Factors Influencing Retinal Pigment Epithelium-Atrophy Progression Rate in Stargardt Disease

PURPOSE: To evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF). METHODS: Retrospective cohort study of patients with STGD1 with ≥2 gradable SW-FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models. RESULTS: Fifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10–0.85) mm(2)/year on SW-FAF and 0.24 (0.08–0.33) mm(2)/year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm(2)/year, P < 0.001), worse visual acuity (0.305 mm(2)/year, P = 0.005), multifocal disease (0.401 mm(2)/year, P = 0.02), and SW-FAF pattern (0.534 mm(2)/year, P =0 .03) were associated with a faster rate of progression (predictive R(2): 0.65). CONCLUSIONS: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPE-atrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression. TRANSLATIONAL RELEVANCE: The knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design.