Visual Loss in Geographic Atrophy: Learnings From the Lampalizumab Trials

Purpose: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.

Participants: Patients with bilateral GA.

Methods: Monthly BCVA and fundus autofluorescence (FAF) at baseline and every 6 months for 2 years were analyzed. Baseline GA area from FAF images was correlated to baseline BCVA and change in BCVA. The lesion growth rate was calculated as the slope of a linear fit from all available GA area measurements of a patient. Association between GA growth rate quartiles and BCVA changes were assessed, subgrouped by GA foveal involvement and/or focality. Time-to-event analysis for BCVA loss of ≥ 5, ≥ 10, and ≥15 letters was performed. A Cox regression model adjusted for baseline factors was performed on these outcomes. Kaplan-Meier (KM) curves are provided for each baseline factor and GA growth rate.

Main outcome measures: Correlations of baseline BCVA, GA area, and growth rate with change in BCVA, and time to ≥ 5, ≥ 10, and ≥ 15-letter loss by foveal involvement and/or focality.

Results: BCVA and GA area at baseline did not correlate with BCVA change at any visit. GA growth rate showed a weak correlation with BCVA loss, which increased over time. The 2 highest GA growth rate quartiles had accelerated BCVA loss in eyes with subfoveal, unifocal lesions. Approximately 75%, 50%, and 25% of study eyes experienced a ≥ 5-, ≥ 10-, and ≥ 15-letter loss by 2 years, respectively.

Conclusions: BCVA and GA area at baseline did not correlate with BCVA loss, but faster GA growth rates appeared to be associated with faster BCVA loss. GA foveal involvement and focality correlated with the rate of BCVA loss with subfoveal lesions at high risk of vision loss over time, especially when the GA lesion was unifocal.