Diabetic retinopathy and systemic factors.

Diabetic retinopathy, an oculardisease, is governed by systemic as well as local ocular factors. These include primarily chronic levels of blood glucose. Individuals with chronically elevated blood glucose levels have substantially more, and more severe, retinopathy than those with lower blood glucose levels. The relationship of blood glucose to retinopathy is continuous, with no threshold although individuals with hemoglobin A1c levels (a measure of chronic glycemia) <6.5%, generally develop little or no retinopathy. Blood pressure levels have been claimed to influence retinopathy development and progression, but multiple controlled clinical trials of antihypertensive agents in diabetic subjects have produced only weak evidence of benefit from blood pressure lowering on the incidence and progression of diabetic retinopathy. Elevated blood lipids seem to play a role in the progression of retinopathy, and two trials of fenofibrate, a lipid-lowering agent that has not proved effective in preventing cardiovascular disease, have shown benefit in preventing retinopathy progression. The mechanism of this effect may not, however, be directly related to the reduction in blood lipids. Finally, there is strong, but only circumstantial, evidence for a genetic or epigenetic influence on the pathogenesis of diabetic retinopathy. Despite the power of large-scale epidemiologic studies and modern molecular biological and computational techniques, the gene or genes, which predispose or protect against the development and progression of diabetic retinopathy remain elusive.