Quantitative Evaluation of Geographic Atrophy Progression Using Geographic Atrophy Lesion Front Displacement

Purpose: To evaluate the temporal behavior and relative variability of a margin-based metric, lesion front displacement, for quantifying geographic atrophy (GA) progression secondary to age-related macular degeneration and to compare its performance with conventional metrics. Methods: This retrospective longitudinal analysis included 103 untreated fellow eyes from the MAHALO clinical trial with GA and 18-month follow-up. Fundus autofluorescence images were obtained at baseline and 6, 12, and 18 months. Five progression metrics were calculated: total area change, square root area change, total perimeter change, perimeter-adjusted growth rate (λ'PA), and lesion front displacement. Linearity was assessed using simple linear regression and the Harvey-Collier test. Variability was evaluated using standard deviation, variance ratios, and the Fligner-Killeen test. Results: Linearity was rejected for area and square root area change but not for lesion front displacement, perimeter change, or λ'PA. Lesion front displacement showed a relatively higher coefficient of determination (R2 = 0.504), whereas area (0.116), square root area (0.104), perimeter (0.001), and λ'PA (0.018) exhibited lower goodness of fit to a linear model. Lesion front displacement demonstrated lower dispersion across follow-up intervals. Variance ratio analysis indicated greater variability for all comparator metrics. Variability was significantly lower for lesion front displacement than for perimeter change and λ'PA at 12 and 18 months (P < 0.05). Conclusions: Lesion front displacement demonstrated more consistent linear approximation and lower variability compared with several conventional GA progression metrics. This margin-based approach may serve as a complementary metric for longitudinal assessment of GA progression.