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

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).

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.

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) mm²/year on SW-FAF and 0.24 (0.08-0.33) mm²/year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm²/year, P < 0.001), worse visual acuity (0.305 mm²/year, P = 0.005), multifocal disease (0.401 mm²/year, P = 0.02), and SW-FAF pattern (0.534 mm²/year, P =0 .03) were associated with a faster rate of progression (predictive R²: 0.65).

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.

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.