Outer nuclear layer hyperreflectivity as an optical coherence tomography finding in Danon disease

PURPOSE: To describe an optical coherence tomography (OCT) finding that is highly prevalent in Danon disease. METHODS: Retrospective observational case series at a single centre, combined with a systematic literature review of PubMed and EMBASE for genetically confirmed Danon disease patients with available macular OCT images. Fifty-two macular OCT scans from 29 genetically confirmed Danon disease patients (5 from our institution; 24 from 11 published studies) were included. For each patient, a single foveal-centred macular OCT scan per eye was selected for analysis. Two independent reviewers assessed images for the presence of outer nuclear layer (ONL) hyperreflectivity, with discrepancies resolved by consensus. RESULTS: Evidence of ONL hyperreflectivity appeared in 39 macular scans (75%). Of the 13 scans without this finding (25%), 10 scans (19%) showed macular atrophy (including bull's-eye maculopathy cases) or cystoid macular oedema that obscured evaluation of outer retinal layers at the fovea, and two scans (4%) used colour-encoded OCT that prevented reliable evaluation of the ONL. In only one scan (2%), ONL hyperreflectivity was absent despite preserved foveal architecture and adequate image quality. CONCLUSION: ONL hyperreflectivity is a highly prevalent OCT finding in Danon disease, most evident in young patients without advanced outer retinal atrophy. This feature may serve as a non-invasive finding of early retinal involvement. Longitudinal studies are warranted to confirm its prognostic value.