The Rate of Progression of Geographic Atrophy Decreases With Increasing Baseline Lesion Size Even After the Square Root Transformation

PURPOSE: To determine the relationship between the progression of geographic atrophy (GA) and its baseline area (BA) using the square root transformation (sqrt) for different atrophy sizes. METHODS: Single eyes of patients with GA visiting the Institut de la Màcula (Barcelona, Spain) between December 2009 and January 2018 with a follow-up of ≥6 months were included. The main outcome was the correlation between BA and growth after the sqrt using Pearson's r and Spearman's rho. The graphical relationship was explored using linear and LOWESS regression. In a secondary, prespecified analysis, progression was compared by BA categories (Age-Related Eye Disease Study [AREDS] classification and BA tertiles). In post hoc analyses, the results were evaluated in subgroups defined by location of atrophy, number of lesions, fundus autofluorescence pattern, and fellow-eye status. RESULTS: We included 128 eyes (mean follow-up, 3.1 years). The correlation between BA and progression was negative (r = −0.30, P = 0.0005; rho = −0.25, P = 0.0042). There was a decrease in the rate of progression in mm/year with increasing BA, but this was significant for tertiles (P = 0.0078) and not AREDS (P = 0.20). The descending trend was driven by high-risk features. CONCLUSIONS: The correlation between GA progression and BA using the sqrt is negative. This has implications for the expected prediction of progression of a given lesion and to avoid overestimating the beneficial effects of interventional therapies. TRANSLATIONAL RELEVANCE: The GA progression/BA relationship using the sqrt currently is regarded as independent. Our results suggest the sqrt slope actually is negative, which should be kept in mind to avoid misinterpretation of results in advanced therapies.