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.