Retinopathies

Question 1

Most common types of Retinopathies

Answer 1

Diabetic Retinopathy

Hypersenive Retinopathy

Question 2

Epidemiology

Answer 2

  ( The World Health Organization (1992) definition of
blindness is vision less than 20/200 in the better eye with best
available spectacle correction. )
  Diabetes is one of the most serious challenges to health care
world-wide. According to recent projections it will affect 239
million people in 2010- doubling in prevalence since 1994.
Diabetes will affect 28 million in western Europe, 18.9
million in North America 138.2 million in Asia, 1.3 million
in Australasia.
  Diabetes mellitus is the most common cause of blindness
among individuals of working-age ( 20-65 years).
  Prevalence of blindness due to diabetic retinopathy (DR) in
Western Communities is estimated as between 1.6-1.9/
100,000

Question 3

Presentation

Answer 3

  About 2% of Type 2 diabetics have Clincally
Significant Macular Edema (CSME) at diagnosis
and 10.2% have other signs of DR already present
when their diabetes is discovered.
  Mitchell and co- workers found that 15.8 % of
undiagnosed diabetics in an elderly Australian
population had signs of DR, according to the Blue
Mountains Eye Study.
  It may often take from 9-12 years for type 2
diabetes to be diagnosed

Question 4

A classification of diabetic retinopathy

Answer 4

  A useful classification according to the types of lesions detected
on fundoscopy is as follows:!
–  Non-proliferative diabetic retinopathy (NPDR)!
–  Mild non-proliferative diabetic retinopathy!
  Microaneurysms!
  Dot and blot hemorrhages!
  Hard ( intra-retinal ) exudates!
–  Moderate-to-severe non-proliferative diabetic retinopathy!
  The above lesions, usually with exacerbation, plus:!
–  Cotton-wool spots!
–  Venous beading and loops!
–  Intraretinal microvascular abnormalities ( IRMA )!
–  Proliferative diabetic retinopathy!
  Neovascularization of the retina, optic disc or iris!
  Fibrous tissue adherent to vitreous face of retina!
  Retinal detachment!
  Vitreous hemorrhage!
  Pre retinal hemorrhage!
–  Maculopathy !
  Clinically significant macular edema (CSME )!
  Ischemic Maculopathy!

Question 5

Pathogenesis of Diabetic Microangiopathy

Answer 5

  Hyperglycemia causes-
–  BM thickening
–  non enzymatic glycosylation
–  increased free radical activity
–  increased flux through the polyol pathway
–  osmotic damage
  Hemostatic abnormalities of the microcirculation-
–  It has also been postulated that platelet abnormalities in diabetics may
contribute to diabetic retinopathy.
–  There are three steps in platelet coagulation:
  initial adhesion
  Secretion
  further aggregation
–  It has been shown that the platelets in diabetic patients are “stickier” than
platelets of non-diabetics
–  Platelets secrete prostaglandins that result in platelet aggregation and
blockage of the vessel with endothelial damage

Question 6

Microaneurysms

Answer 6

  Retinal microaneurysms are focal dilatations of retinal capillaries, 10 to
100 microns in diameter, and appear as red dots. They are usually seen
at the posterior pole, especially temporal to the fovea. They may
apparently disappear while new lesions appear at the edge of areas of
widening capillary non-perfusion. !
–  Microaneurysms are the first ophthalmoscopically detectable change in
diabetic retinopathy. !
  Beginning as dilatations in areas in the capillary wall where pericytes are
absent, microaneurysms are initially thin-walled.!
  Later, endothelial cells proliferate and lay down layers of basement
membrane material around themselves. !
  Fibrin and erythrocytes may accumulate within the aneurysm. !
–  Despite multiple layers of basement membrane, it is permeable to water and
large molecules, allowing the accumulation of water and lipid in the retina. !
–  Since fluorescein passes easily through these capillaries, many more
microaneurysms are usually seen on fluorescein angiography than on
ophthalmoscopy

Question 7

Retinal Haemorrhages

Answer 7

When the wall of capillary or microaneurysmis sufficiently weakened, it may rupture, giving rise to an intraretinal hemorrhage. If the hemorrhage is deep (i.e. in the inner nuclear layer or outer plexiform layer), it usually is round or oval (“dot or blot”)

Dot hemorrhages appear as bright red dots and are the same size as large microaneurysms. Blot hemorrhages are larger lesions they are located within the mid retina and often within or surrounding areas of ischemia.

If the hemorrhage is more superficial and in the nerve fiber layer, it takes a flame or splinter shape, which is indistinguishable from a hemorrhage seen in hypertensive retinopathy. They often absorb slowly after several weeks. Their presence strongly suggests the co-existence of systemic hypertension.

Diabetics with normal blood pressure may have multiple splinter hemorrhages. Nevertheless, when an ophthalmologist sees numerous splinter hemorrhages in a diabetic patient, the patient’s blood pressure must be checked because a frequent complication of diabetes is systemic hypertension.

Question 8

Non-proliferative diabetic retinopathy (NPDR)

Answer 8

Ancillary Studies - Fluorescein injection followed with retinal photography

Question 9

Cotton Wool Spots

Answer 9

Cotton wool spots result from occlusion of retinal precapillary arterioles supplying the nerve fibre layer with concomitant swelling of local nerve fibre axons.

also called “soft exudates” or “nerve fibre layer infarctions” they are white, fluffy lesions in the nere fibre layer.

Fluorescein angiography shows no capillary perfusion in the area of the soft exudate.

They are very common in DR, especially if the patient is also hypertensive

Question 10

Hard exudates ( Intra-retinal lipid 
exudates )

Answer 10

 Hard exudates ( Intra-retinal lipid exudates )
are yellow deposits of lipid and protein
within the sensory retina. Accumulations of
lipids leak from surrounding capillaries and
microaneuryisms, they may form a circinate
pattern. Hyperlipidemia may correlate with
the development of hard exudates.

  Accumulations of 
lipids leak from 
surrounding capillaries 
and microaneuryisms, 
they may form a 
circinate pattern 
around the macula.

Question 11

Late non proliferative

changes

Answer 11

Intra-retinal microvascular abnormalities ( IRMA)
are abnormal, dilated retinal capillaries or may
represent intraretinal neovacularization which has
not breached the internal limiting membrane of the
retina.
  They indicate severe non-proliferative diabetic
retinopathy that may rapidly progress to
proliferative retinopathy. Venous beading has an
appearance resembling sausage-shaped dilatation
of the retinal veins. It is another sign of severe non
proliferative diabetic retinopathy.

Question 12

Clinically Significant Macular Edema - CSME

Answer 12

  Macular edema is an important manifestation of
DR because it is now the leading cause of legal
blindness in diabetics. The intercellular fluid
comes from leaking microaneurysms &/or from
diffuse capillary leakage.
  It should be stressed however that current regimes
now lay emphasis on the treatment of retinal
thickening by grid laser than direct treatment of
microaneuyrisns and other discreet lesions

Question 13

Characteristics of

Clinically Significant Macular Edema (CSME)

Answer 13

  The leading cause of visual loss amongst diabetics. Diagnosed
by stereoscopic assessment of retinal thickening, usually by slit
lamp biomicroscopy.
  Defined as the presence of one or more of the following,
( Modified Airlie -House Criteria )
–  Retinal edema within 500 microns of the centre fovea.
–  Hard exudates within 500 microns of fovea if associated with
adjacent retinal thickening
–  Retinal edema that is one disc diameter or larger, any part of which
is within one disc diameter of the centre of the fovea.
  Laser grid photocoagulation reduces the risk of visual loss by
50% at 2 years

Question 14

Ischemic Maculopathy

Answer 14

  Maculopathy in type 1 diabetics is often due to
drop out of the perifoveal capillaries with non
perfusion and the consequent development of an
ischemic maculopathy.
  Enlargement of the foveal avascular zone (FAZ) is
frequently seen on fluorescein angiography.
Ischaemic maculopathy is not uncommon in type 2
diabetics, maculopathy in this group may show
both changes due to ischemia but also retinal
thickening.

Question 15

Proliferative diabetic retinopathy

Answer 15

  Retinal ischemia due to widespread capillary non
perfusion results in the production of vasoproliferative
substances and to the development of neovascularization.
Neovascularization can involve the retina, optic disc or the
iris (rubeosis iridis).
  Rubeosis iridis is a sign of severe proliferative disease, it
may cause intractable glaucoma.
  Bleeding from fragile new vessels involving the retina or
optic disc can result in vitreous or retinal hemorrhage.
Retinal damage can result from persistent vitreous
hemorrhage.
  Pre-retinal hemorrhages are often associated with retinal
neovascularization, they may dramatically reduce vision
within a few minutes

Question 16

Late Disease

Answer 16

 Contraction of associated fibrous tissue
formed by proliferative disease tissue can
result in deformation of the retina and
tractional retinal detachment

Question 17

General aspects of the ocular care of diabetics

Answer 17

Factors that can worsen diabetic retinopathy- and 
indeed the general prognosis of diabetes, include 
  poor diabetic control 
 systemic hypertension 
 hyperlipidemia 
 cigarette smoking 
 diabetic nephropathy 
 anemia 
 pregnancy 
 cataract surgery

Question 18

Glycemic control

Answer 18

  It is now proven that good diabetic control may slow the
development and progression of diabetic retinopathy in
both type 1 and type 2 diabetes.
  For example, the United Kingdom Prospective Diabetes
Study 1998 (UKPDS) followed 5,102 newly diagnosed
type 2 diabetics prospectively since 1977. Those diabetics
who were intensively treated and achieved tight control
with either insulin or suphonylurea had diabetic endpoints
12% lower than less well controlled diabetics.
  Overall there was a 25% reduction in microvascular end
points in the group exhibiting good glycemic control.

Question 19

Systemic hypertension and DR in type

2 diabetes

Answer 19

  Recent literature indicates that there is a striking
correlation between the presence of systemic
hypertension and progression of diabetic
retinopathy. Recent studies have delineated the
role of treating associated hypertension and the
slowing of the progress of DR. It is important to
note that many type 2 diabetics will need a
combination of anti-hypertensive agents to lower
their blood pressure.

Question 20

ystemic hypertension and DR in type 2

diabetes

Answer 20

  The hypertension in diabetes study was launched within the
original UKPDS study in 1987.
  The study compared diabetics whose blood pressure was tightly
controlled ( BP < 150/85)with ACE inhibitors and beta blockers
with a cohort whose blood pressure was less tightly controlled.
(BP <180/ 95 ) Median follow up was 8.4 years.
  The reduction of macrovascular events was significant with a 32%
reduction in diabetes related deaths. There was a 44% reduction in
stroke and a 34% reduction in overall macrovascular disease.
  UKPDS is a unique study in that it also looked at microvascular
end points in type 2 diabetics. Overall the tight control group had a
37% reduction in microvascular disease, this was a more striking
reduction than tight glycemic control.
  This effect was manifested as a reduction of the risk of having to
undergo laser photocoagulation by 34%.

Question 21

Systemic hypertension and DR in type 2

diabetes

Answer 21

  The risk of reduction of visual acuity was lowered by
47%.
  Atenolol (Tinormin-β-blocker) and Captopril (ACE
inhibitor) were equally effective in reducing the risk
of progression of retinopathy in type 2 diabetics.
  The Hypertension Optimal Treatment ( HOT ) study
indicates that the lowest incidents of cardiac events
occurs when blood pressure is lowered to 136 mmHg
systolic and 82.6 mmHg diastolic.

Question 22

Hyperlipidemia and diabetic

maculopathy

Answer 22

 There is evidence in the literature that
diabetics who have exudative maculopathy
with extensive lipid exudes benefit from
active treatment of hyperlipidemia

Question 23

Insulin & HMG-Co-A Reductase

Answer 23

 Increased serum insulin in the presence of
dietary fat activates HMG-Co-A Reductase,
the rate limiting enzyme in Cholesterol
synthesis
 Adkin’s diet helpful in hypercholesterolemia
and diabetes

Question 24

Pregnancy

Answer 24

  Diabetic retinopathy may worsen during pregnancy.
Screening should therefore be undertaken at
confirmation of pregnancy and every two months
during pregnancy if no retinopathy is present, or
monthly, if retinopathy is present.
  Retinal status should not preclude pregnancy since
contemporary methods of management can result in
satisfactory ocular and pregnancy outcomes even in
the presence of advanced diabetic microvascular
disease providing sufficient care is taken

  Pregnancy may accelerate the progression of diabetic retinopathy.
  Frequency of monitoring NPDR should be increased.
  Women who begin a pregnancy with no retinopathy, the risk of
developing diabetic retinopathy is about 10%.
  Those with DR at the onset of pregnancy may show progression,
with increased haemorrhages, soft exudates, and macular edema.
  There is no doubt that women who maintain good metabolic
control during pregnancy have fewer spontaneous abortions and
fewer children with birth defects.
  Those with untreated PDR at the onset frequently do poorly
unless they are treated with panretinal photocoagulation. Finally,
patients with previously treated PDR often do not worsen during
the pregnancy.
  Women who begin pregnancy with poorly controlled diabetes and
who are suddenly brought under strict control frequently have
severe deterioration of their retinopathy and do not always
recover after delivery

Question 25

Cataract surgery

Answer 25

Cataract surgery

Question 26

Tightening Glycaemic

control

Answer 26

  Tightening of glycemic control may initially produce
worsening of retinopathy. The postulated mechanism
includes lowering of retinal blood flow or overproduction
of IGF-1 by the liver.

  It is therefore recommended that monitoring of retinopathy
is increased if major changes to glycemic control are made
particularly in previously poorly controlled diabetics.
Ideally glycosolated hemoglobin ( HbA1c) should be
maintained below 6.5%.

Question 27

NON-PROLIFERATIVE

DIABETIC RETINOPATHY

Answer 27

MICROANEURYSMS and 
blot-and-dot hemorrhages 
INCREASED VASCULAR 
PERMEABILITY (hard 
exudates) 
ISCHEMIA (cotton-wool 
spots: damage to axoplasmic 
flow in the nerve fiber layer) 

Venous “beading”

IRMA (intra-retinal
microvascular
anomalies)

Extensive capillary
occlusion and ischaemia

Question 28

PROLIFERATIVE DIABETIC

RETINOPATHY

Answer 28

IS CHARACTERIZED BY 
NEWLY FORMED VESSELS 
(neovascularization) which 
originate from vessels of the optic 
nerve or from the surface of the 
retina 
Newly formed vessels are 
abnormal, extremely fragile 
vessels!

Question 29

Perifoveal microaneurysms and hemorrhages

Answer 29

  Retinal microaneurysms are the 1st
ophthalmoscopically detectable change in
a DR
  Retinal microaneurysms are focal
dilatations of retinal capillaries and appear
as red dots.
  They are usually seen at the posterior
pole, especially temporal to the fovea.
  They may apparently disappear while new
lesions appear at the edge of areas of
widening capillary non-perfusion.
  See more microaneurysms on florescein
angiography than on ophthalmoscopy.

Question 30

Cotton Wool Spots

Answer 30

  Cotton wool spots result 
from occlusion of retinal 
pre-capillary arterioles 
supplying the nerve fibre 
layer with concomitant 
swelling of local nerve 
fibre axons. Also called 
"soft exudates" or "nerve 
fibre layer infarctions" 
they are white, fluffy 
lesions in the nerve fibre 
layer.

Question 31

Hard exudates

Intra-retinal lipid exudates

Answer 31

  Hard exudates ( Intra-retinal 
lipid exudates ) are yellow 
deposits of lipid and protein 
within the sensory retina. 
  Accumulations of lipids leak 
from surrounding capillaries 
and microaneuryisms, they may 
form a circinate pattern. 
  Hyperlipidaemia may correlate 
with the development of hard 
exudates.

Question 32

Fundoscopic Examination

Answer 32

  Hypertensive retinopathy
  Diabetic retinopathy
  Bacterial endocarditis
  Athero-emboli

Question 33

Hypertensive Retinopathy

Answer 33

Modified Scheie Classification
  Grade 0: No changes
  Grade 1: Minimal arteriolar narrowing
  Grade 2: Obvious arteriolar narrowing with focal
irregularities
  Grade 3: Grade 2 + retinal hemorrhages and/or exudate
  Grade 4: Grade 3 + swollen optic nerve (Malignant
hypertension)

Question 34

Hypertensive Retinopathy

Grade 2

Answer 34

 Arteriovenous 
nicking in 
association with 
hypertension 
Grade 2 
(yellow arrow)

Question 35

Hypertensive Retinopathy

Grade 3

Answer 35

Flame-shaped 
hemmorhage in 
association with 
severe 
hypertension 
Grade 3 (yellow 
arrow)

Question 36

Hypertensive Retinopathy

Grade 4

Answer 36

  Papilledema from 
malignant HTN 
  There is blurring 
of the borders of 
the optic disk with 
hemorrhages 
(yellow arrows) 
and exudates 
(white arrow)

Question 37

Central Retinal Artery Occlusion

Answer 37

  Etiology:
–  Emboli – cardiac, atherosclerotic, fat
–  Vasculitis
–  Coagulopathy
–  Sickle cell
  Signs and Symptoms:
–  Sudden onset severe monocular vision loss over seconds
–  Usually preceded by amaurosis fugax
–  90% will have visual acuity of counting fingers or less
–  After visual activity, do IOP, pupillary response (RAPD common)
–  dilate pupils immediately and perform fundoscopic exam

  Narrow arterioles 
  Optic disc and retinal 
pallor 
  Cherry red spot at 
fovea (due to maintained 
perfusion of a cilio-retinal 
artery) 
  Emboli seen – 20%