Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials

Abstract

To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531). Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD. Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures. For this study, mesopic macular sensitivity of the central 20° was assessed using MP-1 microperimeter at selected sites. Two exploratory endpoints were developed, namely perilesional sensitivity (average of points adjacent to absolute scotomatous points) and responding sensitivity (average of all nonscotomatous points; > 0 dB at baseline) by using customized masks for each patient. These were compared with conventional MP endpoints (mean macular sensitivity and number of absolute scotomatous points). Of 1881 Chroma and Spectri participants, 277 agreed to participate in the present study. Of these, 197 (LQ4W, n=63; LQ6W, n=68; pooled sham, n=66) had reliable MP results. Enlargement of GA lesion area by approximately 2 mm2/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of macular sensitivity or absolute scotomatous points among treatment groups. Perilesional and responding sensitivities showed greater decline over time than mean macular sensitivity. Change in GA lesion area at week 48 showed better correlation with perilesional sensitivity (r=-0.17) and responding sensitivity (r=-0.20) than mean macular sensitivity (r=-0.03), while the correlation was highest with the number of absolute scotomatous points (r=0.37). Perilesional or responding macular sensitivity measured by MP should be considered more sensitive endpoints than mean macular sensitivity for monitoring functional decline over time in GA. Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation. Proprietary or commercial disclosure may be found after the references.