Projection of long-term visual acuity outcomes based on initial treatment response in neovascular age-related macular degeneration

Abstract

PURPOSE To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3 year visual acuity (VA) outcomes.
DESIGN Observational study from a prospectively collected registry.
PARTICIPANTS Treatment-naïve eyes in the Fight Retinal Blindness! outcomes registry that commenced anti-VEGF therapy between 1st January 2007 and 1st March 2014 that received 3 anti-VEGF injections within the first 3 months.
METHODS The early response was defined as occurring up until the 4th injection. Various early response metrics, which included both continuous and categorical variables, were explored: 1) achieving good VA (≥70 letters [20/40]), 2) absolute change in VA from baseline, 3) time to first grading of the choroidal neovascular lesion as inactive, 4) maximum rate of VA change between successive injections.
MAIN OUTCOME MEASURES Proportion of eyes achieving ≥70 letters at 3 years.
RESULTS This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was significantly associated with 1) having good vision by the 4th injection (odds ratio [95% CI]: 9.8 [6.5, 14.7] for VA≥70 vs. VA<70 letters), 2) small (1-5 letters) or large (>5 letters) early VA gains (1.8 [1.2, 2.6], P = 0.002 and 1.8 [1.3, 2.5], P < 0.001 vs. eyes with early VA loss), 3) fewer injections until first grading of lesion inactivity (1.6 [1.2, 2.1], P < 0.001 for ≤3 vs. >3 injections), 4) gradual change (between -4 and 4 letters) or rapid (>5 letters) gains between successive injections (1.7 [1.1, 2.6], P = 0.015 and 1.6 [1.1, 2.3], P = 0.018 for gradual change and rapid gain vs. rapid loss). Eyes that achieved small or large early gains achieved similar vision at 3 years (65.0 and 64.7 letters respectively), and had better vision than eyes with early VA loss (57.2 letters).
CONCLUSIONS Attainment of good vision by the 4th injection was strongly associated with 3 year visual outcomes, while other early response parameters had a moderate association. The early response during the initial 3 monthly loading doses can be a useful guide for subsequent treatment decisions.