ABSTRACT
PURPOSE: To analyze the genetics, clinical characteristics, and natural history of PDE6A-associated retinitis pigmentosa. DESIGN: Retrospective, longitudinal, observational cohort study. PARTICIPANTS: Patients with molecularly confirmed PDE6A-associated retinal dystrophy in a single tertiary referral center. METHODS: Review of medical records and retinal imaging, including fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT). Genetic results were reviewed, and the detected variants were assessed. RESULTS: Sixteen patients (32 eyes) were identified and evaluated longitudinally. Genetic analysis identified 14 variants in the PDE6A gene, including 8 novel variants. The mean age (±SD, range) was 34.8 years (± 17.4, 12 - 76) at baseline, with a mean follow-up time of 4.8 years. Best-corrected visual acuity (BCVA) was 0.45 ± 0.45 LogMAR (range 0.0 - 1.6) at baseline and 0.65 ± 0.7 LogMAR (range 0.0 - 2.3) at the last visit. BCVA was similar among eyes in 88% of patients. A hyperautofluorescent ring was observed on FAF in 50% and 44% of the eyes at baseline and follow up visit respectively, with a mean area of 9.7 ± 4.5mm2 at baseline and mean of 8.6 ± 4.8 mm2 at the follow-up visit. Mean horizontal ellipsoid zone width (EZW) at baseline was 1765 ± 1093 µm, which decreased to 1580 ± 1077 µm at follow up. Eighteen eyes exhibited cystoid macular oedema at baseline (56%), and 17 eyes (53%) at follow-up. There were statistically significant changes during the follow-up period in terms of BCVA, hyperautoflouroscent ring area and the EZW. CONCLUSIONS: This study highlights the natural history of PDE6A-retinopathy. The majority of the patients in this cohort had mild BCVA loss, and slowly progressive disease, based on FAF and OCT measurements.