{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"
      ],
      "name": "Hatem Jouda"
    },
    {
      "affiliations": [
        "Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England, UK"
      ],
      "name": "Andrew C Browning"
    },
    {
      "affiliations": [
        "Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England, UK"
      ],
      "name": "Akhunzada M Aftab"
    },
    {
      "affiliations": [
        "Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England, UK"
      ],
      "name": "Ikhlas Mahmoud"
    },
    {
      "affiliations": [
        "Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, England, UK"
      ],
      "name": "Saima Bibi"
    },
    {
      "affiliations": [
        "Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Mitochondrial Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK",
        "NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Robert McFarland"
    },
    {
      "affiliations": [
        "NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK",
        "Mitochondrial Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK"
      ],
      "name": "Sarah J Pickett"
    },
    {
      "affiliations": [
        "Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Mitochondrial Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK",
        "NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Faculty of Medical Sciences Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Helen Devine"
    }
  ],
  "title": "Macular OCT inner retinal changes reflect CNS involvement in m.3243A>G disease",
  "uid": "92451163-cd4d-52bc-8d39-4f70fba6ee0d"
}