Macular sensitivity endpoints in geographic atrophy secondary to age-related macular degeneration - exploratory analysis of two parallel randomized phase 3 trials

Abstract

Purpose : To assess different microperimetry (MP) macular sensitivity measures in monitoring functional deterioration in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and the effect of lampalizumab (a selective complement factor D inhibitor).

Methods : Two identically designed Phase 3 double-masked randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531), enrolled participants aged ≥50 years with bilateral GA and no evidence of prior or active neovascular AMD. One eye was selected as the study eye where total lesion size was 1-7 disc areas on fundus autofluorescence (FAF) and the best-corrected visual acuity (BCVA) was ≥ 49 letters. Participants were randomized to receive 10mg of intravitreous lampalizumab every 4 weeks (LQ4W), every 6 weeks (LQ6W) or sham over 96 weeks. Macular sensitivity of the central 20° was assessed using MP-1 (NAVIS 1.7.1; Nidek) at selected sites. Treatment groups were compared across different MP parameters such as absolute scotomatous points (defined as 0dB response at the highest intensity stimulus of 20dB), mean macular sensitivity (average of all 68 points), responding sensitivity (average of non-scotomatous points) and perilesional sensitivity (average of points adjacent to absolute scotomatous points).

Results : A total of 229 participants (pooled sham n=77, LQ4W n=77, LQ6W n=75) had reliable MP results. The enlargement of GA area by FAF of approximately 2mm²/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of retinal sensitivity or absolute scotomatous points between treatment groups (p>0.05). GA area changes at 48 weeks had the highest correlation with absolute scotomatous points (r=0.29) followed by responding sensitivity (r=-0.18), perilesional sensitivity (r=-0.16), and mean macular sensitivity (r=-0.02). Perilesional and responding sensitivities showed more significant decline over time when compared to mean macular sensitivity.

Conclusions : Either perilesional or responding sensitivities by MP should be considered as more sensitive endpoints for monitoring GA functional decline compared to mean sensitivity, despite their weak correlation with GA lesion size. No treatment effect of lampalizumab was observed on MP outcomes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.