The incidence of diabetes is increasing, but that of diabetic retinopathy is falling, probably owing to better management of glucose levels, lipid abnormalities, and hypertension. Clinical trials of VEGF and PPAR-α inhibitors are improving vision and providing insights into pathogenesis.

This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.

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 older-onset 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. Diabetic retinopathy progresses from mild nonproliferative abnormalities, characterized by increased vascular permeability, to moderate and severe nonproliferative diabetic retinopathy (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 …

Diabetic retinopathy diagnostic assessment and treatment options have improved dramatically since the 2002 American Diabetes Association Position Statement (1). These improvements include the widespread adoption of optical coherence tomography to assess retinal thickness and intraretinal pathology and wide-field fundus photography to reveal clinically silent microvascular lesions. Treatment of diabetic macular edema is now achieved by intravitreous injection of anti–vascular endothelial growth factor agents, and the same drugs are now used for proliferative diabetic retinopathy. Improvements in medications and devices for the systemic therapy of diabetes have also improved the ability of patients to optimize their metabolic control. This Position Statement incorporates these recent developments for the use of physicians and patients. Diabetic retinopathy is a highly specific neurovascular complication of both type 1 and type 2 diabetes, the prevalence of which strongly correlates to both the duration of diabetes and level of glycemic control. A pooled meta-analysis involving 35 studies conducted worldwide from 1980 to 2008 estimated global prevalence of any diabetic retinopathy and proliferative diabetic retinopathy (PDR) among patients to be 35.4% and 7.5%, respectively (2). Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20–74 years in developed countries. Glaucoma, cataracts, and other disorders of the eye occur earlier and more frequently in people with diabetes. In addition to diabetes duration, factors that increase the risk of or are associated with retinopathy include chronic hyperglycemia (3,4), nephropathy (5), hypertension (6), and dyslipidemia (7). Intensive diabetes management with the goal of achieving near-normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset and progression of diabetic retinopathy (8,9). Lowering blood pressure has been shown to decrease retinopathy progression in people with type 2 diabetes, although tight targets (systolic blood pressure <120 mmHg) do …

Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes.