Glymphatic System Dysfunction in Thyroid‐Associated Ophthalmopathy: A Multimodal MRI Study

Objective To investigate glymphatic system (GS) alterations in thyroid‐associated ophthalmopathy (TAO) patients and their links to clinical biomarkers, with the aim of understanding underlying mechanisms and potential therapeutic strategies. Methods This study included 28 active patients (AP), 25 inactive patients (IP) with TAO, and 37 healthy controls (HC), matched for age, sex, and educational level. Glymphatic function was evaluated using choroid plexus volume (CPV), diffusion tensor imaging along the perivascular space (DTI‐ALPS) index, and coupling between global blood‐oxygen‐level‐dependent signals and cerebrospinal fluid signals (gBOLD‐CSF coupling). General linear regression analysis was conducted to explore the relationships between the GS and clinical parameters. Results Significant differences were found in the ALPS index between the patient groups and the HC. Both the left (ALPS_L) and right (ALPS_R) ALPS indices, as well as the average ALPS index, were significantly lower in the AP and IP groups than in the HC ( p < 0.01). The overall difference across all three groups was also significant ( p < 0.01). However, no significant differences were observed between the AP and IP groups. However, no significant differences in CPV were observed between either the AP or IP group and the HC. Both the AP and IP groups exhibited lower gBOLD‐CSF coupling than the HC ( p = 0.001; p = 0.013). Significant correlations existed between GS function and clinical parameters in both groups. Conclusion TAO patients demonstrate significant GS impairments linked to neuropsychological symptoms and sleep disturbances. Targeting GS function may improve quality of life in TAO patients.