Early Response to Anti–Vascular Endothelial Growth Factor and Two-Year Outcomes Among Eyes With Diabetic Macular Edema in Protocol T 

Purpose: Assess associations of 2-year visual acuity (VA) outcomes with VA and optical coherence tomography central subfield thickness (CST) after 12 weeks of anti–vascular endothelial growth factor treatment for diabetic macular edema in DRCR.net Protocol T. Design: Randomized clinical trial. Methods: SETTING: Multicenter (89 U.S. sites). PATIENT POPULATION: Eyes with VA and CST data from baseline and 12-week visits (616 of 660 eyes randomized [93.3%]). INTERVENTION: Six monthly injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab; subsequent injections and focal/grid laser as needed for stability. MAIN OUTCOME MEASURES: Change in VA from baseline and VA letter score at 2 years. Results: Twelve-week VA response was associated with 2-year change in VA and 2-year VA letter score for each drug (P <.001) but with substantial individual variability (multivariable R² = 0.38, 0.29, and 0.26 for 2-year change with aflibercept, bevacizumab, and ranibizumab, respectively). Among eyes with less than 5-letter gain at 12 weeks, the percentages of eyes gaining 10 or more letters from baseline at 2 years were 42% (20 of 48), 31% (21 of 68), and 47% (28 of 59), and median 2-year VA was 20/32, 20/32, and 20/25, in the aflibercept, bevacizumab, and ranibizumab groups, respectively. Twelve-week CST response was not strongly associated with 2-year outcomes. Conclusions: A suboptimal response at 12 weeks did not preclude meaningful vision improvement (ie, ≥ 10-letter gain) in many eyes at 2 years. Eyes with less than 5-letter gain at 12 weeks often had good VA at 2 years without switching therapies.