Abstract
BACKGROUND: Infantile esotropia may interfere with white matter maturation during early childhood, a critical period of brain development. Surgical correction not only restores ocular alignment but may also influence neurodevelopmental trajectories. However, the role of age in modulating white matter recovery after surgery remains unclear. This study aimed to investigate the effects of age on white matter rehabilitation following surgical intervention in children with infantile esotropia, with the goal of identifying the optimal therapeutic window to maximize both neurodevelopmental and clinical outcomes. METHODS: We included 29 typically developing children (F/M = 14/15) and 30 children with IE (F/M = 13/17), 17 of whom provided longitudinal data following surgical intervention. All participants underwent MRI scanning and clinical assessments. Diffusion tensor imaging (DTI) was performed to quantify white matter integrity using fractional anisotropy (FA) and mean diffusivity (MD). Automated fiber quantification was applied to analyze microstructural properties across 20 major white matter tracts. Cross-sectional and longitudinal analyses were conducted to evaluate developmental trajectories in patients versus controls. RESULTS: Preoperatively, IE patients exhibited significantly elevated MD across multiple tracts, including the thalamic radiation and forceps minor. Following surgery, MD values decreased significantly in most tracts. FA alterations were less pronounced, with preoperative reductions and postoperative improvement limited to only a few tracts. In controls, age was negatively correlated with MD and FA changes. Longitudinal analysis revealed that surgical intervention was associated with accelerated growth in white matter microstructure compared to typical development, particularly in younger children. CONCLUSIONS: Surgical correction of IE facilitates white matter restoration through mechanisms that operate independently of, and synergistically with, typical neurodevelopment. Earlier intervention is associated with faster rates of microstructural recovery, suggesting a higher sensitive period during which surgery can maximize white matter repair and optimize functional outcomes.