2.1 CLASSIFICATION

Diabetic retinopathy is classified as:

• background retinopathy
• proliferative retinopathy

Each has a different prognosis for vision.

Background diabetic retinopathy (BDR) is further classified as:

• minimal
• moderate
• severe
• very severe

Precise grading for each level of BDR is based on the Airlie House

Grading system (see below) 13. Severe and very severe BDR are 

commonly referred to as preproliferative diabetic retinopathy (PDR).

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BDR which affects the macula is described as:

• diabetic maculopathy

Diabetic maculopathy (DM) is further classified as:

• focal oedema (also known as exudative maculopathy

 
• diffuse oedema

 
• ischaemia or 

 
• mixed

• new vessels on the disc (NVD) or within 1 disc diameter 

of the disc (DD)
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• new vessels elsewhere in the retina (NVE) (more than 

1 DD from the disc)

and according to severity as early PDR, established PDR, florid PDR 

and gliotic PDR. 'Involutionary' PDR is used to describe new vessels 

which have regressed in response to treatment or (rarely) 

spontaneously.

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2.2 BACKGROUND DIABETIC RETiNOPATHY

BDR, also described as non-proliferative diabetic retinopathy (NPDR), 

is so-called because the lesions lie within the retina (i.e. they form 

a 'background' to lesions on the retinal surface such as new vessels 

or within the vitreous such as forward new vessels and vitreous 

haemorrhage). Initially, background retinopathy consists of micro-

aneurysms only (Fig 1), progressing to microaneurysms and small 

haemorrhages ('dots and blots') (Fig 2) which can be graded as mild, 

moderate and severe (Fig 3). Splinter haemorrhages 

are also seen in combined hypertensive/diabetic retinopathy (Fig 4). 

Some grading centres consider a minimum of 4 microaneurysms are

required to diagnose background retinopathy and that they should 

be bilateral.

Figure 1 Background diabetic  retinopathy (BDR) showing  microaneurysms only (arrow).	Figure 2 BDR showing  microaneurysms and small  dot/blot haemorrhages (arrow).
Figure 3 Moderate sized blot  haemorrhages (arrows). Note also  the venous dilatation and beading  (arrowhead).	Figure 4. Splinter haemorrhages and  intraretinal microvascular abnormalities  (IRMAs) (arrows) associated with  combined hypertensive and diabetic  retinopathies.

Exudates, more common in NIDDM, are waxy yellow deposits with discrete 

edges, extending to the equatorial fundus often in clusters or forming 

circinate patterns whose centre may be a leaking microaneurysms (Fig 5). 

'Cotton wool spots' (CWS), previously called soft exudates, are fluffy 

white lesions representing infarcts of the nerve fibre layer hence are only 

found in the posterior retina where the nerve fibre layer is of appreciable 

thickness (Fig 6). They may appear suddenly during periods of changing 

glucose regulation and in association with hypertension.

Figure 5 hard exudates forming a ring  or circinate pattern around a leaking microaneurysm (arrow).

Figure 6 Soft exudates (cotton wool  spots, CWS) in the posterior fundus in  moderate DR (see arrow).

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Venous dilatation may occur as an early sign (see Fig 3) but become 

more pronounced as more of the capillary bed is closed. A general 

dilatation of the veins is observable even when the retinopathy is very 

mild and is to be distinguished from venous beading which is a sign of 

preproliferative retinopathy (Fig 7). Beading is indicative of extensive 

ischaemia of the retina and manifests as saccular bulges in the wall of 

the vein (Fig 7). Fluorescein angiography will invariably show closure 

of the capillary bed on either side of the vessel (Fig 8).

Figure 7 Venous beading (arrow)  indicating widespread retinal ischaemia.

Figure 8 Extensive venous beading  associated with areas of capillary  closure (arrows)

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Other signs of preproliferative retinopathy retinopathy are dilated 

capillaries which can mimic new vessels but are better described as 

intraretinal microvascular abnormalities (IRMA) (see Fig 4). They 

frequently occur adjacent to CWS's, and may be associated with 

other signs such as 'omega' venous loops (Fig 9), venous reduplication 

and white lines which represent occluded arterioles (Fig 10). According 

to the Early Treatment for Diabetic Retinopathy Study (ETDRS) report, 

preproliferative retinopathy is definitely present if the signs conform to 

the 1-2-3 rule: i.e.. the presence of venous beading and/or IRMA and/or 

large blot haemorrhages in 1-3 quadrants of the fundus.

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Figure 9 Omega loop (arrow), IRMA  and CWS in moderate/severe BDR.

Figure 10 'White line' indicating an  occluded vessels.

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Precise classifications for the purposes of clinical trials and other 

studies based on the Airlie House grading system have used the 

following criteria to define each of the grades of BDR:

• mild BDR: at least one microaneurysm

 
• moderate BDR: severe retinal haemorrhages in at least one 

quadrant, or CWS, venous beading or IRMA definitely present
'
• severe BDR: severe retinal haemorrhages in four quadrants; 

or venous beading in 2 quadrants; or extensive IRMA in one 
quadrant.
.
• very severe BDR: any two of the features of severe BDR. 

However, such classifications are difficult to use in clinical practice on a 

routine basis since certain features such as venous beading are common 

to both moderate and severe retinopathy. It is preferable, therefore to 

consider BDR as either midl or 'low risk' (i.e. not requiring regular close 

observation by an ophthalmologist) and severe or 'high risk' (i.e. requiring 

regular close observation as prelude to panretinal photocoagulation, PRP).

For the purposes of defining those patients at risk of developing new 

vessels, the features of 'low risk' (mild) BDR are:

• mildly dilated veins
• microaneurysms
• small haemorrhages
• hard exudates
• occasional CWS's

and the features of 'high risk', preproliferative (severe) BDR are

• IRMA
• venous beading and 'omega' loops
• clusters of large 'blot' or 'blotch' haemorrhages
• multiple CWS's

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2.3 PROLIFERATIVE DIABETIC RETiNOPATHY (PDR)

Proliferative retinopathy (PDR) usually appears late in the disease. 

However, PDR may occur with little warning in young adolescent 

or post adolescent individuals and have a particularly aggressive 

course. These individuals require extensive counselling (see below). 

It is important to emphasize that new vessels by themselves rarely 

produce symptoms; their sequelae are the cause of visual loss. 

New Vessels mostly arise from the venous side of the circulation 

and are recognizable by their abnormal location and their unusual 

pattern (Fig 11). Unlike normal vessels which have a branching 

pattern that divides dichotomously, new vessels form loops or rete 

(arcades). While norm vessels appear to be supplying or draining an 

area of retina, it may be difficult to identify such a role for new 

vessels. For example, a rete of vessels may arise from the main trunk 

of a vein and criss-cross the vessel randomly or a venule may arise 

from the disc and after forming a tortuous loop wind back towards 

the disc (Fig 12, 13). Early new vessels usually lie flat on the surface 

of the retina, but when the vitreous is detached, they are drawn 

forward as a result of vitreous traction.

Figure 11 New vessels elsewhere (NVE)  (arrow); note that new vessels have an  abnormal branching pattern, are very fine  and tend to form closed loops and fronds.	Figure 12 NVE showing three sites of new  vessel growth from one vessel.
Figure 13 New vessels of the disc (NVD)  showing backward looping of the new  vessel growth towards the disc (arrow)

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New vessels arise from the disc (NVD) (Fig 13, 14, 15) or the retina 

(NVE) (Fig 11, 12). Most new vessels arise from veins in a central, 

circular areas about 3½ disc diameter from the disc margin in any of 

4 quadrants. Where there is sectoral ischaemia, new vessels 

characteristically arise at the junction of the perfused and non-

perfused area as demonstrated on fluorescein angiograms (Fig 16a, b). 

In eyes with widespread ischaemia, NVD are common. Disc NVD may 

be flat or forward depending on the position of the posterior vitreous 

face. 

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Figure 14 Early NVD showing a small  frond of vessels arising below the disc  (arrow).

Figure 15 Advanced active NVD.

........... Figure 16 Corresponding fundus photograph a) and fluorescein angiogram b) showing  site of new vessels (arrow) on edge of area of ischaemia.

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Untreated NV (D or E) lead to vitreous haemorrhage (VH) and blindness. 

VH may be subhyaloid before the vitreous is fully detached and present 

as small 'crescents' with a level superior border if the PVD is present 

(Fig 17, 18).

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In the late stage of the natural history of proliferative disease, fibrous 

tissue (gliosis) gathers around the new vessels and contraction of this 

tissue causes repeated bleeding and eventually, tractional retinal 

detachment. Occasionally, fine epiretinal gliosis occurs with minimal 

traction on the retina but this is uncommon.

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Figure 17. Subhyaloid haemorrhage associated with new vessels and  showing a fluid level.	Figure 18 Large subhyaloid  haemorrhage in the premacular area.

2.4 MACULOPATHY

Visual loss in diabetic maculopathy is usually the result of macular 

oedema. Macular oedema may be difficult to detect; characteristically 

it appears as 'retinal thickening' on binocular, stereoscopic slit lamp 

examination. When it occurs within one disc diameter of the fovea, it is 

termed clinically significant macular oedema (CSME)14 since under these 

conditions it is visually threatening. Fluorescein angiography also reveals 

vessels with abnormal permeability causing leakage and pooling of dye in 

the late phase. A classification of maculopathy based on ophthalmological 

features is detailed below. However it is important to note than the terms 

'focal' and 'diffuse' are used to convey a sense of the extent of macular 

involvement, and if the ophthalmological findings are interpreted in 

conjunction with the corrected visual acuity a more accurate impression 

of the severity of disease will be obtained. For instance, diabetic 

maculopathy may occur in the relative absence CSME and fluorescein 

leakage on angiography. In this condition, ischaemia is the likely pathology.

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2.4.1 Clinical types of diabetic maculopathy

2.4.1.1 Focal maculopathy

The characteristic features of focal maculopathy are well circumscribed, 

leaking areas associated with complete or incomplete rings of hard exudates. 

These are often related to microaneurysms, particularly in the centre of 

exudative rings (Fig 5, 19). The exudative rings have a predilection for the 

perifoveal area where the retina is thickest. The focal areas of leakage are 

thickened by retinal oedema and fluorescein angiography is usually not 

necessary to identify them. Recent studies also suggest that retinal 

pigment epithelial damage may contribute to the macular oedema probably 

by failing to remove the tissue fluid accumulating in the retina from the 

leaking capillaries15.

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2.4.1.2 Diffuse maculopathy

Diffuse maculopathy consists of generalized leakage from dilated capillaries

in the macular area. Severe oedema is a feature and it is often associated 

with cystic changes. The other features of diabetic retinopathy may not be 

present and in particular there may be no exudates. In severe cases it may 

be impossible to identify the fovea due to the diffuse retinal thickening. The 

fluorescein angiogram is more dramatic than the ophthalmoscopic picture

(FIg 20 a, b).

Figure 20 Diffuse maculopathy showing retinal thickening a) and  extensive leakage on fluorescein angiography b).

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2.4.1.3 Ischaemia maculopathy

Ischaemia maculopathy is almost a diagnosis of exclusion, based on 

unexplained visual loss in the presence of a relatively normal looking 

macula. Blot haemorrhages in the paramacular region may be indicative 

of ischaemic maculopathy. There may be associated haemorrhages and 

exudates elsewhere. The exact extent of the ischaemia can only be seen 

on fluorescein angiography (Fig 21a, b). It is therefore important that 

patients with maculopathy in which ischaemia is suspected are investigated 

with this technique. There does not appear to be a direct correlation 

between visual acuity Dan the degree of ischaemia.

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Figure 21 Ischaemia maculopathy showing relatively non-specific changes at the macular a) with areas of non-perfusion on fluorescein angiography. 

2.4.1.4 Mixed maculopathy

Many cases do not fit exactly into the groups described above. Frequently, 

there is combined pathology particularly of diffuse oedema and ischaemia. 

Nevertheless, classifying the maculopathy according to its predominant features 

is useful form a therapeutic prognostic point of view.