Diabetic Retinopathy

PATHOGENESIS

POLYOL PATHWAY

*** POLYOL PATHWAY ALDOSE REDUCTASE

Retinal pigment epithelial cells /

Neurons /
Ganglion
cells
/
Mller
cells
Pericytes / Retinal endothelial cell

NADPH
Cofactor - Glutathione reductase
Reduce glutathione
level in cell
Reduce antioxidant
capacity
Oxidative
stress

NADH

Shift NADH/NAD+ ratio

trigger NADH oxidase
activity
Increase Reactive
oxygen species

SORBITOL

Membrane
impermeability
Accumulates within
the cell
Osmotic
damage

FRUCTOSE

Phosphorylated - Fructose-3Phosphate
Degraded - 3Deoxyglucosone
Strong glycating
agent
Produce
AGEs
AGEs (Advances Glycation End
product)

- main pathogenic

PROTEIN GLYCATION

PROTEIN KINASE C ACTIVATION

Glycolysis - increase DAG

synthesis
(PKCAngiogenic
activator) factor
Release

(VEGF)
ECM synthesis &
Endothelial & Leukocyte
remodeling
dysfunction
- Change in retinal blood
flow
- Capillary occlusion
-

PROTEIN KINASE C ACTIVATION

- Neovascularization
Hemorrhage
- Inflammation
Macular
- Change hemodynamics
edema

DIABETIC RETINOPATHY

- Alteration in retinal blood low

- Blood-Retinal dysfunction
- Basement membrane
thickening
- Capillary degeneration &
Microaneurysm
- Neurodegeneration & Glial
cell dysfunction

DIABETIC

Non

RETINOPATHY

proliferative retinopathy ;

retinal edema ,
NO neovascularization .
A. Mild NPDR
microaneurysm or dot-blot hemorrhage in 1
quadrant
B. Moderate NPDR
cotton wool spot , venous beading
C.Severe NPDR 4:2:1 ; 1 of 3
1.Diffuse intraretinal hemorrhage and
microaneurysm in 4 quadrant
2.venous beading in 2 quadrants
3.IRMA in at least 1 quadrants
D.Very severe NPDR ; 2 of 3

 Proliferative
Retinal

edema

retinopathy

Neovascularization
Vitreous

hemorrhage
Tractional retinal detachment : blindness
NVI / rubeosis iridis : neovascular glaucoma
1.Low-risk PDR ; not qualify for high risk
2.High-risk PDR
2.1 Mild NVD , < 1/4 of retina with preretinal
hemorrhage
2.2 Moderate to severe NVD , 1/4 to 1/3 of retina
with/with out preretinal hemorrhage
2.3 Moderate NVE , 1/2 of retina with preretinal
hemorrhage

PREVALENCE

Leading cause of new case blindness ; 2nd from

cataract

25 times blindness more than non-DM

20% of DM patients
80% of 15 years DM patients

2%

: blindness
10% : severe vision loss

PDR is much more in type I than type II

DR in Type I is more severe than type II

RISK FACTORS
The duration of DM : the longer , higher
risk
Glycemic control
Pregnancy ; hormonal change
Systemic HT
Renal disease
Anemia ; decreased in oxygen
Elevated serum lipid
Carotid artery occlusive disease
Alcohol
Obesity

MANAGEMENT

Prevention
Blood

glucose control ; non-DR and DR

Blood

pressure control

Blood

lipids control ; hard euxudates

No

smoking

Exercise

EARLY DETECTION
Type I ; within 3 years
Type II ; on diagnosis time
Pregnant ; within first trimester and every 3
monthes
At least annual eye examination

FOLLOW- UP
Normal/rare microanerysm annual
Mild NPDR
9 mo
Moderate NPDR
6 mo
Severe NPDR
4 mo
CSME
2-4 mo
PDR
2-3 mo

TREATMET

Laser photocoagulation
Focal laser photocoagulation
: macular edema , CSME
Pan retinal photocoagulation
; very severe NPDR , PDR ,high risk PDR ,
; reduce NV
Pars Plana Vitrectomy
; tractional retinal detachment , vitreous
hemorrhage

MANAGEMENT

Anti-VGEF ; Ranibizumab
Short

onset

Complication

; infection in vitreoues,vitreous
hemorrhage,retinal detahment

 DM

is the major health problem of

Thailand

DR

is a major complication of DM

Blindness
Slow

, Psycosocial

progress and no alarm sign

Advices

Referring to ophthalmologists
On controlling blood sugar

REFERANCE

Diabetic retinopathy ; medscape

Diabetic retinopathy

Kittantong A.
Department of Opthalmology ,Faculty of Medicine
Prince of Songkla University
Songkla Med J 2006;24 (2) ;127-132

NON-PROLIFERATIVE
DIABETIC RETINOPAT
HY
examples

CASE 1: RAPID
PROGRESSION OF DIABETIC
RETINOPATHY
Reference: REED T. GIBB, O.D.; HARALD E.
OLAFSSON, O.D., F.A.A.O.

Optometric Management http://

www.optometricmanagement.com/articleviewer.asp
x?articleID=71734

BACKGROUND
A 54-year-old male presented for an annual
diabetic visual evaluation.
The patient had no visual complaints and
stated that his blood sugar normally reads ab
out 155mg/dl, with an occasional reading of
200mg/dl.
His last eye exam was about two years ago.

HISTORY
A diagnosis of mild non-proliferative diabetic
retinopathy (NPDR) without clinically significa
nt macular edema (CSME).
We noted hard exudates in the posterior
pole, but away from foveal tissue.
All other ocular history was unremarkable.
No related social history was noted.

MEDICAL HISTORY
Renal insufficiency
Depression
Hyperlipidemia
Hypertension
Cellulitis of the leg
Type II diabetes with renal and ophthalmic
manifestations.
Medications include insulin injections b.i.d.
Dressings to treat cellulitis of the leg.

EXAM FINDINGS
Upon examination, all entrance testing was
normal, other than entering acuities of 20/402 O.U.
Best-corrected visual acuity (BCVA) was
20/25 O.U.
Tonometry revealed intraocular pressure
(IOP) of 12mm Hg O.D. and 15mm Hg O.S.

HARD EXUDATES WITHIN 500

MICRONS ON THE FOVEA

Pertinent biomicroscopy findings included

no rubeosis (medical condition of the iris
of the eye in which new abnormal blood v
essels (i.e. neovascularization) are found
on the surface of the iris), mild cataract d
evelopment O.U., and most importantly,
exudates and hemorrhages within 500 mi
crons of the fovea O.D. with retinal thicke
ning.

EXAM FINDINGS
Microaneurysms and hemorrhages are noted
in all four quadrants.
Diagnosis: Type II diabetes mellitus with
mild/ moderate NPDR, CSME O.D. and O.S.

We

also suspect glaucoma secondary to IOP

asymmetry and optic nerve head appearance but
we will not address the glaucoma aspect of this c
ase since it had minimal impact in the ending vis
ual acuity.

Scheduled the patient for fluorescein

angiography (FA) to visualize the CSME in pre
paration for focal grid treatment.

SCATTERED EDEMA FROM

MICROANEURYSM FORMATION

A fluorescein study showed scattered

perfusion from microaneurysms O.S. grea
ter than O.D. The patient was treated wit
h focal grid argon laser, with 27 burns O.
D. and 57 O.S

1ST FOLLOW-UP
Six months later, this patient presented for a
follow-up visit with entering acuities of 20/30
O.U.
The assessment included type II DM,
moderate NPDR and minimal CSME O.U.
The retinal practitioner at that time believed
the CSME O.S. was resolving and we schedul
ed the patient for a four-month follow-up visit
.

2ND FOLLOW-UP: APPROXIMATELY

3.5 MONTHS LATER
The patient reported that everything was now blurry and
he could no longer drive.
He noted a gradual change in visual acuity over the past
one to two months.
He reported that his glucose levels were good and
measured 113mg/dl that morning.
He said his vision was stable after the laser treatment,
but that his glasses did not help anymore.
His entering acuities for that visit were counting fingers
at five feet O.D. and 20/60-2 O.S.; no improvement with
pinhole.

2ND FOLLOW-UP: APPROXIMATELY

3.5 MONTHS LATER
After examination, we altered his diagnosis
to Type II DM with severe NPDR and diffuse C
SME O.U.
We performed an FA the same day and
observed a marked increase in retinal edema
.
Diffuse focal grid was applied O.D. and O.S.
with an evaluation for possible intravitreal tri
amcinolone acetonide injection or pan-retinal
photocoagulation (PRP) upon follow-up.

FLUORESCEIN ANGIOGRAPHY SHOWS SEVERIT

Y OF RETINAL EDEMA IN THE RIGHT EYE WITH
FLAME AND DOT-BLOT TYPE HEMORRHAGES

3RD FOLLOW-UP: 5 MONTHS

LATER

PRP treatment O.D. of 1400 burns and 1450

burns O.S.

4TH FOLLOW-UP: 2 MONTHS LATER

Severe PDR with both
NVD and NVE

Entering acuity of bare

light perception O.U.

Proliferative changes were

noted and diagnosed type II D
M with severe PDR O.U.

POST-VITRECTOMY VIEW OF THE

LEFT EYE

Scheduled a pars plana vitrectomy in the

left eye. Figure 6 shows the eye four mon
ths after surgery was completed.

DISCUSSION
Why this patient had such a dramatic change in
vision comes to any practitioner's mind?
This case illustrates why you must conduct an
objective analysis of a patient's underlying medi
cal condition.
Careful review of the medical history in this
case revealed several important pieces of infor
mation.
The most relevant is his glucose control over
the past several years.
Further analysis of the patient's primary care
practitioner's notes revealed consistently poor d
ietary compliance over several years.

HBA1C READINGS OVER NINE

YEARS

Collected data on this patient's serum glucose levels, as well as his Hemoglobin A1c counts,
show extremely high levels show poor prognosis for retinal health.

DISCUSSION
A patient is considered a suspect for diabetes
when fasting serum glucose levels reach between
100 and 140mg/dl. The diagnosis is likely when th
at number is over 140mg/dl. Further, the hemoglo
bin A1c count is also utilized. If elevated above 7.
0, a positive diagnosis is likely.
Both were extremely elevated in this patient over
several years. When you take into account this
new information, discussion of ocular treatment o
ptions becomes moot because the disease is alrea
dy out of control.
In cases such as this, despite our best efforts, it's
only a matter of time before vision is permanently
damaged, if not lost.

CASE 2: A 28-YEAR-OLD
MAN WITH DIABETIC
RETINOPATHY

Reference: Arthur D. Fu, MD, Sam S. Yang, MD, and

H. Richard McDonald, MD

Johns Hopkins Advanced Studies in Medicine http://

www.jhasio.com/files/articlefiles/pdf/XASIO_Issue_4_
1p35_37.pdf

BACKGROUND
A 28-year-old male with a history of type 1
diabetes mellitus presented with partial
vision loss in both eyes.
The problem has persisted for several
months and has begun to interfere with his d
aily functioning.
He is anxious to hear his prognosis

MEDICAL HISTORY
The patient was diagnosed with type 1
diabetes mellitus at the age of 5 years.
He has no history of hypertension or
dyslipidemia.
He is taking regular insulin 20 U three times
daily and lente insulin 25 U/day.

PAST OCULAR HISTORY

The patient was first treated 8 months ago
with grid-pattern photocoagulation to the
right eye.
He underwent a 2nd grid-pattern
photocoagulation 4months ago.

REVIEW OF SYSTEMS
The review of systems findings shows that
the patient is otherwise healthy, with no othe
r symptoms.
He has an adequate appetite, has no
peripheral pain,and is not fatigued.
He has not experienced any recent
headaches, dizziness, fever, or chills.
He has no reported allergies and is taking no
other medications.

FAMILY HISTORY
The patient is the only child of divorced
parents.
His mother has a history of type 1 diabetes
mellitus; his father is in good health.
Family history is otherwise noncontributory.

SOCIAL HISTORY
The patient is a mathematics teacher at a
local high school.
He acts as an advisor to the high school
chess team and routinely attends his student
s competitions.
He rarely engages in physical exercise
because he has always preferred intellectual
pursuits.
He is single and has no children, but hopes to
get married someday and have a family of
his own.
He has no history of tobacco or recreational
drug use.

PHYSICALEXAMINATION
At presentation, the patient appeared to be an alert, observant,
cooperative, but slightly anxious adult male.
Physical examination indicated the following results:

weight, 204 pounds;

height, 71 inches;
blood pressure,130/80;
pulse, 80 beats/min.

His heart rate was slightly elevated over his normal rate, as shown
in his medical records; this elevation was likely caused by anxiety r
elated to his medical examination.
Cardiac rhythm was within a normal range, with no murmur
detected.
No further abnormalities were noted.

OPHTHALMIC EXAMINATION

The best corrected visual acuity of the patients right eye

OD

20/80
OS 20/25.

The extraocular motility examination, confrontation visual field

test, and papillary examination were in the nor-mal range in bot
h eyes.
The intraocular pressure (IOP)was 15 mmHg in both eyes.
The slit lamp examination showed normal eyelids and
conjunctiva in both eyes. The iris examination showed no eviden
ce of rubeosis in either eye.
The anterior chamber was quiet and the lens was clear in each
eye.

OPHTHALMIC EXAMINATION
The fundus examination of the right eye
showed diffuse dot and blot hemorrhages wit
h few cotton wool spots and exudates in the
posterior pole.
A significant amount of diffuse macula
edema was noted.
Prior grid-pattern laser scars were noted
within the macula.
There was no evidence of neovascularization
of the disc or elsewhere.
The fundus examination of the left eye
showed normal optic disc and retinal vessels.

DIFFUSE MACULAR EDEMA

OPHTHALMIC EXAMINATION
There was a moderate
amount of dot
hemorrhages and
exudates temporally w
ithin the macula.
Clinically significant
macular edema was
noted temporal to the
fovea.
There was no
evidence of
neovascularization of
the disc or elsewhere.

EARLY-PHASE DIFFUSE MACULAR

EDEMA

The fluorescein angiogram of the right

eye showed diffuse punctate hyperfluore
scence with late leakage consistent with
diffuse macular edema.

LATE-PHASE DIFFUSE MACULAR

EDEMA

The fluorescein angiogram of the right

eye showed diffuse punctate hyperfluore
scence with late leakage consistent with
diffuse macular edema.

ANGIOGRAPHIC MACULAR EDEMA

TEMPORAL TO
FOVEA

The fluorescein angiogram of the left eye

showed significant angiographic macular
edema temporal to the fovea.

STUDIES

No significant capillary non-perfusion or

neovascularization was noted.

INTRARETINAL CYSTOID CHANGES AND

SIGNIFICANT RETINAL THICKENING

The optical coherence tomography (OCT)

of the right eye revealed intraretinal cyst
oid changes and significant retinal thicke
ning consistent with diffuse macular ede
ma.

NO INTRARETINAL CYSTOID CHANGES OR

SIGNIFICANT RETINAL THICKENING

The OCT of the left eye showed no

intraretinal cystoid changes or significant
central macular thickening.

COURSE OF MANAGEMENT
The patient was treated with grid-pattern photocoagulation to the right eye.
The left eye was treated with focal
photocoagulation temporally within the macula.
One month later, the vision of the left eye had i
mproved to 20/20.
However, the vision of the right eye had
decreased to 20/160 with persistent diffuse
macular edema.
The right eye was then treated with a 4-mg
intravitreal triamcinolone acetonide injection.
At the 3-month postinjection follow-up visit, the
vision of the right eye had improved to 20/60.

COURSE OF MANAGEMENT
The OCT of the right eye showed a significant
decrease of retinal thickening (foveal thickness of
207 m) and resolution of the intraretinal cystoid c
hanges.
The IOP of the right eye was 33 mm Hg.
An antiglaucomatous eyedrop was started on the
right eye.
At the 5-month post-injection follow-up visit, vision
in both eyes had improved:

OD:

20/50
OS: 20/20.

The IOP of the right eye returned to normal and use

of the antiglaucomatous eyedrop was discontinued.

SIGNIFICANT DECREASE OF RETINAL THICKENING

AND RESOLUTION OF INTRARETINAL CYSTOID
CHANGES
The optimal coherence tomography (OCT)
demonstrated normalizing of foveal anatomy with
resolution of the intraretinal cystoid changes

The OCT map showed significant decrease of retinal

thickness. Normal value of foveal thickness is less th
an 265 m; this image showed foveal thickness of ap
proximately 208 m, thus the retina is normal

PROLIFERATIVE DIABETIC
RETINOPATHY
(PDR)

HISTORY

Have Diabetes mellitus for 5 or more years.

In the initial stages : generally asymptomatic

more advanced stages : may experience

symptoms that include floaters, blurred visio
n, distortion, and progressive visual acuity lo
ss.

ON OPHTHALMOSCOPE
Neovascularization is the hallmark of PDR :
It most often occurs near the optic disc
(neovascularization of the disc [NVD]) or within
3 disc diameters of the major retinal vessels (n
eovascularization elsewhere [NVE])

ON OPHTHALMOSCOPE
Neovascularization is the hallmark of PDR
Preretinal hemorrhages :
appear as pockets of blood within the potential
space between the retina and the posterior
hyaloid face

ON OPHTHALMOSCOPE
Neovascularization is the hallmark of PDR
Preretinal hemorrhages
Vitreous hemorrhage :
may appear as a diffuse haze or as clumps of
blood clots within the gel

ON OPHTHALMOSCOPE
Neovascularization is the hallmark of PDR
Preretinal hemorrhages
Vitreous hemorrhage
Fibrovascular tissue proliferation :
usually seen associated with the neovascular
complex and also may appear avascular when
the vessels have already regressed.

ON OPHTHALMOSCOPE
Neovascularization is the hallmark of PDR
Preretinal hemorrhages
Vitreous hemorrhage
Fibrovascular tissue proliferation
Traction retinal detachments :
usually appear tented up, immobile, and
concave.

The mainstay of diagnosing diabetic retinopathy is

a
complete ophthalmic examination and
dilated retinal examination
by an ophthalmologist or retina specialist or retina
surgeon.

Recommendation for eye

examination
Type I DM : within 3
years after diagnosis
Type II DM : at the time
of diagnosis

IMAGING STUDIES
Fluorescein angiography: Microaneurysms
appear as pinpoint, hyperfluorescent lesions
in early phases of the angiogram and typicall
y leak in the later phases of the test
Optical coherence tomography scanning:
Administered to determine the thickness of
the retina and the presence of swelling withi
n the retina, as well as vitreomacular traction
B-scan ultrasonography

CASE 1
A 51-year-old man presented to the clinic with
a history of central visual loss has accelerated
over the past 6 months. His central visual acuit
y varies during the day. This patient has type 2
DM and HT for 15 years. He has had difficulties
maintaining good glycemic control for the past
5 years

DILATED FUNDUSCOPIC EXAMINATION REVEAL

Dilated funduscopic examination reveal

severe bilateral clinically significant macular
edema.

CASE 2
A 26-year-old type 1 present with 18 years DM
and good control.

CASE3
A 28-year-old male with a history of type 1 DM
presented with partial visual loss in both eye. T
he problem were pesistented for several month
and has begun to interfere with his daily life. H
e is anxious to hear his prognosis

THE FUNDUS OF THE RIGHT EYE

SHOWS

The fundus of the right eye showsdiffuse dot

and brot hemorrhage with few cotton wool
spots and exudate at posterior pole.

THE FUNDUS OF THE LEFT EYE

SHOWS

The fundus of the left eye showsnormal optic

disc and retinal vessel. There was a moderate
amount of dot hemorrhage and exudate tempo
rally within the macula.

CASE4
54-year-old male presented for an annual
diabetic visual evaluation. The patient had no v
isual complaints and stated that his blood suga
r normally reads about 155mg/dl, with an occa
sional reading of 200mg/dl. His last eye exam
was about two years ago.

hard exudates (HE) in the posterior pole, but

away from foveal tissue
mild non-proliferative diabetic retinopathy
(NPDR) without clinically significant macular
edema (CSME)

exudates and hemorrhages within 500

microns of the fovea O.D.
microaneurysms and hemorrhages in all four
quadrants.
type II diabetes mellitus with mild/ moderate
NPDR, CSME
Focal laser treatment for macula edema

6 months later, patient reported that

everything was now blurry and he could no lon
ger drive. He noted a gradual change in visual
acuity over the past one to two months. He rep
orted that his glucose levels were good and me
asured 113mg/dl that morning. He said his visi
on was stable after the laser treatment, but th
at his glasses did not help anymore. His enteri
ng acuities for that visit were counting fingers
at five feet.

Fluorescein angiography shows severity of

retinal edema in the right eye with flame and
dot-blot type hemorrhages.