Preliminary Diffusion‐Tensor Imaging Evidence for Trans‐Synaptic Axonal Degeneration in Dysthyroid Optic Neuropathy Due to Thyroid‐Associated Ophthalmopathy

Abstract

BackgroundThe mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion‐tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON.PurposeTo assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans‐synaptic damage（TSD） pathogenesis in DON with DTI.Study TypeCross‐sectional.PopulationSixty‐four patients with bilateral thyroid‐associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age‐ and sex‐matched healthy controls (HCs).Field Strength/Sequence3 T/DTI (A single‐shot diffusion‐weighted echo‐planar imaging sequence).AssessmentDifferences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients.Statistical TestsStudent's t‐test, chi‐square test; ANOVA with post‐hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P < 0.05.ResultsTAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non‐DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs.Data ConclusionDTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON.Evidence Level: 4Technical Efficacy: Stage 5

Thyroid-associated ophthalmopathy: Using diffusion tensor imaging to evaluate visual pathway microstructural changes

“…The correlation results further demonstrated the possibility of utilizing DTI to assess visual pathway changes in TAO, showing that disruptions in the visual pathway progress along with increased inflammation and crowding of the orbital tissues. As previous research stated ( 12 ), OR–MD showed no significant correlation with any of the clinical variables, which were consistent with our study. While the OR–FA was positively correlated with VA and IOP, which is in direct contrast to our findings.…”

“…However, current research on the TAO visual pathway is mainly limited to the intraorbital optic nerve, and there is very little research on other parts of the optic pathway. Liu et al ( 12 ) evaluated the microstructural changes along the whole visual pathway in TAO patients using DTI. The result of our findings is consistent with the findings of Liu et al: the visual pathway FA and MD values are associated with disease severity.…”

“…However, previous studies that applied DTI to assess microstructural changes in TAO patients are still limited, with most research focusing on the intraorbital optic nerve and orbital soft tissue (9)(10)(11). To our knowledge, there are very few studies on changes in the visual pathway in TAO patients (12). It has been proven the trans-synaptic degeneration (TSD) is a damage mechanism that occurred in the visual pathway (13).…”

Editorial for “Functional and Morphological Brain Alterations in Dysthyroid Optic Neuropathy: A Combined Resting‐State fMRI and Voxel‐Based Morphometry Study”

“…Controversy still exists regarding the pathogenesis of DON as it appears to be multifactorial 4 . Recent neuroimaging studies reported alterations of the brain structure and function in regions associated with vision in DON patients 5,6 . Therefore, current evidence suggests that patients with DON may demonstrate neural alterations in the visual pathway of DON.…”

“…4 Recent neuroimaging studies reported alterations of the brain structure and function in regions associated with vision in DON patients. 5,6 Therefore, current evidence suggests that patients with DON may demonstrate neural alterations in the visual pathway of DON. However, the exact structural and functional brain network alterations in DON remain elusive.In this issue of JMRI, Zhang et al further examined the morphological and functional brain alterations in DON using resting-state functional MRI (rs-fMRI).…”