UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: Thyroid-associated ophthalmopathy (TAO) is considered to be an organ-specific autoimmune disease. Polymorphonuclear neutrophils (PMN) have been implicated in the pathogenesis of TAO. However, little is known about the role of PMN in the development of TAO, much less the relationship between PMN with B cells and CD4+T cells in TAO.
UNASSIGNED: This study aims to investigate the phenotypic characteristics of PMN and the relationship between PMN with CD4+T cell and B cell subsets in the pathogenesis of TAO.
UNASSIGNED: Blood routine information was collected from 135 TAO patients, 95 Grave\'s disease without TAO (GD) patients, and 116 normal controls (NC), while surface marker expression of PMN and the level of CD4+T cell and B cell subsets in peripheral blood from 40 TAO patients, 17 GD patients, and 45 NC was assessed by flow cytometry.
UNASSIGNED: The level of PMN, CD62L+PMN, CD54+PMN, CD4+T cells, and Th17 cells displayed an increase in TAO patients than NC, while Treg cells were lower in the TAO group compared to NC. There was no statistical difference in Th1 and plasma cells among the groups. PMN were positively correlated with Th17 cells, but not the Th1, Treg, and plasma cells.
UNASSIGNED: In the present study, we found that the percentage of PMN and PMN subset cells was significantly higher in TAO than in NC, and PMN were positively correlated with Th17 cells. It suggests that PMN may be involved in the immunopathogenesis of TAO and modulate the Th17 cell response during this process.

UNASSIGNED: Thyroid-associated ophthalmopathy (TAO) is an autoimmune-driven orbital inflammatory disease. Despite research efforts, its exact pathogenesis remains unclear. This study aimed to characterize the intestinal flora and metabolic changes in patients with TAO to identify the flora and metabolites associated with disease development.
UNASSIGNED: Thirty patients with TAO and 29 healthy controls were included in the study. The intestinal flora and metabolites were analyzed using high-throughput sequencing of the 16S rRNA gene and non-targeted metabolomics technology, respectively. Fresh fecal samples were collected from both populations for analysis.
UNASSIGNED: Reduced gut richness and diversity were observed in patients with TAO. Compared to healthy controls, significant differences in relative abundance were observed in patients with TAO at the order level Clostridiales, family level Staphylococcaceae, genus level Staphylococcus, Fournierella, Eubacterium siraeum, CAG-56, Ruminococcus gnavus, Intestinibacter, Actinomyces, and Erysipelotrichaceae UCG-003 (logFC>1 and P<0.05). Veillonella and Megamonas were closely associated with clinical symptoms in patients with TAO. Among the 184 significantly different metabolites, 63 were upregulated, and 121 were downregulated in patients with TAO compared to healthy controls. The biosynthesis of unsaturated fatty acids was the significantly enriched metabolic pathway. Correlation analysis revealed Actinomyces was positively correlated with NAGlySer 15:0/16:0, FAHFA 3:0/20:0, and Lignoceric Acid, while Ruminococcus gnavu was positively correlated with Cer 18:0;2O/16:0; (3OH) and ST 24:1;O4/18:2.
UNASSIGNED: Specific intestinal flora and metabolites are closely associated with TAO development. Further investigation into the functional associations between these flora and metabolites will enhance our understanding of TAO pathogenesis.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition affecting the eyes, characterized by proptosis, extraocular muscle involvement, and in severe cases, vision impairment including diplopia, optic neuropathy, and potential blindness. The exact etiology of TAO remains elusive; however, increased oxidative stress and decreased antioxidant capacity are pivotal in its pathogenesis. Elevated oxidative stress not only directly damages orbital tissues but also influences thyroid function and autoimmune responses, exacerbating tissue destruction. This review explores the role of oxidative stress in TAO, elucidates its mechanisms, and evaluates the efficacy and limitations of antioxidant therapies in managing TAO. The findings aim to enhance understanding of oxidative stress mechanisms in TAO and propose potential antioxidant strategies for future therapeutic development.

OBJECTIVE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters.
METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ).
RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients.
CONCLUSIONS: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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) ≥ 2 mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505 mm) 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: 2.095 mm) 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: 2.095 mm) and 0.78 for LPS_SIR (cutoff: 1.197).
UNASSIGNED: The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncRNA/circRNA/mRNA sequencing data, as well as several RNA methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding RNA, and RNA methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding RNA. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by RNA epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.

OBJECTIVE: To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO).
METHODS: Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate.
RESULTS: Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p < 0.05). The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were independently associated with active TAO (all p < 0.05). The combination of the EOM-SIRmean, LG-SIRmean, and LG-FFmean values showed better performance than the EOM-SIRmean value alone in staging TAO in both the training (AUC, 0.820 vs 0.793; p = 0.016) and validation (AUC, 0.751 vs 0.733, p = 0.341) cohorts.
CONCLUSIONS: Dixon MRI-based parameters of EOMs, LGs, and IF are useful for differentiating active from inactive TAO. The integration of multiple parameters can further improve staging performance.
UNASSIGNED: In this study, the authors explored the combined value of quantitative parameters of EOMs, IF, and LGs derived from Dixon MRI in staging TAO patients, which can support the establishment of a proper therapeutic plan.
CONCLUSIONS: The quantitative parameters of EOMs, LGs, and IF are useful for staging TAO. The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were found to independently correlate with active TAO. Joint evaluation of orbital tissue improved the ability to assess TAO activity.

BACKGROUND: Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED.
METHODS: Orbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA.
RESULTS: IGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients.
CONCLUSIONS: IGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.

Thyroid-associated ophthalmopathy (TAO), also referred to as Graves\' ophthalmopathy, is a medical condition wherein ocular complications arise due to autoimmune thyroid illness. The diagnosis of TAO, reliant on imaging, typical ocular symptoms, and abnormalities in thyroid function or thyroid-associated antibodies, is generally graded and staged. In recent years, Artificial intelligence(AI), particularly deep learning(DL) technology, has gained widespread use in the diagnosis and treatment of ophthalmic diseases. This paper presents a discussion on specific studies involving AI, specifically DL, in the context of TAO, highlighting their applications in TAO diagnosis, staging, grading, and treatment decisions. Additionally, it addresses certain limitations in AI research on TAO and potential future directions for the field.