Glymphatic system impairment in dysthyroid optic neuropathy: relation with ocular cerebrospinal fluid circulation and visual function.

PURPOSE: To evaluate brain glymphatic system–related diffusivity characteristics in dysthyroid optic neuropathy (DON) using the diffusion along perivascular space (ALPS) index and to explore its associations with orbital cerebrospinal fluid (CSF) dynamics and visual function. MATERIALS AND

METHODS

This retrospective study included 35 patients with DON, 32 with thyroid-associated ophthalmopathy (TAO) without DON, and 30 age- and sex-matched healthy controls. Orbital MRI and diffusion tensor imaging (DTI) were performed to assess optic nerve sheath CSF dynamics and brain glymphatic activity, with the latter indirectly evaluated using the ALPS index. Correlation and mediation analyses were conducted to evaluate the relationships between inflammatory activity (clinical activity score, CAS), CSF circulation parameters, ALPS index, and visual function.

RESULTS

DON patients had significantly lower ALPS index than TAO (p = 0.014) and controls (p = 0.007). Reduced ALPS values were correlated with greater ONSD and ONSS (r = − 0.38 to  − 0.51, all p < 0.01), and poorer visual fields (mean deviation r = − 0.30, p = 0.023). Mediation analysis showed that ONSS6 (indirect effect =  − 0.067; 95% CI  − 0.132 to  − 0.004), ONSD3 ( − 0.106; 95% CI  − 0.240 to  − 0.016), and ONSD6 ( − 0.146; 95% CI  − 0.280 to  − 0.026) significantly mediated the association between CAS and ALPS.

CONCLUSIONS

Glymphatic system alterations may be present in DON and is associated with abnormal orbital CSF circulation and visual impairment. Mediation analysis indicates orbital CSF circulation may mediate the effect of inflammatory activity on possible glymphatic impairment, providing new understanding of mechanisms of ocular–brain involvement and visual pathway injury.