DIABETIC RETINOPATHY

DIABETIC RETINOPATHY:

 Exudate in the right macular area.

                          
                             cotton wool spot.

 NVD.

 Red flame and Blot haemorrhage.

























Modifiable risk factors:
1) Blood  Glucose
2) Blood Presssure
3) Smoking
4) Lipid level
Non modifiable Risk Factors:
1) Duration
2) age
3) genetic predisposition
4) ethnicity


Pathophysiologic events in  diabetic retinopathy:

1) Basement membrane thickening
2) Pericyte loss
3) Increased capillary  permeability
4) Microaneurysms
5) capillary weaking
6) Rettinal blood flow
7) smooth muscle death


Investigative techniques to assess diabetic  retinopathy

Retinal photography
Fundus f uorescein angiography
Optical coherence tomography
Ultrasound B scan examination
perimetry

LESIONS:

Microaneurysms and retinal hemorrhages
The lesions that the Early Treatment Diabetic Retinopathy Study (ETDRS)  described as critical to the stages of progression of DR were:
• Microaneurysms – a microaneurysm is defined as a red spot < 125 μ m (approximate width of vein at disc margin) and sharp margins.
• Small retinal hemorrhages – a hemorrhage is defined as a red spot, which has irregular margins and/or uneven density, particularly when surrounding a smaller central lesion considered to be a microaneurysm.
Hemorrhage/microaneurysm (HMa) – because the ETDRS recognized that it was very difficult to differentiate between microaneurysms and small hemorrhages, the concept of HMa was introduced, which is a small hemorrhage or microaneurysm .


Other larger  retinal hemorrhages:
• Flame hemorrhages – superficial hemorrhages just under the nerve fiber layer.

Blot hemorrhages – deeper hemorrhages, which are a sign of retinal ischemia in the area of the retina in which they occur.

Hard exudates: Hard exudates (sometimes now just referred to as exudates) are defined as small white or yellowish - white deposits with sharp margins, located typically in the outer layers of the retina, but
they may be more superficial, particularly when retinal edema is present .
Cotton wool spots : Cotton wool spots (referred to as soft exudates in the ETDRS, but this term is now rarely used) are fluffy white opaque areas caused by an accumulation of axoplasm in the nerve fiber layer of the retina, which is caused by an arteriolar occlusion in that area of retina that is apparent on a fl uorescein angiogram.

Intraretinal microvascular abnormalities
IRMA are defined as tortuous intraretinal vascular segments, varying in caliber, derived from remodeling of the retinal capillaries and small collateral vessels in areas of microvascular occlusion and are therefore a sign of retinal ischemia
Venous abnormalities:
• Venous loops – abrupt curving deviations of a vein from its normal path
• Venous beading – in the ETDRS, venous beading is described as a localized increase in caliber of the vein and the severity is dependent on the increase in caliber and the length of vein involved. It is associated with retinal ischemia .
Other venous changes that occur in DR are as follow:
• Venous dilatation;
• Venous narrowing;
• Opacification of the venous wall
• Perivenous exudate

Arteriolar abnormalities
Other arteriolar changes that occur in DR are as follow:
• Arteriolar narrowing;
• Opacification of arteriolar walls
• Arteriovenous nipping.
Fibrous proliferation at the disc
Fibrous proliferation at the disc (FPD) usually occurs when new vessels at the disc start to regress and fi brosis occurs.
Fibrous proliferation elsewhere
Fibrous proliferation elsewhere (FPE) usually occurs when new vessels elsewhere start to regress and fi brosis occurs.

New  vessels on and/or within 1 disc diameter of the disc For new vessels on and/or within 1 disc diameter (DD) of the disc (NVD),

New vessels elsewhere
For new vessels elsewhere (NVE),

Vitreous hemorrhage
Vitreous hemorrhage (VH) is a hemorrhage that is in the vitreous gel.

Preretinal hemorrhage
Preretinal hemorrhages (PRH) are boat - shaped hemorrhages and roughly round, confl uent or linear patches of hemorrhage just anterior to the retina or under the internal limiting membrane.
Post laser treatment:
Photocoagulation laser scars may be seen both after macular or
panretinal laser treatment

Maculopathy
Clinical classification of diabetic maculopathy
Pathophysiology o f macular edema:

In focal macular edema, focal leakage tends to occur from microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage In diffuse macular edema, there is a generalized breakdown of the blood – retina barrier and profuse early leakage from the entire capillary bed of the posterior pole . causing extracellular fluid accumulation, often accompanied by cystoid macular edema, which is caused by cellular swelling. In ischemic maculopathy, enlargement of the foveal avascular zone as a result of capillary closure is found inducdiabetic maculopathy edema by 50% or more. It also described
“ clinically signifi cant macular edema, ” which defi ned the parameters for treatment as :
• Thickening of the retina at or within 500 μ m of the center of the macula;
• Hard exudates at or within 500 μ m of the center of the fovea, if associated with thickening of the adjacent retina (not residual hard exudates remaining after disappearance of retinal thickening);
• A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 DD of the center of the macula



Mild non - proliferative diabetic retinopathy and background diabetic retinopathy :
The earliest sign of mild non - proliferative DR (mild NPDR) or background DR is microaneurysms.
Microaneurysms
Patients with no DR and microaneurysms only were not included in the ETDRS study. In the Wisconsin Epidemiological Study of Diabetic Retinopathy, the rate of progression to proliferative retinopathy 4 years after the initial evaluation showed “ no DR ” was 0.4% for young patients < 30 years with T1DM, 0% for older patients ≥ 30 years with diabetes taking insulin and 0.6% for those not using insulin. For those with microaneurysms or one hemorrhage in one eye only, the rate of progression to proliferative retinopathy 4 years after the initial evaluation was 3.0% for young patients < 30 years with T1DM, 0% for older patients ≥ 30 years with T1DM and 1.5% for those not using insulin. The other signs of mild NPDR are one or more of the following:
• Retinal hemorrhages . In mild NPDR, retinal hemorrhages are
usually small dot hemorrhages or fl ame - shaped hemorrhages
(Figures 36.9 and 36.10 ). Because small retinal hemorrhages can
be diffi cult to differentiate from microaneurysms they are commonly
referred to as HMa.
• Exudates (or hard exudates) are a feature of mild NPDR
• Cotton wool spots may be present in mild NPDR or background DR but are caused by an arteriolar occlusion in that area of retina, but despite this being the underlying cause, they are not a good
sign of increasing retinal ischemia. They are often associated with hypertension
• A single venous loop. The ETDRS included a single venous loop in their classifi cation of mild NPDR; however, this rarely occurs in isolation without other signifi cant signs of retinal ischemia and a venous loop is therefore not a feature of the English Screening defi nition of background DR .
For mild NPDR, there is a 6.2% risk of progression to proliferative retinopathy within 1 year.
The International classification of DR recommends that anyone who has a more severe disorder than microaneurysms is referred to an ophthalmologist . In the UK, patients who are screened and who show signs of background DR are only rescreened annually. For the purposes of the English National
Screening Programme, background DR is defined by the following
lesions
• Microaneurysm(s); and
• Retinal hemorrhage(s) with or without any exudate

Moderate and severe non - proliferative
diabetic r etinopathy:
The main features that warrant classifying a DR level in the higher levels of moderate and severe NPDR  (or pre - proliferative DR  are increasing signs of retinal ischemia.
Lesions associated with increasing retinal ischemia:
• Retinal hemorrhages especially blot hemorrhages
• Intraretinal microvascular abnormality
Intraretinal microvascular abnormalities are derived from remodeling of the retinal capillaries and small collateral vessels in areas of microvascular occlusion. They are usually found on the borders of areas of non - perfused retina.
• Venous beading  is found to be associated with retinal ischemia and is used for assessment of severity
of DR. With increasing ischemia, there is an increasing risk of progression to proliferative in 1 year. The risk increases from approximately 11.3% in the lower levels of moderate NPDR to 54.8% progression to proliferative in 1 year in the most severe NPDR level. ETDRS defi nitions have been simplifi ed to make them easier for everyday clinical use both in the International classifi cation and in the English classifi cation for screening. The ETDRS “ 4 : 2 : 1 rule ” indicates that the presence of severe hemorrhages in four quadrants ( ≥ 20), VB in two quadrants or IRMA in a single quadrant represents this severity of retinopathy,severe NPDR. In the International classifi cation, severe NPDR is defi ned by any of the following:
• Extensive intraretinal hemorrhages ( > 20) in four quadrants;
• Definite VB in two or more quadrants;
• Prominent IRMA in one or more quadrant, and no signs of PDR. Moderate NPDR is classifi ed in the International classifi cation as more than “ microaneurysms only ” and less severe than the
4 : 2 : 1 rule.In the English Screening classifi cation, pre - proliferative DR is defined by any of the following:
• VB
• Venous loop or reduplication;
• IRMA; or
• Multiple deep, round or blot hemorrhages.


Proliferative d iabetic r etinopathy and
a dvanced d iabetic r etinopathy

New vessels arise from the post capillary venule in areas of ischemic retina. New vessel growth originates either within 1 DD of the optic disc (new vessels at the disc [NVD]) or developing
from retinal vessels more than 1 DD away from the edge of the optic disc (new vessels elsewhere [NVE]).


Diabetic Retinopathy Study
The Diabetic Retinopathy Study (DRS)  recommended prompt treatment in the presence of DRS high - risk characteristics, which reduced the 2 - year risk of severe visual loss by 50% or
more and were defined by:
• Presence of preretinal or vitreous hemorrhage;
• Eyes with NVD equalling or exceeding one - quarter to one - third disc area in extent with no hemorrhage;
• NVE equalling more than half disc area with hemorrhage.

Untreated, eyes with high risk characteristics had a 25.6 – 36.9% chance of severe visual loss within 2 years, depending on the size and location of the new vessels and whether or not hemorrhage was present.

“ Low risk ” proliferative patients
In eyes with PDR without high risk characteristics, there were still the following risks of severe visual loss:
• Untreated: 2 year 7.0%, 4 years 20.9%;
• Treated: 2 year 3.2%, 4 years 7.4%.

These risks need to be balanced against the potential adverse effects of laser treatment.
Adverse effects of laser treatment:

• Loss of peripheral areas of visual fi eld was attributed to argon laser in approximately 10% of eyes and fi eld loss was nearly three times more common in the xenon arc treated group.
• Visual acuity loss at the 6 - week follow - up visit was assumed to be brought about by treatment. Among eyes with NPDR, 14.3% more argon - treated and 29.7% of xenon - treated eyes than control subjects had an early persistent loss of one or more lines.
Other possible adverse effects of panretinal laser treatment are as follow:
• Unintended laser absorption (e.g. to the lens) or uptake of laser from a fl ame - shaped hemorrhage, which may result in a burn and destruction of the nerve fiber layer that lies on its surface.
• Inadvertent coagulation (e.g. to the fovea).
• Choroidal detachment is usually as a result of a large dose of laser treatment being applied in a single session, which usually resolves spontaneously within 10 days.

Factors other than h igh risk c haracteristics influencing the decision to laser
Anterior s egment n eovascularization
Extensive neovascularization in the anterior chamber angle is an urgent indication for scatter laser photocoagulation, if it is feasible Signs of ischemia
Large IRMA, VB in more than one quadrant, extensive retinal hemorrhages and opaque small arteriolar branches are signs suggesting
severe retinal ischemia
Macular edema





Pregnancy and the diabetic eye
Risk factors for progression of d iabetic retinopathy in pregnancy
The known risk factors for progression of DR in pregnancy
are:
 Pregnancy itself is independently associated with progression of DR
• Baseline severity of DR
• Poor metabolic control at conception [91] ;
• Rapid improvement of glycemic control [90– 93];
• Poor metabolic control during pregnancy or the early postpartum period
• Duration of diabetes
• Chronic hypertension and pregnancy- induced hypertension





source: text book of Diabetes, Pickup,jossling and Harrison internal medicine.