Macular OCT inner retinal changes reflect CNS involvement in m.3243A>G disease

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• The m.3243A>G mitochondrial DNA variant is a primary cause of adult mitochondrial disease, presenting diverse clinical symptoms.
• The retina and optic nerve, highly metabolic tissues, are susceptible to mitochondrial dysfunction.
• Optical coherence tomography (OCT) has shown retinal nerve fibre layer (RNFL) thinning in neurodegenerative conditions.

Purpose of the Study:

• To investigate the association between temporal RNFL thinning and central nervous system (CNS) involvement in individuals with the m.3243A>G variant.
• To explore the potential of RNFL changes as a biomarker for neurological dysfunction in mitochondrial disease.

Main Methods:

• High-resolution OCT was employed to measure peripapillary RNFL thickness and macular segmentation.
• Participants were grouped based on normal RNFL or temporal RNFL thinning.
• Demographic data, m.3243A>G heteroplasmy levels, and neurological assessments using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) were compared.

Main Results:

• Temporal RNFL thinning showed a significant association with neurological features (p=0.027).
• RNFL thinning and age were independent predictors of neurological involvement in multivariable analysis.
• Macular OCT indicated thinning of the ganglion cell-inner plexiform (GC-IPL) complex in the RNFL thinning group, suggesting primary retinal ganglion cell vulnerability.

Conclusions:

• Temporal RNFL thinning, with associated GC-IPL loss, correlates with neurological involvement in m.3243A>G mitochondrial disease.
• These retinal changes may serve as a non-invasive biomarker for CNS dysfunction.
• Further longitudinal studies are required to assess the progression and predictive value of these retinal findings for neurological decline.