Genetic spectrum, retinal phenotypes, and visual function in female carriers of RPGR

Abstract Purpose To explore the detailed clinical manifestations and analyze the influential factors of disease severity in a large cohort of Chinese RPGR -variant heterozygotes. Methods The study included 54 RPGR heterozygotes from 49 unrelated families. Detailed ophthalmic examinations were performed to evaluate phenotype variability. Statistical analysis and comparisons were conducted on a cross-sectional basis to analyze phenotypic variability. Results Thirty-seven heterozygous RPGR variants were detected. The mean logMAR BCVA was 0.39 ± 0.51 in the worse-seeing eye and 0.19 ± 0.41 in the better-seeing eye, with a mean interocular difference of 0.20 ± 0.33. 64% of the patients showed a spherical equivalent (SE) lower than − 6 D in at least one eye. The mean absolute interocular difference in SE was 2.44 ± 3.00 D. On optical coherence tomography (OCT), a normal macular structure was observed in 62.0% of eyes (57/90 eyes). The radial spoke–shaped reflexes extending from the central macular area in a radial pattern was the most common fundus autofluorescence (FAF) pattern, observed in 37.8% of eyes (34/90 eyes). In this cross-sectional cohort, analysis revealed no significant correlations between age and other ocular parameters. The ratio of variants in Exons 1–14 tended to be higher in more severe cases, as manifested in OCT ( P = 0.03) and FAF ( P = 0.01), though these findings should be interpreted with caution given the small sample sizes of the severe subgroups. LogMAR BCVA was positively correlated with MD in VF ( P < 0.01) and the absolute interocular difference in SE ( P < 0.01), while it was negatively correlated with SE ( P < 0.01) and photopic 3.0 ERG ( P < 0.05). Conclusions Although most female carriers exhibit mild retinal changes, clinically severe phenotypes are still not uncommon. High myopia and anisometropia are common features in RPGR -variant heterozygotes, which may be associated with more severe retinal phenotypes and lead to poor visual acuity.