Abstract
Purpose :
Retinitis pigmentosa (RP) is a leading cause of inherited blindness and severe low-vision worldwide. X-linked RP (XLRP) is the most common and severe form of recessive RP, but currently, there is no clinically approved effective treatment available. This retrospective, observational clinical study aims to describe any differences in disease course between two common genotypes of XLRP in order to better target preventative and therapeutic measures.
Methods :
Using the EPIC database (2007-2022) and under the approval of the University of Utah IRB #00152879, 58 patients with XLRP were identified by ICD-9 and -10 codes and confirmed by genetic testing. Asymptomatic female carriers and patients with no best-corrected visual acuity (BCVA) data were excluded, leaving 41 eligible patients. Age, sex, genotype (classified as an RPGR or RP2 mutation), and BCVA data were collected. Legal blindness was defined as BCVA of 20/200 vision or worse in both eyes. The average age at date of first diagnosis (clinical or genetic, whichever came earlier) and age at first recorded legal blindness were calculated across all patients and separately for the RPGR and RP2 groups. The groups were then compared using two-tailed t-tests assuming unequal variance.
Results :
XLRP was caused by mutations in the RPGR gene in 37 of 41 (90.2%) patients, while RP2 mutations were responsible for the remaining 4 cases (9.8%). 37 (90.2%) patients were male, including all 4 RP2 patients and 33 of 37 (89.2%) RPGR patients. Average age at date of initial diagnosis was 17.6 years (SD=13.6), which did not differ significantly between genotypic groups (p=0.63). The average age at first recorded legal blindness was 42.8 years (SD=17.9) across all 9 patients who met the criteria for legal blindness. The average age at first recorded legal blindness was significantly younger in patients with an RP2 mutation (23.7 years, SD=6.0, n=3) versus patients with an RPGR mutation (52.3 years, SD=12.9, n=6; p=0.003).
Conclusions :
The typical XLRP disease course may include diagnosis in youth and eventual blindness in early- to mid-adulthood. RP2-linked RP appears to progress to legal blindness more rapidly than RPGR variants. Understanding disease progression by genotype can help inform future interventional gene therapy clinical studies so that patients’ outcomes are optimized.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.