Diabetic retinopathy is the leading cause of blindness in the United States and Western Europe among adults less than age 55 years. It affects both genders and all races, although African Americans are more frequently and more severely affected than Caucasians.

The best predictor of diabetic retinopathy is the duration of disease. For type 1 diabetic patients there is no risk of retinopathy for roughly 5 years after initial diagnosis. Some retinopathy is present in up to 50% of patients 10 years after diagnosis. After 15 years, 95% of patients show some retinopathy. Proliferative retinopathy is very uncommon with less than 10 years’ duration of disease. Forty percent of patients have proliferative disease by 25 years.

The trend for type 2 diabetic patients is very similar. Many patients will have asymptomatic, occult diabetes for many years prior to diagnosis, however, and therefore may present with retinopathy even at the time of diagnosis of diabetes mellitus.

Age is another important risk factor in the prevalence of diabetic retinopathy. Diabetic retinopathy is very rare prior to puberty. Its prevalence increases dramatically after puberty, however, and over 50% of patients will develop retinopathy by their early twenties.

Hyperglycemia is a key factor in the development of diabetic retinopathy. The mechanism of retinopathy development may be related to:

Histopathologically, thickening of retinal capillary basement membranes and loss of pericytes have been shown consistently.

Patients are often asymptomatic but may have blurry vision or floaters. More extensive visual loss occurs with large vitreous hemorrhages or retinal detachment.

Nonproliferative Diabetic retinopathy (NPDR) is the preferred term for this less severe manifestation of diabetic retinopathy. It may be arbitrarily subdivided into mild, moderate, and severe categories.

Earliest fundus manifestations of diabetic retinopathy. Features reflect retinal capillary hyperpermeability. May be manifested as:

This degree of retinopathy is characterized by increased number and size of intraretinal hemorrhaging with greater evidence for exudation as manifested by more HYE (Fig. 3-5) and macular edema than is present in mild nonproliferative retinopathy. (Standardized photographs exist to establish the transition points between the various stages of nonproliferative retinopathy, but it should be remembered that this classification reflects a continuum of disease severity.) In moderate nonproliferative retinopathy one also begins to see evidence of capillary occlusive disease. This is reflected by the development of:

Vision loss in moderate NPDR may be the result of macular edema or, less frequently, loss of some of the normal perifoveolar capillary bed. Frequently, both problems may be present.

In severe NPDR there is worsening of the exudative aspect of diabetic retinopathy and, especially, evidence for capillary occlusive changes. More extensive intraretinal hemorrhaging, venous beading, IRMA, as well
as edema and exudate are the features that define severe nonproliferative retinopathy (Figs. 3-8 to 3-10). The presence of certain fundus features predicts the progression toward proliferative retinopathy (Table 3-1).

Cornea—decrease of corneal sensitivity; increased risk abrasion

Cataract—typically nuclear and cortical cataract formation is chronic and progressive; acute cortical cataract formation with profound elevations in blood glucose

Glaucoma—greater incidence of primary open-angle glaucoma

Cranial nerve palsy—isolated palsy, most often sixth

Other causes of retinal capillary leakage and occlusion include:

The most important aspect of the evaluation of NPDR is a magnified, stereoscopic, slit-lamp biomicroscopic examination of the posterior pole and midperipheral retina using a handheld indirect lens or contact lens. A critical determination is the presence or absence of clinically significant macular edema (CSME; Table 3-2).

Fluorescein angiography is a valuable ancillary test in evaluation of NPDR. Indications include:

Optical coherence tomography (OCT) is another ancillary test that is important in managing diabetic macular edema. OCT provides a noncontrast, photographic method for determining the presence of fluid within and under the retina, quantifying the extent of that fluid and monitor the response to therapy (Fig. 3-14).

NPDR tends to progress gradually over months to years. The risk of vision loss increases with increasing severity of retinopathy. Treatment of systemic disease reduces but does not eliminate the risk of progression and vision loss (Table 3-3). Newer medications under development may actually reverse retinopathy.

Ocular treatment consists of macular laser photocoagulation for macular edema (Fig. 3-15). Early treatment diabetic retinopathy study (ETDRS) guidelines are widely applied (Table 3-4). The utility and timing of retreatment, the role of early treatment before ETDRS threshold is reached, and the application of alternative treatment strategies are less uniformly accepted.

The ETDRS addressed three questions: