Natural progression of choroideremia carriers using multimodal imaging: a longitudinal study

Abstract

Purpose : Female carriers of choroideremia present with a spectrum of disease severity, as defined using fundus autofluorescence (FAF). Unlike in males, the rate of disease progression has not been well characterised in female carriers. In the current study, multimodal imaging and microperimetry was used to determine the rate of retinal degeneration in choroideremia carriers.

Methods : A longitudinal study assessed retinal changes in 30 eyes of 15 female carriers of choroideremia between 2012 and 2023. Macular centred optical coherence tomography (OCT, volume scans), FAF (55 degrees), and MAIA microperimetry (10-2, 68-points) were performed at baseline and follow up. Image analysis was performed using Voxeleron Orion for OCT segmentation and Fiji ImageJ for FAF grayscale quantification of the central 10 degrees. Rate of change was assessed via mixed-effects models to account for correlation between right and left eyes, adjusting for age and retinal classification.

Results : Median age of choroideremia carriers was 44 [range: 15-73] years at baseline and median follow up duration of 7 [range: 1-11] years. At baseline, there were 4 eyes with fine, 10 eyes with coarse, 12 eyes with geographic, and 4 eyes with male-pattern phenotypes. Retinal severity grading did not typically change over time (only 1 carrier from fine to coarse in both eyes, and 1 eye from geographic to male-pattern degeneration). However, there was a decline in average retinal sensitivity threshold (-0.6dB/year, p<0.001), FAF area of geographic loss (-1.9mm²/year, p<0.001), FAF grayscale (2 pixels darker/year, p<0.001), and total retinal thickness of 1-5 degrees from fovea (1.9 microns/year thinning at 1-3 degrees, p=0.006; and 1.7 microns/year thinning at 3-5 degrees, p<0.001). Higher rates of progression were consistently observed for carriers with male-pattern degeneration for all retinal parameters.

Conclusions : Female carriers of choroideremia exhibit retinal degeneration that progresses over time, as evident by multimodal imaging. Clinicians should not rely solely on retinal severity grading to determine progression in female carriers. Larger natural history studies are required to investigate the association between genotype and phenotype and determine which carriers are at higher risk of progression.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.