Macular Atrophy and Phenotypic Variability in Autosomal Dominant Stargardt-like Macular Dystrophy due to PROM1 mutation.

PURPOSE: To describe the phenotypic variability and rates of progression of atrophy in patients with PROM1-associated macular dystrophy (PAMD).

METHODS: Patients in this retrospective, longitudinal case series from a tertiary center had clinical exam and multi-modal imaging performed. Areas of retinal pigment epithelium and ellipsoid zone loss over time via OCT were calculated by two independent graders.

RESULTS: Fifteen patients from five kindreds with an Arg373Cys mutation in PROM1 were studied. Average age was 39 years; 80% were female. Visual acuity was 20/40 at presentation and 20/57 at last follow up (average 4.8 years). Three distinct macular phenotypes were observed: 1) central geographic atrophy (GA;13%), 2) multifocal GA (20%), and 3) bull's eye maculopathy (BEM;67%). Overall rate of atrophy progression was 0.36 mm2/year, but the average rate of atrophy progression varied by macular phenotype: 1.08 mm2/year for central GA; 0.53 mm2/year for multifocal GA; and, 0.23 mm2/year for BEM.

CONCLUSIONS: Patients with PAMD demonstrate distinct phenotypes, with BEM being the most common. Average rate of atrophy progression may be similar to reported rates for ABCA4-related Stargardt disease and less than age-related macular degeneration. These results provide important measures for following treatment response in future gene and stem-cell based therapies.