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© 2003 by the American Diabetes Association, Inc.
Reviews/Commentaries/Position Statements |
Diabetic Retinopathy and Diabetic Macular Edema
Pathophysiology, screening, and novel therapies
1 Midwest Eye Institute, Indianapolis, Indiana
2 Lilly Research Laboratories, Indianapolis, Indiana
3 Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, University of Toronto, Toronto, Canada
Address correspondence and reprint requests to Bernard Zinman, MDCM, FRCP(C), FACP, Director, Leadership Sinai Centre for Diabetes, 600 University Ave., Suite 782, Toronto, Ontario, Canada. E-mail: zinman{at}mshri.on.ca
Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including protein kinase C–ß activation, increased vascular endothelial growth factor production, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of intervention for DR at earlier non–sight-threatening stages. To implement new therapies effectively, more individuals will need to be screened for DR/DME at earlier stages—a process requiring both improved technology and interdisciplinary cooperation among physicians caring for patients with diabetes.
Abbreviations: AGE, advanced glycation end product • ARI, aldose reductase inhibitor • CSME, clinically significant macular edema • DAG, diacylglycerol • DME, diabetic macular edema • DR, diabetic retinopathy • ETDRS, Early Treatment Diabetic Retinopathy Study • FA, fluorescein angiography • IC50, half-maximal inhibition concentration • PEDR, pigment endothelium-derived factor • PDR, proliferative diabetic retinopathy • PKC, protein kinase C • ROS, reactive oxygen species • VA, visual acuity • VEGF, vascular endothelial growth factor
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