Natural history study of PRPF31-mediated retinal dystrophy

Abstract

Purpose : This study aimed to describe the characteristics at baseline of patients with autosomal dominant (AD) PRPF31-mediated retinal dystrophy participating in the RP11 Project.

Methods : In an ongoing prospective 4-year natural history study of PRPF31-mediated retinal dystrophy, the participants underwent multimodal investigation. An age-and gender matched control group enrolled for comparison of results. Functional outcomes selected for analysis included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), microperimetry (MAIA; mesopic and scotopic), and full-field stimulus threshold sensitivity (FST; Diagnosys). Strength of association between the functional measurements, disease duration and age were evaluated with Spearman correlation coefficients (r_s). The Mann-Whitney U test was used to investigate differences between the patients and the control group.

Results : 20 adult patients (65% female) enrolled in the study between 2021 to 2023. Median age at baseline was 50 years (range 23-84). Eleven different PRPF31-variants were identified. All patients had phenotypes consistent with bilateral classic RP, in stages ranging from early to advanced. The median (range) BCVA was 74.5 (0-88) and median LLVA 61.5 (0-79) ETDRS score. Mean dB for mesopic and scotopic microperimetry were 7.9 (7.3) and 2.8 (4.5) respectively. Eleven patients were unable to perform scotopic microperimetry. All measurements were significantly reduced in the patient group compared to the control group (p<0.001). BCVA correlated well with LLVA, mesopic and scotopic microperimetry and red, white and blue FSTs (r_s=0.68-0.88, all p<0.001). Additionally, there was strong correlation between both age and disease duration and all FST measurements (r_s=0.71-0.83, all p>0,001), and red FST with all other measurements (r_s=0.79-0.90, all p>0.001).

Conclusions : Baseline results reveal reductions in all measurements in the PRPF31-retinal dystrophy patient group compared to the age-gender matched healthy control group. There were several strong correlations amongst the functional measurements, age and disease duration; red FST particularly with all other measurements. The RP11 Project will facilitate increased knowledge on this rare subgroup through studies on patient-derived retinal organoids and multimodal investigations and help determine efficacy endpoints in future clinical trials.

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