Five-Year Outcomes after Initial Aflibercept, Bevacizumab, or Ranibizumab Treatment for Diabetic Macular Edema (Protocol T Extension Study)

Abstract Purpose Assess follow-up treatment and clinical outcomes at 5 years in eyes initially treated with anti-VEGF therapy for center involved diabetic macular edema (CI-DME) in a 2-year randomized clinical trial. Design Multicenter cohort study. Participants Participants with DME and visual acuity (VA) 20/32 to 20/320 enrolled in DRCR.net Protocol T with visits 5 years after randomization (3 years after Protocol T completion). Methods Participants were assigned randomly to aflibercept, bevacizumab, or ranibizumab with protocol-defined follow-up and retreatment for 2 years. Thereafter, participants were managed at clinician discretion and recalled for a 5-year visit. Main Outcome Measures Anti-VEGF treatment, VA letter score, and central subfield thickness. Results Sixty-eight percent (317 of 463) of eligible participants completed the 5-year visit. Between years 2 and 5, 68% (217 of 317) of study eyes received at least one anti-VEGF treatment (median [interquartile range] 4 [0, 12]). At 5 years, mean VA improved from baseline by 7.4 letters (95% confidence interval [CI]: 5.9 to 9.0), but decreased by 4.7 letters (95%CI: 3.3 to 6.0) between 2 and 5 years. When baseline VA was 20/50 to 20/320, mean 5-year VA was 11.9 letters (95%CI: 9.3 to 14.5) better than baseline, but 4.8 letters (95% CI: 2.5 to 7.0) worse than 2 years. When baseline VA was 20/32 to 20/40, mean 5-year VA was 3.2 letters (95% CI: 1.4 to 5.0) better than baseline, but 4.6 letters (95% CI: 3.1 to 6.1) worse than 2 years. Mean central subfield thickness decreased from baseline to 5 years by 154μm (95% CI: 142 to 166) and was stable between 2 and 5 years (-1μm [95% CI: -12 to 9]). Conclusions Among the two-thirds of eligible Protocol T participants who completed a 5-year visit, mean VA improved from baseline to 5 years without protocol-defined treatment after follow-up ended at 2 years. Although mean retinal thickness was similar at 2 and 5 years, mean VA worsened during this period. Additional investigation into strategies to improve long-term outcomes in eyes with DME seems warranted to determine if VA can be better maintained with different management approaches.