Clinical Characteristics and Genetic Variants of a Large Cohort of Patients with Retinitis Pigmentosa Using Multimodal Imaging and Next Generation Sequencing

Abstract

This retrospective study identifies patients with RP at the Inherited Retinal Disease Clinic at the University of Minnesota (UMN)/M Health System who had genetic testing via next generation sequencing. A database was curated to record history and examination, genetic findings, and ocular imaging. Causative pathogenic and likely pathogenic variants were recorded. Disease status was further characterized by ocular coherence tomography (OCT) and fundus autofluorescence (AF). Our study cohort included a total of 199 patients evaluated between 1 May 2015–5 August 2022. The cohort included 151 patients with non-syndromic RP and 48 with syndromic RP. Presenting symptoms included nyctalopia (85.4%) photosensitivity/hemeralopia (60.5%), and decreased color vision (55.8%). On average, 38.9% had visual acuity of worse than 20/80. Ellipsoid zone band width on OCT scan of less than 1500 μm was noted in 73.6%. Ninety-nine percent had fundus autofluorescence (AF) findings of a hypo- or hyper-fluorescent ring within the macula and/or peripheral hypo-AF. Of the 127 subjects who underwent genetic testing, a diagnostic pathogenic and/or likely pathogenic variant was identified in 67 (52.8%) patients—33.3% of syndromic RP and 66.6% of non-syndromic RP patients had a diagnostic gene variant identified. It was found that 23.6% of the cohort had negative genetic testing results or only variants of uncertain significance identified, which were deemed as non-diagnostic. We concluded that patients with RP often present with advanced disease. In our population, next generation sequencing panels identified a genotype consistent with the exam in just over half the patients. Additional work will be needed to identify the underlying genetic etiology for the remainder.