Abstract
Purpose: High myopia is a feature of several inherited retinal diseases, including X-linked retinitis pigmentosa (XLRP) which is characterized by childhood onset, centripetal photoreceptor degeneration, and rapid progression to blindness by the fourth decade. Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause over 90% of XLRP cases. It presents with a varied clinical phenotype, categorized into the predominant rod-cone, cone-rod, and cone dystrophy. This case-series study examines the clinical characteristics of patients with RPGR-related retinal dystrophy to identify associations with refractive error. Methods: Data collected between October 2023 and April 2024 from retinal imaging, clinical ophthalmic examination, and genetic analysis were retrospectively analyzed. Results: Twenty-four male patients were identified, with a mean age of 30 years (range 7-57). The median (IQR) best-corrected visual acuity was 60 (55-66) letters in the cone-rod/cone phenotype and 65 (49-73) letters in the rod-cone phenotype. High axial myopia showed preponderance in cone-dominated degenerations. Estimated mean refractive error was -7.92DS (95% CI: [-11.39, -4.44]) in the cone-rod phenotype and -3.52DS (95% CI: [-5.87, -1.17]) in the rod-cone phenotype, adjusting for age and genetic mutation. This difference between phenotype was significant (p=0.041). In a subanalysis, no significant association was found between refractive error and nucleotide position. Evaluation of disease progression found that all patients with a fast-progressing, rod-cone phenotype had high myopia. Conversely, one patient who presented with a slow-progressing, cone-rod phenotype did not have high myopia. Conclusions: Refractive trends in this cohort suggest that cone photoreceptor degeneration occurring during early childhood is associated with high myopia. Image degradation primarily due to cone photoreceptor dysfunction may act as a stimulus to drive myopia development in early childhood. These observations advocate for the earlier treatment of myopia in cone-dominated RPGR-related retinal dystrophy to preserve retinal function and minimize the risks of retinal gene therapy surgery for patients enrolling in clinical trials. Trial Registration: ClinicalTrials.gov identifier: NCT03116113.