Thyroid-associated Ophthalmopathy Group Research Articles

Topological organization of the brain network in thyroid-associated ophthalmopathy using graph theoretical analysis.

Mounting neuroimaging evidence indicates that patients with thyroid-associated ophthalmopathy (TAO) demonstrate altered brain function and structure. Nonetheless, the alterations in the topological properties of the functional brain connectome in TAO patients are not yet fully understood. This study aimed to investigate the topological organization of the functional brain connectome in TAO patients using graph-theoretic methods. Twenty-five TAO patients (10 males and 15 females) and 25 age-, sex-, and education-matched healthy controls (HCs) (10 males and 15 females) (the TAO and HC data are from the same dataset in previous studies) underwent resting-state MRI scans. Graph-theoretic analysis was used to study the global, nodal, and edge topological properties of the brain's functional connectome. Both the TAO and HC groups exhibited high-efficiency small-world networks in their brain functional networks. However, there were no significant differences in small-world properties (Cp, γ, λ, Lp, and σ) and network efficiency [global and local efficiencies (Eloc)] between the two groups. In addition, the TAO group demonstrated reduced betweenness centrality in the right fusiform and increased nodal Eloc in the right intraparietal sulcus (P < 0.05, Bonferroni-corrected). Furthermore, the TAO group displayed altered functional connections among the default-mode network (DMN), visual network (VN), sensorimotor network (SMN), and cingulo-opercular network (CON). Patients with TAO exhibited abnormal topological organization of the human brain connectome, including decreased betweenness centrality and increased nodal Eloc. Moreover, the TAO group displayed altered functional connections primarily within the DMN, VN, SMN, and CON. These findings provide crucial insights into the neural mechanisms underlying visual loss, abnormal emotion regulation, and cognitive deficits in TAO patients.

Assessing the relationship between levator palpebrae superioris and thyroid-associated ophthalmopathy using the Dixon-T2WI sequence.

The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI. The retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS_T) and signal intensity ratio (LPS_SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS_T and LPS_SIR. In the TAO group, LPS_T and LPS_SIR were higher than those in the normal group (p < 2.2e-16). The upper lid retraction (ULR) ≥ 2mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505mm) and 0.81 for LPS_SIR (cutoff: 1.170). LPS_T (p = 2.8e-07) and LPS_SIR (p = 3.9e-12) in the active phase were higher than in the inactive phase. LPS_T and LPS_SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups (p < 0.05). ROC showed an AUC of 0.70 for LPS_T (cutoff: 2.095mm) in judging the active phase, and 0.78 for LPS_SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS_T (cutoff: 2.095mm) and 0.78 for LPS_SIR (cutoff: 1.197). The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

Early diagnosis of thyroid-associated ophthalmopathy using label-free Raman spectroscopy and multivariate analysis

Thyroid-associated ophthalmopathy (TAO) is the most common orbital disease in adults, with complex clinical manifestations and significant impacts on the life quality of patients. The current diagnosis of TAO lacks reliable biomarkers for early and non-invasive screening and detection, easily leading to poor prognosis. Therefore, it is essential to explore new methods for accurately predicting TAO development in its early stage. In this study, Raman spectroscopy, with non-destructive, label-free, and high-sensitivity characteristics, was used to analyze the differences in biochemical components of orbital adipocyte and tear samples between TAO and control groups. Furthermore, a multivariate analysis method (i.e., Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA)) was applied for data processing and analysis. Compared with controls, PCA-LDA yielded TAO diagnostic accuracies of 72.7% and 75.0% using orbital adipocytes and tears, respectively. Our proof-of-concept results suggest that Raman spectroscopy holds potential for exploring the underlying pathogenesis of TAO, and its potential application in early screening of other thyroid-associated diseases can be further expanded.

Specific static and dynamic functional network connectivity changes in thyroid-associated ophthalmopathy and it predictive values using machine learning.

Thyroid-associated ophthalmopathy (TAO) is a prevalent autoimmune disease characterized by ocular symptoms like eyelid retraction and exophthalmos. Prior neuroimaging studies have revealed structural and functional brain abnormalities in TAO patients, along with central nervous system symptoms such as cognitive deficits. Nonetheless, the changes in the static and dynamic functional network connectivity of the brain in TAO patients are currently unknown. This study delved into the modifications in static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) among thyroid-associated ophthalmopathy patients using independent component analysis (ICA). Thirty-two patients diagnosed with thyroid-associated ophthalmopathy and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. ICA method was utilized to extract the sFNC and dFNC changes of both groups. In comparison to the HC group, the TAO group exhibited significantly increased intra-network functional connectivity (FC) in the right inferior temporal gyrus of the executive control network (ECN) and the visual network (VN), along with significantly decreased intra-network FC in the dorsal attentional network (DAN), the default mode network (DMN), and the left middle cingulum of the ECN. On the other hand, FNC analysis revealed substantially reduced connectivity intra- VN and inter- cerebellum network (CN) and high-level cognitive networks (DAN, DMN, and ECN) in the TAO group compared to the HC group. Regarding dFNC, TAO patients displayed abnormal connectivity across all five states, characterized by notably reduced intra-VN connectivity and CN connectivity with high-level cognitive networks (DAN, DMN, and ECN), alongside compensatory increased connectivity between DMN and low-level perceptual networks (VN and basal ganglia network). No significant differences were observed between the two groups for the three dynamic temporal metrics. Furthermore, excluding the classification outcomes of FC within VN (with an accuracy of 51.61% and area under the curve of 0.35208), the FC-based support vector machine (SVM) model demonstrated improved performance in distinguishing between TAO and HC, achieving accuracies ranging from 69.35 to 77.42% and areas under the curve from 0.68229 to 0.81667. The FNC-based SVM classification yielded an accuracy of 61.29% and an area under the curve of 0.57292. In summary, our study revealed that significant alterations in the visual network and high-level cognitive networks. These discoveries contribute to our understanding of the neural mechanisms in individuals with TAO, offering a valuable target for exploring future central nervous system changes in thyroid-associated eye diseases.

Increased brain iron in patients with thyroid-associated ophthalmopathy: a whole-brain analysis.

To investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM). Forty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs. Compared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%). Patients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO.

Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT-PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.

An evaluation of corneal endothelial cell morphology in patients with thyroid-associated ophthalmopathy.

To evaluate corneal endothelial cell morphology in patients with thyroid-associated ophthalmopathy (TAO). Seventy-two eyes of 36 patients with TAO presenting to the ophthalmology department between January 2018 and January 2022 were included in the study. The findings were compared with 98 eyes of 49 healthy individuals. Mean endothelial cell density (ECD), coefficient of variation (CV), maximum cell area, minimum cell area, average cell area, and hexagonality ratio were obtained using non-contact specular microscopy. The thicknesses of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) were measured using optical coherence tomography (OCT). The TAO group consisted of 36 patients, 11 (30.6%) men and 25 (69.4%) women, and the control group of 49 healthy individuals, 14 (28.6%) men and 35 (71.4%). No significant differences were determined between the TAO and control groups in terms of the specular microscopy findings of mean ECD, CV, or hexagonality ratio values (p > 0,05). However, the mean Hertel values differed significantly between the two groups (p = 0.001). When the TAO group was divided into two subgroups based on patients who had previously received prednisolone therapy and those who had not, significant differences were observed in terms of mean ECD, CV, and hexagonality ratio values (p > 0.05). Comparison of patients diagnosed with active TAO and receiving prednisolone therapy and the TAO patients with inactive disease revealed lower ECD, higher CV values, and lower hexagonality ratios in the prednisolone therapy group. These findings all suggest that inflammation in patients undergoing active disease affects the corneal endothelium.

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy.

Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.

Functional and Morphological Brain Alterations in Dysthyroid Optic Neuropathy: A Combined Resting-State fMRI and Voxel-Based Morphometry Study.

Increasing evidence has indicated that the entire visual pathway from retina to visual cortex may be involved in dysthyroid optic neuropathy (DON) pathological mechanisms. To explore the functional and morphological brain characteristics in DON and their relationship with ophthalmologic performance. Retrospective. A total of 30 DON patients, 40 thyroid-associated ophthalmopathy (TAO) without DON patients and 21 healthy-controls (HCs). A 3.0 T, 3D T1-weighted spoiled gradient-recalled echo and gradient-recalled echo-planar imaging. Functional and structural alterations in brain regions were evaluated with fractional amplitude of low-frequency fluctuations, degree centrality (DC), and gray matter volume (GMV). Clinical activity score (CAS) is assessed across patients. One-way analysis of variance with post hoc two sample t-tests (GRF-corrected, voxel level: P< 0.005, cluster level: P< 0.05) and correlation analysis (significance level: P< 0.05). Compared to HCs, DON patients had significantly decreased DC values in the bilateral BA17 and BA18 regions. Compared to the TAO group, DON patients had decreased GMV in the left anterior cingulate cortex, left middle frontal gyrus, left lingual gyrus, left parietal gyrus, right Rolandic operculum, left supplementary motor area, and right middle temporal gyrus. In addition, GMV in the right Rolandic operculum was significantly positively correlated with CAS (correlation coefficient: r= 0.448). This study showed significant morphological and functional alterations in visual cortex and morphological alterations in partial default mode network regions of DON patients, which may provide insights into the mechanism of vision loss and may facilitate the diagnosis and treatment of DON. 3. Stage 3.

Elevated expression of interleukin-27, IL-35, and decreased IL-12 in patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disease. The interleukin-12 (IL-12) family includes IL-12, IL-23, IL-27, and IL-35, all of which play important roles in autoimmunity. Thus far, the relationship between IL-12, IL-27, and IL-35 and the TAO has not been evaluated. Seventy-five serum samples from patients with TAO were collected. Serum samples from 90 healthy controls (HC), 55 patients with Graves' disease (GD), 38 patients with uveitis (UV), 17 patients with Sjogren's syndrome (SS), and 65 patients with rheumatoid arthritis (RA) were collected as controls. The associations between IL-27, IL-35, IL-12, and other clinical parameters were analyzed. Elevated serum levels of IL-27/IL-35 and decreased serum IL-12 levels were observed in TAO patients compared to those in HC (p < 0.001). For HC, we observed good diagnostic ability to predict TAO (area under the curve = 0.74, 0.78, and 0.78, for IL-27, IL-35, and IL-12, respectively). For other autoimmune diseases, IL-27, IL-35, and IL-12 had the ability to discriminate between UV, RA, and SS (area under the curve = 0.80, 0.83, and 0.85 for IL-27; 0.52, 0.69, and 0.67 for IL-35). The positive detection rates of IL-12 were significantly lower in the TAO group than in the UV and RA groups (p = 0.002, 0.01). IL-12, IL-27, and IL-35 have the potential as biomarkers for TAO.

Peripapillary structural and microvascular alterations in early dysthyroid optic neuropathy

BackgroundTo explore the changes in blood supply and structure around the optic nerve head (ONH) in thyroid-associated ophthalmopathy (TAO) patients with suspected dysthyroid optic neuropathy (DON).MethodsTAO patients [19 with DON; 24 non-DON (NDON); 20 with equivocal DON (EDON)], and 34 control subjects were examined. Optical coherence tomography angiography (OCTA) was used to obtain peripapillary retinal nerve fiber layer (p-RNFL) and vessel density parameters, including the ONH whole image vessel density (ONH-wiVD) and the radial peripapillary capillary vessel density (RPC-VD) in early DON.ResultsAlthough there were no differences in p-RNFL thickness among the groups, there were differences in the ONH-wiVD of each grid section and the RPC-VD in all areas (P < 0.01). Compared with healthy controls, the EDON eyes had significantly lower RPC-VDs in all aeras (P < 0.05).The peripapillary region was further divided into eight sectors, and the RPC-VD in the temporal upper, superior temporal, and temporal lower sectors in the EDON group were significantly lower than in the controls. The visual impairment was closely related to the loss of peripapillary capillary vessel density. Univariate correlation analysis showed that the ONH-wiVD and RPC-VD of the TAO groups were negatively correlated with the intraocular pressure (r = − 0.296, P = 0.006; r = − 0.258, P = 0.016 respectively).ConclusionsEDON patients had significantly lower ONH-wiVD and RPC-VD than control subjects, and the temporal and upper VDs were more likely to be affected in the early stage of TAO. The combined use of spectral domain optical coherence tomography and OCTA technologies offer a new method for early diagnosis of suspected DON patients.

Morphological brain changes between active and inactive phases of thyroid-associated ophthalmopathy: A voxel-based morphometry study

AimTo explore the morphological brain changes among active thyroid-associated ophthalmopathy (TAO) patients, inactive TAO patients and healthy controls and to investigate the neuropathological relationship of TAO using magnetic resonance imaging (MRI) data. MethodsIn this observational case-control study, we included 35 inactive TAO patients, 37 active TAO patients and 23 healthy controls. Voxel-based morphometry (VBM) analysis was conducted to evaluate the gray matter volume (GMV) changes among groups, and the correlations between GMV alterations and clinical parameters in active and inactive TAO groups were investigated. ResultsActive TAO patients showed significantly increased GMV in the right inferior frontal gyrus, left superior frontal gyrus (SFG), orbital superior frontal gyrus, orbital middle frontal gyrus, precuneus and postcentral gyrus compared with controls and significantly increased GMV in the right middle temporal gyrus, left SFG and precuneus compared with the inactive TAO group. No significant differences were observed between the inactive TAO group and healthy controls. Notably, the receiver operating characteristic (ROC) curve analysis demonstrated altered GMV among groups and significantly (p < 0.001) differentiated active TAO from inactive TAO and healthy controls. In addition, the mean GMV in precuneus and postcentral gyrus were significantly associated with clinical parameters in active TAO. ConclusionOur findings suggested the localized GMV alterations among groups were associated with the pathophysiology of TAO and served as a potential discriminative pattern to detect clinical phases of TAO at the individual level. The altered brain morphometry may suggest a corresponding process of self-repair and remodeling of the brain structure as the disease progresses in TAO.

Identification of tRNA-Related Fragments and Their Potential Regulatory Effects in Thyroid-Associated Ophthalmopathy.

Recently, the potential role of tRNA-related fragments (tRFs) in ophthalmic diseases has been extensively researched. However, systematic studies on the potential regulatory effects of tRFs in thyroid-associated ophthalmopathy (TAO) are lacking. We used high-throughput sequencing techniques to measure expression levels of mRNAs and tRFs in patients with TAO, and the results were verified by real-time quantitative reverse transcription polymerase chain reaction (q-PCR). Next, the potential biological regulatory effect of differentially expressed tRFs was analyzed, and potential downstream target RNAs of differentially expressed tRFs were predicted to explore the potential role of tRFs as therapeutic targets and biomarkers of TAO. A total of 50 tRFs and 361 mRNAs were dysregulated in the TAO group, and tRF5-GluCTC, PMAIP1, HSD17B2 and ATF3 were verified to be significantly differentially expressed in TAO. Our research reveals that several associated pathways likely play a role in the pathogenesis of TAO. By targeting ATF3, HSD17B2 and PMAIP1, tRF5-GluCTC may play a potential role in regulating the orbital fibroblast adipogenic response and fibrotic hyperplasia in patients with TAO.

Management of Patients with Thyroid-Associated Ophthalmopathy: Role of Spectral Domain Optical Coherence Tomography

AIM: To demonstrate the changes in optic nerve head (ONH), retinal nerve fiber layer (RNFL) and macula in patients with thyroid-associated ophthalmopathy (TAO) by spectral domain optical coherence tomography (SD-OCT). &#x0D; METHODS: We included forty-one eyes of 41 patients with a diagnosis of TAO and forty-eight eyes of 48 age- and sex-matched healthy subjects (control group) from June 2016 to July 2018. The ONH parameters, RNFL and macular thicknesses in the nine macular quadrants according to ETDRS were measured with SD-OCT. Proptosis level was determined by Hertel exophthalmometer. Clinical activity score (CAS) according to the European Group of Graves' Orbitopathy (EUGOGO) guidelines was determined in all patients. &#x0D; RESULTS: Superior, inferior and average RNFL thicknesses were significantly lower in the TAO group compared to the control group (p &lt; 0.05). Optic disc area was significantly larger in the TAO group. Outer quadrant macular thicknesses and average macular thickness were significantly lower in the TAO group (p &lt; 0.05). CAS had a weak correlation with RNFL thickness and average macular thickness. &#x0D; CONCLUSION: Alterations in RNFL thicknesses and macular thicknesses according to ETDRS template can be detected before the development of ocular symptoms in patients with TAO. OCT is a convenient, non-invasive tool for the evaluation and follow-up of macular structural changes. Patients can be diagnosed at an early stage prior to the development of functional damage. However, the low number of studies investigating this subject and the conflicting findings of existing studies necessitate further studies.

Correlation between extent of lacrimal gland prolapse and clinical features of thyroid-associated ophthalmopathy: a retrospective observational study

BackgroundStudies on the factors related to lacrimal gland prolapse (LGP) in patients with thyroid-associated ophthalmopathy (TAO) are limited. This study aimed to assess the factors associated with LGP on magnetic resonance imaging (MRI) and its relation to TAO activity .MethodsThirty-six patients (72 orbits) with inactive TAO (43 orbits, Clinical Activity Score [CAS] < 3) or active TAO (29 orbits, CAS ≥3) were investigated retrospectively. All patients underwent ophthalmic evaluation and orbital magnetic resonance imaging. The severity of LGP and proptosis and the extraocular muscle (EOM) volume were measured. LGP and related factors were assessed by correlational and linear regression analyses. The value of LGP for discriminating the activity of TAO was evaluated by receiver-operating characteristic curve analysis.ResultsThe mean LGP was significantly higher in the active TAO group than in the inactive TAO group (P < 0.001). There were significant positive correlations between LGP severity and the CAS (r = 0.51, P < 0.001), proptosis (r = 0.72, P < 0.001), and EOM volume (superior rectus [r = 0.49, P < 0.001], inferior rectus [r = 0.47, P < 0.001], lateral rectus [r = 0.59, P < 0.001], medial rectus [r = 0.62, P < 0.001], superior oblique [r = 0.48, P < 0.001], and all EOMs [r = 0.59, P < 0.001]). Receiver-operating characteristic curve analysis revealed an LGP of 13.65 mm (area under the curve, 0.824; sensitivity, 79.3%; specificity, 81.4%) to be the cut-off value that differentiated active and inactive TAO.ConclusionsLGP measurements obtained from orbital magnetic resonance images were positively correlated with CAS, proptosis and EOM volume. The extent of LGP appears to be a good indicator of disease activity in patients with TAO.

Spontaneous brain activity alterations in thyroid-associated ophthalmopathy patients using amplitude of low-frequency fluctuation: A resting-state fMRI study.

Previous studies demonstrated that thyroid-associated ophthalmopathy (TAO) patients were accompanied by cognitive decline. However, The exact neural mechanisms of cognitive decline in TAO patients remain unclear. Our study aimed to investigate the spontaneous brain activity alterations using amplitude of low-frequency fluctuation (ALFF) method and their relationships with clinical features in TAO patients. In total, twenty-one patients with TAO (14 men and 7 women) and 21 healthy control (HC) subjects (14 men and 7 women) were enrolled in this study. The ALFF method was used to assess the spontaneous brain activity changes. Meanwhile, receiver operating characteristic (ROC) curve was used to distinguish TAO group and HCs group. And Pearson correlation was performed to calculate the relationship between the observed mean ALFF values of the altered regions in patients with TAO and their clinical features. Compared with the HCs, TAO patients had significantly lower ALFF values in the right superior occipital gyrus (SOG) and bilateral precuneus (preCUN). In contrast, TAO patients showed higher ALFF values in the left cerebellum (CER) and left insula (INS). our result highlighted that TAO patients showed altered intrinsic brain activities in the preCUN, left CER, left INS and right SOG, which might provide useful information for explaining neural mechanisms in patients with TAO.

Quantitative T1 mapping MRI for the assessment of extraocular muscle fibrosis in thyroid-associated ophthalmopathy.

We aimed to investigate the performance of T1 mapping and its histological correlation with extraocular muscle fibrosis in thyroid-associated ophthalmopathy (TAO). We prospectively recruited 12 cases of active TAO, 12 cases of inactive TAO, and 15 cases of control subjects. All participants underwent magnetic resonance imaging (MRI) scan with pre-/postcontrast T1 mapping and short-time inversion-recovery (STIR) sequence. The images were analyzed to obtain precontrast T1, extracellular-volume (ECV) fraction on T1 mapping, and signal-intensity ratio (SIR) on STIR for each rectus. Muscle biopsy was performed at lateral rectus to quantify-collagen volume fraction, glycosaminoglycan (GAG)-volume fraction, and extracellular space component. The relationship between MRI and histopathology was examined with Pearson correlation coefficient. The active TAO group was characterized with GAG accumulation, while the inactive TAO group presented with substantial fibrosis. The MRI parameters achieved acceptable interobserver and intraobserver agreement. The precontrast T1 and ECV remarkably increased in the TAO groups than the control group, and ECV positively correlated with collagen-volume fraction (r = 0.913) and extracellular-space component (r = 0.886) in the inactive TAO group. The SIR statistically increased in the active TAO group, and SIR positively correlated with GAG-volume fraction in all three groups. The performance of ECV (cutoff > 48.1%) to screen out extraocular muscle fibrosis in inactive TAO was 60.9% sensitivity and 93.3% specificity. The ECV parameter on T1 mapping MRI is a reliable tool to quantify extraocular muscle fibrosis, providing insights into noninvasive evaluation of pathological changes in TAO orbit. ChiCTR2000040394; Date of registration: 28 November 2020.

Choroidal vascularity index in thyroid-associated ophthalmopathy

ObjectiveTo investigate the choroidal vascularity index (CVI) in patients with thyroid-associated ophthalmopathy (TAO) and its relationship with clinical features and clinical activity score MethodsRight eyes of 53 patients with TAO and 53 healthy subjects were scanned for subfoveal choroidal thickness (SFCT), CVI, choroid-stromal area (C-SA), choroid-luminal area (C-LA), choroidal stromal index (CSI), choroid-stromal-to-luminal-area ratio, and CVI and CSI within the central 1500 µm of the macula (CVI1500 and CSI1500) by enhanced-depth imaging optical coherence tomography. The results of the TAO group and the healthy controls were compared. ResultsThe SFCT was significantly greater in the TAO group than in the control group (p = 0.02). The values of C-LA, C-SA, and total choroidal area (TCA) in the TAO group were significantly higher than those in the control group (p = 0.01, p = 0.04, and p = 0.01, respectively). The increases in SFCT, C-LA, C-SA, and TCA were 12.1%, 12.2%, 16.2%, and 13.6%, respectively. There was no statistically significant difference between the groups for CVI, CSI, CVI1500, CSI1500, and choroid-stromal-to-luminal-area ratio (p > 0.05). CVI1500 and CSI1500 have displayed a statistically significant correlation with exophthalmometry and clinical activity score (p < 0.05). ConclusionThe alterations in stromal and vascular structures are proportionally similar in TAO; thus CVI may not be affected significantly. However, CVI1500 and CSI1500 may be associated with disease activity. The choroidal thickening in TAO may be the result not only of vascular mechanisms but also by an increase in stromal contents.

Usefulness of readout-segmented EPI-based diffusion tensor imaging of lacrimal gland for detection and disease staging in thyroid-associated ophthalmopathy

BackgroundDysfunction of lacrimal gland (LG) gains increasing attention in patients with thyroid-associated ophthalmopathy (TAO), while the underlying pathological change is still not fully established. This study aimed to evaluate the utility of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in non-invasively detecting microstructural alterations of LG in patients with TAO, as well as in discriminating disease activity.MethodsThirty TAO patients and 15 age- and sex- matched healthy controls, who underwent rs-EPI-based DTI, were retrospectively enrolled. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of LG, and clinical-endocrinological variables were collected and compared. The correlations between FA and ADC values of LG and serum thyroid biochemical markers were also assessed.ResultsTAO group showed significantly lower FA (P < 0.001) and higher ADC (P = 0.014) of LG than healthy group. Active subgroup had significantly lower FA (P < 0.001) and higher ADC (P < 0.001) than inactive subgroup. In TAO group, FA of LG was significantly and negatively correlated with TRAb (r=-0.475, P = 0.008), while ADC of LG showed no significant correlation (P > 0.05). The area under receiver operating characteristic curve of FA was significantly greater than that under curve of ADC for discriminating disease activity (0.832 vs. 0.570, P = 0.009).Conclusionsrs-EPI-based DTI is a useful tool to characterize the microstructural change of LG in patients with TAO. The derived metrics, particularly FA, can help to reveal disease activity.

Blood Count-derived Immunoinflammatory Markers in Thyroidassociated Ophthalmopathy.

PurposeTo investigate the diagnostic and prognostic significance of the blood-count derived systemic immunoinflammatory parameters in patients with thyroid-associated ophthalmopathy (TAO).MethodsIn this retrospective case-control study, the blood-count parameters and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, and systemic immune-inflammatory index (SII), thyroid peroxidase antibody, and anti-thyroglobulin antibody were evaluated in 46 patients with TAO and 46 matched controls. The associations of the immunoinflammatory parameters with clinical outcomes were analyzed among TAO patients.ResultsSignificant differences were found in NLR, PLR, SII, and lymphocyte count between the controls and the TAO group (p < 0.05 for all). In logistic regression analysis, these inflammatory parameters did not have any prognostic effect on the clinical outcomes of the TAO (p > 0.05 for all). The patients, who needed systemic treatment due to any ocular involvement of TAO during the follow-up period, had significantly lower platelet count (p = 0.001) and PLR (p = 0.02) at the time of initial diagnosis when compared to the no treatment-needed group of the TAO patients. The initial platelet count was significantly associated with the subsequent steroid need due to TAO during the follow-up period (β = −0.02, p = 0.03).ConclusionsNLR, PLR, and SII may serve as potential inflammatory markers in the identification of the TAO, although they have no evident prognostic significance in TAO. However, the relatively lower platelet count at initial diagnosis may be associated with the need for systemic therapy during the follow-up in patients with TAO.