Local progression kinetics of macular atrophy in recessive Stargardt disease

Background: To determine the effect of lesion topography on progression in Stargardt disease (STGD1). Methods: Fundus autofluoresence (excitation 488 nm) images of 193 eyes in patients with proven ABCA4 mutation were semi-automatically segmented for autofluoresence changes: (DDAF) and questionably decreased autofluoresence (QDAF), which are proxies for retinal pigment epithelial (RPE) atrophy. We calculated topographic incidence of DDAF and DDAF + QDAF, as well as velocity of progression of the border of lesions using Euclidean distance mapping. Results: Incidence of atrophy was highest near the fovea, then decreased in incidence with increased foveal eccentricity. However, the rate of atrophy progression followed the opposite pattern; rate of atrophy increased with distance from foveal center. The mean growth rate 500 microns from the foveal center for DDAF + QDAF was 39 microns per year (95% CI = 28–49), whereas the mean growth rate 3000 microns from the foveal center was 342 microns per year (95% CI = 194–522). No difference in growth rate was noted by axis around the fovea. Conclusions: Incidence and progression of atrophy by fundus autofluorescence follow opposite patterns in STGD1. Further, atrophy progression increases significantly with distance from foveal center, which should be taken into consideration in clinical trials.