EARLY FINDINGS FROM A NATURAL HISTORY STUDY OF PATIENTS WITH THE PATHOGENIC p.Gly208Asp PRPH2 VARIANT ASSOCIATED WITH RETINAL DYSTROPHY.

Abstract

The aim of this study was to describe the longitudinal retinal degenerative changes associated with the p.Gly208Asp PRPH2 variant using multimodal imaging. A prospective, longitudinal cohort study was conducted, including seven patients heterozygous for the pathogenic p.Gly208Asp PRPH2 variant and nine age-matched controls. Demographics and best-corrected visual acuity (BCVA) were obtained. Imaging included optical coherence tomography (OCT) and fundus autofluorescence (FAF). Mesopic microperimetry assessed retinal sensitivity. At baseline, all cases exhibited a central areolar chorioretinal dystrophy (CACD) phenotype with 4 cases exhibiting stage IV and 3 cases at stage II. Six patients had longitudinal data with a mean follow-up of 1 year. Overall, the mean retinal thickness significantly reduced ( P = 0.001), although microperimetric mean sensitivity was not significantly altered with follow-up. In atrophic eyes, areas of definitely decreased autofluorescence increased significantly ( P < 0.001) with follow-up. This study highlights an association with the CACD phenotype in patients carrying the p.Gly208Asp PRPH2 variant. Multimodal imaging identified short-term markers of progression that may be useful for disease monitoring and potential future clinical trials.