Using multi-modal imaging to refine the phenotype of PRPH2-associated retinal degeneration

Abstract

To refine retinal PRPH2-associated retinal degeneration (PARD) phenotypes using multimodal imaging. Retrospective review of clinical records and multimodal imaging. Patients who visited the inherited retinal degeneration (IRD) clinic at two tertiary referral eye centers with molecularly confirmed IRD due to PRPH2 variants. Retinal imaging was reviewed using ultra-widefield (UWF) pseudocolor, UWF fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Phenotypes were identified in the macular or peripheral region. A combined phenotype was considered if any phenotypes were present in both macular and peripheral regions. Mixed phenotypes in the macula or peripheral retina were considered if there were two distinct phenotypes identified in the same eye. The presence or absence of atrophy in the macular or peripheral area was also noted. Grading of multimodal imaging by phenotype and atrophy. A total of 144 eyes of 72 patients were included in this study. The majority of the eyes had combined macular and peripheral phenotypes (89/14, 61.8%), while 44 (30.6%) eyes had isolated macular findings, and 11 (7.6%) had isolated peripheral findings. Twenty-five eyes were classified with mixed macular phenotypes while fundus flavimaculatus dystrophy type was the most common combined macular and peripheral phenotype (54/144, 37.5%): n = 10 with macular dystrophy and macular flavimaculatus dystrophy, and n = 15 with butterfly pattern dystrophy and macular flavimaculatus dystrophy. Nearly half of the eyes (71/144, 49.3%) were identified to have concomitant outer retinal atrophy. Fundus flavimaculatus type dystrophy was also associated with the highest proportion of concomitant atrophy (57/71, 80.3%). PARD demonstrates a wide array of phenotypes using multimodal imaging. We report that combinations of classically described phenotypes were often seen. Additionally, macular and peripheral atrophy were often associated with PARD phenotypes. Refinement of PARD phenotypes using newer multimodal imaging techniques will likely assist diagnosis and future clinical trials.