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

• Published in: Ophthalmology (Rochester, Minn.) Vol. 126; no. 1; pp. 87 - 95
• Main Authors: Sun, Jennifer K., Glassman, Adam R., Beaulieu, Wesley T., Stockdale, Cynthia R., Bressler, Neil M., Flaxel, Christina, Gross, Jeffrey G., Shami, Michel, Jampol, Lee M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: Adult; Algorithms; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - therapeutic use; Clinical Protocols; Diabetic Retinopathy - diagnosis; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - physiopathology; Female; Follow-Up Studies; Humans; Intravitreal Injections; Laser Coagulation; Male; Middle Aged; Ranibizumab - administration & dosage; Ranibizumab - therapeutic use; Retinal Neovascularization - diagnosis; Retinal Neovascularization - drug therapy; Retinal Neovascularization - physiopathology; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Visual Acuity; DRCR.net; VEGF; CLARITY; CI-DME; IQR; DME; PDR; PRP
• ISSN: 0161-6420; 1549-4713; 1549-4713
• DOI: 10.1016/j.ophtha.2018.08.001

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. Post hoc analyses from a randomized clinical trial. Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). 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. Neovascularization status through 2 years. 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 < 0.001). Injections were deferred in 68 of 73 eyes (93%) meeting sustained stability at least once during the study; 62% (42 of 68) resumed injections within 16 weeks after deferral. At 2 years, 43% (66 of 154) showed neovascularization resolution, 5% (7) showed improvement, 23% (36) were stable, and 27% (42) had worsened since the last visit. Only 3 eyes met criteria for failure or futility through 2 years. 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.