CLASSIFICATION OF DIABETIC RETINOPATHY

The initial clinical features of diabetic retinopathy are microaneurysms, small retinal haemorrhages and small areas of capillary closure (Table 15.1). Visual acuity is commonly normal at this stage, although subclinical changes in colour vision and contrast sensitivity might be found. This is followed by vascular leakage, hard exudate and cotton-wool spots. Retinopathy may progress to compromise vision in two ways: (1) maculopathy develops with oedema, lipid exudation or ischaemia, or (2) a proliferative retinopathy occurs, in which retinal hypoxia and neovascularization predominate and reduce vision by vitreous haemorrhage or traction retinal detachment. Not uncommonly, both mechanisms coexist in the same patient. Diabetic retinopathy is staged by its clinical features. Maculopathy is classified by extent as focal or diffuse, and by mechanism as exudative, ischaemic or mixed.

Table 15.1 Classification of diabetic retinopathy

Fig. 15.5 A flow diagram illustrates the concept of progression from initial nonproliferative or ‘background’ retinopathy to visual loss from maculopathy or proliferative retinopathy.

NATURAL HISTORY

Visual loss is a late event in diabetic retinopathy. Retinopathy normally develops many years after the onset of diabetes, although in some adults it may be the first presenting sign of the disease. About 25 per cent of type I diabetics have some retinopathy after 10 years of disease, whereas type II diabetics seem to develop retinopathy earlier with significant numbers being affected by 5 years after diagnosis and 50 per cent by 10 years. Diabetics lose vision as a result of either maculopathy or proliferative retinopathy. In general, type I diabetics are more likely to have proliferative retinopathy whereas type II diabetics are more likely to have maculopathy. More than 80 per cent of visual loss in diabetics is due to maculopathy, due in part to the 10-fold greater number of type II patients. These patients lose central vision but retain navigating sight. Proliferative retinopathy is much more serious as about 70 per cent of these eyes would be totally blind within 5 years from vitreous haemorrhage and retinal traction detachment if left untreated.

Risk factors for the progression of retinopathy are the duration of diabetes and the type (type I is worse than type II). Recent clinical trials have shown that meticulous long-term glycaemic and blood pressure control retards the onset and progression of diabetic retinopathy. Tightening poor glycaemic control may, however, initially markedly worsen retinopathy and cause neovascularization, possibly because initiating good control lowers retinal blood flow and exacerbates ischaemia. Careful monitoring of diabetic retinopathy when altering glycaemic control is therefore critical. Pregnancy, renal disease and cataract surgery may worsen the retinopathy whereas high myopia, optic atrophy, glaucoma, central retinal artery occlusion and carotid artery stenosis appear to protect, possibly by reducing retinal metabolic demand (Table 15.2). Diabetic retinopathy is not seen before puberty.

Table 15.2 Risk and protective factors for progression of retinopathy

MILD AND MODERATE NONPROLIFERATIVE DIABETIC RETINOPATHY (NPDR)

Previously termed ‘background’, this is the commonest form of diabetic retinopathy. Microaneurysms, dot haemorrhages (indistinguishable from microaneurysms without fluorescein angiography) and small, deep, blotchy haemorrhages are seen in the posterior pole and become more numerous as the retinopathy progresses. Initially, NPDR tends to be most prominent in the retina temporal to the macula, possibly because this is a watershed area in the retinal circulation. Splinter haemorrhages are a feature of combined hypertensive–diabetic retinopathy. Small focal areas of closure in the capillary bed are common. Hard exudates appear in relationship to focal vascular leakage, and the occasional cotton-wool spot may be seen. Fluorescein angiography shows more extensive changes than can be seen ophthalmoscopically.

Fig. 15.6 This patient shows the typical changes of early retinopathy with scattered microaneurysms, blot haemorrhages and hard exudates and cotton-wool spots in the posterior pole. The macula and visual acuity are normal. The retinopathy can fluctuate, improving or deteriorating over a period of time. Fluorescein angiography demonstrates extensive microvascular changes throughout the posterior pole with scattered microaneurysms and minimal vascular leakage. Many more microaneurysms are visible that can be seen clinically. Although in some areas capillary patterns around the macula are irregular and show minor areas of capillary closure, they are, in the main, complete.

Fig. 15.7 With early retinopathy, the retina temporal to the macula is often susceptible to earlier and more pronounced changes; elsewhere in the posterior pole of this patient, retinopathy is comparatively sparse.

Fig. 15.8 These patients show a more marked nonproliferative retinopathy.

Fig. 15.9 Background retinopathy appearances can fluctuate and do not progress relentlessly. These photographs were taken 18 months apart. The later photograph (top right) shows that the exudates temporal to the macula have been absorbed spontaneously and new exudate has appeared inferior to the macula. Comparison of angiograms from the same patient shows there has been a considerable change in the pattern of the microaneurysms. New microaneurysms have formed and others, on the temporal side of the macula in particular, have disappeared over the same period of time.

SEVERE NONPROLIFERATIVE DIABETIC RETINOPATHY

Previously the stage between background and proliferative retinopathy was called ‘preproliferative diabetic retinopathy’, but is now termed severe or very severe nonproliferative diabetic retinopathy. These patients have a substantial risk of progressing to proliferative diabetic retinopathy (PDR). Severe or very severe NPDR is characterized by signs of marked retinal hypoxia such as cotton-wool spots, capillary nonperfusion, numerous intraretinal haemorrhages, venous beading and loops, and intraretinal microvascular abnormalities (IRMAs). Cotton-wool spots have often been considered the hallmark of preproliferative diabetic retinopathy, but the Early Treatment Diabetic Retinopathy Study (ETDRS) found that IRMAs, venous changes and many deep haemorrhages were more predictive of imminent PDR. The retinopathy is defined as severe when one of the following signs is present and as very severe when two of the signs are present: (1) deep haemorrhages in four quadrants, (2) venous abnormalities in two or more quadrants, and (3) IRMAs in one or more quadrants.

Fig. 15.10 Numerous cotton-wool spots, which persist for longer in diabetes (up to 3 months) than with other causes indicate marked retinal ischaemia, as confirmed on angiography.

Fig. 15.11 Areas of intraretinal microvascular abnormalities (IRMAs) with dilated tortuous veins along the inferior temporal arcade are seen in this patient. IRMAs represent intraretinal neovascularization and are found at the border of areas of nonperfusion. They are entirely intraretinal and do not leak fluorescein. As they are associated with nonperfusion it is not surprising that they are associated with an increased risk of PDR.

Fig. 15.12 Areas of nonperfusion can often be recognized ophthalmoscopically by their flat featureless appearance and relative absence of microvascular changes.

Fig. 15.13 Blotchy, deep, retinal cluster haemorrhages are a feature of nonperfusion.

Fig. 15.14 Venous beading is seen where a vein traverses an area of capillary nonperfusion.

Fig. 15.15 This patient shows an extensive venous loop or ‘omega anomaly’. There is early neovascularization on the disc and deep cluster haemorrhages temporal to the macula.

PROLIFERATIVE DIABETIC RETINOPATHY (PDR)

This tends to occur in diabetics who have evidence of other diabetic complications with renal, vascular and neurological complications. The prognosis of these patients has improved considerably in recent years with better medical management.

The stimulus for neovascularization, as in other neovascular retinopathies, appears to be retinal hypoxia from extensive areas of retinal capillary closure. This leads to a reduction of the increased retinal blood flow which is a feature of nonproliferative retinopathy. Neovascularization starts to appear from the capillaries on the venous side of the circulation on either the optic disc or retina, usually at the junction of normal and hypoxic retina. At first the new vessels lie as vascular membranes flat on the retinal surface, but induced changes in the vitreous gel cause the gel to collapse and detach from the retina. New vessels that have penetrated the internal limiting membrane are dragged forwards on the posterior hyaloid face which acts as a scaffold for further proliferation. The neovascular tissue proliferates on the posterior hyaloid face but does not penetrate the vitreous gel.

In common with neovascularization elsewhere in the eye these vessels have fenestrated endothelial cell junctions and tend to leak, while minor trauma and vitreous traction causes them to tear and bleed to cloud the ocular media. Subsequent formation of fibrous tissue produces traction bands between the retina and posterior vitreous face; these eventually contract and detach the retina (see Ch. 12).