Huang, Yi-HanYi-HanHuangHuang, Yu-ShuYu-ShuHuangLin, Chien-YuChien-YuLinLai, Ying-JuYing-JuLaiCHANG-HAO YANGTZYY-CHANG HOPO-TING YEHHSIEH YI TINGLAI TSO TINGCHAO WEN LINCHUNG-MAY YANGPEI-LUNG CHENTA-CHING CHEN2025-05-192025-05-192025-04-01https://scholars.lib.ntu.edu.tw/handle/123456789/729420PURPOSE. This study documents the natural disease progression and genotype-phenotype correlation in RPGR-related retinitis pigmentosa (RP) in the Taiwanese population. METHODS. A retrospective analysis was conducted on individuals with molecularly confirmed RPGR-related disease-causing variant(s). Demographics, best-corrected visual acuity (BCVA), spherical equivalent (SE), fundus autofluorescence, and optical coherence tomography were assessed. RESULTS. Fifty-two individuals from 31 families were diagnosed with RPGR-related disease-causing variant(s). Mean follow-up time was 4.2 years. Among 21 genetic variants, 67% involved the open reading frame 15 region (ORF15) variant, and 33% were Exon 1–14 variants. Male patients (69%) had a mean BCVA of 0.9 logMAR and SE of −3.8 D in the right eye and −3.0 D in the left eye, with high myopia in 19% to 20%. BCVA progression was 0.031 logMAR/year in the ORF15 group (P < 0.001) and 0.011 logMAR/year (P = 0.457) in the Exon 1–14 group. An exponential decay model revealed rapid ellipsoid zone (EZ) constriction during childhood in the ORF15 group. Female patients/carriers (31%) had a mean BCVA of 0.3 logMAR and SE of −4.3D, with high myopia of 31% in the right eye and 46% in the left eye. Among symptomatic females, 73% exhibited clinically significant disease. The most common mutation was the c.2592dup variant (15%). CONCLUSIONS. This first longitudinal analysis of RPGR-related RP in Taiwan presents a predictive model of EZ constriction. Findings suggest earlier onset in Exon 1–14 variants and a tendency for faster progression in the ORF15 group, informing insights for genetic therapy development and disease management.en[SDGs]SDG3journal article10.1167/iovs.66.4.5940257782