syndrome classification of congenital glaucoma

1. primary congenital glaucoma, in which the developmental anomaly is restricted to a


maldevelopment of the trabecular meshwork

a. Congenital open-angle glaucoma

b. Autosomal dominant juvenile glaucoma

2. glaucoma associated with specific ocular or systemic congenital anomalies

a. Glaucoma associated with systemic abnormalities

b. Glaucoma associated with ocular abnormalities

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3. glaucoma secondary to miscellaneous pediatric conditions involving the eye, such as


inflammation,trauma, or tumors.

A. Traumatic glaucoma

B. Glaucoma secondary to intraocular neoplasm

C. Uveitic glaucoma

D. Lens-induced glaucoma

E. Glaucoma after congenital cataract surgery

F. Steroid-induced glaucoma

G. Neovascular glaucoma

H. Secondary angle-closure glaucoma

I. Glaucoma with increased episcleral venous pressure

J. Glaucoma secondary to intraocular infections

Hoskins Clinical anatomic classification of developmental glaucoma

I. Isolated trabeculodysgenesis (malformation of trabecular meshwork in the absence of iris


or corneal anomalies) - 50% of infants and juvenile,
A. Flat iris insertion
1. Anterior insertion
2. Posterior insertion
3. Mixed insertion
B. Concave (wrap-around) iris insertion
C. Unclassified

II. Iridodysgenesis (iris anomalies are usually seen with trabeculodysgenesis)


A. Anterior stromal defects
1. Hypoplasia
2. Hyperplasia (a/w Sturge-Weber syndrome)
B. Anomalous iris vessels
1. Persistence of tunica vasculosa lentis
2. Anomalous superficial vessels
C. Structural anomalies
1. Holes
2. Colobomata
3. Aniridia

III. Corneodysgenesis (corneal anomalies are usually seen with iridodysgenesis)


A. Peripheral: posterior embryotoxin, Axenfeld’s anomaly
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B. Midperipheral: Rieger’s anomaly


C. Central: Peter’s anomaly, posterior ulcer of von Hippel, and posterior keratoconus
D. Corneal size
1. Macrocornea: microphthalmos, nanophthalmos, Rieger’s anomaly, persistent hyperplastic
primary vitreous, and congenital rubella syndrome
2. Microcornea: Axenfeld’s syndrome or in X-linked recessive megalocornea.

Clinical presentation

epiphora, photophobia and blepharospasm

enlargement mainly at the corneoscleral junction

breaks in Descemet’s membrane (Haab’s striae)

progressive myopia

Examination under anesthesia

 IOP:

o applanation (Goldmann or hand-held Perkins)

o indentation (Schiøtz)

o indentation-applanation hybrid (pneumotonometer)

o non-contact air-puff (Keeler Pulsair)

o electronic (TonoPen or Mackay-Marg)

 corneal diameters

Newborns 9.5–10.5

1 year 10–11.5

2 years 11.5–12

>2 years 12

 corneal thickness

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o applanation IOP readings are profoundly affected by the CCT (viz., thicker CCTs
‘overestimate’ and thinner CCTs ‘underestimate’ true IOPs)

o is a significant risk factor for developing glaucoma damage, independent of IOP


corrections, with thinner CCTs.

 Gonioscopy:

o smooth-domed Koeppe 14- to 16-mm lens, with a Barkan light and hand-held
binocular microscope

o Although the angle is usually avascular, loops of vessels from the major arterial
circle may be seen above the iris ("Loch Ness Monster phenomenon").

o In addition, the peripheral iris may be covered by a fine, fluffy tissue ("Lister's
morning mist").

 Ophthalmoscopy: With successful control of the IOP, the cup will either remain stable or
its size will decrease

 axial length measurements

 ultrasonic biomicroscopy

 cycloplegic retinoscopy

Primary congenital glaucoma

 1 in 10 000 live births in western literature, 1 in 4000 in india

 40% at birth, 70% between 1 and 6 months, and 80% before 1 year.

 Most cases sporadic, 10% autosomal recessive

 most common form of infantile glaucoma, representing 50% of all cases of congenital
glaucoma

 75% bilateral

 CF

o Epiphora, photophobia, and blepharospasm form the classic triad

o Buphthalmos

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o Horizontal corneal diameter greater than 12 mm in an infant is highly suggestive of


congenital glaucoma.

o corneal cloudiness, tears in Descemet's membrane (Haab's striae), deep anterior


chamber, intraocular pressure greater than 21 mm Hg, iris stroma hypoplasia,
isolated trabeculodysgenesis on gonioscopy, and increased optic nerve cupping.

o Cup-to-disc ratios greater than 0.3 are rare in normal infants

o Asymmetry of optic nerve cupping > 0.2

o anterior chamber angle

 flat iris insertion

 concave iris insertion

Differential diagnosis

I. Other glaucomas
A. Glaucoma associated with congenital anomalies
B. Secondary glaucoma

II. Other causes of corneal enlargement or clouding


A. Megalocornea
B. Sclerocornea
C. High myopia
D. Metabolic diseases
E. Posterior polymorphous dystrophy
F. Congenital hereditary endothelial dystrophy
G. Obstetric trauma
H. Inflammation (keratitis, iridocyclitis)

III. Other causes of epiphora or photophobia


A. Nasolacrimal duct obstruction
B. Conjunctivitis
C. Corneal abrasion
D. Meesman’s corneal dystrophy
E. Reis-Buckler’s dystrophy

IV. Other causes of optic nerve abnormalities


A. Pit
B. Coloboma
C. Hypoplasia
D. Tilted disc
E. Large physiologic cup

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Management

 Early surgery is essential

 Beta Blockers, such as timolol 0.25% or betaxolol suspension 0.25%


 Prostaglandin anaologs are usually well tolerated, without demonstrable toxicity in
pregnant mothers or children

 Brimonidine should be avoided, as it may produce bradycardia, hypotension, hypothermia,


and apnea in infants.

 Goniotomy
o requires a clear cornea for visualization of the angle.
o goniotome and direct gonioscopy lens
o Barkan's goniolens
o modified Swan–Jacob lens

 trabeculectomy
o cloudy or opacified corneas
o trabecular meshwork is broken using a trabeculotome
o suture (usually propylene) through Schlemm's canal (Lynch procedure).
o fiber optic catheter (iCath, iScience), which has the advantage of an illuminated
tip that identifies the location of the catheter

Glaucoma Associated with Congenital Anomalies

Aniridia
 rudimentary iris stump

 Two-thirds of cases are dominantly transmitted with a high-degree penetrance. Twenty


percent are associated with Wilms' tumor.

 short arm of chromosome 11

 foveal and optic nerve hypoplasia, keratopathy, cataract (60% to 80%), and ectopia lentis

 Photophobia, nystagmus, decreased vision, and strabismus

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 Progressive corneal opacification and pannus

 AN1- 85%
Familial aniridia (most cases in this category)
Autosomal dominant with incomplete penetrance and expression
Isolated ocular defect, foveal hypoplasia, corneal "dystrophy”, glaucoma, etc.

 AN2- 13% (Miller's Syndrome, WAGR) Sporadic nonfamilial aniridia and Wilms' tumor
Deletion or mutation in short arm of chromosome 11 (11p-)
Associations include:
o Wilms' tumor of kidney (nephroblastoma),genitourinary abnormalities, mental
o retardation, craniofacial dysmorphism, hemihypertrophy
o Incidence of aniridia in patients with Wilms' tumor is 1/73 (1.4%)
o Incidence of Wilms' tumor in sporadic aniridia is 34%

 AN3- 2% (Gillespie's Syndrome)


Autosomal recessive aniridia, Mental retardation, cerebellar ataxia

 Glaucoma:

o late childhood or early adulthood.

o result of trabeculodysgenesis or of progressive closure of the trabecular meshwork


by the residual iris stump

o Early goniotomy or Trabeculectomy if early presentation

o Late presentation: medical therapy, filtering procedure, Cyclodestructive


procedures

Axenfeld's Anomaly
 Bilateral

 AD

 peripheral cornea, anterior chamber angle, and iris anomalies.

 prominent Schwalbe's line, referred to as posterior embryotoxon

 Iris strands attaching to the posterior embryotoxon and hypoplasia of the anterior iris
stroma may be present.

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 Axenfeld's syndrome

o includes glaucoma and occurs in 50% of patients with the anomaly

Rieger's Anomaly
 Bilateral

 AD

 advanced degree of angle dysgenesis

 marked iris hypoplasia is observed with polycoria and corectopia.

 >50% glaucoma

 Rieger's Syndrome

o Dental abnormalities include a reduction of crown size (microdontia), a decreased


but evenly spaced number of teeth, and a focal absence of teeth (commonly the
anterior maxillary primary and permanent central incisors

o Facial bones defect: maxillary hypoplasia

 All are collectively known as anterior chamber cleavage syndrome and mesodermal
dysgenesis of cornea and iris. They are also referred to as Axenfeld–Rieger syndrome.

Peter's Anomaly
 major degree of anterior chamber developmental disorder

 corneal opacity associated with a posterior stromal defect  Von Hippel's corneal ulcer

 iris is adherent to the cornea at the collarette

 bilateral and frequently associated with glaucoma and cataract.

Neurofibromatosis
 primarily affects tissue derived from the neural crest, particularly the sensitive nerves,
Schwann's cells, and melanocytes.

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 Ophthalmic involvement

o Iris hamartomas, clinically observed as bilateral, raised, smooth-surfaced, dome-


shaped lesions

o Plexiform neurofibromas of the upper lid, which appear clinically as an area of


thickening of the lid margin with ptosis and an S-shaped deformity

o Retinal tumors, most commonly astrocytic hamartomas

o Optic nerve gliomas, which manifest as unilateral decreased visual acuity or


strabismus and have been observed in 25% of cases

o Ipsilateral glaucoma is also occasionally seen and is usually associated with


plexiform neurofibroma of the upper lid.

Medical management of Glaucoma

Glaucoma Suspect

Glaucoma suspect type I: Normal intraocular pressure, no damage

Glaucoma suspect type II: Normal intraocular pressure, possible damage

Glaucoma suspect type III: High intraocular pressure, no damage

Glaucoma suspect type IV: High intraocular pressure, possible damage

Possible glaucomatous damage

Visual field
Generalized depression
Baring of blind spot
Nasal step < 10°
Relative scotoma < 5°
Statistical field loss index P = 0.05–0.10
Visual function
Reduced color vision
Reduced temporal contrast sensitivity
Abnormal pattern electroretinogram
Optic nerve head
Cup-to-disc ratio > 0.5
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Asymmetry of disc cups > 0.2 cup-to-disc ratio


Disc hemorrhage
Disc pit
Rim area < 1.10 mm2
Vertically oval cup
Diffuse or localized nerve fiber layer defect
Chamber angle
Peripheral anterior synechiae

Risk factors for progression from ocular hypertension to manifest glaucoma

Corneal thickness under 535 microns


Elevated IOP
Increasing age
Enlarged vertical cup-to-disc ratio
Increased pattern standard deviation on static threshold perimetry

Risk factors for progression of manifest glaucoma

Established
Elevated IOP
Over 18 mmHg any of the time
Increased fluctuation of IOP
Increasing age
Exfoliation of the lens capsule
Advanced cupping
Advanced visual field loss

Putative
Sleep apnea
Thin corneas
Nocturnal systemic hypotension

Target pressure
 An IOP of 21 mmHg or lower – the previously sought goal – may not be low enough for
many glaucomatous eyes.

 AGIS: 18mmHg

 lower the IOP to a level that is ‘safe’ for that particular eye

 depends on

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o initial IOP

o degree of existing damage

o how hard the patient has to work to achieve the goal

o the realities of adherence expectations for that invidual

o what potential side effects, complications, and cost that particular regimen might
entail.

 Many formulae available (may refer book for details)

Adrenergic agonists

 1900: Darier treated glaucoma patients with subconjunctival injections of epinephrine

 1920: Hamburger: epinephrine topically to reduce intraocular pressure

 five major types are recognized: alpha 1 & 2, beta 1,2,3

 alpha 1 stimulation: mydriasis, vasoconstriction, elevation of IOP, and eyelid retraction

 alpha 2 stimulation: decreased aqueous humor formation and, probably, increased


outflow of aqueous

 combined A and B agonists: epinephrine

 A2 agonist: brimonidine

 A1 A2 agonist: apraclonidine

 B agonist: isoproterenol

 A antagonist: bunazocin

 B antagonist: timolol

Mechanism of action

 Epinephrine

o increases both conventional and unconventional outflow


 Dipivefrin
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o Prodrug  converted to epinephrine by esterase enzymes in the cornea


 Norepinephrine
o decrease in IOP by increasing the trabecular outflow facility+
o too modest for clinical effectiveness
 Alpha1 Adrenergic agonists

o Phenylephrine
o acts predominantly on alpha 1-adrenergic receptors
o 0.125–10% Vasoconstriction or mydriasis or to break posterior synechiae

 Alpha2 Adrenergic agonists

o Clonidine
o 0.125% and 0.05%,
o central and peripheral adrenergic mechanisms to reduce aqueous humor formation

o Apraclonidine
o reduces the risk of systemic hypotension
o may reduce episcleral venous pressure and, unlike clonidine, may increase trabecular outflow
o peak effect in 1-2 hours, do used before lasr PI etc.

o Brimonidine
o Selective for alpha
o decreases IOP by reducing aqueous formation; in addition, it acts by increasing uveoscleral
outflow.
o effectiveness may be reduced by concomitant administration of non-steroidal anti-inflammatory
agents;
o 0.2%. 0.15% & 0.1%
o cardiovascular instability in infants and is therefore contraindicated in the first 5 years of life.
o Sleepiness and lethargy in <15 years age

 Beta Adrenergic agonists

o Isoproterenol
o Salbutamol

 Dopaminergic agonists

 Nonadrenergic activators of adenylate cyclase

o plant derivative forskolin (non-proprietary name colforsin).

Drugs in clinical use

 non-selective

o Epinephrine

o hydrochloride, bitartrate, and borate

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o 0.5%, 1%, and 2%

o IOP begins to fall in 1 hour, reaches a minimum in 2–6 hours, and returns to baseline in 12–24
hours

o Dipivefrin (Propine)

o 0.1%

o less external irritation, burning, and systemic side effects than does epinephrine

o Side Effects

Lid and conjunctiva: Hyperemia, Burning/stinging, Tearing, Blepharoconjunctivitis, Skin


blanching, Adrenochrome deposits, Madarosis, Ocular pemphigoid

Lacrimal system: Lacrimal stones

Cornea: Epithelial edema, Endothelial toxicity, Epithelial erosion from tarsal adrenochrome
deposits, Adrenochrome deposits, Soft contact lens staining

Iris and uveal tract: Mydriasis and angle closure, Visual distortion/blurred vision, Photophobia,
Iridocyclitis

Retina: Cystoid macular edema

Systemic: Headache/browache, Tachycardia/dysrhythmia, Premature ventricular contractions,


Palpitations
Anxiety/nervousness/pallor/faintness, Tremor, Increased blood pressure, Cerebrovascular
accident, Myocardial infarction, Death

o Contraindications

o severe hypertension

o cardiac disease

o thyrotoxicosis

 Alpha 2 Agonists

o Clonidine

o Side Effects

Systemic: Dry mouth, Fatigue, Drowsiness, Headache, Hypotension, Bradycardia in


neonates, Hypothermia in neonates

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Ocular: Allergy, Blurred vision, Burning/stinging, Follicular conjunctival response,


Hyperemia, Itching, Photophobia

Adrenergic antagonists

1967: Phillips, IV propranolol decreases IOP  topical

Mechanism of action

o B-Adrenergic receptors are found in the ciliary processes which produces aqueous

 Five different topical B-blocking agents are available for clinical use in the United States: timolol,
levobunolol, betaxolol, metipranolol, and carteolol.

Timolol maleate

 nonselective B1 B2 adrenergic antagonist

Prostaglandins

 first identified in seminal fluid in the 1930s

 1955, Ambache identified a substance in iris tissue that he called irin  Irritation

Mechanism of action

 High doses: signs of inflammation & INCREASED IOP

 low doses: DECREASES IOP

 receptor types have been positively identified; DP, EP, FP, IP, and TP.
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 currently available clinical agents: activity at a FP receptor

o Functional: increase in outflow facility without significant effect on aqueous


formation, trabecular outflow facility, or episcleral venous pressure

o Structural: extracellular matrix remodeling, widening of intermuscular spaces


along the longitudinal ciliary muscle bundles, and dissolution of collagen types I
and III.

o Ciliary muscle relaxation which also widens the connective tissue spaces. This is
responsible for the initial fall in IOP with topical prostaglandins

 Latanoprost & Travoprost: FP receptor  increases uveoscleral outfloe

 Bimatoprost ?? – prostamides  increases uveoscleral and trabecular outflow

 Unoprostone ?? – docosanoids

 Tafluprost: DP receptor agonist

Drugs in clinical use

 first prostaglandin analog: PF F2-tromethamine salt (PGF2-TS)

 first usable prostaglandin: Japan. Isopropyl unoprostone (Rescula)

 PHXA34

 PHXA41= Latanoprost= Just R epimer of PHXA34

 Latanoprost (xalatan, phxa41)

o 0.005%

o persist over 24 hours

o no evidence of tachyphylaxis

o prodrug

o NTG, pigmentary glaucoma, steroid induced glaucoma

 Bimatoprost (Lumigan)

o 0.03%

o prostaglandin F2 alpha analog

o slightly improved pressure control or works in a greater percentage of patients


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o most potent of these agents but with a concomitant increase in local side effects

o higher incidence of hyperemia

 Travoprost (Travatan)

o 0.004%

o Isopropyl ester of a potent prostaglandin F2 alpha agonist

o Prodrug

o greater duration of action – over 40 hours from a single dose

o the only with a different preservative than BAK  Travatan Z™

 Isopropyl unoprostone (uf-021,rescula™)

o No longer available

o docosanoid

o prodrug derived from a pulmonary metabolite of PGF2.

o 0.06% or 0.12%

o BID dosage

o Side effects: conjunctival hyperemia, corneal epithelial defect, and headache. Increased iris
pigmentation

 Tafluprost

o is a new difluoro prostaglandin analog undergoing clinical trials in Japan.

o prostanoid EP3 receptor

o It is approved in some countries (Demark since April 2008 and Germany since May
2008)

o preservative free 0.0015% solution for once daily dosing.

Side effects

 conjunctival hyperemia B >> T >> L >> U

 foreign body sensation

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 eye irritation

 superficial punctate keratopathy

 Activation of latent herpes simplex

 Periocular hyperpigmentation B >> L

 Darkening and increase in length of the eyelashes (able to induce resting follicles to
enter the growth phase and prolong it)

 vellus hairs & poliosis

 anterior uveitis

 CME: 1–2% of Aphakic or pseudophakic eyes. (Mx: NSAID can be given along with it) ,
should be discontinued before surgery and resumed after 6-8 weeks of surgery

 choroidal effusions

 darkening of iris color (stimulate the formation of extra melanin granules in the individual
iris stromal melanocytes due to increase in tyrosinase transcription associated with
latanoprost administration)

 Systemic: joint or muscle pains, dry mouth, backache, bitter taste, and allergic skin
reactions, wheezing, Urge incontinence

Carbonic anhydrase inhibitors

 MOA

o CO2 + OH --- CA - HCO3

o Direct Effect: decreases CA activity in non-pigmented epithelium of the ciliary processes

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o Indirect Effect:

 interfere with this buffering system and indirectly reduce aqueous humor formation.

 Vasoconstriction in the anterior uveal tract

 decreased episcleral venous pressure

 CA is present in renal cortex, gastric mucosa, red blood cells (RBCs), lung, pancreas, and central
nervous system (CNS).

 in the eye: corneal endothelium, non-pigmented iris epithelium, pigmented and non-pigmented
epithelium of the ciliary processes, Müller cells, and retinal pigment epithelium

 mostly its type 2 in the eye, (3,4 also present)

 CAI in full doses reduce aqueous humor formation by about 40%. This means that at least 60% of aqueous
humor formation is independent of the enzyme CA.

 More than 99% of the enzyme activity must be inhibited before aqueous production is reduced

Topical carbonic anhydrase inhibitors

 original agent (ethoxzolamide gel)  not successful

 Finally, dorzolamide & brinzolamide came

Dorzolamide

 Trusopt

 free sulfonamide group and a second amine group

 isoenzymes II and IV > I

 RBC CA is depressed to 21% of normal level

 2% solution is the most effective, BD or TDS

 Also in pediatrics

 Cosopt (with timolol)

Brinzolamide

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 Azopt

 1% TDS or BD

Systemic carbonic anhydrase inhibitors

Acetazolamide

 Diamox

 125 and 250 mg tablets and as a 500 mg sustained-release (SR) preparation

 Oral: IOP begins to drop in 1–2 hours, reaches a minimum in 2–4 hours, and returns to baseline in 4–12
hours.

 IV/IM: IOP begins to fall within minutes, reaches a minimum in 15–30 minutes, and returns to baseline in
4–6 hours.

 5–10 mg/kg every 6 hours

 Serum half life: 4 hours

 plasma acetazolamide concentrations of 4–20 microgram/ml

 actively secreted by the renal tubules and then passively resorbed by non-ionic diffusion.

Methazolamide

 50-100 mg BD

 not actively secreted by the kidneys,

 less bound to plasma protein

Ethoxzolamide

 most potent of the clinically used CAIs

 62.5–250 mg every 4–8 hours

Dichlorphenamide

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 25–200 mg every 6–8

Side effects

 Side effects with TOPICAL


Ocular

Stinging  10%
Allergy
Dryness
Superficial punctate keratopathy  10%
Induced myopia

Systemic

Metallic taste
Urticaria
Neutropenia
Headache
Gastrointestinal distress
Dizziness
Paresthesias
?Aplastic anemia
?Stevens-Johnson syndrome

 Side effects with ORAL


Myopic shift*

Paresthesias of fingers, toes, circumoral region: Decreased dexterity

Electrolyte disturbances: Metabolic acidosis, Potassium depletion associated with


concomitant use of diuretics or corticosteroid, Chloride depletion associated with use of
dichlorphenamide, Uric acid retention

Gastrointestinal: Abdominal cramping/discomfort, Metallic taste to carbonated beverages,


Nausea, Diarrhea*, Anorexia, Weight loss*, Constipation

Genitourinary: Nocturia, Urolithiasis*, Impotence, Frequency with polydypsia* (especially in


the first week of treatment), Hypersensitivity nephropathy*

Central nervous system: Malaise*, Excitement, Elevated cerebrospinal fluid pressure, Fatigue,
Confusion, Depression*, Drowsiness*, Headache, Decreased libido, Vertigo, Irritability*,
Insomnia, Tremor

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Blood dyscrasias: Thrombocytopenia*, Agranulocytosis*, Hyperchromic anemia, Aplastic


anemia*, Neutropenia, Interference with anticholinesterase treatment of myasthenia gravis,
Exacerbation of effect of diphenylhydantoin on bone demineralization, Dyspnea*, Leg cramps,
Hearing loss, Birth defects, Hypersensitivity hepatitis

Dermatologic: Rash, Exfoliative dermatitis* (Stevens-Johnson syndrome), Pruritis, Hair loss,


Flushing, Hirsutism

If you want to start Diamox in a patient with HTN, just check they are not on HCTZ, as it will
accentuate hypokalemia.

 Non Glaucoma use of CAI

o Chromic macular edema

o BIH

o Mountain sickness

Cholinergics

 oldest effective medical treatment

 Laqueur: physostigmine

 Weber: pilocarpine

 MOA

o effect on parasympathetic receptors in the iris and ciliary body.

o Angle-closure glaucoma

 constrict the pupillary sphincter, tighten the iris, decrease the volume of iris tissue
in the angle, and pull the peripheral iris away

 ischemic pupil may not respond

o Open-angle glaucoma

 increasing the facility of outflow

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 stimulate the ciliary muscle, putting traction on the scleral spur and the trabecular
meshwork, which separates the trabecular sheets and prevents Schlemm’s canal
from collapsing

Direct-acting cholinergic agents

Acetylcholine

 not used for the treatment of glaucoma because it penetrates the cornea poorly and is destroyed rapidly
by cholinesterase.

Pilocarpine

 more potent at muscarinic than at nicotinic receptor sites

 0.25–10% - QID

 reduction in IOP that begins in an hour and lasts for 4 to 8 hours

 binds to melanin in the iris and ciliary body, iris color may influence IOP response.

 Alternative drug delivery systems

o Pilocarpine in 1.6% polyvinylpyrrolidone (Adsorbocarpine)

o Soft contact lenses

o Membrane-controlled delivery (Ocusert): 20 ug per hour or 40 ug per hour,

o Pilocarpine gel (Pilopine HS gel)

o Pilocarpine polymer (Piloplex)

Methacholine

 Unstable in solution

Carbachol

 0.75–3% and is administered 3–4 times

 As a substitute for pilocarpine

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Indirect (anticholinesterase) agents

Echothiophate iodide (phospholine iodide)

Demecarium bromide (Humorsol, Tosmilen)

Isoflurophate

Physostigmine (eserine)

Neostigmine (prostigmine)

Side effects

More with indirect acting

Ocular

o Miosis, decreased vision in dim illumination


o Ciliary muscle spasm, fluctuating vision, headache
o Orbicularis muscle spasm, lid twitching, periocular pain
o Vascular dilation, conjunctival and iris hyperemia
o Increased vascular permeability, formation of posterior synechiae,
o postoperative inflammation
o Production or enhancement of angle-closure glaucoma
o Temporary increase in IOP
o Cataract formation
o Stinging, irritation
o Tearing
o Allergic blepharoconjunctivitis
o Cyst of the iris pigment epithelium
o Retinal hole, retinal detachment, vitreous hemorrhage
o Lacrimal obstruction, ocular pseudopemphigoid
o Corneal epithelial staining, vascularization
o Atypical band keratopathy caused by phenylmercuric nitrate preservative

Systemic

o Bronchial spasm, asthma, pulmonary edema


o Nausea, vomiting, abdominal pain
o Weakness, fatigue, muscle spasm – may mimic myasthenia gravis
o Paresthesia
o Prolonged respiratory paralysis after general anesthesia including succinylcholine

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o Toxic reactions to local anesthetics containing an ester linkage group


o Sweating, salivation, lacrimation
o Hypotension, bradycardia
o Nightmares, depression, delusions
o Exacerbation of myasthenia gravis and interference with its drug treatment

Contraindications

 intraocular inflammation or known hypersensitivity

 chronic obstructive airway disease, peptic ulcer, Parkinson’s disease, bradycardia, hypotension,
myasthenia gravis, peripheral retinal degeneration, high myopia, and a history of retinal detachment.

Hyperosmotic agents

Mechanisms of action

o drawing water from the eye into the circulation via the blood vessels of the retina and uveal tract

o decrease aqueous humor production via a central nervous system (CNS) pathway involving
osmoreceptors in the hypothalamus.

Oral agents

Glycerol

 50% solution
 dose of 1.5–3 ml/kg

 lower IOP in 10–30 minutes, reaches a maximum effect in 45–120 minutes, and has a duration of effect
of 4–5 hours

 intense, sweet taste

 given in an iced unsweetened fruit juice or cola base

 disadvantage

o associated nausea and vomiting

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o produces 4.32 kcal/g of energy

o not suitable in DM

Isosorbide

 45% solution

 1.5–4 ml/kgs

Ethyl alcohol

 1.0–1.8 ml/kg of absolute alcohol (about 1–2 ml/kg of a 40–50% solution (80–100 proof )).

Intravenous agents

Mannitol

 2.5–7.0 ml/kg of the 20% solution

 lower IOP in 15–30 minutes, reaches a maximum effect in 30–60 minutes, and has a duration of action of
approximately 6 hours.

 Disadvantages

o cellular dehydration: dementia and disorientation

o intolerable load on patients with congestive heart failure

Urea

 30% solution
 dose of 2.0–7.0 ml/kg
 lower IOP in 15–30 minutes, reaches a maximum effect in 60 minutes, and has a duration of action of 4–6
hours

Side effects

GI: Nausea, Vomiting, Diarrhea, Abdominal cramping

Cardiovascular: Angina, Congestive heart failure, Pulmonary edema

Central nervous system: Headache, Backache, Confusion, Disorientation, Chills, Fever, Subdural hematoma

Renal/genitourinary: Diuresis, Loss of potassium, Urinary retention, Anuria46

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Miscellaneous: Arm pain, Skin slough, Thrombophlebitis, Acidosis, Diabetic ketoacidosis, Hyperosmolar non-
ketotic coma, Urticaria, Laryngeal edema, Anaphylactic reaction, Hyphema, Suprachoroidal hemorrhage

Preservative Free Drops

Clinical Effects on Chronic Glaucoma Medications

Decreased mucus layer of the tear film

Reduced tear secretion, basal Schirmers and TBUT

Increased Rose-Bengal staining of cornea

Foreshortening of the inferior conjunctival fornix

Inflammatory cell infiltration in trabecular meshwork

Currently Available “Preservative Free” Glaucoma Medications

1. Zioptan (tafluprost 0.0015)

2. Cosopt PF (dozolamide/timolol)

3. Timoptic in Ocudose (timolol)

4. Timolast

5. Timolet OD

Currently Available “BAK Free” Glaucoma Medications

1. Travatan Z (travoprst)

2. Xovatra

3. Alphagan P (brimonidine)

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Neuroprotection in Glaucoma

 Kerr’s concept of neuronal death Neuronal death can be conjectured to occur in three
stages: axonal injury, death of the injured neuron and injury to and death of the
neighbouring intact neurons through secondary degeneration.

 Yoles and Schwartz: explain progression of glaucomatous damage despite reduction of


intraocular pressure and the fact that patients with severe pre-existing damage are more
likely to deteriorate despite lower IOPs than those who do not have visual field loss at the
time of diagnosis.

o neurotrophin factor deprivation

o insufficient blood perfusion to the optic nerve head

o Glial cell activation may also be an important factor contributing to RGC death in
glaucoma.

o glial fibrillary acidic protein is significantly increased in glaucoma by astrocytes


and Muller’s cells.

o neuronal damage through release of Cytokines, Reactive Oxygen species or Nitric


oxide.

 Calcium channel Blockers:

o inhibit the entry of Calcium ions into vascular smooth muscle

o protect the optic nerve head by improving vascular perfusion especially in Normal
tension glaucoma.

o Nimodipine has been found to have significant improvement in both visual field
indices and colour vision.

o However, systemic hypotension prohibits extensive use of the drug. Nocturnal


hypotension secondary to antihypertensive medications have been associated with
visual field loss in patients with Normal tension glaucoma.

o Flunarizine, a potent Calcium channel blocker has been found to enhance RGC
survival after optic nerve transaction in mice.

 Antiglaucoma medications:

o Betoxolol posseses both calcium channel blocking activity resulting in


vasodilatation and also exerts actions on retinal ganglion cells by reversibly
blocking glutamate gated currents and subsequent firing of RPG cells.
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o Brimonidine has also been demonstrated to neuroprotective action in animal


studies by its ability to reduce rate of RGC loss and also to increase endogenous
Brain derived neurophin factor.

 N-methyl-D-aspartate Antagonists:

o The NMDA receptor is an ion channel that gets activated when glutamate and
glycine bind to the receptor complex thus allowing calcium to enter the cell.
Excessive activation of the NMDA signaling cascade leads to “Excitotoxicity”
wherein intracellular calcium overloads neurons and causes cell death by
apoptosis. This excessive calcium activates destructive pathways in the
mitochondria, stimulates nitric oxide production and certain mitogen activated
protein kinases.

o An NMDA antagonist Memantine has shown great promise as an effective agent for
the prevention of GON progression. Memantine is a noncompetitive NMDA receptor
antagonist derived from Amantidine which blocks the toxic effects of glutamate
without significant effects on normal cellular function.

o Eliprodil is another noncompetitive antagonist which provides protection from


glutamate mediated cytotoxicity to retinal ganglion cells.

 Nitric oxide synthetase inhibitors:

o Local production of nitric oxide may play a significant role in the development of
multiple neurodegenerative diseases. It is produced by the enzyme nitric oxide
synthetase. It has been seen that production of nitric oxide at the ONH has a role
in the pathogenesis of glaucoma. Therefore pharmacological agents that inhibit
NOS-2 may have therapeutic value.

o Aminoguanidine, a selective inhibitor of iNOS (inducible nitric oxide synthetase)


has been seen to reduce retinal ganglion cell loss by about 70% in a rat ocular
hypertension model. A prodrug of an iNOS inhibitor, L-N (1-iminoethyl) lysine 5-
tetrazole amide has also been found to have similar results.

 Antioxidants:

o These agents neutralize other suicide triggers like reactive oxygen species
emanating from the glutamate cascade. Free radical scavengers like Catalase,
superoxide dismutase and vitamins C and E mop up loose byproducts during
secondary degeneration.

 Neurotrophins:

o These agents increase retinal ganglion cell survival and are capable of being
produced by retinal cells. Delivery of this agent by means of a viral vector has

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been tried in animal models. Another method of delivering this agent to the eye
could be repeated intravitreal injections which may not be well tolerated.
Systemic administration will be difficult as these are large protein molecules and
cannot readily cross the blood-retinal barrier. Implantation of a sustained release
intraocular implant or a transscleral delivery are other modalities of drug delivery
but none of these strategies have proved to have any value.

 Vaccination:

o T lymphocytes localize in damaged neural tissue in case of injury. It has been


found in animal models that a subset of these T lymphocytes have receptors
specific to proteins of the myelin sheath, such as MBP, which have a protective
effect on ganglion cell death ,suggesting thereby that a vaccine based on myelin
sheath antigens may have therapeutic value in treating optic nerve damage and
possibly glaucoma. However, MBP immunization and T cells specific for MBP induce
a severe paralytic condition known as EAE thereby preventing its use as a vaccine.
A vaccine called COP-1 has shown to reduce ganglion cell death in animal models
and therefore this vaccine may play a role in glaucoma therapy as it does not have
side effects like MBP immunization.

 Ginkgo Biloba extracts:

o Ginkgo Biloba influences a number of biological processes including intracellular


signaling and neutralizing reactive oxygen species .It is claimed to be effective in a
variety of disorders associated with ageing and has also been found to improve
both peripheral and cerebral blood flow. Therapy with Ginkgo biloba extracts has
shown to improve preexisting visual field defects in normal tension glaucoma in
one clinical trial.

Laser therapy for Glaucoma


Tissue effects of laser

Thermal effects (photocoagulation, photovaporization)

 long exposures by lasers at relatively low energy  coagulative effect that shrinks collagen

 Higher energy  can vaporize tissue.

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Photodisruption
 optical breakdown of molecules

 short-pulsed

Photoablation
 excimer lasers (excited dimer)

 intense ultraviolet energy beams

 193 micron: argon fluoride

 308 nm: xenon chloride

Photochemical
 Photodynamic therapy:

 destruction of tumors previously sensitized by hematoporphyrin derivatives and precise chorioretinal


thermal damage for subretinal neovascularization

Laser treatment for internal flow block

 The technique of creating laser holes through the trabecular meshwork is known as laser
trabeculopuncture (trabeculotomy). This technique is the earliest attempt to treat
glaucoma using laser technology, but it has not been successful in people or in animal
models.

Laser peripheral iridotomy


 Meyer-Schwickerath in 1956: xenon

 Firm indications

o Acute angle-closure glaucoma

o Chronic angle-closure glaucoma with peripheral anterior synechiae

o Intermittent angle-closure glaucoma with classic symptoms of angle closure


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o Aphakic or pseudophakic pupillary block

o Anatomically narrow angles and signs of previous attacks

o Narrow-angle eye with acute angle-closure glaucoma in the fellow eye

o Incomplete surgical iridectomy

o Luxated or subluxated crystalline lens

o Anterior chamber lens implant

o Nanophthalmos

o Pupillary block from silicone oil after vitrectomy

o Mixed-mechanism forms of glaucoma when filtering surgery might not be necessary


for adequate pressure control

 Relative indications

o Critically narrow angles in asymptomatic patients

o Younger patients, especially those who live some distance from medical care or
who travel frequently

o Narrow angles with positive provocative test

o Iris–trabecular contact demonstrated by compression gonioscopy

 Lenses

o Abraham iridotomy lens

o Wise lens modicafication

o Pollack lens

 11 to 1 o’clock, avoid 12 o’clock (air bubble can block view, if bleeding occurs then
visual axis can be spared)

 good sign of complete perforation

o direct observation of the anterior lens capsule

o Transillumination

o direct the aiming beam into the depths of the iridotomy, If the opening is through-and-through
the iris, the aiming beam will disappear

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Complications

 Iritis

 Pressure elevation: commonly occurs 1–4 hours after

 Cataract: lens capsule perforation, or localized cataract

 Hyphema: common after Nd:YAG,

 Corneal epithelial injury

 Endothelial damage

 Corneal stroma: if poorly focused, spectacular effect called corneal emphysema

 Failure to perforate: second treatment required in 1–3 days.

 Late closure: 15 micron hole is adequate for aqueous flow through the eye. To prevent subsequent
closure, it is best to have an opening of at least 100 micron.

 Retinal burn

 Aphakia and pseudophakia with pupillary block

Laser iridoplasty (gonioplasty)


 used to contract the peripheral iris, pulling it away from the angle.
 100–200 micron spot size and 100–30 mW at 0.1 second

Lasers in malignant glaucoma


 If ciliary processes are visible through an iridotomy, 2–4 ciliary processes can be shrunk with an argon or
solid-state laser using 200–800 mW for 0.1 second with a 100–200 micron spot size
 Disruption of ciliovitreal compression: Nd YAG hyaloidtomy

Laser treatment for outflow obstruction

Argon Laser trabeculoplasty


 Krasnov: temporary lowering of intraocular pressure (IOP) after ‘trabeculopuncture’

 in 1979 by Witter and Wise

 Mechanisms:

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o The first theory suggested that these contraction burns over the angle mechanically helped
adjacent trabecular beams open wider, thus allowing easier aqueous outflow.

o The second theory suggested that the laser irradiation stimulated trabecular endothelial cells to
replicate

o laser spot is aimed at the junction of the pigmented and nonpigmented trabecular
meshwork.

 50 micron spot is used with 0.1 second exposure time, 400–500 mW, 3–4° apart so that approximately
20–25 spots are created per quadrant

 initial treatment of 180 degrees, 50 spots  4-6 weeks

 Success

o Positive predictors of a favorable response include heavy pigmentation of the


trabecular meshwork, age (older patients), and diagnosis (pigmentary glaucoma,
primary open-angle glaucoma, and exfoliation syndrome).

o typically reduces 20% to 30% below baseline levels with ALT.

o 77% success rate at 1 year, to 49% at 5 years, and to 32% at 10 years

 Argon LTP is effective in most forms of open-angle glaucoma

 Retreatment: Repeat argon LTP is often not advised.

Selective laser trabeculoplasty


 pulsed-frequency doubled neodymium (Nd):YAG laser was introduced in 1998 by Latina
 selectively target pigmented tissue and minimize any collateral effect.
 selective photothermolysis, relies on selective absorption of a short laser pulse to generate and spatially
confine heat to pigmented targets within trabecular meshwork cells.
 short pulse durations of 3–10 ns

 mechanism

o SLT results in a stretching of the trabecular meshwork beams, their mobility is increased
following SLT

o targeted only the pigmented cells  Recruitment of macrophages  chemical mediators that
regulate the outflow rate  Elevated interleukin levels

o stimulates endothelial cell replication

 400 micron spot size (Significantly larger spot size of SLT)

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 energy level for SLT treatment is set initially at 0.8 mJ  decreased in 0.1-mJ intervals until minimal
bubble formation

 Success

o ALT and SLT have equivalent efficacy

o lowers the intraocular pressure by 24% to 35%

o Positive predictors of success include higher baseline intraocular pressure and the
2-week postlaser pressure response.

o no apparent structural damage with SLT, repeat SLT is generally safe

Contraindications
 inadequate visualization of the trabecular meshwork

 hazy media

 closure of the iridocorneal angle

 corneal edema

 uveitic glaucoma

 juvenile glaucoma (usually)

 patient age of 35 years or less

 need for IOP-lowering greater than 7–10 mmHg.

Complications
 Intraocular pressure elevation

 Sustained intraocular pressure increase

 Hyphema

 Peripheral anterior synechiae

 Iritis

 Uveitis

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Excimer laser trabeculostomy ELT

 first used clinically in 1998


 xenon-chloride (XeCl) 308-nm wavelength excimer laser energy is fiber-optically transmissible and
became the wavelength of choice for these types of ab-interno fistulizing procedures
 delivers photoablative energy to precisely remove the tissue which obstructs fluid outflow with minimal
thermal damage to adjacent tissue
 inner wall of Schlemm’s canal without damaging the outer wall of Schlemm’s canal or the collector
channels. It creates no filtering fistula or bleb.

Laser sclerostomy
 better results than repeat trabeculectomy in eyes that have undergone prior filtering surgery

Cyclodestructive Procedures

 Indications

o reserved for use in patients who have failed previous treatment with medicines or
surgeries.

o beneficial in controlling pain in blind, painful eyes, and may allow the patient to avoid
removal of the eye as long as visualization or ultrasound reveals no intraocular tumor.

o Types of glaucoma

 Refractory med & surgically uncontrollable gl.

 Post PK glaucoma.

 NVG.

 Cong glaucoma.

 Aphakic/pseudophakic OAG.

o who are not willing to undergo filtration surgery, those who cannot undergo surgery
owing to medical conditions, and patients in underdeveloped countries.

 Contraindications

o phakic patient with good vision

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o Marked uveitis

o Blind nonpainful eye as this includes risk of SO in other eye

 Principle: light absorption by melanin pigment

 Various wavelengths

o Ruby laser (694)

o Argon laser(514)

o Nd YAG Laser(1064)

o continuous wave diode laser(804)

Types

1. noncontact transscleral CPC

2. contact transscleral CPC

3. cyclocryotherapy (CCT)

4. transpupillary CPC

5. ECP.

 avoid the 3 and 9 o'clock meridians in order to avoid coagulating the long posterior ciliary
arteries and causing anterior segment necrosis.

1. noncontact transscleral CPC

o Nd YAG

o contact lens developed by Bruce Shields may or may not be used

o Eight to ten burns are placed 1.5 mm from limbus

o Energy levels of 4 to 8 J

2. contact transscleral CPC

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o most popular

o contact diode laser probe that is relatively small and portable (G-Probe of Gaasterland;
IRIDEX Corporation, Mountain View, CA).

o Krypton and Nd:YAG lasers can also be used

o Diode: 1.5-2.0 W, 1.5-2.0 SEC, 25-30 spots

o The energy level is titrated to be slightly below (250 mW lower) the audible pop, because
audible pops are associated with greater inflammation and hyphema.

o Grading of gross lesions

0. NO EFFECT:

1. MILD: Inconsistent, just noticeable shrinkage.

2. Moderate: Just noticeable shrinkage, slight tissue blanching.

3. Good: Obvious shrinkage & tissue blanching, pig dispersal,occ. popping

4. Excessive: Hole formation with large burn.

o Success rate of DLCP –38 to75%.

o Re treatment required in 42% of pt.

o Average IOP reduction—35-50% of pre-treatment levels.

3. Cyclocryotherapy

o nitrous oxide cryosurgical unit is used to cool the 2.5-mm probe to -80 °C, which is
placed approximately 1 mm posterior to the limbus for 60 seconds.

4. Transpupillary Cpc

o continuous-wave argon laser is delivered via a biomicroscope.

o Goldmann-type gonioprism and scleral depression are necessary to visualize ciliary


process

o Laser settings of 50- to 100-µm spot size, 700 to 1000 mW, for 0.1 second

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5. Endoscopic Cyclophotocoagulation

o limbal approach

o pars plana approach

COMPLICATIONS

 Common: Conjunctival burn, AC inflammation, transient IOP rise

 Uncommon: conjunctival inflammation, severe uveitis, anterior vitritis, >10 IOP rise

 Rare:

o sterile hypopyon.

o Hyphema.

o Vit. H’age.

o Hypotony<2mm.

o Phthisis bulbi.

o Vision loss(2 lines or more)

o CME/macular pucker.

o Malignant glaucoma

o Neurotrophic c ulcer.

o Pupillary distortion/staphyloma formation

o Scleral perforation

Surgical Management of Glaucoma

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Glaucoma Outflow Procedures

 Incisional surgery to relieve outflow block:

o external filtration (e.g., trabeculectomy or full-thickness filtering procedures)

o internal filtration (e.g., cyclodialysis)

o it may essentially disrupt the trabecular meshwork from the outflow pathway
(e.g., trabeculotomy ab externo and goniotomy).

 lowest IOP that can be tolerated by the eye is generally above 5 mmHg.

External Filtration Surgery

 new drainage pathway  allows aqueous to pass from the anterior chamber into the subconjunctival
space.

 15 micron diameter hole that (theoretically) is adequate for total aqueous flow out of the eye.

 two basic types

o Guarded Procedures

 Trabeculectomy: the filtering sclerostomy is protected from excessive flow either by


partially closing it with a scleral flap or by suturing techniques.

o Full-Thickness Procedures (Scheie procedure)

 thermal sclerostomy, posterior or anterior lip sclerectomy, or Elliott’s trephination

 Conjunctival Flaps

o Limbal based vs Fornix based

o IOP control is comparable with both techniques

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Fornix - Based

Advantages : intraoperative benefits and better bleb morphology

Disadvantage : increased incidence of early bleb leaks

Limbus - Based

Advantage : more secure wound closure

Disadvantages : late complications of leaks & infection

 Wise closure

 Khaw closure

Guarded Filtration Procedure


Trabeculectomy

 1960: Cairns, modern-day trabeculectomy (modification of Sugar’s procedure)

 most commonly used surgical procedure in patients with glaucoma

 Standard technique

 Moorfields Safer Surgery System technique

o fornix-based conjunctival flap, Lewicke anterior chamber maintainer, a standardized punch


technique, and a combination of adjustable and releasable sutures.

 Success rates:

o 80% in first 2 years in POAG (without antimetabolites)

o 50 % in 5 years (without antimetabolites)

o 65% at 5 years and (with antimetabolite)

o 40% over 10 years (with antimetabolite)

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Surgical Technique
 Any type of regional anesthesia

 superior limbus, because inferiorly high rate of infections

 fixation or traction suture is used to keep the eye in down

o corneal traction suture in the quadrant of the planned surgery

o superior rectus traction suture

 A limbus or fornix-based conjunctival flap is made with Westcott scissors

 Scleral flap dissection: thickness should be between one-half and two-thirds,


approximately 1 mm into clear cornea-to cross scleral spur

 corneal paracentesis is made before opening the globe

 Two radial incisions into cornea extending 1 mm behind, then rectangular piece of tissue
is removed or Kelly or Gass punch used to enter AC

 peripheral iridectomy: recommended in patients with shallow AC

 scleral flap is sutured initially with two interrupted 10–0 nylon sutures

 anterior chamber is filled through the paracentesis, and the flow around the scleral flap is
observed

 Externalized releasable sutures

 Conjunctival closure

 fill the anterior chamber BSS through the paracentesis track to elevate the conjunctival
bleb and test for leaks

Post operative Care

 Topical steroids, antibiotics and cycloplegics

 Digital ocular compression applied to the inferior sclera or cornea through inferior eyelid

 focal compression with a moistened cotton tip at the posterior edge of the scleral flap

 in early failure (e.g., vascularized and thickened blebs): subconjunctival 5-FU (5 mg in 0.1
mL solution) and anti-VEGF therapy

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 Laser suture lysis

 necessary when there is a high IOP, a flat filtration bleb, and a deep anterior chamber.

 without magnification with the edge of a four-mirror Zeiss gonioprism or with the Hoskins
laser suture lens

 High-magnification suturelysis contact lenses are commercially available (e.g.,


Mandlekorn lens or Blumenthal lens)

 Gonioscopy must be performed prior to the laser treatment to confirm an open


sclerostomy with no tissue or clot occluding its entrance

 Anti-VEGF Therapy for Bleb Vascularization

o potentially lead to a healthier bleb with less scarring and better long-term IOP
control.

o subconjunctival anti-VEGF (bevacizumab 1 mg) after glaucoma surgery

o proximal to blebs after trabeculectomy at the earliest sign of vascularization

 Bleb Needling

o In cases of subconjunctival–episcleral fibrosis an external revision or bleb needling


can be tried

o 27- or 25-gauge needle is used to cut the edge of the scleral flap and restore
aqueous outflow.

o Entry of the needle tip into the anterior chamber beneath the flap is important but
should be undertaken with extreme caution in phakic eyes

o Repeated subconjunctival injections of 5-FU after revision increases the probability


of success.

Antimetabolites

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 Antimetabolites are usually used during trabeculectomy surgery to prevent bleb failure
due to scarring by the wound healing process. The most commonly used antimetabolites
are 5-fluorouracil (5-FU) or mitomycin C (MMC).

o BAPN (beta-aminoproprionitrile), an inhibitor of lysyl oxidase, blocks collagen cross-


linking
o 5-FU inhibits fibroblast proliferation by acting selectively on the S phase of the cell
cycle
o mitomycin-C is an alkylating agent that decreases DNA synthesis by causing DNA
cross-linking
o Colchicine affects collagen cross-linking and thereby decreases scar formation.

 5-Fluorouracil
o pyrimidine analogue which blocks DNA synthesis.
o sponge may be removed after 30 seconds to 5 minutes.
o can be injected into the subconjunctival space intraoperatively or in the early
postoperative period.
o Advantages
o Inexpensive
o No dilution or dosage calculations required
o Stable at room temperature
o Better safety margin than MMC
o Disadvantages
o Less effective than MMC
o Multiple injections
o High incidence of corneal toxicity

 MMC
o antitumor antibiotic isolated from Streptomyces caespitosus.
o DNA cross-linker which inhibits fibroblast proliferation.
o Advantages
o More potent than 5-FU
o Results in lower intraocular pressures
o Disadvantages
o Expensive
o Reconstituted from powder
o Not stable at room temperature
o Possibly more complications

READ -- Releasable Sutures

 introduced by Schaffer et al, but popularized by Cohen and Osher.

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 minimized the incidence of shallow anterior chamber and hypotony in the early
postoperative period

 combines the benefits of partial thickness filtration surgery by allowing a formed anterior
chamber in the immediate post operative period along with those of full thickness
filtration surgery by allowing a freer flow of aqueous and consequently lower intraocular
pressures (IOP) once the sutures are removed in the later post operative period.

 Seventy percent of eyes had a reduction in IOP more than 5 mm Hg if released within the
first week compared to 20% after the third week

 Astigmatism

Technique

 start sclera  end cornea

 start cornea  end cornea

Filtering Bleb

 Filtration surgery creates a fistula between anterior chamber & subconjunctival


epithelium. Successful filtration surgery is associated with a blister-like elevation of the
conjunctiva over the sclerostomy site “a filtration bleb”. The appearance of filtration
bleb is an important factor in evaluating the outcome of glaucoma filtering surgery.

 The ideal bleb is diffuse with microcystic conjunctival changes, mildly elevated, with
moderate thickness of wall AND with relative paucity of vessels.

 Types:

I. WELL FILTERING: Thin, polycystic, Transconjunctival flow of aqueous

II. Shallow ,diffuse: Thin-walled with relatively avascular appearance, Microcysts


usually seen

III. Poor Filtering: Flat with engorged surface blood vessels, No microcystic spaces,
Episcleral fibrosis

IV. ENCAPSULATED: Localized dome shaped elevation, Hypertrophied tenon”s capsule,


2-8 weeks post-op

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 Histology:

o While subepithelial connective tissue apears thin in normal persons ,failed blebs
show a large amount of collagen with hypercellular response ,mainly of activated
fibroblasts.

 Causes of failure

o Extraocular- Subconjuctival\ episcleral fibrosis, encapsulated bleb

o Scleral- tight suturing, scarring of scleral bed

o Intraocular- blockage of sclerostomy, blockage of internal opening

o EARLY FAILING BLEB-bleb- within the first postoperative month.

 internal obstruction by blood, fibrinous clot, vitreous, iris, scleral tissue,


fibrosis, membrane

o LATE FAILING BLEB- Those with a history of good bleb function with adequate IOP
control for at least 1 month

 Subconjunctival and episcleral fibrosis most common cause

 Prevention of Failure

o Topical steroid used routinely in the post-operative period& then tapered after 6-
8 weeks

o Adjunctive anti-metabolites- Adjunctive mitomycin-C or 5-FU inhibits fbroblast


proliferation & subsequent scar tissue formation

 Management:

 Conservative

o Topical steroids

o Digital compression-if compression is effective, IOP will fall & bleb will appear
inflated

o Focal compression-at the edge of scleral flap under slit-lamp

o Suture manipulation- (7-14 days post-operatively)- Releasable sutures cut or


released, Argon laser suture lysis

o Needling of encysted bleb- using Mitomycin-C or 5 FU using a tuberculin syringe

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o ND Yag laser can be used as internal (gonioscopic reopening of blocked ostium) or


External (trans-conjunctival revision of a late failing bleb dye to episcleral fibrosis)

 Surgical

o Where conservative measures alone are not enough to treat the condition

o In grade III shallow AC– ie in cases of lens-corneal touch urgent surgery is


indicated

o External conjunctival cryopexy

o Thermal coagulation by cautery,argon laser,N-D Yag laser

o Direct suturing of the conjunctival hole

o Patching with corneal scleral graft

o Free and pedunculated conjunctival graft

 Complications

o Flat AC and endothelial decompensation

o Endophthalmitis

o Peripheral anterior synechiae formation

o hypotony

o Choroidal detachment

o Blebitis

o Hypotonic maculopathy

Moorfields Bleb Grading System

 height and to vascularity in three zones: central bleb, peripheral bleb and non-bleb

(1) Central bleb area: an estimation into five categories of percentages (0%, 25%, 50%,
75%, and 100%) is made of the relative size of the central demarcated area of the bleb
relative to the visible conjunctival field superiorly. Often this is confined to the area

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over the scleral flap; in a uniform bleb, central and peripheral estimations are
congruent.

(2) Peripheral bleb area: the maximal extent of the bleb is assessed using a similar scale
of five percentage estimations. This parameter assesses the maximal diffusion area of
the bleb, as evidenced by slight bogginess or guttering at the edges.

(3) Bleb height: in reference to the standardized photographs, the maximal central bleb
height is scaled as flat, low, moderately elevated, or maximally elevated.

(4) Vascularity: considered the most important prognostic parameter for bleb failure, this
scale is applied to three areas: the central demarcated bleb, the bleb’s peripheral
extent of diffusion, and the surrounding non-bleb conjunctiva. Five grades of
vascularity are used: avascular, normal, mild vascularity, moderate vascularity, and
severe vascularity. Subconjunctival blood is also notated.

Indiana Bleb Grading System

(1) Bleb height: this describes the maximal vertical elevation of the bleb: flat, low, medium,
or high.

(2) Horizontal extent: the maximal horizontal extent is described relative to limbal clock
hours: <1 hr, 1–2 hr, >2–<4 hr, and >4 hr.

(3) Vascularity: five simple categories are elaborated: white and avascular, cystic and
avascular (with microcysts), mild vascularity, moderate vascularity, and extensive vascularity.

(4) Seidel leakage: in the testing for a bleb leak with a fluorescein strip at the slit lamp, the
bleb is categorized as showing no leak, multiple pinpoint leaks without streaming, or brisk
streaming within 5 seconds.

Full-Thickness Filtration Procedures

1. Thermal sclerostomy (scheie Procedure)


2. Sclerectomy: Posterior lip sclerectomy, Anterior lip sclerectomy
3. Trephination
4. Iridencleisis: Historical procedure, from observation that that inadvertently incarcerated iris in
the wound after intracapsular cataract extraction or surgical iridectomy sometimes resulted in IOP
lowering

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Implantable Collagen Matrix


 Ologen (Optous, Roseville, California) collagen-matrix implant

 marketed initially as OculusGen™ and currently as Ologen™ and iGen™

 consists of a collagen-based scaffold containing thousands of microscopic pores. The


implant is placed directly over the scleral flap and influences the healing process by
forcing fibroblasts and myofibroblasts to grow into the pores and secrete connective tissue
in the form of a loose matrix

 decreased scar formation and improved surgical success over trabeculectomy performed
without the adjunctive use of antifibrotic agents

Glaucoma Drainage Devices

 The first attempt to implant a drainage device was made by Rollet and Moreau in 1907
when they performed a double paracentesis and used horse hair

 Molteno in 1969  functioning implant with an episcleral plate and tube

 basic design:

o plastic tube that extends from the anterior chamber to a plate

o Explant: disc or encircling band beneath conjunctiva and Tenon’s capsule

 posterior explant stimulates fibrovascular encapsulation and allows aqueous to passively


flow across a pressure gradient, across the capsule wall to be subsequently absorbed by
conjunctival capillaries and lymphatics

 Types of implants :

1. Non-valved / non restrictive implants: Molteno, Baerveldt, Schocket.

2. Valved / restrictive implants: Ahmed, Krupin, Joseph, Optimed, White.

 Indications:

o Previously failed filtration procedures in acquired or congenital glaucoma

o Neovascular glaucoma.

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o Silicone-oil glaucoma.

o Aphakic / Pseudophakic glaucoma.

o Complicated glaucoma- eg Aniridia/ICE/ Uveitis

o Traumatized eyes with conjunctival scarring

o Dryness which precludes standard glaucoma surgery

Ex-Press Mini Glaucoma Shunt

 small stainless-steel implant that is inserted through the limbus into the anterior chamber
under a 4 to 5-mm–wide partial-thickness scleral flap

 several models with different shapes and sizes (length range from 2.4 to 2.9 mm).

 internal lumen diameter varies between 50 µm (most commonly used) and 200 µm.

 outer 250-350 um

 more uniform, consistent, and reliable postoperative course than standard


trabeculectomy

 can be placed either subconjunctivally or under a scleral flap. Owing to an unacceptably


high rate of choroidal effusion and SCH subconjunctival placement is no longer
recommended.

Complications:
Early- occurring within few days-

1) Hypotony / choroidal detachment: Can be prevented by temporarily obstructing the tube


lumen. Manage by reforming anterior chamber via the paracentesis, ligating or even removing
the tube. Cause is excessive flow of aqueous through the tube, rarely leakage around the tube
arising from too large an entry incision.

2) Hyphema- transient and usually resolves, in cases of neovascular glaucoma it may be


massive enough to cause IOP rise and tube blockage. The latter maybe prevented by anterior
retinal cryopexy in NVG cases prior to surgery.

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3) Corneal endothelial touch – usually seen when the tube has not been placed accurately or
the bevel has not been cut in the proximal orifice. The other reason for this complication is
shallow anterior chamber. This maybe exacerbated by blinking or eye rubbing.

4) Elevated IOP: Early post operative IOP elevation may be due to obstruction of tube by
fibrin, blood, iris tissue, or vitreous. This occurs in 5-11% of cases. Laser tube revision by
Nd:YAG/ Nd:YLF is on temporary benefit. But still this non invasive procedure should be
attempted first. Intracameral injection of tissue plasminogen activator is an expensive option,
but may work. The ultimate solution is tube revision. Late IOP elevation, is usually due to an
excessively thick fibrous capsule. This can be dealt by removing a portion of the capsule
beneath the conjunctival flap.

5) Hypotony Maculopathy:

6) Suprachoroidal Hemorrhage

7) Flat AC

8) Aqueous Misdirection

Late complications – occurring within weeks or months:

1. Increased IOP- cause may be tube blockage, non functioning bleb, resurgence of disease
eg uveitis, rubeosis, fibrous ingrowth.

2. Endothelial touch - intermittent or constant leads to endothelial decompensation. If


progressive tube repositioning and tight anchorage maybe indicated.

3. Tube exposure/ migration/ extrusion - Tube exposure incidence varies from 0- 15%. To
prevent it prophylactic use of donor sclera to cover it in areas of scleral thinning, adequate
anchorage to scleral bed by sutures, the superficial flap must be evenly dissected. Treatment
of this complication may be initially by rotating an adjacent partial; thickness flap to cover
the tube but ultimately a fresh site needs to be selected. Tube migration is usually due to
slippage of anchoring sutures.

4. Insufficient aqueous absorption inspite of patent tube – thickened fibrous capsule over
the distal end of the tube or less surface area of drainage. Persisting inflammation is a
common culprit and a stringent antifibrotic regimen consisting of steroids and non steroidal
anti inflammatory

5. Others - Cataract progression in almost 36%/ Endophthalmitis/ Retinal detachment.

6. Ocular Motility Disturbance : Exotropia, hypertropia, or limitation of ocular rotation,


usually occurs with larger, plates eg; Baerveldt and Krupin implant but can also occur with
smaller plates. This is usually due to bulk effects or from direct impingement on or scarring of
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the rectus/ oblique muscles. Diplopia occurring commonly with Baerveldt’s implants led to
the discontinuation of 500 mm sq. explant and its redesigning with fenestrations to allow
fibrous ingrowth, thereby reducing the bleb height. Placing the implant in the spacious
supero-temporal quadrant minimizes this complication

7. Loss of visual acuity: Occurs due to hypotonous maculopathy, retinal detachment, vitreous
hemorrhage and cystoid macular edema.

8. Epithelial down growth- in fornix based conjunctival flaps careful closure of conjunctiva
keeping the epithelium facing away from the tubes is advocated. This complication is
minimized by limbal based flaps.

Non-penetrating glaucoma surgeries

Principle: Removal of deep scleral flap, external wall of SC, corneal stroma behind the
anterior trabeculum and the DM, thus creating a scleral lake →Aqueous leaves the AC through
the intact Trabeculo-Descemet’s membrane (TDM)

Indications:

 When conventional trabeculectomy has failed:

o OAG

o High myopia

o PDG

o PXG

o Aphakic/ pseudophakic Glaucoma

 Where NPGS are safer

o Congenital and juvenile glaucoma

o SWS

o Aniridia and anterior segment dysgenesis

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o Post uveitis glaucoma

Contraindications:

Narrow angle glaucoma

Post-trauma angle recession glaucoma

Post-laser trabeculoplasty

NVG (absolute contraindication)

Deep sclerectomy

 Aka nonpenetrating trabeculectomy and external trabeculectomy.

 Epstein and Krasnov in the late 1950s

 Deep sclerectomy involves creating two partial-thickness scleral flaps with the second,
deeper flat at 99% depth. During the procedure, the inner flap is removed, creating an
intrascleral lake.

 MOA:

o Aqueous flow through Trabecular-Descemet’s Membrane (TDM): The resistance


offered by TDM is significantly low enough to ensure low IOP and high enough to
maintain deep AC

o Aqueous reabsorption:

 Subconjunctival filtering bleb

 Intrascleral bleb

 Suprachoroidal passage

 Episcleral drainage via schlemn canal

 Advantage

o minimal intraocular inflammation

o risk of flat anterior chamber is very low

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 Postoperative Care

o infection prophylaxis and treatment of inflammation

o steroids

o trabeculodescemetic membrane is so thin that it can break and the implant can
enter the anterior chamber if at all, so do gonioscopy in follow up

o The bleb can become encapsulated and can benefit from needling.

Schlem's Canal-based Surgery

Indications

1. Canal-based procedures have been used successfully in the full spectrum of open-angle
glaucomas from congenital to adult primary open angle including pigmentary and
pseudoexfoliation.

2. Open angles are the only prerequisite.

3. Clear media is necessary for the ab interno-based Trabectome and iStent.

4. Canaloplasty is performed ab externo and can be performed in the presence of hazy


media or scarred cornea.

Canaloplasty

 The first nonpenetrating procedure to utilize a microcatheter iTrack

 Mechanism of Action

o canal is dilated, the TM is tensioned, and after removal of the deep scleral flap, a
Descemet's window is created

o primarily by enhancing conventional circumferential outflow through the canal and


the collector system

 Hypotony, choroidal detachment, and bleb infections were reported in less than 1% of all
cases. The most common side effect is transient hyphema.

 safer than trabeculectomy.

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 200-µm–diameter catheter with a 250-µm tip is attached to a battery-powered light source


with a second attachment to facilitate injecting viscoelastic to dilate the canal upon
removal

Trabectome

 minimally invasive ab interno procedur

 Mechanism of Action

o ablate the juxtacanalicular area to eliminate the area of resistance, creating


direct flow into the canal and collectors.

 The presence of blood reflux at the conclusion of the procedure is confirmation of


reduced outflow resistance. This is a transient complication that usually resolves within 1
to 2 weeks.

 allows sparing of the conjunctiva; thus, future filtering or drainage device surgery will not
be compromised.

iStent

 trabecular micro-bypass system

 heparin-coated, nonferromagnetic, surgical-grade titanium stent approximately 0.3 mm in


height

 smallest implant placed in humans

 Mechanism of Action

o iStent re-establishes outflow and reduces IOP.

o placing more than one stent provides greater IOP lowering.

Viscocanalostomy

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 Proposed by Robert Stegman 1991.

 Surgical steps being the same as in Deep sclerectomy upto Schlemm’s canal being
deroofed. Then by a paracentesis the IOP is lowered, the 2 cut ends of the SC are
cannulated by a 165 um blunt needle and a high molecular sodium hyluronate is slowly
injected into the canal. Upto 1-2 clock hrs of the canal is a-traumatically dilated. The
slow injection is repeated 6-7 times on each side. A 2nd site of injection is between
superficial scleral flap and deep scleral bed to display the potent anti-inflammatory
properties of the high visco