Neurovascular Coupling Disruption and Glymphatic Dysfunction Are Associated With Visual Impairment in Pediatric Monocular Anisometropic Amblyopia

Purpose: To investigate abnormalities in neurovascular coupling and the glymphatic metabolic clearance in children with monocular anisometropic amblyopia, as well as their associations with visual acuity (VA) status. Methods: Multimodal magnetic resonance imaging scans were acquired from 33 children with anisometropic amblyopia and 31 age-matched normal controls. Neurovascular coupling was quantified as the spatial correlation between fractional amplitude of low-frequency fluctuations and cerebral blood flow across 90 cortical regions. Glymphatic metabolic clearance was evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). VA was assessed by measuring uncorrected VA (UCVA) and best-corrected VA (BCVA). Results: Compared with controls, children with amblyopia exhibited altered neurovascular coupling in eight visual cortical regions (false discovery rate-corrected P < 0.05) and reduced DTI-ALPS indices in the hemisphere contralateral to the amblyopic eye (1.41 ± 0.13 vs. 1.55 ± 0.11; Bonferroni-corrected P < 0.001), with lower mean DTI-ALPS indices as well (1.46 ± 0.08 vs. 1.56 ± 0.08; Bonferroni-corrected P < 0.001). Neurovascular coupling in the contralateral middle and inferior occipital gyri showed significant negative correlations with both UCVA (r = -0.698, -0.694) and BCVA (r = -0.645, -0.663) of the amblyopic eye; similarly, the contralateral DTI-ALPS and mean indices demonstrated negative correlations with UCVA (r = -0.672, -0.580) and BCVA (r = -0.668, -0.554) of the amblyopic eye (all false discovery rate-corrected P < 0.05). Conclusions: Neurovascular coupling and glymphatic clearance are altered in monocular anisometropic amblyopia and correlate with VA impairment, supporting their roles in the pathophysiology of amblyopia.