R E V I E W Current and future approaches in the prevention and treatment of diabetic retinopathy Louis K Chang1 David Sarraf1, 2 1Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; 2Department of Ophthalmology, Greater LA VA Healthcare Center, Los Angeles, CA Correspondence: David Sarraf Jules Stein Eye Institute, UCLA, 100 Stein Plaza, Los Angeles, CA 90095, USA Tel: +1 310 825 3090 Fax: +1 310 825 0441 Email dsarraf@ucla.edu Abstract: Diabetic retinopathy (DR) is a major cause of blindness worldwide and is the number one cause of blindness in working-age individuals in developed countries. We review the cur- rent literature and discuss the pathogenesis, modifying risk factors, genetics, and treatment of DR. Special focus is placed on the rationale and effectiveness of therapeutic modalities, both current and future. Introduction Diabetes mellitus (DM) is a major cause of morbidity and mortality worldwide, especially in developed nations. Worldwide 135 million suffer from DM and in the United States alone, roughly 18 million individuals are affected with DM, 4.1 million of whom have sight-threatening diabetic retinopathy (DR). Complications from DR account for the leading cause of vision loss in the US working population (Klein et al 1984a; Klein et al 1984b). Clinically, DR can be classiﬁed as nonproliferative or proliferative diabetic retinop- athy (NPDR and PDR, respectively). Signs of NPDR include retinal microaneursyms, intraretinal dot and blot hemorrhages (DB), hard exudates (HE), and cotton wool spots (CWS). Intraretinal microvascular abnormalities (IRMA) and venous beading (VB) may be seen in severe NPDR or preproliferative diabetic retinopathy (Chew and Ferris 2006). Signs of PDR include retinal and optic disc neovascularization, which may cause preretinal, subhyaloid, and vitreous hemorrhage (VH) and tractional retinal detachment (TRD). DR accounts for the vast majority of diabetes-related vision impairment. Microvascular damage increases retinal vascular permeability and may lead to diabetic macular edema (DME). The increased permeability allows egress of ﬂuid and plasma components, leading to thickening of the macula and lipoprotein deposition. DME prevalence increases with the grade of retinopathy and is the most common cause of vision loss in NPDR (Chew and Ferris 2006). Capillary closure within the macula may lead to foveal avascular zone enlargement or macular ischemia. VH and/or RD may complicate PDR; the former is the most common cause of blindness in diabetics (Klein et al 1984a; Klein et al 1984b). With extensive ischemia, neovascularization may occur in the iris and occlude the angle leading to neovascular glaucoma, which has a high-risk of severe, irreversible vision loss. Along with macular edema and ischemia, cell dysfunction and/or death may contribute to visual impairment in the setting of DM. This concept is supported by the ﬁnding that, in addition to greater severity of DR and increased ﬂuorescein leak- age, decreased summed electroretinographic oscillatory potentials was found to be an independent predictor of progression to severe PDR (Bresnick and Palta 1987a, 1987b). Moreover, increased apoptosis of cells in all layers of the retina has been observed in animal models of DR and in post-mortem analysis of retinas from diabetic Clinical Ophthalmology 2008:2(2) 425–433 © 2008 Dove Medical Press Limited. All rights reserved 425