Characterization of Flavimaculatus-Like Phenotype in PRPH2 associated Inherited Retinal Disease

Abstract

Purpose : Pathogenic variants in PRPH2 have been associated with multiple clinical inherited retinal disease (IRD) phenotypes. Several studies have highlighted marked PRPH2 phenotypic heterogeneity between pathogenic variants at different loci and even at a single locus. There is a lack of data on the characterization of certain PRPH2 endophenotypes. We aim to address this knowledge gap by describing retinal flecks findings in a cohort of PRPH2-associated IRD patients from two IRD referral centers.

Methods : Cases with molecularly confirmed PRPH2 IRD seen at the IRD clinics University of California San Diego, and Oregon Health & Science University were reviewed. Data collected included demographics, disease phenotype, genotype, best corrected visual acuity (BCVA), ultra-widefield fundus autofluorescence (FAF) photos, and spectral domain optical coherence tomography. Staging of the retinal flecks was performed using Fishman staging classification originally used for Stargardt disease and the topographic distribution was investigated using a Boston Grid. The statistical analysis was conducted per subject eye level through Linear Mixed Effects modeling using R statistical software.

Results : In total, 73 patients were reviewed. Of these, 37 patients (74 eyes) had retinal flecks and were included in the final analysis. The mean age was 57.3 (range 53.1, 61.5) years and 24 (65%) patients were female. Fishman stage 2 was the most common stage affecting 33 (44.6%) eyes (Figure 1). PRPH2 c.828+3A>T was the most common pathogenic variant affecting 12 (32.4%) of the subjects.
Fishman stage 4 demonstrated the worst BCVA (1.046 LogMAR (95% CI, 0.783, 1.309)) compared to other stages (p<0.001) (Figure 2). Central subfield thickness was significantly thicker in Fishman stage 4 eyes (300.7 µm (95% CI, 264.6, 335.9) compared to other stages (p<0.001) (Figure 2).
No significant association was found between different Fishman stages and the topographic distribution of the retinal flecks using Boston Grid.

Conclusions : The Flavimaculatus Like phenotype appears to be a common form of PRPH2 associated IRD that is not restricted to a certain topographic distribution and is associated with structural changes to the central macula.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1: Distribution of different Fishman Classification stages in the entire cohort.

 

Figure 2: Correlation between different Fishman stages and best corrected visual acuity and central subfield thickness