A review of clinical trials of anti-VEGF agents for diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population worldwide. Many observational and preclinical studies have implicated vascular endothelial growth factor (VEGF) in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration (AMD) have prompted research into the application of anti-VEGF drugs to DR. Here we review the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of diabetic retinopathy. For diabetic macular edema, phase II trials of intravitreal pegaptanib and intravitreal ranibizumab have shown short-term benefit in visual acuity. Intravitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness. For proliferative diabetic retinopathy (PDR), early studies suggest that intravitreal bevacizumab temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment (TRD). Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy (PPV) for TRD. Finally, three small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of DME after cataract surgery. Use of anti-VEGF medications for any of these indications is off-label. Despite promising early reports on the safety of these medications, we eagerly await the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy.