Natural History of the Progression of RPGR-Associated X-Linked Retinitis Pigmentosa (XOLARIS) Study: Cross-Sectional Analysis of Baseline Characteristics

Abstract

Purpose : The objective of the XOLARIS study is to gain a better understanding of disease progression over time in male subjects with RPGR-associated X-linked retinitis pigmentosa (XLRP). Here we present baseline characteristics and correlations among potential endpoints within the available time frame.

Methods : This is a multicenter, prospective, international, observational study consisting of 7 visits over a 24 months period. Subjects must be males, ≥16 years of age, with XLRP and genetically confirmed pathogenic mutations in the RPGRgene. In at least 1 eye, active disease must be clinically visible within the macular region, determined through assessment of compromised ellipsoid zone by spectral domain optical coherence tomography (SD-OCT), and best-corrected visual acuity (BCVA) must be ≥34 letters using the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale. Clinical measures include BCVA, low-luminance visual acuity, MAIA microperimetry, visual field; lens opacity grading, SD-OCT, autofluorescence, fundus photography, color vision, and the 25-item visual function questionnaire.

Results : This study is ongoing, with 53 subjects (47 white, 3 other race, 2 Asian, 1 black) currently enrolled. Of the defined RPGRmutations, the majority are exon (n=20)and ORF15(n=19). The mean age is 30.3±11.9 years (range 16–84). The data for both eyes are presented for ophthalmic outcomes. BCVA at baseline was 65.9±12.7 ETDRS letters (median = 67; range 0-91). The mean central ellipsoid area (EZ area) was 1.2±2.0 mm²(median = 0.5; range 0–10.3). The central horizontal ellipsoid width (EZ width) was 975±909 microns (median = 752; range 0–4170). Microperimetry (mean retinal sensitivity in 68 loci) was 4.9±4.7 decibels (median 3.5; range 0–21).

Conclusions : Wide variability is observed in XLRP patients, largely as a function of age and duration of disease, and disease severity. Understanding the baseline characteristics of this rare disease in a large cohort will allow us to define its progression and the precise measures and endpoints that may be modifiable with intervention.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.