Longitudinal Analysis of Mesopic Microperimetry in a Phase II Trial Evaluating Minocycline for Geographic Atrophy
09/2025
Journal Article
Authors:
Arunachalam, Thilaka;
Abraham, Maria;
Orndahl, Christine;
Menezes, Supriya;
Mukherjee, Souvick;
Duic, Cameron ;
Prasad, Minali;
Siddig, Fares;
Bellur, Sunil;
Thavikulwat, Alisa T.;
Bailey, Clare;
Sadda, SriniVas R.;
Wong, Wai T.;
Chew, Emily Y.;
Jeffrey, Brett G. ;
Keenan, Tiarnán D. L.
Volume:
5
Issue:
5
Journal:
Ophthalmology Science
URL:
https://www.sciencedirect.com/science/article/pii/S2666914525000818
DOI:
https://doi.org/10.1016/j.xops.2025.100783
Keywords:
Age-related macular degeneration Clinical trials Geographic atrophy Microperimetry Visual function
Abstract:
Purpose To analyze mesopic microperimetry data from a recent phase II trial of minocycline for geographic atrophy (GA) for possible efficacy on the change in visual function and, in the absence of efficacy, to perform longitudinal analyses as a natural history study. Design Phase II, prospective, single-arm, nonrandomized trial. After a 9-month run-in phase, participants began oral minocycline 100 mg twice daily for 3 years. Participants Individuals with GA in ≥1 eye. Methods Participants underwent mesopic microperimetry at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern. Rates of change in microperimetry parameters were compared between the 24-month treatment phase and 9-month run-in phase by linear spline regression. Main Outcome Measures The mean macular and responding sensitivity; the mean perilesional and extralesional sensitivity; number of absolute and relative scotomatous loci. Results Thirty study eyes from 30 participants (mean age 74.1 years) underwent microperimetry (mean follow-up 27.4 months). For 5 of the 6 microperimetry parameters, no significant difference in the rate of change between the treatment and run-in phases was observed. The difference between the 2 phases was −0.74 decibels (dB)/year (standard error [SE] 0.85; P = 0.39) for mean macular sensitivity, −0.30 dB/year (SE 0.85; P = 0.72) for mean responding sensitivity, 1.23 dB/year (SE 1.01; P = 0.22) for mean perilesional sensitivity, and −0.02 (SE 0.01; P = 0.31) for transformed mean extralesional sensitivity. The difference in incidence rate ratios between the 2 phases was 1.17 (SE 0.11; P = 0.14) for absolute scotomatous loci and 0.73 (SE 0.11; P = 0.004) for relative scotomatous loci. Conclusions The results do not appear consistent with a clinically meaningful effect of minocycline on the rate of visual function decline from GA progression. This is consistent with previous analyses of the corresponding structural data. The findings demonstrate the advantages and disadvantages of different microperimetry parameters. The optimal testing patterns and parameters represent a trade-off between greater sensitivity vs. greater risk of floor/ceiling effects, with regional averages providing a useful compromise. The results may provide insights to guide the development of microperimetry end points for clinical trials. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
