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

Abstract

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.