Abstract
Purpose :
Autosomal dominant Stargardt-like macular dystrophy due to p.R373C mutation in prominin-1 (PROM1) results in significant loss of central vision from macular atrophy starting in early adulthood. We aim to describe the natural history and phenotypic variability as well as establish rates of progression of geographic atrophy using multimodal imaging.
Methods :
This was a retrospective, longitudinal chart review of patients with a p.R373C mutation in PROM1 at the University of Iowa. Outcomes studied included best-corrected visual acuity (BCVA), funduscopic findings, visual field examination, autofluorescence, and optical coherence tomography (OCT). Manual delineation of atrophic areas on confocal scanning laser ophthalmoscope (SLO) images and OCT volume scans was performed by two independent graders, and rates of atrophy progression were estimated for those with longitudinal imaging over at least 12 months.
Results :
Thirteen patients (average age 45, range 25 to 82 years old) from six families were included in the study. Six patients had at least two OCTs separated by at least 12 months enabling calculation of rates of atrophy progression. The mean BCVA at presentation was 20/70 (range 20/25 to 20/320) with symptoms of decreased central acuity initially manifesting in the 2nd and 3rd decades of life. Significant phenotypic variability was observed, and three distinct macular phenotypes were noted: 1) central geographic atrophy (GA), 2) multifocal GA, and 3) bull’s eye maculopathy; average rate of atrophy progression was 1.08 mm2/year; 0.53 mm2/year; 0.23 mm2/year, respectively. Choroidal neovascular membranes were not observed in any patient.
Conclusions :
Patients with PROM1-associated autosomal-dominant Stargardt-like macular dystrophy due to mutation demonstrate phenotypic variability in the size and distribution of macular atrophy. The average rate of atrophy progression measured in our study is similar to reported rates for ABCA4-related Stargardt disease, and less than those typically reported for age-related macular degeneration. These data are important for the evaluation of efficacy for future novel therapeutics such as gene and stem-cell based retinal therapies and contribute to our understanding of mechanisms of geographic atrophy in various disease states.
This is a 2020 ARVO Annual Meeting abstract.