Julie Jantzi, O.D.

Mallory Cranmer, O.D.

Neal Shastri, O.D.
Noushin Ahmed, O.D.
Seidenberg Protzko Eye Associates
 Epidemiology

• ~15 per 100,000 in U.S. each year

• Causes 10% of blindness in U.S.
• Third leading cause of blindness in developed countries
• Prevalence varies by location, age, and date of study
• Highest among >65 years of age
• Females
• Chronic and unilateral
• Anterior Uveitis most common
 Pathophysiology

• Inflammation of the uvea

• Infectious, traumatic,
neoplastic, autoimmune,
idiopathic

• Inflammatory response:
chemical mediators result
in vasodilation, increased
vascular permeability, and
chemotaxis of
inflammatory cells in eye.
Inflammatory Cascade

Photo Credit: Studyblue.net

 Classification

Location Duration Type

Anterior Uveitis Acute Granulomatous
Intermediate Chronic Non-
Uveitis granulomatous

Posterior Uveitis
Panuveitis
 Symptoms

• Redness

• Pain

• Photophobia

• Epiphora

• Blur

• Scotoma

• Floaters
Photo Credit: www.sunglasswarehouse.com
Clinical Signs
Anterior to Posterior
 Eyelid

• Vitiligo

• Nodules

• Lesions

Photo credit: http://www.pcds.org.uk/clinical-guidance/vitiligo

Conjunctiva & Episclera
• Ciliary Flush

• Diffuse injection

Photo credit: http://www.mastereyeassociates.com/eye-

diseases-treatments/iritis---anterior-uveitis/
 Cornea

• Keratic Precipitates
• Granulomatous
• Non-granulomatous

• Fibrin

• Pigment

• Corneal Edema

• Band Keratopathy*
Photo Credit:
http://www.optometricmanagement.com/articleviewer.aspx?artic
leid=71765
 Anterior Chamber

• Cells

• Flare (serous)

• Pigment

• Hypopyon (purulent)

• Plasmoid (Fibrinous)

• Hyphema + hypopyon
(sanguinoid)
Grading
 Iris
• Nodules
• Busacca
• Koeppe

• Posterior synechiae

• Heterochromia

• Granulomas

• Atrophy (stromal)*

• Cyclitic membrane
formation*
 Angle

• Nodule (Berlin)

• Vascularization

• Peripheral anterior
synechiae

• Secondary Ciliary body

detachment*
 IOP
• Hypotony

• Secondary Glaucoma*

(Van Bus-kirk EM: Clinical Atlas of Glaucoma. Philadelphia: WB Saunders, 1986.)

 Vitreous

• Cells

• Flare

• Snowball Opacities

• Snowbanking
• Active
• Inactive Photo credit: Mohawk Valley Retina

• Vitreal Strands
 Retina

• Retinal/choroidal
inflammatory infiltrates

• Sheathing of arteries/veins

• Retinal detachment

• Schwartz syndrome

• RPE hypertrophy/atrophy

• Atrophy/swelling of retina,
choroid, optic nerve head Photo Credit: Oculist.net

• Macular edema
 Major Complications

• Cataracts

• Glaucoma

• Band Keratopathy

• Cystoid Macular Edema

 Differential Diagnoses
• Infections

• Non-infectious

• Masquerade syndromes

• Large cell Lymphoma, retinoblastoma, leukemia, malignant melanoma

• Juvenile Xanthogranuloma

• Pigment dispersion syndrome

• Retinal Detachment

• Retinitis pigmentosa

• Ocular Ishchemic Syndrome

Non-Infectious Uveitis
ANTERIOR UVEITIS: POSTERIOR UVEITIS:

• Acute nongranulomatous Iritis • Collagen Vascular Disease

and Iridocyclitis
• White Dot Syndromes
• Chronic Anterior Uveitis

PANUVEITIS
INTRMEDIATE UVEITIS:
• Sarcoidosis
• Pars Planitis
• Sympathetic Ophthalmia
• Multiple Sclerosis
• Vogt-Koyanagi-Harada Syndrome

• Behcet Disease
Acute Anterior Uveitis
HLA-B27 diseases
Glaucomatocyclitic crisis
Lens associated uveitiis
Postoperative inflammation: IOL associated
 HLA-B27 DISEASES
• Class 1 surface antigen

• Seronegative spondyloarthropathies are strongly associated with acute

anterior uveitis and HLA-B27

• spondylitis and sacroiliitis

Include:

• Ankylosing spondylitis

• Reactive arthritis syndrome

• Inflammatory bowel disease

• Psoriatic arthritis
 Ankylosing
Spondylitis
• lower back pain and
stiffness
• men, 20-40‟s
• HLA-B27: 90%
• dx: sacroiliac imaging
studies - “bamboo spine”

Ocular findings (40%):

• acute anterior uveitis - fibrin
and hypopon not
uncommon
 Reactive Arthritis Syndrome

• Triad: nonspecific urethritis,

polyarthritis, and conjunctivitis
often accompanied by iritis

• HLA-B27: 95%, young adult men

• arthritis in knees, ankles, feet,

sacroiliitis in 70% of pts

Ocular findings:

• Mucopurulent and papillary

conjunctivits, acute
nongranulomatous iritis in 10%

Keratoderma blennorrhagicum
 Psoriatic Arthritis

• Inflammatory arthritis occurs in 30% of

pts with chronic psoriasis

Inflammatory Bowel Disease • cutaneous changes, distal phalangeal

joint inflammation, ungula involvement

• 12% of ulcerative colitis pts • 20% may have sacroiliitis

and 2.4% of Chrons
disease pts develop acute • 25% develop iritis
anterior
• 20% have sacroiliitis
• 60% HLA-B27 positive
Glaucomatocyclitic Crisis

• Recurrent unilateral mild

acute iritis

• Elevated IOP, corneal edema,

fine KPs, low-grade cell and
flare, slightly dilated pupil

• Duration: hours to days

• Associated with HLA-B54

 Lens-associated
Uveitis
• Immune reaction to lens
material: granulomatous or
nongranulmatous
• KPs can be small or large,
cells mild to severe, hypopon,
PS, elevated IOP, vitritis
Phthisis bulbi, persistent uveitis,
or glaucoma often occurs in
these eyes
Postoperative
inflammation:
IOL-associated
Mild inflammation to UGH syndrome
(uveitis-glaucoma-hyphema)
• IOL implantation can activate
complement cascade, cellular deposits
on IOL, synechiae formation, capsular
opacification
• Retained lens material
• iris chafing caused by the edges or
loops of IOL – mechanical irritation and
inflammation
 Drug Induced Uveitis
• Systemic Drugs • Topical Drugs

1. Rifabutin 1. Metipranolol

2. Miotics
2. Bisphosphonates
3. Prostaglandins
3. Sulphonamides
• Intracameral Drugs
4. Diethylcarbamazine
1. Cidofovir
5. Cidofovir (intravenous)
2. Antibiotics

3. Urokinase

• Vaccines
Chronic Anterior
Uveitis
Juvenile idiopathic arthritis
Fuchs heterochromic iridocyclitis
Idiopathic iridocyclitis
 • most common systemic disorder
Juvenile Idiopathic associated with iridocyclitis in
children
Arthritis
• iritis develops within 5-7 yrs of
onset of joint disease

• RF: female, pauciarticular onset,

ANA

• negative RF

• eye is usually white and un-

inflamed, some pts do not have
pain

• Ocular findings: fine KPS, flare and

cells, posterior synechiae, cataract,
glaucoma, band keratopathy,
vitreous debris, ME, chronic
hypotony, phthisis
Fuchs
Heterochromic
Iridocyclitis

• Unilateral uveitis,
heterochromia, iris stromal
atrophy, small white stellate
KPs scattered diffusely over
endothelium
• synechiae almost never
forms but glaucoma and
cataracts often occur
• Associations with
toxoplamosis, HSV, and
CMV infections
 Idiopathic Iridocyclitis

• In many cases of chronic iridocyclitis the cause is unknown

Intermediate Uveitis
Pars Planitis
Multiple Sclerosis
 • absence of infection and systemic
disease
Pars Planitis
• 85-90% of intermediate uveitis
cases

• 5-40 yrs, healthy individuals

• associated with HLA-DR15 and HLA-

DR51 alleles

Clinical Characteristics:

• 80% bilateral

• Ocular manifestations: spillover into

anterior chamber, vitreous cells,
snowballs, peripheral phlebitis and
retinal venous sheathing

• Ddx: Syphilis, lyme, sarcoidosis, MS,

toxicarasis, lymphoma
Multiple Sclerosis

• 30% of MS pts will get

uveitis
• 15% of pts with pars planitis
will eventually develop MS
• women, 20-50 yrs
• HLA-DR2 and DR15
• Granulomatous anterior
uveitis, intermediate uveitis,
panuveitis
 Posterior Uveitis
Collagen Vascular Diseases
Inflammatory Chorioretinopathies of Unknown Etiology
Collagen Vascular Disorders

Systemic Lupus Erythematosus

Polyarteritis Nodosa and Microscopic polyangiitis

Wegener‟s Granulomatosis
 • Multisystem autoimmune
Systemic Lupus connective tissue disorder
Erythematosus
• Type 3 hypersensitivity reaction:
Antibody-immune complexes
precipitate and cause further
immune response

• Affects heart, nervous system,

joints, skin, lungs, blood vessels,
liver, and kidney

• Women, 15-45 years

• Labs: ANA

• Malar “butterfly” rash -70-80%

 Clinical findings

Ocular manifestations in 50%

• Keratoconjunctivitis sicca
(20%)
• Lupus retinopathy -CWS
• Cutaneous lesions on the
eyelids
• Scleral inflammatory
disease
• Neuro-ophthalmic disorders
• Retinal vasculopathy
• In rare cases uveitis
 Polyarteritis nodosa
and microscopic
polyangiitis

• Systemic vasculitis –
necrotizing inflammation of
medium and small sized
arteries
• 40-60 yrs, men, hepatitis B
• Ocular involvement in 20%
• Mortality rate of untreated
PAN is 90% by 5 yrs
• Labs: p-ANCA, ESR, CRP,
tissue biopsy
 Wegener‟s
Granulomatosis
• Triad: necrotizing granulomatous vasculitis of upper and lower respiratory
tract, glomerulonephritis, necrotizing vasculitis of small arteries and veins

• Involvement of paranasal sinuses is most characteristic feature

• Ocular involvement in 50%:

-- orbital involvement: pseudotumor, cellulitis, dacryocystitis

-- anterior, intermediate, or posterior uveitis

--scleritis (necrotizing), uveitis, retinal vascular involvement

Dx: tissue biopsy, chest x-ray, CRP, ESR, c-ANCA

 White Dot Syndromes

• Group of chorioretinopathies that are inflammatory in

nature presenting with discrete, multiple, yellow-white
lesions

• Symptoms: photopsia, blurred vision, floaters,

nyctalopia, enlarged blind spot

• Young females
• Acute posterior multifocal placoid
pigment epitheliopathy (APMPPE)

• Birdshot choroidopathy

• Multiple evanescent white dot

syndrome (MEWDS)

• Acute zonal occult outer retinopathy

(AZOOR)

• Multifocal choroiditis (MCP)

• Punctate inner choroidopathy (PIC)

• Serpiginous choroiditis
 Panuveitis
Sarcoidosis
Sympathetic Ophthalmia
Vogt Koyanagi-Harada Syndrome
Behcet Disease
Sarcoidoses
• Multisystem non-caseating
granulomatous disorder of
unknown etiology

• Intrathoracic : 90%, intraocular:

50%

• Affect lymph nodes, skin, eyes,

CNS, bones and joints, liver, and
heart

• African American, females, 20-50

years

• Dx: chest x-ray, lymph node biopsy,

elevated ACE and lysozyme levels
 Ocular Findings

• can involve any ocular tissue

• most common: Anterior
granulomatous uveitis
–mutton fat KP‟s, koeppe and
busacca iris nodules, synechiae
• Posterior segment in 20% of
ocular sarcoidosis
--vitreous infiltration “string of
pearls” or “snow balls”
--granulomas seen in retinal,
choroid
--perivascular sheathing,
occlusive vascular disease
• Eyelid granulomas
• Conjunctival nodules
• Lacrimal gland infiltration
 Sympathetic Ophthalmia
• Bilateral, diffuse granulomatous, non-necrotizing
panuveitis

• Autoimmune inflammatory response toward ocular

antigens – delayed hypersensitivity to melanin
containing structures?

• Occurs after surgery or trauma to an eye

• 2% of uveitis cases

• Anterior Uveitis: mutton fat KPs, PS, thickening of

iris from lymphocytic infiltration

• Posterior vitritis, dalen-fuchs nodules,

peripapillary choroidal lesions, exudative RD
 • Cell-mediated autoimmune process
driven by T lymphocyctes directed
Vogt-Koyanagi- against self-antigens associated with
melanocytes of all organ systems
Harada Syndrome
• Higher association in darkly pigmented
ethnic groups

• 4% of uveitis referrals in US

• Chronic, bilateral, diffuse,

granulomatous panuveitis with
integumentary, neurologic, and auditory
involvement
Stages

Acute: bilateral granulomatous

anterior uveitis, vitritis,
thickening of choroid, edema
and hyperemia of optic nerve,
multiple serous retinal
detachments

Convalescent: “sunset glow”

fundus, skin changes: vitiligo,
alopecia, poliosis

Chronic recurrent: repeated

bouts of uveitis
Behcet Disease

• chronic, relapsing,
occlusive systemic
nongranulomatous
vasculitis of unknown
etiology
• recurrent oral ulcers,
skin lesions, genital
ulcers, ocular
inflammatory disease
(70%)
• can affect all portions
of uveal tract
 Ocular Findings
80% bilateral
• Anterior uveitis:
hypopyon in 25% of
cases
• Posterior segment:
necrotizing retinal
vasculitis affects both
veins and arteries
• Optic nerve affected in
25% of pts
• Visual prognosis is
guarded -25% VA <
20/200
Infectious Uveitis

•Viral – Herpetic, CMV

•Fungal
•Protozoal - Toxoplasmosis
•Helminthic - Toxocara
•Bacterial – Syphilis, Lyme, Tuberculosis, other
 Viral

• Herpes Simplex:

• Usually iritis is a keratouveitis but can be: corneal,

cutaneous, retinal
• arborized
• +/- KPs, +/- Hypopyon
• HSV-1 is generally oral-labial HSV-2 generally genital
infections, although crossover does occur.

Image: C. Blake Perry. Source: http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/HSV-epithelial-keratitis.htm

 Viral

• Herpes Zoster

• 72 hours PHN
• ¼ ocular involvement
• Infiltrative pseudodendrites (negative stain)
• Typically elderly and immunocompromised
Image:Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 223. Print.
•
Viral
ARN
• VZV>HSV>CMV
• Immunocompetent
• Starts unilateral but 36%Fellow eye
• Within 6 weeks of onset
• Painful, Floaters, LOV
• Peripheral „creamy‟ necrosis that spread,
occlusive vascular involvement, Panuveitis
• Poor Prognosis, RD in 75%
• PORN
• VZV mainly
• Immunocompromised
• Posterior pole involved early
• Patchy confluent necrosis, weak or
absent uveitis, no vascular involvement
• Poor Prognosis, RD in 70%
Images: Baumal, Caroline et al. Duane‟s Ophthalmology ,2006.‟Acute Retinal
Necrosis and Progresive Outer Retinal Necrosis Syndromes Accessed online:
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v3/v3c028.html#ref
 Viral

• CMV
• CD4 <50-100
• Most common opportunistic infection in AIDS
• In congenital cases + birth defects
• Before HAART ~30% of CD4<50
• After HAART incidence decreased 75-80%
• May start by looking like CWS (small infiltrates)
• Perivascular hemorrhages, white necrotic retina, frosted
branches /vasculitis
Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 796. Print.
 Protozoal
• Toxoplasmosis
• Toxoplasma gondii
• Undercooked meat /cat feces
• Most common posterior uveitis in immunocompetent
individuals
• Often acquired in utero (0.2-1% of pregnancies)
• Further Trimester = increased chance of exposure, worst if
acquired early (spontaneous abortion)
• Majority do not develop ocular manifestations
Image: Tabbara. Khalid. „Toxoplasmosis‟. Duane‟s Ophthalmology 2006. Accessed online:
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c046.html
 Protozoal

• Toxoplasmosis

• „Headlights in the fog‟

• Focal chorioretinal scar with adjacent necrosis and dense
vitritis
• With AIDS may have multiple lesions
• Often self-resolving over months
• May use sulfadiazine, pyramethamine, steroids.
Image: Tabbara. Khalid. „Toxoplasmosis‟. Duane‟s Ophthalmology 2006. Accessed online:
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c046.html
Helminthic Parasites

• Toxocaraisis
• Ingesting eggs of Toxocara
• Dogs >cats
• Acquired through soil, or uncooked food
• Particularly affects kids with pica
• Yellow white mass with tractional component, may have
vitritis.
• Often leads to TRD
• Treat uveitis, consider anti-helminthics (albendazole)
Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 834. Print.
 Bacterial
• Syphilis
• Treponema pallidum
• „Great Mimicker/Masquerader/Imitator‟
• Enters through intact mucosa
• Ocular Syphilis in 2‟ and 3‟ stages (2-6 mo after)
• Uveitis most common ocular manifestation (up to 10%)
• Affects immunocompetent or immunocompromised

Image: „Syphilis‟. WebMD. Accessed Online: http://www.webmd.com/sexual-conditions/guide/syphilis

 Bacterial
• Syphilis
• Dilated iris capillaries (iris roseola)
• Chorioretinitis, „salt and pepper‟
• Vasculitis, vitritis, neuroretinitis, CNV, optic neuritis
• Granulomatous or non-granulomatous uveitis
• Argyll Robertson
• Interstitial Keratitis
• Tests:
• Nontreponemal (VDRL / RPR)
• Treponemal (FTA-ABS / MHA- TP)
• Tx: Penicillin
Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 800. Print.
 Bacterial
• Lyme

• Borrelia burgdorferi
• 1: rash (e. migrans)
• 2: dermatologic, neurologic, cardiac
• 3: Late arthritis, cranial and peripheral nerves
• 50% reported no hx of tick bite
Image: Sources for Rashes: Poster: "Looking for a Bull's-Eye Rash? Look again - erythema migrans can take many
forms. A collaborative effort between the Maryland Department of Health and Mental Hygeine and the Lyme
Disease Research Foundation of Maryland Maryland.http://www.bayarealyme.org/get-help/lymes-many-symptoms
 Bacterial
• Lyme

1. Conjunctivitis early
2.Motility / CN palsies, optic neuropathy, PTC,
chorioretinitis, uveitis
3. Stromal keratitis, symblepharon
ELISA, Western Immuoblot
Tx: Doxycycline, amoxicillin, if needed ceftriaxone

Image: Pediatric Associates of Connecticut. „Tick Bites and Lyme Disease, Accessed Online:
http://www.pediatricdoc.com/newsletter.cfm?nid=625
 Bacterial
• Tuberculosis

• Mycobacterium tuberculosis
• Incidence: Annually ~9.3 million patients worldwide
• Communicable: inhaled aerosolized droplets
• Primarily involves the lungs
• Uveitis is common
• Cough, fever, night sweats
• Caseating necrotic granulomas
• CXR
• PPD / Mantoux testing
• TB blood tests: interferon-gamma release assays (IGRAs)
Images taken from wikipedia . Accessed online: http://en.wikipedia.org/wiki/Tuberculosis_diagnosis
 Bacterial
• Tuberculosis

• Granulomatous anterior, intermediate or posterior uveitis

• Vasculitis with choroiditis, or choroidal tubercles
• Phlyctenular conjunctivitis
• Tx: Rifampin, Isoniazid, Pyrazinamide, Ethambutol
Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 808. Print.
 Infectious
Endophthalmitis
• Endogenous (<10%)
• Systemic via blood stream
• Organisms causing endocarditis and GI tract are primary sources,
usually with sepsis, immunocompromise, IV drug abuse,
catheders.
• Typically less pain and inflammation, and can be bilateral

• Exogenous
• Trauma, Surgery, Infection
• Acutely is usually gram + (normal flora)
• Decrease in occurrence over the last 30 years.
• Bleb-associated may occur at any time.
• Acute 0.061-0.3%
• Delayed 0.2-18% (variable reports)
Image taken from „Endophthalmitis‟ by the American Academy of Ophthalmology 2013. Accessed Online:
http://www.aao.org/theeyeshaveit/red-eye/endophthalmitis.cfm
Infectious
Endophthalmitis
• EVS
• used <6 weeks, for cataract PO (Acute Onset)
• Blur (94%), red eye (82%), pain (74%), hypopyon
(86%)
• No view of retinal vessels in 79%
• Red reflex present in only 32%
• Immediate vitrectomy if LP or worse.

• B scan
• Tx: culture, Vancomycin/Amikacin/Ceftazidime +/-
Dexamethasone
 Masquerade
Syndromes
Accounts for nearly 5% of all patients with uveitis at tertiary referral.

Neoplastic Masquerade Nonneoplastic Masquerade

• Lymphoma • Retinitis Pigmentosa
• Uveal melanoma • Ocular Ischemic Syndrome
• Retinoblastoma • Retinal detachment
• Juvenile xanthrogranuloma • Intraocular Foreign Bodies
• Metastatic tumors • Pigment Dispersion Syndrome
 Lymphoma
• 5th to 7th decade of life

• 25% ocular involvement

• 15% ocular as initial presentation

• 56% with ocular involvement develop

CNS involvement

• Variable uveitic presentations

unresponsive to therapy

• Can mimic chronic uveitis

Lymphoma: Ocular Findings

• Benign reactive uveal • Anterior uveitis

lymphoid hyperplasia
• CME
• Mobile, fleshy
episcleral/conj mass

• Retinal findings: classic

creamy-yellow sub-retinal
infiltrates with overlying
RPE detachments
mimicking sarcoid or
birdshot
 Lymphoma

• Diagnosis • Treatment
• MRI • Intravenous and
• Cerebrospinal fluid intravitreal methotrexate
analysis • Radiation & IV
• Tissue diagnosis Cytarabine
(definitive method)
• >60 years = chemo only
• <60 years = combination
radiation & chemo
• Prognosis = poor
Uveal Melanoma
• 5% ocular inflammation
• Episcleritis, ant/post
uveitis, endophthalmitis
• Ultrasound: low internal
reflectivity
Retinoblastoma
• 1-3 % with ocular
inflammation
• White pseudohypopyon
• Conjunctival chemosis
• Diffuse infiltrating variant
• 4-6 years old
• Limited visibility of fundus
 Juvenile
Xanthogranuloma
• Occurs before age 1

• Red-yellow skin lesions

• Lesions can involve iris =

spontaneous hyphemas

• Skin of eyelid involved,

globe usually spared

• Treatment: topical,
periocular, systemic
steroids
 Metastic Tumors

• Adults • Metastic melanoma: brown

• Most common: Cutaneous
Melanoma
• Lung, GI, breast
• Vitritis, serous detachment,
CME
spherules in retina
• Others: white-yellow
• Perivascular sheathing,
necrotizing retinitis, retinal
vasculitis

• Iris nodules, NVI, high IOP

• Anterior uveitis

• Bilateral and multifocal

• Rare
 Nonneoplastic
Masquerade
• RP
• Waxy disc pallor,
attenuation of arterioles,
bone-spicule mid-periphery
• +FHx
• Nyctolopia
• Vitritis, CME
• ERG depressed early

Source: http://www.rpfightingblindness.org.uk
 Ocular Ischemic
Syndrome
• Males >65
• CC: decreased vision, mild
pain
• Corneal edema, A/C
reaction, flare>cells, NVI,
NVA,
• decreased IOP (ischemia),
high with NVG
• Mild disc edema, dilated
tortous veins
• mid peripheral hemes
• NVD/NVE
• FA
• Delayed arteriole filling
• Diffuse leakage
• Capillary non-perfusion
• Carotid doppler > 90%
diagnostic
• Treatment
• Endarterectomy
• Topical corticosteroids &
cycloplegics
• PRP for neo
• Anti-VEGF injection
• 5 year mortality rate of
patients 40%
• Transient improvement,
usually worsens
 Retinal Detachment
• Chronic Peripheral
• Photoreceptor outer
Rhegmatogenous
segments may be present
• AC reaction in AC simulating
inflammatory response
• Vitreous inflammatory &
pigment cells • IOP elevated, OAG

• Good vision, may worsen • Schwartz syndrome

due to CME

• DFE with scleral

depression

• Peripheral demarcation
lines, subretinal fluid,
retinal breaks, subretinal
fibrosis, peripheral cysts
http://gridironforgirls.blogspot.com
Intraocular FB Pigment Dispersion Syndrome

• Chronic inflammation • Pigment released from iris

and/or ciliary body
• Mechanical, chemical,
toxic, or inflammatory • Simulates anterior uveitis
inflammation of ciliary
body

• Gonio, ultrasound, CT of
eye/orbits

• Complications:
proliferative
vitreoretinopathy and
endophthalmitis
Management and
Treatment
Cycloplegics and mydriatics
Corticosteriods
Immunomodulating Agents
Pressure-lowering medications
 • These opthalmic
preparations block the
Cycloplegics responses of the iris
sphincter and the
Mydriatics accommodative muscle of
the ciliary body to
cholinergic stimulation,
producing pupillary dilation
(mydriasis) and paralysis of
accommodation
(cycloplegia)
• Tropicamide 1%,
cyclopentolate and atropine
have both properties
• Phenylephrine has only
mydriasis.
www.lookfordiagnosis.com/mesh_info.php?term=
Cycloplegics
Purpose:
•To break or prevent posterior
synechiae and to relieve ciliary
spasm induced photophobia.
•Short acting vs. long acting
cycloplegics
•Dosing depends on the extent
of inflammation
•(1-2xdaily atropine, 3xdaily
tropicamide and
phenylephrine)
www.opsweb.org/?page=Scien
tificExhibit
portalcodgdh.min-
saude.pt/index.php/Dissecção
_

Posterior synechiae
Antigen-dependent lymphocyte activation and STEROID/NSAID
activation sites

Cunningham, Emmett. Practical approach to the use of corticosteroids in patients

with uveitis. Can J Opthalmol 2010; 45:352-8
Corticosteroids:

Produced through the

hypothalamus, pituitary and adrenal axis
(HPA) to control inflammation in uveitis

http://pubs.niaaa.nih.gov/publications/arcr
344/images/stephens01.png
 Common uses of
corticosteroids
-Mainstay of initial therapy

Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with

uveitis. Can J Opthalmol 2010; 45:352-8
Ocular Surface
Penetration
Durezol>Pred
Forte> FML
larrazabaleye.com/cvep.html
www.revoptom.com/content/c
/216
www.revoptom.com/content/c
/216

TOPICAL STEROIDS
 Topical Steroids

Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can
J Opthalmol 2010; 45:352-8
 Topical Steroids

•Suspension vs.
emulsion
•Concentration vs.
efficacy
www.pharmainfo.net/reviews/microemulsions-
novel
 Potency

Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with

uveitis. Can J Opthalmol 2010; 45:352-8
Adverse Effects of
Corticosteroids
 Adverse Effects continued

www.amardeepeyecare.com/ptosis.html
continued

www.lpeyecare.com/eyeconditions/252-2
 Intravitreal Injections

Cunningham, Emmett. Practical approach to the use of corticosteroids in

patients with uveitis. Can J Opthalmol 2010; 45:352-8
 NSAIDS

• www.uninet.edu/cin2001-old/conf/bala/bala.html

• www.thedrugmonitor.com/coxi.html
 Systemic NSAIDS
• Complications of prolonged use:

-myocardial infarction

-hypertension

-stroke (selective Cox-2 inhibitors)

www.mayoclinic.com/health/medic

www.ohioinjurylaw.com/ohio-
attorney/medical-mal
 Immunomodulating
Medications (IMT)
• Antimetabolites

• T cell signaling Inhibitors

• Alkylating Agents

• Biologic response modifiers

www.riskindoc.com/new_psoria
 Indications for IMT
 inadequate response of uveitis to corticosteroid therapy for greater than 3
months with doses exceeding 5-10mg/day.

 contraindications to corticosteroid use:

1. (diabetes, hypertension, peptic ulcer, GERD, immunocompromised

state, psychiatric conditions)

2. exacerbated side effects

3.chronic corticosteroid dependence

www.fortiusfitness.com/blog/steroi
d-side-effects
 Precautions
 No infection present

 No hepatic or hematologic contraindications

 Close physician follow up

 Teratogenic

mamaprayed.blogspot.com/2012/08/if-you-give-m
 Antimetabolites
• Azathioprine, methotrexate, mycophenolate mofetil

• Azathioprine (purine nucleoside analogue)

-interferes with DNA replication and RNA transcription

-found beneficial in VKHsyndrome, int. uveitis, Behcet uveitis, sympathetic

opthalmia and necrotizing scleritis

-GI side effects (nausea, upset stomach) are cause for D/C.

-CBC, LFT every 4-6 weeks.

-Thiopurine S-methyltransferase (TPMT) testing (metabolizes 6-

mercaptopurine,ie 6-MP)

www.lookfordiagnosis.com/mesh_info.php?term
 Methotrexate
• Folic Acid analogue

• Inhibitor of dihydrofolate
reductase and it’s DNA
replication

• Causes extracellular
accumulation of adenosine to
create an anti-inflammatory
effect.

• Useful for JIA (first line choice

IMT treatment for
children), sarcoidosis, panuveiti
s, various other types of uveitis

• Prospective study for IV inj. for

refractory uveitis and uveitic www.humira.com/jia/what-is-jia.aspx
CME.
 Mycophenolate Mofetil

• Inhibits inosine monophosphate dehydrogenase

and DNA replication

• Side effects: reversible GI distress, diarrhea;

20%pt. pop.

• CBC monthly

• 85% effectivity in chronic uveitis patients and a

good second choice IMT for children.
 T Cell Signaling Inhibitors

Cyclosporine and tacrolimus:

• Calcineurin inhibitors- disrupt

T-cell receptor signal
transduction and down regulate
IL-2 transcription and CD4 T
lymphocyte receptor expression.

Sirolimus:

• Non-calcineurin inhibitor-
disrupts T cell signaling that
inhibits Ab production and B-
lymphocytes.
www.bdbiosciences.com/research/tcell/reg
 Cyclosporine

• SE: Nephrotoxicity and systemic hypertension;

paresthesia,hypertrichosis.

• BP, CBC, serum creatinine monthly.

• Used for int. uveitis and posterior uveitis cases from

Behcets and VKH.

• Used in combination with corticosteroids for modest

improvement
 Tacrolimus

• AE: nephrotoxicity

• Low dose and increased potency to cyclosporine

• Less risk of hypertension and hyperlipidemia

• Useful for chronic int. and posterior uveitis.

 Sirolimus
• One open-label, prospective study it was found useful in
treatment for refractory noninfectious uveitis

• GI side effects

• Under active investigation for use in treating uveitis

 Alkylating Agents
Cyclophosphamide

• Active metabolites alkylate purines in DNA and RNA, creating

impaired DNA replication and cell death

• Cytotoxic to dividing and resting lymphocytes

• AE:myelosuppression, hemorrhagic cystitis, sterility

Chlorambucil

• Interferes with DNA replication

• AE:myelosuppression, sterility

Treatment for int. uveitis, VKH, SO, Behcet

Significant AE: increased risk for malignancy (leukemia, various cancers)

 Biologic Response
Modifiers
Infliximab

• Chimeric, monoclonal IgG1k antibody against TNFalpha

• Treatment for Behcet, sarcoidosis and VKH. Some HLA

B27 ant. uveitis

• Drug induced toxicity (lupus, systemic vascular

thrombosis, CHF, malignancy, demyelinating disease and
vitreous hemorrhage)

• +PPD, contraindication

• Adalimumab, less AE, same effectiveness

 Alternative Therapy Under
FDA Investigation
• Rituximab:chimeric monoclonal antibody against CD20
positive cells (B lymphocytes)

• Daclizumab: monoclonal Ab to IL-2

• IFNalpha2a: antiviral, immunomodulatory and

antiangiogenic effects (leukopenia and thrombocytopenia
side effects)
 Management/Follow up
• Encounter visit determines
extent of ocular inflammation
(ant., int., panuveitis, etc).

• Make a differential list and

send out for further pertinent
lab work to confirm/rule out
differentials.

super-trainer.com/fitness-business-becoming-a-bu
 Anterior Uveitis
• Cycloplegic

• Steroid

• Dosage depends on severity

• Follow up in 2-3 days

• If 2-3 additional follow up

appt. prove no
improvement, referral to
uveitis specialist

medlibes.com/entry/anterior-uveitis
Intermediate/Posterior Uveitis

• Determine extent of
inflammation, if anterior
involvement, start on
cycloplegic and steroid.

• Refer to retinal specialist for

periocular steroid injections (if
deemed non-infectious)

• Intravitreal injections for

chronic anterior uveitis or
inflammation not responsive
to periocular injection

www.retinaeye.com/uveitis.html
 Uveitic Treatment
Adverse Effects
• Steroid responders:

Need to lower IOP by utilizing beta blockers, alpha2

agonists,CAI, prostaglandins and their combinations
where appropriate.
Case #1

• 70+ yr old cauc. male

• Redness, mild pain, blurry

vision in the right eye.

• Slit lamp: 2+ AC WBC

reaction; florrid NVI,NVA,
corneal edema with descemet
folds; IOP 16mmHg OD
 Differentials?
• Neovascular glaucoma

• OIS

• PDR
 OIS!

• DFE: mid-peripheral blot hemorrhages

• No CME, NVD, NVE

• Tx: Prednisolone Forte q2hrs, Atropine BID OD

• Referral to retinal consult for PRP and possible injections of anti-vegf

• Contact PCP for carotid doppler, echocardiogram, EKG

 Case #2
• 17 yr cauc. female

• CC:
redness, pain, photophobia, bl
urry vision

• Review of systems was

unremarkable

• Second episode, first episode

two years ago in GA.
 Review of Systems
• General - Weight loss, fatigue, fever Skin - Rash, nodules, changes in
nails

• Neck - Lymphadenopathy

• Respiratory - Cough, wheezing

• Cardiac - Chest pain/discomfort, dyspnea

• Gastrointestinal - Hepatomegaly, diarrhea, frequent bowel movements

• Genitourinary - Delayed secondary sexual characteristics

• Musculoskeletal - Muscle or joint pain, arthritis, back pain, limitation

of motion

(refer to uveitis.org for more information and questionnaire)

 Differentials?
• JIA, lyme disease, lupus, sarcoid

• ?????

• Ran pertinent lab tests for her age (CBC c diff.,ANA, ACE,
Lyme titer,ESR,RF, HLA B27)

• Durezol q2hrs, Atropine BID OD. Pledget of 10%

phenylephrine to break posterior synechiae

• CBC with diff., lyme titre, RF, ANA, ACE, serum lysozyme

• Blood results…negative. Consult with uveitis specialist.

Case 3
 Chief Complaint

• 46 year old WM
• Redness OS x 5 days, gradually getting worse
that is constant throughout the day
• (+) photophobia, epiphora
• ( - ) eye pain, flashes, floaters, cold sores
• He was seen at Patient First 3 days ago where
they diagnosed him with shingles over the left
eyelid, noting ocular involvement
• Treated with 20 mg Pred, mild pred taper and 1
gm of Valtrex tid x 10 days
 History

• Medical History
• Hypertension, GERD
• Treated with Omeprazole and Diovan

• Family Medical History

• Unremarkable
 Examination

• VA sc 20/25 OD, OS, OU

• OD unremarkable findings

• OS
• Lid: vesicles along upper
forehead & nose, lid
erythema, small hordeolum
• Conj: nasal injection
 Examination

• Cornea
• Punctate Epithelial Keratitis
• Inferior stromal haze

• Anterior Chamber
• Cells – WBC 2+
• ( - ) Flare

• IOP 16, 19 mm Hg

• Fundus
• Unremarkable OU
 Examination
• Fundus Unremarkable, OU
 Assessment

1. Redness/Discharge of 1. Educated patient on

Eye OS findings

2. H. Zoster 2. Neomycin ung on

Keratoconjunctivitis OS vesicles, BID

3. H. Zoster Iridocyclitis, OS 3. Pred Forte TID, OS

4. H. Zoster of Eyelid 4. Cool compresses and

antibiotic ung on vesicles
 Follow Up: 2 days later

• Patient now complains

of eye pain in the
morning

• Thinks it is getting
worse

• Currently taking pred

forte tid OS and will
finish Valtrex the
following week
 Examination: 2 days
• VA sc 20/25 OD; 20/40 OS PHNI

• OD unremarkable

• OS Lid: Vesicles along upper

forehead & nose with lid
erythema, hordeolum on superior
lid

• Cornea
• Prominent pseudodendrites

• Anterior Chamber
• 2+ WBC

• IOP 16, 27

• Fundus: Unremarkable OU
 Assessment: 2 days

1. Zoster, Eyelid OS 1. Continue ointment

2. Zoster Iridocyclitis, OS 2. Continue pred forte tid,

atropine instilled in office
Due to increased IOP:
Combigan OS bid
RTO 1 week
 Follow up: 1 week later

• Currently on pred forte TID, Combigan BID, OS

only

• Finished Valtrex

• Feels improvement
 Examination: 1 week
• VA sc 20/25 OD, 20/40-2
PH 20/25-, OS

• OD unremarkable

• OS
• Lids: healed vesicles, mild
ptosis
• Conjunctiva: Trace injection
• Cornea: Pseudodendrites
with endothelialitis inferiorly
• Anterior Chamber: 2+ WBC

• IOP 17, 20
 Assessment: 1 week

1. Redness/discharge of 1. Injection improved, less

eye OS tearing

2. H. Zoster of eyelid OS 2. Complete resolution

3. Zoster iridocyclitis 3. Durezol QID, atropine in

office (increased IOP);
4. H Zoster continue combigan BID
keratoconjunctivis OS

4. Pseudodendrites stable
 Follow up 2 weeks later
• Patient reports improvement
• VA sc 20/30 PH 20/25 OD, OS
• OD unremarkable
• OS
• Lid: no vesicles
• Conjunctiva: trace injection
• Cornea: punctate staining
• Anterior chamber: KP‟s less
evident

• IOP 16, 18 mm Hg
 Assessment: 2 weeks

1. H Zoster Iridocyclitis, OS 1. Improvement with quiet

A/C, IOP stable

--Continue Combigan BID OS

--Taper durezol over 2 weeks,

then D/C

--RTO 5 weeks
 Follow up 5 weeks later
• Patient currently on
Combigan BID OS only
• VA sc 20/25 OD; 20/30
• OD unremarkable
• OS
• Conjunctiva: tr injection
• Cornea: punctate staining
• Anterior chamber: NO cells
• Assessment
• H. Zoster Iridicyclitis
• No signs of recurrent
inflammation; IOP well
• D/C combigan
• Follow up 1 month for IOP
check

• IOP 16, 18 mm Hg
 References
• Cunningham, Emmett. Practical approach to the use of corticosteroids
in patients with uveitis. Can J Opthalmol 2010; 45:352-8

• Moorthy, Ramana. Intraocular Inflammation and Uveitis.American

Academy of Opthalmology. Section 9. pgs 98-116.

• http://www.uveitis.org/uveitis-questionnaire

• http://emedicine.medscape.com/article/1209891-clinical

• “Care of the Patient with Anterior Uveitis,” Optometric Clinical Practice

Guideline. American Optometric Association.