Maturi RK, Glassman AR, Josic K, et al. - Researchers conducted this randomized clinical trial to determine the effectiveness of intravitreous aflibercept injections vs sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe nonproliferative diabetic retinopathy (NPDR). Eyes were randomly assigned to receive 2.0 mg aflibercept injections (n = 200) or sham injections (n = 199) at baseline, 1, 2, and 4 months, and every 4 months for the next 2 years. The 2-year cumulative probability of developing center-involved diabetic macular edema (CI-DME) with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham among the 328 candidates (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years). The proportion of eyes that developed PDR or vision-reducing CI-DME with periodic aflibercept was lower among eyes with moderate to severe NPDR compared with sham treatment. However, over the course of two years, preventive treatment did not improve visual acuity when compared with observation plus aflibercept treatment only after the development of PDR or vision-reducing CI-DME. The 4-year results will be critical in determining long-term visual acuity outcomes.