Rudy Bilous, MD, FRCP
Richard Donnelly, MD, PHD, FRCP, FRACP
Pathology and clinical appearances: Retinopathy
Essentially, diabetic retinopathy can be classified as non-proliferative (now often split into background and pre-proliferative) and proliferative.
The earliest pathological features are thickening of the retinal capillary basement membrane, loss of tight junctions in the retinal endothelium, and loss of pericytes, which are the contractile cells enveloping the capillaries and which control vessel and thus perfusion (Figure 15.1). Physiologically, an increase in retinal blood flow is an early feature of diabetes and it is possible that this creates mechanical stress that leads to endothelial separation and pericyte loss.
The first noticeable lesions on ophthalmoscopy are micro-aneurysms, which appear as small red dots varying in size from 20 to 200μm in diameter (Figures 15.2, 15.3). They are blind pouches arising from capillaries, probably from weakened endothelial cell junctions adjacent to an area of pericyte loss. Microaneurysms are rarely sight threatening (unless occurring in the macula) and can seem to disappear although this is probably a result of thrombosis within the aneurysm or closure of the feeding capillary. Capillary closure is a feature of advancing retinopathy and the resultant ischemia is a driver for subsequent proliferation.
Hemorrhages can occur superficially when they tend to be flame-shaped (limited by nerve fibers) or deep (blot or round-shaped and indicative of underlying ischemia) (Figure 15.4).
Hard exudates are the result of leakage of lipid rich proteins into the retina (Figure 15.5). They appear as discrete yellow-creamy white patches, which are often ring-shaped or circinate around a central area of ischemia and capillary leakage.
Capillary closure causes microinfarcts in the nerve fiber layer and these appear as indistinct white patches and are termed cotton wool spots (previously known as soft exudates) (Figure 15.6). More advanced ischemia results with the development of intraretinal microvascular abnormalities (IRMAs) (Figure 15.7), which are clumps of small irregularly branching vessels within the retina, and venous dilatation, beading (segmental dilatation resembling a string of sausages) (Figure 15.8), loops and reduplication, sometimes into multiple loops resembling a four-leafed clover.