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Introduction: 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. Objective: 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. Methods: 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. Result: 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. Conclusion: 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.

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Background: 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). Methods: 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. Results: 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. Conclusion: 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.

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BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition commonly linked with Graves' disease (GD), characterized by orbital tissue inflammation and fibrosis. It is hypothesized that gene polymorphisms may influence production of the IL-17 and IL-38 cytokines, thereby impacting TAO development and progression. This study focused on investigating the gene polymorphisms of IL-17 (rs9463772 C/T in IL17F) and IL-38 (rs3811058 C/T, rs7570267 A/G in IL1F10) in patients with GD. METHODS: A case-control study was conducted on 132 patients with TAO and 153 patients without TAO according to eligibility criteria. After clinical examination blood samples were collected for further investigations. Genotyping was performed with the TaqMan™ Master Mix kit. Allele and genotype frequencies were compared between studied groups and subgroups. RESULTS: No significant differences were found in age, duration of GD, or thyroid hormone between patients with and without TAO. However, a higher predisposition to develop TAO was observed among smokers (OR = 1.682, p = 0.03). Overall, no significant associations between gene polymorphisms and TAO development were identified in GD patients. Further analysis revealed that the CC genotype in IL1F10 rs3811058 polymorphism among Caucasians was associated with an increased risk of TAO (OR = 2.7, p = 0.02), as well as allele differences were also significant (OR = 2.8, p = 0.001). CONCLUSIONS: These findings shed light on TAO genetic predispositions in Kazakhstani GD patients, notably among Caucasians, underscoring the need for further research. These results may offer valuable targets for the development of novel treatments for TAO.

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Thyroid-associated ophthalmopathy (TAO) is a hallmark autoimmune condition, and the treatment of TAO requires a multidisciplinary approach. Radiation therapy (RT) is a viable treatment option for active TAO, IMRT is a more precise technology in radiation oncology. This study aims to evaluate the efficacy, feasibility, and safety of orbital intensity-modulated radiation therapy (IMRT) in the treatment of TAO. A single-center retrospective analysis was conducted, including patients diagnosed with moderate to severe active TAO at the Department of Radiation Oncology, Peking University Third Hospital, from October 2020 to October 2023, who had poor responses to corticosteroid treatment. These patients subsequently received IMRT treatment, followed by a period of follow-up and retrospective analysis. The study focused on the outcomes of treatment efficacy, safety, and acute toxic reactions induced by radiation therapy. Improvements in clinical activity score (CAS) at 4 and 12 months were considered as primary and secondary study endpoints, respectively, along with the incidence rate of adverse events. The median follow-up period was 12 months. The median follow-up time after radiation therapy was 12 months. There was no statistically significant difference in CAS between before and 4 months after radiation therapy (CAS: 5.53 ± 2.07 vs.4.68 ± 2.62; R squared: 0.21; 95% CI: - 1.01-0.02; P = 0.054). However, there was a significant reduction in CAS 12 months post-treatment compared to pre-treatment (CAS: 5.53 ± 2.07 vs. 3.06 ± 2.38; R squared: 0.66; 95% CI: 3.42 - 1.52; P < 0.001). The CAS showed a progressively decreasing trend at both 4 months and 12 months post-treatment. In the combined radiotherapy with glucocorticoid treatment group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 6.38 ± 2.00 vs. 3.88 ± 2.85; R squared: 0.66; 95% CI - 4.11 to 0.89; P = 0.008). In the radiotherapy alone group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 4.78 ± 1.92 vs. 2.33 ± 1.73; R squared: 0.66; 95% CI - 3.89 to 1.00; P = 0.005). A few patients experienced Grade I periorbital edema, conjunctival congestion, and dry eye syndrome, but no adverse events such as cataracts, radiation retinopathy, or radiation-induced optic neuropathy were observed by the end of the follow-up period. Orbital IMRT is an effective treatment modality for moderate to severe active TAO, demonstrating significant efficacy even in patients who had not achieved success with previous treatments such as corticosteroids. This retrospective study was approved by the Ethics Committee of Peking University Third Hospital. The permit number was M2024220 and data of registration was April I, 2024.

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Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

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BACKGROUND: The first line treatment for moderate to severe active thyroid associated ophthalmopathy is glucocorticoid pulse therapy, but for patients with contraindications to hormone therapy or hormone resistance, it is urgent to find a suitable treatment plan. AIMS: To find a reliable alternative to hormone pulse therapy for thyroid associated ophthalmopathy by comparing the efficacy with first-line treatment regimens. METHODS: Search PubMed, Ovid, Web of science, Cochrane library, and Clinical Trials.gov for randomized controlled trials on the treatment of thyroid associated ophthalmopathy published as of July 7, 2024. Quality evaluation and Bayesian network analysis were conducted using RevMan 5.3 software, STATA15.0 software, and ADDIS 1.16.8 software. RESULTS: A total of 666 patients were included in 11 studies and 8 interventions. Network analysis showed that the three interventions of mycophenolate mofetil combined with glucocorticoids, Teprotumumab and 99Tc-MDP were superior to glucocorticoid pulse therapy in improving clinical activity scores and proptosis. The regimen of glucocorticoids combined with statins can improve the quality of life score and diplopia score of patients. Neither methotrexate combined with glucocorticoids nor rituximab alone showed additional advantages when compared with glucocorticoid pulse therapy. CONCLUSION: Mycophenolate mofetil combined with glucocorticoid therapy is very beneficial for moderate to severe active thyroid associated ophthalmopathy. Mycophenolate mofetil may be a good choice when patients have contraindications to hormone use or hormone resistance. Teprotumumab is very promising and may be able to avoid patients undergoing orbital decompression surgery. The durability and safety of its long-term efficacy need to be further observed.

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PURPOSE: To quantify interocular differences in the retinal microvasculature between disparate eyes and explore associations between the retinal microvasculature and visual field abnormalities within the same asymmetric thyroid-associated ophthalmopathy (TAO) patients. METHODS: Within the same asymmetric TAO eye, the eye with a severer visual field abnormality (based on the mean deviation [MD]) was considered a severe eye, and the fellow eye was considered mild. The densities of radial peripapillary capillary (RPC) and superficial retinal capillary plexuses (SRCP) were determined using optical coherence tomography angiography. Interocular differences in RPC and SRCP densities were analyzed. A generalized estimating equation (GEE) was used to form a predictive model for visual field abnormalities. Pearson's correlation was used to show the correlation between MD and the densities of RPC and SRCP. RESULTS: In 57 asymmetric TAO patients, the global RPC density in severe eyes was lower than that in mild eyes (P < 0.001), but there was no significant difference in SRCP density between the two groups (P = 0.114). In a multivariate GEE model with MD as the outcome, MD was associated only with global RPC density (coefficient ß=0.327, P < 0.001). The global RPC density was correlated with MD (r = 0.360, P = 0.003) in severe eyes, but not in mild eyes (r = 0.179, P = 0.092). No significant correlation was observed between global SRCP density and MD in either group (Both P > 0.05). CONCLUSIONS: RPC density decreased significantly and correlated with visual field abnormalities in severe eyes of TAO patients. Alterations in RPC density may contribute to visual field abnormalities in TAO eyes.

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OBJECTIVE: To investigate the value of fat-suppression (FS) T2 relaxation time (T2RT) derived from FS T2 mapping and water fraction (WF) derived from T2 IDEAL to predict the treatment response to intravenous glucocorticoids (IVGC) in patients with thyroid-associated ophthalmopathy (TAO) based on texture analysis. MATERIALS AND METHODS: In this study, 89 patients clinically diagnosed with active and moderate-to-severe TAO were enroled (responsive group, 48 patients; unresponsive group, 41 patients). The baseline clinical characteristics and texture features were compared between the two groups. Multivariate analysis was performed to identify the independent predictors of treatment response to IVGC. ROC analysis and the DeLong test were used to assess and compare the predictive performance of different models. RESULTS: The responsive group exhibited significantly shorter disease duration and higher 90th percentile of FS T2RT and kurtosis of WF in the extraocular muscle (EOM) and 95th percentile of WF in the orbital fat (OF) than the unresponsive group. Model 2 (disease duration + WF; AUC, 0.816) and model 3 (disease duration + FS T2RT + WF; AUC, 0.823) demonstrated superior predictive efficacy compared to model 1 (disease duration + FS T2RT; AUC, 0.756), while there was no significant difference between models 2 and 3. CONCLUSIONS: The orbital tissues of responders exhibited more oedema and heterogeneity. Furthermore, OF is as valuable as EOM for assessing the therapeutic efficacy of IVGC. Finally, WF derived from T2 IDEAL processed by texture analysis can provide valuable information for predicting the treatment response to IVGC in patients with active and moderate-to-severe TAO. CLINICAL RELEVANCE STATEMENT: The texture features of FS T2RT and WF are different between responders and non-responders, which can be the predictive tool for treatment response to IVGC. KEY POINTS: Texture analysis can be used for predicting response to IVGC in TAO patients. TAO patients responsive to IVGC show more oedema and heterogeneity in the orbital tissues. WF from T2 IDEAL is a tool to predict the therapeutic response of TAO.

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PURPOSE: To determine the rate of re-treatment in patients who receive a full course of teprotumumab therapy for thyroid eye disease (TED) and drivers of re-treatment. DESIGN: Multicenter retrospective study. PARTICIPANTS: All patients who received a full course of treatment and had available data at 1 year after initial treatment were included. METHODS: Charts were reviewed for the following information: age, sex, months since diagnosis of TED, smoking status, and prior treatments. Further, the clinical activity score (CAS), proptosis, and the Gorman diplopia score were reviewed at baseline, at the end of the first course, and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of re-treatment. MAIN OUTCOME MEASURES: Rate of re-treatment and the drivers of re-treatment. RESULTS: One hundred nineteen patients were included from 3 centers across the United States. The overall re-treatment rate was 24% (29/119). No difference was found among the 3 sites (P = 0.6). In univariable analyses, at baseline, no difference was found in proptosis (P = 0.07), diplopia score (P = 0.4), or duration of TED (P = 0.4) between patients who were re-treated and those not re-treated. From the re-treated group, 82% showed a significant proptosis response (≥ 2-mm reduction from baseline) after the initial course, whereas 68% of patients who were not re-treated showed a clinically significant proptosis response (P = 0.16). The mean ± standard deviation difference between the end of the first treatment and at baseline before the second treatment (in those who received it) was 2 ± 2 for CAS, 2 ± 4 mm for proptosis, and 1 ± 1 for diplopia score. Age was the only significant driver of re-treatment (P < 0.05). Re-treated patients were 7 years older than patients who were not re-treated (60 years vs. 53 years; P < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of re-treatment was 24%. Age was the only driver of re-treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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PURPOSE: 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. CONCLUSION: 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.

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Introduction: Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Methods: Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Results: Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. Conclusion: This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

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PURPOSE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. CONCLUSION: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

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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.

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Background: 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. Methods: 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. Results: 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). Conclusion: The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

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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.

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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. CONCLUSION: 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. CRITICAL RELEVANCE STATEMENT: 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. KEY POINTS: 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.

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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.

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INTRODUCTION AND OBJECTIVES: Lid retraction is one of the most common symptoms of Thyroid-Associated Ophthalmopathy (TAO), which potentially precipitates various complications, such as dry eyes, exposure keratopathy, and cosmetic concerns. Local corticosteroid injections, such as triamcinolone, have been proposed as a choice of treatment for TAO. This approach may be a favorable alternative for patients intolerant to the systemic effects of high-dose methylprednisolone. However, the efficacy of this intervention remains unestablished. Hence, our review aims to evaluate the efficacy of triamcinolone injection in reducing lid retraction. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted in three databases (PubMed, Science Direct, and ProQuest). This review included studies that use local triamcinolone injections for patients with thyroid-associated ophthalmopathy. The outcome of interest in this review is lid retraction parameters. RESULTS: From six studies, a total of 392 patients were included. All studies showed significant improvement in lid retraction in the patient who received triamcinolone (all p < 0.05) as shown by ΔMRD (-0.93 mm in 1 month and -1.38 mm in 3 months), ΔMLD (-1.98 mm at 6 months), and Δpalpebral fissure height (-1.68 in 1 month). The majority of studies showed rapid improvement in lid retraction in the first month of therapy. CONCLUSION: Triamcinolone injection is an effective therapy for lid retraction related to thyroid-associated ophthalmopathy.

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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.

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Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.

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