Diabetic retinopathy have reported that vitreous levels of erythropoietin in eyes future advances, prevention of DR by optimizing control of with PDR are signiﬁcantly higher than control (Katsura et al modiﬁable risk factors, especially glycemic and blood pres- 2005; Watanabe et al 2005). Aqueous levels of erythropoietin sure control, will undoubtedly continue to have the most from eyes with DME were signiﬁcantly higher than those important role in the control of this disease process. with neovascular AMD or control eyes.(Jonas and Neumaier 2007) Another study found a stronger correlation between grade of PDR and erythropoietin than that with VEGF (Watanabe et al 2005). Carbonic anyhdrase Carbonic anhydrase I was recently identiﬁed as one of 117 proteins upregulated in vitreous samples of eyes with proliferative diabetic retinopathy using an unbiased, mass spectroscopy-based proteomic analysis (Gao et al 2007). In an animal model, carbonic anhydrase I increased retinal vascular leakage and retinal thickness through a kallikrein and bradykinin-dependent pathway. Acetazolamide, a car- bonic anhydrase inhibitor, is widely used for treatment of glaucoma and cystoid macular edema in the setting of retinitis pigmentosa. Previously, in a small pilot case-control study of 12 diabetics, oral acetazolamide improved angiographic edema, but had an equivocal beneﬁt for visual acuity (Giusti et al 2001). Further study is needed to validate the biological and clinical importance of this pathway in DR and DME. Benfotiamine Benfotiamine, a thiamine derivative, inhibits three biochemical pathways of hyperglycemia-induced endothelial dysfunction, namely the hexosamine, AGE formation, and diacylglycerol-PKC pathways (Brownlee 2001). When administered to streptozocin-treated diabetic rats, benfotiamine decreased capillary changes from diabetic retinopathy (Hammes et al 2003). This treatment modality is currently under investigation for treatment of diabetic peripheral neuropathy (Haupt et al 2005) and holds promise in the prevention of DR. Conclusions DR remains a challenging clinical entity, both in terms of prevalence and morbidity. Laser photocoagulation remains the gold standard of care for vision-threatening complications of DR. Newer treatment modalities, especially triamcinolone and anti-VEGF therapy, are currently in widespread use, but there are no consensus guidelines regarding their use. Further understanding of the environmental, genetic, and biochemical factors that contribute to the development and progression of DR will continue to yield promising new targets for more effective and better-tolerated treatments. Despite current and Clinical Ophthalmology 2008:2(2) Methods A comprehensive literature search was performed using the PubMed database. 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