@article {1586140,
	title = {Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial},
	journal = {JAMA Ophthalmol},
	volume = {139},
	number = {7},
	year = {2021},
	month = {2021 Jul 01},
	pages = {701-712},
	abstract = {Importance: The role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, Setting, and Participants: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (>=10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main Outcomes and Measures: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results: Among the 328 participants (57.6\% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3\% with aflibercept vs 43.5\% with sham. The overall hazard ratio for either outcome was 0.32 (97.5\% CI, 0.21-0.50; P \&lt; .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5\% in the aflibercept group vs 33.2\% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1\% in the aflibercept group vs 14.8\% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5\% CI, -1.0 to 1.9 letters]; P = .47). Conclusions and Relevance: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333.},
	issn = {2168-6173},
	doi = {10.1001/jamaophthalmol.2021.0606},
	author = {Maturi, Raj K and Glassman, Adam R and Josic, Kristin and Antoszyk, Andrew N and Blodi, Barbara A and Jampol, Lee M and Marcus, Dennis M and Martin, Daniel F and Melia, Michele and Salehi-Had, Hani and Stockdale, Cynthia R and Punjabi, Omar S and Sun, Jennifer K and DRCR Retina Network}
}
