Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial

Purpose

To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.

Design

Secondary analysis of a randomized controlled trial.

Participants

Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.

Methods

Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.

Main Outcome Measures

Longitudinal changes in RAFH and GA area.

Results

Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (P < 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm²/year (Spearman’s ρ = 0.53; P < 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, P = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, P = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; P = 0.29).

Conclusions

Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.

Financial Disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.