PDE6A-Associated Retinitis Pigmentosa, Clinical Characteristics, Genetics, and Natural History

Abstract

To analyze the genetics, clinical characteristics, and natural history of PDE6A-associated retinitis pigmentosa. Retrospective, longitudinal, observational cohort study. Patients with molecularly confirmed PDE6A-associated retinal dystrophy in a single tertiary referral center. Review of medical records and retinal imaging, including fundus autofluorescence (FAF) imaging and spectral-domain OCT. Genetic results were reviewed, and the detected variants were assessed. Molecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), qualitative and quantitative retinal imaging analysis. 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 (± standard deviation, 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 was 0.45 ± 0.45 logarithm of the minimum angle of resolution (logMAR) (range 0.0-1.6) at baseline and 0.65 ± 0.7 logMAR (range 0.0-2.3) at the last visit. Best-corrected visual acuity was similar among eyes in 88% of patients. A hyperautofluorescent ring was observed on FAF in 50% and 43.8% of the eyes at baseline and follow-up visit, respectively, with a mean area of 9.7 ± 4.5 mm2 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 edema at baseline (56%), and 17 eyes (53%) at follow-up. There were statistically significant changes during the follow-up period in terms of BCVA, hyperautofluorescent ring area, and the EZW. This study highlights the natural history of PDE6A-retinopathy. Most patients in this cohort had mild BCVA loss, and slowly progressive disease, based on FAF and OCT measurements. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.