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Diabetic Retinopathy

  1. Donald S. Fong, MD, MPH12,
  2. Lloyd P. Aiello, MD, PHD34,
  3. Frederick L. Ferris III, MD5 and
  4. Ronald Klein, MD6
  1. 1Department of Ophthalmology, Southern California Permanente Medical Group, Baldwin Park, California
  2. 2Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, California
  3. 3Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts
  4. 4Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  5. 5Department of Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland
  6. 6Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin
  1. Address correspondence and reprint requests to Donald S. Fong, MD, MPH, Department of Research and Evaluation, Southern California Permanente Medical Group, 100 S. Los Robles, Pasadena, CA 91101
Diabetes Care 2004 Oct; 27(10): 2540-2553. https://doi.org/10.2337/diacare.27.10.2540
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  • ABCD, Appropriate Blood Pressure Control in Diabetes
  • ACCORD, Action to Control Cardiovascular Risk in Diabetes
  • AGE, advanced glycation end product
  • ARI, aldose reductase inhibitor
  • DCCT, Diabetes Control and Complications Trial
  • DIRECT, Diabetic Retinopathy Candesartan Trial
  • DME, diabetic macular edema
  • EDTRS, Early Treatment Diabetic Retinopathy Study
  • EUCLID, Eurodiab Controlled Trial of Lisinopril in Insulin Dependent Diabetes
  • FPG, fasting plasma glucose
  • NPDR, nonproliferative diabetic retinopathy
  • PDR, proliferative diabetic retinopathy
  • PEDF, pigment epithelium–derived growth factor
  • PKC, protein kinase C
  • QALY, quality-adjusted life-year
  • ROS, reactive oxygen species
  • SSF, seven standard field
  • SNMDP, single-field digital monochromatic nonmydriatic photography
  • TGF-β, transforming growth factor-β
  • UKPDS, U.K. Prospective Diabetes Study
  • VEGF, vascular endothelial growth factor
  • WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy

Over 135 million individuals are afflicted with diabetes across the world. In the U.S., diabetes affects over 18.2 million people (or 6.3% of the total population) and 800,000 new cases of type 2 diabetes are diagnosed each year (1). Retinopathy is the most common microvascular complication of diabetes, resulting in blindness for over 10,000 people with diabetes per year. Epidemiological studies have described the natural history of and treatment for diabetic retinopathy. There is evidence that retinopathy begins to develop at least 7 years before the clinical diagnosis of type 2 diabetes (2). Clinical trials have demonstrated the effectiveness of photocoagulation, vitrectomy, and control of hyperglycemia and hypertension for diabetic retinopathy (Table 1). The current review will discuss the pathophysiology, screening, medical treatment, and future research for diabetic retinopathy.

PATHOPHYSIOLOGY

Several biochemical pathways have been proposed to link hyperglycemia and microvascular complications. These include polyol accumulation, formation of advanced glycation end products (AGEs), oxidative stress, and activation of protein kinase C (PKC). These processes are thought to modulate the disease process through effects on cellular metabolism, signaling, and growth factors.

Polyol accumulation

Accumulation of polyol occurs in experimental hyperglycemia, which in rats and dogs is associated with the development of basement thickening, pericyte loss, and microaneurysm formation (3,4). High concentrations of glucose increase flux through the polyol pathway with the enzymatic activity of aldose reductase, leading to an elevation of intracellular sorbitol concentrations. This rise in intracellular sorbitol accumulation has been hypothesized to cause osmotic damage to vascular cells (5). Aldose reductase inhibitors (ARIs) have been evaluated for the prevention of retinal and neural damage in diabetes (6). However, three clinical trials of ARIs in humans have not shown efficacy in preventing the incidence or progression of retinopathy (7,8 and S. Feman [St. Louis University, St. Louis, MO], personal …

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Diabetes Care: 27 (10)

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October 2004, 27(10)
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Diabetic Retinopathy
Donald S. Fong, Lloyd P. Aiello, Frederick L. Ferris, Ronald Klein
Diabetes Care Oct 2004, 27 (10) 2540-2553; DOI: 10.2337/diacare.27.10.2540

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Diabetic Retinopathy
Donald S. Fong, Lloyd P. Aiello, Frederick L. Ferris, Ronald Klein
Diabetes Care Oct 2004, 27 (10) 2540-2553; DOI: 10.2337/diacare.27.10.2540
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