Aberrant visual pathway development in albinism: from retina to cortex

Albinism refers to a group of genetic abnormalities in melanogenesis that are associated neuronal misrouting through the optic chiasm. Previous imaging studies have shown structural alterations at different points along the visual pathway of people with albinism (PWA) including foveal hypoplasia, optic nerve and chiasm size alterations and visual cortex reorganisation, but fail to provide a holistic in-vivo characterisation of the visual neurodevelopmental alterations from retina to visual cortex. We perform quantitative assessment of visual pathway structure and function in 23 PWA and 20 matched controls using optical coherence tomography (OCT), volumetric magnetic resonance imaging (MRI), diffusion tensor imaging and visual evoked potentials (VEP). PWA had a higher streamline decussation index (percentage of total tractography streamlines decussating at the chiasm) compared to controls (Z=-2.24, p=0.025), and streamline decussation index correlated weakly significantly with inter-hemispheric asymmetry measured using VEP (r=0.484, p=0.042). For PWA, a significant correlation was found between foveal development index and total number of streamlines (r=0.662, p less than 0.001). Optic nerve (p=0.001) and tract (p=0.010) width, and chiasm width (P less than 0.001), area (p=0.006) and volume (p=0.005), were significantly smaller in PWA compared to controls. Significant positive correlations were found between peri-papillary retinal nerve fibre layer thickness and optic nerve (r=0.642, p less than 0.001) and tract (r=0.663, p less than 0.001) width. Occipital pole cortical thickness was 6.88% higher (Z=-4.10, p less than 0.001) in PWA and was related to anterior visual pathway structures including foveal retinal pigment epithelium complex thickness (r=-0.579, p=0.005), optic disc (r=0.478, p=0.021) and rim areas (r=0.597, p=0.003). We were unable to demonstrate a significant relationship between OCT-derived foveal or optic nerve measures and MRI-derived chiasm size or streamline decussation index. Non-invasive imaging techniques demonstrate aberrant development throughout the visual pathways of PWA compared to controls. Our novel tractographic demonstration of altered chiasmatic decussation in PWA corresponds to VEP measured cortical asymmetry and is consistent with chiasmatic misrouting in albinism. We also demonstrate a significant relationship between retinal pigment epithelium and visual cortex thickness indicating that retinal pigmentation defects in albinism lead to downstream structural reorganisation of the visual cortex