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Current and Emerging Therapies for Diabetic Retinopathy

US Sensory Disorders Review, 2006:13-6 DOI:
Received: January 11, 2011 Accepted: January 11, 2011

Diabetes mellitus (DM) is an important cause of visual morbidity that affects an estimated 11.8 million diagnosed and 4.9 million undiagnosed individuals in the US.1 Among individuals 40 years and older with DM, it is estimated that 40.3% have some degree of diabetic retinopathy (DR) and 8.2% have visionthreatening retinopathy.2 The rates of retinopathy and vision-threatening retinopathy are higher in individuals with type 1 DM, occurring in 82.3% and 32.2% of affected individuals, respectively.3 The medical cost of DR has been estimated to be US$500 million per year in the US alone.4 In addition, individuals with visual loss secondary to DR suffer from a substantial decrease in patient utility value and quality of life and are more likely to be depressed.5,6

Risk factors associated with the development and progression of DR include prolonged hyperglycemia, hypertension, and hyperlipidemia.7-9 Although not fully understood, it is believed that advanced glycation end products contribute to the initiation and progression of DR by breaking down the inner blood retinal barrier and by upregulating vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1).10-12 VEGF is a potent angiogenic and vasopermeability stimulus whereas ICAM-1 contributes to leukocyte adhesion resulting in capillary occlusion and vascular cell death.13-15 Chronic hyperglycemia is also implicated in enhanced lowdensity lipoprotein peroxidation, which contributes to diabetic vascular disease.16 Hyperlipidemia is further associated with increased blood viscosity and alterations in the fibrinolytic system.17,18

Hypertension is thought to contribute to endothelial damage as a result of increased shear stress from loss of retinal vascular autoregulation.19 Endothelial damage, basement membrane thickening, and pericyte loss result in macular edema, microaneurysm formation, and capillary onperfusion. 20 Progressive retinal ischemia may induce neovascularization of the iris, disc, and retina resulting in vitreous hemorrhage (VH) and tractional retinal detachment. Other findings that may be present at any stage of DR include cotton wool spots, intraretinal hemorrhages, and hard exudates.

Control of Systemic Risk Factors
In addition to regular ophthalmic screening, systemic control of modifiable risk factors is an important adjunct to the management of the ocular complications of DM. It is well-known that rigorous control of blood glucose reduces the incidence of microvascular complications and retinopathy in individuals with type 1 or 2 DM.21,22 Among the numerous agents available to control blood glucose levels, it is important to note that the thiazolidinediones (glitazone) class of oral hypoglycemic agents used to reduce insulin resistance in type 2 diabetics has been associated with fluid retention and the development of macular edema in 5–15% of individuals.23,24 Resolution of macular edema in these patients occurred over variable periods after discontinuing pioglitazone or rosiglitazone, but was not necessarily associated with an improvement in vision.
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