Autosomal dominant optic atrophy: volumetric brain analysis and associated retinal thinning

Abstract Dominant optic atrophy (DOA), an inherited mitochondrial disorder, leads to retinal thinning and gradual visual loss. The symptoms could develop in associated with other presentations like progressive external ophthalmoplegia, myopathy or deafness and will be called as DOA-plus (DOA+). While central nervous system involvement is known to cause cortical and cerebellar atrophy, specific patterns remain unspecified. This study aims to reveal cortical lobe abnormalities in DOA+ patients compared to healthy controls and explore the correlation between the primary visual cortex (V1) and retinal thinning in DOA+ patients. Seven DOA+ patients and seven age- and sex-matched healthy controls underwent a 3T-MRI of the brain to obtain 3D T1-weighted images and optical coherence tomography. Cortical analyses of the whole brain including surface area, gray matter volume, and average thickness was performed by Freesurfer software. DOA+ patients demonstrated a significant atrophy in the V1 and all cortical lobes (p < 0.001), where the occipital lobe exhibited the highest degree of gray matter volume atrophy and surface area loss (25.1% reduction, p<0.001). The atrophy of V1 showed a strong positive correlation with retinal thinning (p<0.001). This suggests retinal thinning might be associated with trans-synaptic degeneration, leading to V1 atrophy.