Characterising PRPF31-associated retinal dystrophy: Clinical insights from baseline data in a natural history study.

PURPOSE: To characterise the baseline clinical features and genotypes of adults with pre-mRNA processing factor 31 (PRPF31)-associated retinal dystrophy (RD) enrolled in a prospective, multicentre 4-year natural history study, and to explore correlations between selected baseline parameters.

METHODS: Thirty-one patients with PRPF31-RD underwent comprehensive multimodal assessment, including slit-lamp ophthalmoscopy, best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic and scotopic microperimetry (MP), full-field stimulus threshold (FST) testing, spectral-domain optical coherence tomography (SD-OCT) to assess retinal structure and measure ellipsoid zone (EZ) width, and ultra-widefield fundus autofluorescence (UWF-FAF) to define hyperautofluorescent ring (HAR) area. Correlations between structural and functional measures were analysed using Spearman's rank correlation.

RESULTS: Patients from 21 families carrying 17 distinct disease-causing variants in the PRPF31 gene were identified. The median age was 38 years (range 19-84). Thirty patients exhibited a classic retinitis pigmentosa (RP) phenotype, and one had a pericentral pattern of dystrophy. Frequent findings included cystoid macular oedema (52%), epiretinal membrane (55%) and current or prior cataract (71%). Most patients could complete FST (84%-90%) and mesopic MP testing (77%), while measures of scotopic MP (57%), HAR area (52%) and EZ (68%) excluded the more advanced-staged patients. The HAR area correlated strongly with the functional measures mesopic MP and FST white. The HAR area, EZ width and scotopic MP were also strongly correlated.

CONCLUSION: This study confirms phenotypic variability in PRPF31-RD and expands the spectrum with pericentral RD. The feasibility of structural and functional assessments depended on disease stage, with scotopic cyan MP limited to eyes with preserved HAR and EZ.