Rationale and Application of the Protocol S Anti–Vascular Endothelial Growth Factor Algorithm for Proliferative Diabetic Retinopathy

Purpose To present the rationale, guidelines, and results of ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network ( DRCR.net ) Protocol S. Design Post hoc analyses from a randomized clinical trial. Participants Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). Methods Intravitreous ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes (n = 191) received monthly injections for 6 months unless resolution was achieved after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. Panretinal photocoagulation could be initiated for failure or futility criteria. Main Outcome Measures Neovascularization status through 2 years. Results At 1 month, 19% (35 of 188) of ranibizumab-assigned eyes showed complete neovascularization resolution and an additional 60% (113) showed improvement. At 6 months, 52% (80 of 153) showed neovascularization resolution, 3% (4) were improved, 37% (56) were stable, and 8% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1–7; n = 73) versus 7 (4–11; n = 67; P Conclusions The DRCR.net treatment algorithm for PDR can provide excellent clinical outcomes through 2 years for patients initiating anti–vascular endothelial growth factor (VEGF) therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by consideration of the relative advantages of each therapeutic method and anticipated patient compliance with follow-up and treatment recommendations.