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

To describe an optical coherence tomography (OCT) finding that is highly prevalent in Danon disease.

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.

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.

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.