Peripapillary retinal nerve fibre layer thinning, perfusion changes and optic neuropathy in carriers of Leber hereditary optic neuropathy-associated mitochondrial variants

• Published in: BMJ open ophthalmology Vol. 9; no. 1; p. e001295
• Main Authors: Quigley, Clare, Stephenson, Kirk A J, Kenna, Paul F, Cassidy, Lorraine
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 11.03.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Age; Asymptomatic; Blood vessels; Females; Humans; Males; Medical imaging; Mitochondrial DNA; Mutation; Nerve Fibers; Neuro-Ophthalmology; Optic Atrophy, Hereditary, Leber - diagnosis; Optic Nerve; Optics; Pathology; Patients; Perfusion; Retinal Ganglion Cells; Software; Tomography; Visual acuity; Pathology; Optic Nerve
• ISSN: 2397-3269; 2397-3269
• DOI: 10.1136/bmjophth-2023-001295

BackgroundWe investigated Leber hereditary optic neuropathy (LHON) families for variation in peripapillary retinal nerve fibre layer thickness and perfusion, and associated optic nerve dysfunction.MethodA group of LHON-affected patients (n=12) and their asymptomatic maternal relatives (n=16) underwent examination including visual acuity (VA), visual-evoked-potential and optic nerve imaging including optical coherence tomography (OCT) and OCT angiography of the peripapillary retinal nerve fibre layer (RNFL). A control sample was also examined (n=10). The software imageJ was used to measure perfusion by assessing vessel density (VD), and statistical software ‘R’ was used to analyse data.ResultsThe LHON-affected group (n=12) had significantly reduced peripapillary VD (median 7.9%, p=0.046). Overall, the LHON asymptomatic relatives (n=16) had no significant change in peripapillary VD (p=0.166), though three eyes had VD which fell below the derived normal range at 6% each, with variable VA from normal to blindness; LogMAR median 0, range 0–2.4. In contrast, RNFL thickness was significantly reduced in the LHON-affected group (median 51 µm, p=0.003), and in asymptomatic relatives (median 90 µm, p=0.01), compared with controls (median 101 µm). RNFL thinning had greater specificity compared with reduced perfusion for optic nerve dysfunction in asymptomatic carriers (92% vs 66%).ConclusionOverall, reduced peripapillary retinal nerve fibre layer perfusion was observed in those affected by LHON but was not reduced in their asymptomatic relatives, unlike RNFL thinning which was significantly reduced in both groups versus controls. The presence of RNFL changes was associated with signs of optic neuropathy in asymptomatic relatives.