The Eye-Brain Axis in High Myopia: From Retinal Deformation to Cortical Network Reorganization

Abstract: High myopia is a major cause of irreversible visual impairment and is increasingly recognized as a condition involving interactions between ocular remodeling and central neural systems. This scoping review synthesizes current evidence on structural, functional, genetic, and regulatory links between the eye and brain in high myopia. We systematically searched PubMed and Web of Science from database inception to August 2026, identifying 54 eligible primary studies. The available evidence indicates that high myopia is associated with retinal and optic nerve abnormalities, altered white matter microstructure, occipital cortical changes, and functional reorganization across visual and higher-order brain networks. However, most neuroimaging evidence is cross-sectional, and Mendelian randomization analyses have not provided evidence for a clear causal effect of myopia on brain volumes. Genetic studies suggest modest overlap between refractive error and cognitive traits, whereas educational exposure appears to contribute causally to myopic refractive development. Experimental and observational evidence also supports reciprocal regulation of ocular growth through circadian, dopaminergic, autonomic, and behavioral pathways, although several proposed mechanisms remain incompletely established in humans. Overall, the eye-brain axis provides a useful integrative framework for understanding high myopia, but longitudinal and interventional studies are required to determine causal relationships and evaluate whether neural or behavioral targets can improve clinical outcomes. Keywords: high myopia, eye-brain axis, neuroplasticity, visual cortex, trans-synaptic degeneration, functional connectivity