The natural history of choroideremia; progressive loss of visual function and retinal structure

Abstract

Purpose : Choroideremia (CHM) is an X-linked recessive condition caused by mutations in the CHM gene encoding Rab escort protein-1 (REP1). Initial symptoms include night blindness, which can occur in early childhood, and progressive narrowing of the field of vision followed by eventual blindness. This ongoing study (NCT02994368) evaluated the rate of progression of CHM as measured by visual function tests and anatomical biomarkers.

Methods : 55 male patients, 14-70 years of age, with genetically confirmed CHM were enrolled in a multicenter (5 sites), prospective, observational study. Both eyes were followed in semi-annual assessments. Inclusion criteria included a ≥ 30° kinetic visual field diameter (III4e) and a preserved ellipsoid zone within the central 10°. Measures included full-field electroretinography (ERG), BCVA, static and kinetic perimetry (Octopus 900), SD-OCT and fundus autofluorescence imaging (FAF) with a Heidelberg Spectralis, and a visual function questionnaire (VFQ-25).

Results : Baseline BCVA was 77.9 ± 12.7 ETDRS letters (median=82, range 28-94) and the horizontal EZ width was 3.11 ± 1.99 mm (median = 2.78, range 3.58-8.97). Results were analyzed from 44 (80%) patients who completed at least 12-months of follow-up as of 31 Oct 2019. BCVA showed no significant change. Consistent with results reported last year from a single site, EZ width showed significant disease progression over 12 months (p<0.01), as did the area of preserved autofluorescence (p<0.001). Visual fields (kinetic perimetry) showed significant progression over 12 months for all isopters: V4e, III4e, and I4e (all p<0.05).

Conclusions : Although variability was observed in rates of progression for individual patients, a significant disease progression over 12 months could be established for EZ width, the area of preserved autofluorescence and, interestingly, for all isopters measured by full-field semi-automated kinetic perimetry. The rate of decline of visual field measured by kinetic perimetry may be an attractive functional endpoint for future interventional treatment trials.

This is a 2020 ARVO Annual Meeting abstract.