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Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20 –74 years. During the first two decades of disease, nearly all patients with type 1 diabetes and 60% of patients with type 2 diabetes have retinopathy. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), 3.6% of younger-onset patients (type 1 diabetes) and 1.6% of olderonset patients (type 2 diabetes) were legally blind. In the younger-onset group, 86% of blindness was attributable to diabetic retinopathy. In the older-onset group, in which other eye diseases were common, one-third of the cases of legal blindness were due to diabetic retinopathy. NATURAL HISTORY OF DIABETIC RETINOPATHY Diabetic retinopathy progresses from mild nonproliferative abnormalities, characterized by increased vascular permeability, to moderate and severe nonproliferative d iabetic r etinopathy (NPDR), characterized by vascular closure, to proliferative diabetic retinopathy (PDR), characterized by the growth of new blood vessels on the retina and posterior surface of the vitreous. Macular edema, characterized by retinal thickening from leaky blood vessels, can develop at all stages of retinopathy. Pregnancy, puberty, blood glucose control, hypertension, and cataract surgery can accelerate these changes. Vision-threatening retinopathy is rare in type 1 diabetic patients in the first 3–5 years of diabetes or before puberty. During the next two decades, nearly all type 1 diabetic patients develop retinopathy. Up to 21% of patients with type 2 diabetes have retinopathy at the time of first diagnosis of diabetes, and most develop some degree of retinopathy over time. Vision loss due to diabetic retinopathy results from several mechanisms. Central vision may be impaired by macular edema or capillary nonperfusion. New blood vessels of PDR and contraction of the accompanying fibrous tissue can distort the retina and lead to tractional retinal detachment, producing severe and often irreversible vision loss. In addition, the new blood vessels may bleed, adding the further complication of preretinal or vitreous hemorrhage. Finally, neovascular glaucoma associated with PDR can be a cause of visual loss.