Immune-related visual dysfunction in thyroid eye disease. A combined orbital and brain neuroimaging study

To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients.