Progression of Atrophy as a Function of ABCA4 Variants and Age of Onset in Stargardt Disease.

Purpose: The purpose of this study was to assess the natural course of the retinal atrophy growth rate in patients with Stargardt disease (STGD1) with particular mutations in ABCA4, which may be eligible for mutation-specific therapy.

Methods: Fundus autofluorescence images (Heidelberg Spectralis) were gathered from 221 patients (436 eyes) in two centers: Radboud UMC and Ghent University Hospital. The area of definitely decreased autofluorescence and total decreased autofluorescence was measured using the Heidelberg RegionFinder software tool. Square root transformation was used to correct for two-dimensional growth. A mixed model was used to determine the atrophy growth rates. Atrophy growth rates were calculated for all eyes and were categorized into subgroups based on ABCA4 mutations potentially suitable for mutation-specific therapy (c.4539+2001G>A; c.5461-10T>C; c.5882G>A; c.768G>T), or subgroups based on age of onset.

Results: The mean square root-transformed growth rate of atrophy was 0.1446 mm/year (95% CI, 0.1382-0.1510 mm/year) for definitely decreased autofluorescence and 0.1459 mm/year (95% CI, 0.1402-0.1515 mm/year) for total decreased autofluorescence. Definitely decreased autofluorescence square root-transformed atrophy growth was slower in patients heterozygous for c.5882G>A (0.0821 mm/year) and c.4539+2001G>A (0.0686 mm/year) than c.768G>T (0.1299 mm/year) and c.5461-10T>C (0.1565 mm/year). Eyes of patients with late-onset STGD1 had the fastest atrophy growth (0.1782 mm/year), compared with eyes of patients with early-onset STGD1 (0.1655 mm/year) and patients with intermediate-onset STGD1 (0.1269 mm/year).

Conclusions: Atrophy growth rates vary among subgroups of patients with STGD1, depending on both specific mutations and age of onset. This pattern may have implications for the design of clinical trials for mutation-specific therapies.