Natural history of the progression of choroideremia; 24-month follow-up

Abstract

Purpose : Choroideremia (CHM) is a progressive, blinding X-linked chorioretinal dystrophy caused by mutations in the CHM gene encoding Rab escort protein-1. The purpose of our ongoing study (NCT02994368) is to evaluate the rate of progression of CHM using functional and anatomical assessments and to establish valid endpoints for future interventional trials.

Methods : Key eligibility criteria for this observational study include males age ≥ 14 years with a clinical and molecular diagnosis of CHM; best-corrected visual acuity (BCVA) score ≥34 ETDRS in the worst eye; presence of preserved ellipsoid zone (EZ) and outer nuclear layer within the central 10^o (using SD-OCT); and measurable visual fields. Each eye’s disease stage was characterized based on preserved visual fields (VF) using the Goldmann III_4e spot size or equivalent; Type 1 is advanced with < 30 degree VF and Type 2 is early/intermediate with ≥ 30 degree VF. Both eyes were followed with semi-annual assessments for 24 months. Study assessments included BCVA, preserved fundus autofluorescence area (PFAF), and static perimetry (SP) with mean sensitivity, total hill of vision (V_TOT) and central vision (V₃₀) analyses. A central reading center graded PFAF images and visual fields.

Results : Subjects (n=55) were enrolled at 5 sites in the US and Canada; 4 subjects discontinued after the screening visit. The majority were non-Hispanic White (92.7%). Mean age ± SD was 32.8 ± 11.2 years. Most eyes at screening were assessed as Type 2 (81%); analysis by disease stage was limited due to the small proportion of Type 1 eyes (14%) enrolled. Subjects who completed the 24-month follow up visit (n=47, 85%) were included in the analysis. Baseline values and annualized rates of change are shown in Table 1. Correlations with PFAF area for SP mean sensitivity, SP V_TOT, and SP V₃₀ at baseline are shown in Table 2. Analysis based on disease stage or pooled sample yielded similar results.

Conclusions : Similar to previous reports, BCVA remained stable, but PFAF and visual field parameters declined significantly over 24 months. Strong correlations were observed between PFAF area and visual field parameters at each visit. These findings have important implications for quantification and monitoring of structural and functional disease progression in CHM future interventional treatment trials.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.