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Lookup NU author(s): Hatem Jouda, Andrew Browning, Professor Bobby McFarlandORCiD, Dr Sarah PickettORCiD, Dr Helen DevineORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.Background The m.3243A>G mitochondrial DNA variant is the most common cause of adult mitochondrial disease and is associated with a heterogeneous clinical phenotype. The retina and optic nerve are among the most metabolically active tissues, making them vulnerable to mitochondrial dysfunction. Optical coherence tomography (OCT) studies have demonstrated retinal nerve fibre layer (RNFL) thinning in mitochondrial and other neurodegenerative diseases. We investigated whether temporal RNFL thinning is associated with central nervous system (CNS) involvement in individuals with the m.3243A>G variant. Methods High-resolution OCT was used to assess peripapillary RNFL thickness and perform macular segmentation. Participants were categorised into normal RNFL (n=14) or temporal RNFL thinning (n=15) groups. Demographic data, mean-corrected m.3243A>G heteroplasmy, Newcastle Mitochondrial Disease Adult Scale (NMDAS) scaled scores and NMDAS neurological traits were compared. Results Temporal RNFL thinning was significantly associated with neurological features (Fisher’s exact test, p=0.027). In multivariable analysis, RNFL thinning and age were independent predictors of neurological involvement. Macular OCT revealed concomitant thinning of the ganglion cell-inner plexiform (GC-IPL) complex in the RNFL thinning group, with preservation of outer retinal layers, supporting primary retinal ganglion cell vulnerability. No significant associations were found between RNFL thinning and m.3243A>G heteroplasmy or NMDAS scaled scores. Conclusion Temporal RNFL thinning, accompanied by GC-IPL loss, is associated with neurological involvement in m.3243A>G-related mitochondrial disease, supporting its potential as a non-invasive biomarker of CNS dysfunction. Longitudinal studies are needed to determine whether these retinal changes are progressive and predictive of neurological decline.
Author(s): Jouda H, Browning AC, Aftab AM, Mahmoud I, Bibi S, McFarland R, Pickett SJ, Devine H
Publication type: Article
Publication status: Published
Journal: BMJ Neurology Open
Year: 2025
Volume: 7
Issue: 2
Online publication date: 20/10/2025
Acceptance date: 17/09/2025
Date deposited: 11/11/2025
ISSN (electronic): 2632-6140
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/ bmjno-2025-001232
DOI: 10.1136/bmjno-2025-001232
Data Access Statement: Data are available upon reasonable request
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