LAUSR

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.