Effect of oral minocycline on geographic atrophy progression: longitudinal microperimetry results of a phase II trial

Abstract

Purpose : Progression of geographic atrophy (GA) in age-related macular degeneration (AMD) may be triggered by innate immune cells, such as activated microglia near the atrophic lesion. Minocycline, a tetracycline antibiotic, has anti-inflammatory and microglia-inhibitory properties. A recent phase II trial of oral minocycline (NCT02564978) demonstrated no significant efficacy in slowing GA progression, based on the structural endpoint of GA enlargement rate. This exploratory analysis evaluated possible efficacy in the same trial, based on the functional endpoint of the rate of change in macular sensitivity.

Methods : Patients with GA were enrolled in a single-arm, phase II trial. Following a 9-month run-in phase, participants were administered oral minocycline 100 mg twice daily for at least 24 months. Participants underwent mesopic microperimetry (Nidek MP-1) at baseline, month 3, and every 6 months until study completion. A custom T-shaped test grid was used (Arunachalam T, et al., IOVS 2023;64:ARVO E-Abstract 2252). Table 1 lists the microperimetry parameters analyzed at each study visit. Rates of change in these parameters were compared between the 24-month treatment phase and 9-month run-in phase by generalized linear mixed models with a knot at treatment initiation.

Results : Microperimetry data were analyzed from 30 eyes of 30 participants over a mean follow-up of 26.8 months. There were no significant differences in the rate of change for all microperimetry parameters comparing treatment phase versus run-in phase. The differences between the two phases were: -0.74 dB/year (SE 0.85; p=0.39) for mean sensitivity across all loci, -0.63 dB/year (SE 0.79; p=0.42) for mean sensitivity across non-scotomatous loci, and 1.17 loci/year (SE 0.11; p=0.14) for the rate of increase in the number of scotomatous loci.

Conclusions : In this phase II trial, oral minocycline did not lead to a decrease in the rate of decline in several macular sensitivity outcomes over 24 months, compared to the run-in phase. The results of these functional analyses align with our structural analyses of GA enlargement performed earlier. Overall, oral minocycline at this dose likely does not slow GA enlargement in AMD. This novel custom microperimetry testing approach appears suitable for monitoring functional decline during GA progression and generating functional outcome measures for future studies.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.