Volumetric brain analysis and associated retinal thinning in autosomal dominant optic atrophy patients

Dominant optic atrophy (DOA) is an inherited mitochondrial disorder characterized by retinal thinning and progressive visual loss. When accompanied by additional neurological or systemic features, such as progressive external ophthalmoplegia, myopathy, or deafness, it is classified as DOA-plus (DOA+). Although central nervous system involvement has been associated with cortical and cerebellar atrophy, specific regional patterns remain unclear. This study aimed to investigate cortical lobe alterations in DOA+ patients and examine the association between retinal thinning and structural changes in the primary visual cortex (V1).

Seven DOA+ patients and seven age- and sex-matched healthy controls underwent 3T brain MRI, including 3D T1-weighted imaging, and optical coherence tomography (OCT). Cortical parameters including surface area, gray matter volume, and cortical thickness were quantified using automated whole-brain analysis. Comparisons between DOA+ patients and control groups were performed using independent t-tests, and associations between OCT metrics and V1 cortical measures were assessed with Spearman's rank correlation.

DOA+ patients showed a trend toward atrophy in V1 and across all cortical lobes, with statistically significant differences observed only in V1 and occipital lobe (p < 0.001). The occipital lobe demonstrated the greatest reduction in gray matter volume (25.1%, p < 0.001). A positive correlation was observed between average RNFL thickness and average V1 thickness (ρ = 0.90, p = 0.037).

DOA+ patients showed significant atrophy in occipital lobe. An association between retinal thinning and average V1 thickness was observed. However, a definite causal relationship cannot be established. Further studies in larger, genetically diverse cohorts are needed to validate these findings.