Retinal Characteristics of Female Choroideremia Carriers: Multimodal Imaging, Microperimetry, and Genetics

Sena A Gocuk; Thomas L Edwards; Jasleen K Jolly; Myra B McGuinness; Robert E MacLaren; Fred K Chen; Laura J Taylor; Terri L McLaren; Tina M Lamey; Jennifer A Thompson; Lauren N Ayton

doi:10.1016/j.oret.2024.06.011

Retinal Characteristics of Female Choroideremia Carriers: Multimodal Imaging, Microperimetry, and Genetics

Ophthalmol Retina. 2024 Jun 25:S2468-6530(24)00304-X. doi: 10.1016/j.oret.2024.06.011. Online ahead of print.

Authors

Affiliations

¹ Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
² Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
³ Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, United Kingdom; Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
⁴ Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
⁶ Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia; Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia.
⁷ Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁸ Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁹ Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia. Electronic address: layton@unimelb.edu.au.

PMID: 38936773
DOI: 10.1016/j.oret.2024.06.011

Abstract

Purpose: To describe visual function and retinal features of female carriers of choroideremia (CHM), using multimodal imaging and microperimetry.

Design: Cross-sectional cohort study.

Participants and controls: Choroideremia carriers seen in Australia (Melbourne or Perth) or the United Kingdom (Oxford or Cambridge) between 2012 and 2023. Healthy age-matched controls seen in Melbourne, Australia, between 2022 and 2023.

Methods: Participants had visual acuity, fundus-tracked microperimetry, OCT, and fundus autofluorescence imaging performed. Choroideremia carriers were either genetically or clinically confirmed (i.e., obligate carriers). Choroideremia carriers were grouped according to their retinal phenotype and compared with healthy controls. Statistical analyses were performed on StataBE (v18.0).

Main outcome measures: Best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), average retinal sensitivity, volume of macular hill of vision (HoV), inner retinal thickness, and photoreceptor complex (PRC) thickness.

Results: Eighty-six eyes of 43 CHM carriers and 60 eyes of 30 healthy controls were examined using multimodal imaging and microperimetry. Median age was 54 and 48.5 years for CHM carriers and controls, respectively (P = 0.18). Most CHM carriers (86%) were genetically confirmed. Choroideremia carriers and controls had strong intereye correlation between eyes for BCVA and average retinal sensitivity (P < 0.001). Low-luminance visual acuity and macular HoV tests were sensitive tests to detect changes in CHM carriers with mild phenotypes (i.e., fine and coarse). Choroideremia carriers with geographic or male-pattern phenotypes had reduced BCVA, LLVA, retinal sensitivity, and retinal thinning, compared with healthy controls. Retinal thickening of the inner retina was observed in the central 1°, despite generalized thinning of the PRC in the central 7°, indicating retinal remodeling in CHM carriers, compared with controls. There were no genotype-phenotype correlations observed.

Conclusions: Female carriers of CHM with severe retinal phenotypes (i.e., geographic or male pattern) have significantly decreased visual function and retinal structural changes when compared with age-matched controls and those carriers with milder phenotypes. Low-luminance visual acuity and volumetric measures of the macular HoV were found to be the most sensitive functional tests to detect milder retinal disease (fine and coarse phenotypes) in CHM carriers.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Cross-sectional; Genotype; Microperimetry; OCT; Phenotype.