Thyroid-associated Ophthalmopathy Patients Research Articles

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ± 4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ± 5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Altered Static and Dynamic Brain Functional Topological Organization in Patients with Dysthyroid Optic Neuropathy.

Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional MRI with graph theory method. A cross-sectional study. Grade A tertiary hospital. Sixty-six TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). Topological properties of functional networks. For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. Both DON and non-DON patients exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in orbitofrontal cortex and visual network (VN). For dynamic properties, DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. Functional network alterations were observed in both DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON.

Diagnosis of dysthyroid optic neuropathy: combined value of orbital MRI and intracranial visual pathway diffusion kurtosis imaging.

To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI-based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy.

Retinal Photograph-based Deep Learning System for Detection of Thyroid-Associated Ophthalmopathy

Background: The diagnosis of thyroid-associated ophthalmopathy (TAO) usually requires a comprehensive examination, including clinical symptoms, radiological examinations, and blood tests. Therefore, cost-effective and noninvasive methods for the detection of TAO are needed. This study aimed to establish a deep learning-based system to detect TAO based on retinal photographs. Materials and methods: The multicenter observational study included retinal photographs taken from TAO patients and normal participants in 2 hospitals in China. Forty-five-degree retinal photographs, centered on the midpoint between the optic disc and the macula, were captured by trained ophthalmologists. The authors first trained a convolutional neural network model to identify TAO using data collected from one hospital. After internal validation, the model was further evaluated in another hospital as an external validation data set. Results: The study included 1182 retinal photographs of 708 participants for model development, and 365 retinal photographs (189 participants) were obtained as the external validation data set. In the internal validation, the area under the receiver operator curve was 0.900 (95% CI: 0.889–0.910) and the accuracy was 0.860 (95% CI: 0.849–0.869). In the external data set, the model reached an area under the curve of 0.747 (95% CI: 0.728–0.763) and achieved an accuracy of 0.709 (95% CI: 0.690–0.724). Conclusions: Deep learning-based systems may be promising for identifying TAO in normal subjects using retinal fundus photographs. It may serve as a cost-effective and noninvasive method to detect TAO in the future.

Structural and Functional Brain Changes After Glucocorticoid Therapy in Thyroid-Associated Ophthalmopathy.

To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Between 2019 and 2022, 32 patients with TAO and 23 healthy controls underwent pre-therapy MRI in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. At 3 months after end of therapy, 26 patients were available for rescanned MRI. VBM, ALFF, and ReHo were used to evaluate the brain structural and functional differences. Before therapy, TAO patients showed significantly decreased gray matter volume (GMV) in the left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex and lower values in bilateral cuneus. Patients also showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased GMV in the left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, and increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased GMV in left ORBsup was observed in post-therapy TAO patients. Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to deeper understanding of the pathophysiological mechanism behind TAO.

HbA1c: an independent risk factor for dysthyroid optic neuropathy.

We aimed to explore the frequencies of islet β-cell autoantibodies and insulin resistance (IR) in thyroid-associated ophthalmopathy (TAO) and identify specific diabetes mellitus (DM) indicators as early predictors for dysthyroid optic neuropathy (DON). Ninety-eight TAO patients (57 DON and 41 non-DON patients) and 48 healthy control (HC) participants were recruited for this prospective cross-sectional study. Serum thyroxine, serum thyroid autoantibodies, serum humoral immune markers against islet β-cell, fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting c-peptide (FCP), and glycosylated hemoglobin A1 (HbA1c) were measured. Logistic regression analysis was used to evaluate the correlation of patients' age, body mass index (BMI), FPG, HbA1c, and related indexes of islet β-cell function to the occurrence of DON. The DON group had higher FPG (P<0.001, 0.016) and HbA1c (P<0.0001, P<0.001) levels than the HC and non-DON groups. The homeostasis model assessment (HOMA)-IR level was the highest in the DON group (HC 2.15 ± 0.89, non-DON 2.41 ± 1.24, and DON 2.82 ± 2.65), while the HOMA-β level was the lowest (HC 101.8 ± 44.75%, non-DON 102.9 ± 54.61%, and DON 88.29 ± 52.75%), with no significant differences (P=1, P>0.05). On univariate analysis, age (P=0.006), BMI (P=0.022), history of steroid use (P=0.014), FPG (P=0.013), and HbA1c (P=0.001) levels were significantly associated with the presence/absence of DON. In addition, after adjusting for potential confounds, the HbA1c level was an independent factor associated with DON (P=0.009, OR=4.012). HbA1c is an independent risk factor for DON. Given the interconnected link between thyroid dysfunction and DM, the use of HbA1c as a potential biomarker for DON warrants further investigation.

Use of extreme gradient boosting, light gradient boosting machine, and deep neural networks to evaluate the activity stage of extraocular muscles in thyroid-associated ophthalmopathy.

To develop a machine learning model to evaluate the activity stage of extraocular muscles in thyroid-associated ophthalmopathy (TAO). This study retrospectively analysed data from patients with TAO who underwent contrast-enhanced magnetic resonance imaging (MRI) from 2015 to 2022. Three independent machine learning models, namely, extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and deep neural networks (DNNs), were constructed using common clinical features. The performance of these models was compared using evaluation metrics such as the area under the receiver operating curve (AUC), accuracy, precision, recall, and F1 score. The importance of features was explained using Shapley additive explanations (SHAP). A total of 2561 eyes of 1479 TAO patients were included in this study. The original dataset was randomly divided into a training set (80%, n = 2048) and a test set (20%, n = 513). In the performance evaluation of the test set, the LightGBM model had the best diagnostic performance (AUC 0.9260). According to the SHAP results, features such as conjunctival congestion, swollen caruncles, oedema of the upper eyelid, course of TAO, and intraocular pressure had the most significant impact on the LightGBM model. This study used contrast-enhanced MRI as an objective evaluation criterion and constructed a LightGBM model based on readily accessible clinical data. The model had good classification performance, making it a promising artificial intelligence (AI)-assisted tool to help community hospitals evaluate the inflammatory activity of extraocular muscles in TAO patients in a timely manner.

Study on relationship between intraocular pressure and hyperthyroidism

Thyroid-associated ophthalmopathy (TAO) represents a persistent autoimmune inflammatory condition impacting various ocular components, including orbital fat (OF), extraocular muscles (EOMs), the eyeball, and associated eye structures. This disorder is closely associated with autoimmune thyroid pathology. A body of research has indicated an elevated susceptibility to heightened intraocular pressure (IOP) and glaucoma among individuals with thyroid-related ailments. Nonetheless, certain studies have expressed reservations about affirming these conclusions. Furthermore, there exists a diversity of viewpoints regarding the optimal approaches for managing elevated IOP in TAO patients afflicted with ocular hypertensionA prospective research investigation was undertaken within the Department of Ophthalmology at a Tertiary Care Teaching Hospital, spanning a duration of 12 months. The techniques employed for the diagnosis of open-angle glaucoma (OAG) have been comprehensively outlined. Goldmann applanation tonometry was utilized to determine intraocular pressure (IOP). Employing a Zeiss FF3 fundus camera, a series of dilated stereoscopic 300-color retinal and optic disc images were captured. The evaluation of optic disc photographs was conducted by one of two evaluators, both of whom remained masked to the study's particulars, employing a customized protocol. In order to ascertain optic disc dimensions, adjustments for camera magnification were performed, accounting for the spherical equivalent refraction of each individual eye.A total of 90 patients were examined. Of the 90 cases, male preponderance was noted. Among 90 patients, 20 (22.2%) were hyperthyroid, 61 (67.8%) were hypothyroid, and 9 (10%) patients were euthyroid. In our study shows the frequency of different symptoms among the study group. Most of the patients came with complaint itching of (27.8%). The second most common symptom was foreign body sensation (21.1%). In this study shows the different types of signs among these two groups. In hyperthyroid lid, retraction was more common (12%). In hypothyroid lid, edema was more common (18.5%). Frequency of dry eye syndrome in patients with TD was present; 29 (26.4%) patients had dry eye disease. Among 90 patients, proptosis was present in 4 patients had proptosis. Most of the patients were myopic.Our results imply the potential link between intraocular pressure (IOP) and thyroid-related disorders, particularly in individuals undergoing thyroxine treatment. Conducting further comprehensive investigations to explore and substantiate this prospective association is advisable.

Prognostic value of extraocular muscles for intraocular pressure in thyroid-associated ophthalmopathy patients.

Persistent increase in intraocular pressure (IOP) is often observed in eyes with thyroid-associated ophthalmopathy (TAO), which has irreversible effects on the visual function of patients. This retrospective cross-sectional study evaluated the value of magnetic resonance imaging (MRI) measurements of extraocular muscle (EOM) volume in prognosing IOP in patients with TAO. This single-center study was conducted in Beijing Friendship Hospital (Beijing, China), a tertiary hospital. From 35 participants, 70 eyes (normal IOP group: 50 eyes; high IOP group: 20 eyes; random samples) were enrolled in this study. Basic data from patients were collected and compared using 2-sample t-tests and chi-squared tests. The volume of the EOM, orbit fat, and whole orbit were measured by orbital MRI. Moreover, proptosis, optic nerve (ON) sheath diameter, optic nerve angle (ONA), and gaze angle were additionally measured with MRI. These parameters were compared between the two groups using 2-sample t-tests and chi-squared tests. Before and after post-methylprednisolone therapy, the MRI data of 20 eyes were obtained and compared with a paired t-test. Peripapillary retinal nerve fiber layer (RNFL) thickness was obtained using an optical coherence tomography (OCT) scan. Spearman rank correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curves were performed to evaluate the role of these factors in IOP changes. The EOM volume and axial and sagittal ONAs in the high-IOP group were significantly increased compared to the normal-IOP group (P<0.001, P=0.001, P=0.02, respectively). Logistic regression analysis indicate that the cutoff value for EOM volume for the diagnosis of high IOP was significantly larger than that of the other parameters except orbit volume (P=0.03, P=0.004, P=0.08, respectively). Spearman correlation analysis revealed a significant correlation between EOM volume and ON sheath diameter and average RNFL thickness (P=0.01, P=0.02, respectively). A paired t-test indicated a significant decrease of EOM volume and ON sheath diameter as well as a significant enlargement of the axial ONAs after methylprednisolone therapy (P=0.002, P=0.02, P=0.05, respectively). EOM volume was an effective diagnostic factor for tracking IOP changes and ON patterns in patients with TAO. Methylprednisolone therapy is recommended for patients with TAO with secondary glaucoma to quickly reduce the EOM volume.

Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy.

To evaluate the clinical significance of detecting serum IgG4 and the IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy (TAO) and to explore whether high serum IgG4 levels and the IgG4/IgG ratio are associated with the severity and activity of TAO, we retrospectively assessed the records of 78 TAO patients and 32 controls collected in our hospital from July 2020 to July 2022. The TAO patients were divided into TAO inactive and TAO active phase groups according to the clinical activity score (CAS), and we evaluated the association between the serum IgG4 levels, the IgG4/IgG ratio, and the clinical data of the participants. The levels of IgG4 significantly increased in the TAO active group compared to those in the inactive and control groups (P < 0.05). Additionally, the number of patients with increased IgG4 levels (≥135 mg/dL) in the TAO active group was markedly higher than that in the inactive and control groups (P < 0.05). The IgG4/IgG ratio was also significantly enhanced in the TAO active group compared to the inactive and control groups (P < 0.05). CAS was identified as an independent factor influencing IgG4 levels in patients with TAO. The levels of serum IgG4, as well as the IgG4/IgG ratio, were significantly increased in some patients with active TAO, and they were related to the CAS, suggesting that the pathogenesis of TAO may be heterogeneous.

Measurement of Sub-Foveal Choroidal Thickness in Hyperthyroid Patients with Thyroid Associated Ophthalmopathy, Using Spectral Domain OCT

Background Thyroid associated ophthalmopathy (TAO) is an auto-immune orbitopathy, associated with thyroid dysfunction. It results in compression of the orbital contents, impairment of the blood flow and thus affects the choroidal and retinal microstructure and function. Aim of the Work The purpose of this study is to measure the central choroidal thickness in active and inactive TAO using Optical Coherence Tomography (OCT) and compare it to the control group. Patients and Methods The cross section study was conducted on participants recruited from the ophthalmology clinic of the National Institute of Diabetes and Endocrinology (NIDE). The study included 160 eyes from 80 participants (40 hyperthyroidism patients and 40 control subjects). Data was collected during the period of December 2019 to June 2020. Results There was no significant difference regarding age, gender, vision and IOP between TAO patients (either active or inactive) and normal subjects. Our study showed that there was a significant increase in sub-foveal choroidal thickness in patients with TAO compared to the control group. It also showed a significant increase in sub-foveal choroidal thickness in the active subgroup more than the inactive subgroup. In addition, a decrease in central foveal thickness was found in patients with TAO compared to the control group, but there was no significant difference found between active and inactive subgroups. Conclusion The findings of this study suggest that there is a significant affection of sub-foveal choroidal thickness and central foveal thickness in thyroid-associated-ophthalmopathy (TAO) patients.

Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy.

Although previous neuroimaging evidence has confirmed the brain functional disturbances in thyroid-associated ophthalmopathy (TAO), the dynamic characteristics of brain activity and functional connectivity (FC) in TAO were rarely concerned. The present study aims to investigate the alterations of temporal variability of brain activity and FC in TAO using resting-state functional magnetic resonance imaging (rs-fMRI). Forty-seven TAO patients and 30 age-, gender-, education-, and handedness-matched healthy controls (HCs) were enrolled and underwent rs-fMRI scanning. The dynamic amplitude of low-frequency fluctuation (dALFF) was first calculated using a sliding window approach to characterize the temporal variability of brain activity. Based on the dALFF results, seed-based dynamic functional connectivity (dFC) analysis was performed to identify the temporal variability of efficient communication between brain regions in TAO. Additionally, correlations between dALFF and dFC and the clinical indicators were analyzed. Compared with HCs, TAO patients displayed decreased dALFF in the left superior occipital gyrus (SOG) and cuneus (CUN), while showing increased dALFF in the left triangular part of inferior frontal gyrus (IFGtriang), insula (INS), orbital part of inferior frontal gyrus (ORBinf), superior temporal gyrus (STG) and temporal pole of superior temporal gyrus (TPOsup). Furthermore, TAO patients exhibited decreased dFC between the left STG and the right middle occipital gyrus (MOG), as well as decreased dFC between the left TPOsup and the right calcarine fissure and surrounding cortex (CAL) and MOG. Correlation analyses showed that the altered dALFF in the left SOG/CUN was positively related to visual acuity (r = .409, p = .004), as well as the score of QoL for visual functioning (r = .375, p = .009). TAO patients developed abnormal temporal variability of brain activity in areas related to vision, emotion, and cognition, as well as reduced temporal variability of FC associated with vision deficits. These findings provided additional insights into the neurobiological mechanisms of TAO.

Abnormal regional spontaneous neural activity and functional connectivity in thyroid-associated ophthalmopathy patients with different activity: a resting-state fMRI study.

We aimed to evaluate the spontaneous neuronal activity and functional connectivity pattern variations using resting-state functional magnetic resonance imaging (rs-fMRI) measures, such as amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and functional connectivity (FC), in patients with thyroid-associated ophthalmopathy (TAO). A total of 24 active TAO patients, 26 inactive TAO patients, and 27 matched healthy controls (HCs) were included. First, ALFF and fALFF were used to detect local neural activity changes, the MRI data were analyzed, and regions with group differences were taken as seeds. Second, FC analysis was performed to explore the altered connection between seeds and other brain regions. A correlation analysis was performed to assess the relationship between functional brain activity and clinical indices and neuropsychiatric behaviors. Compared to HCs, both active and inactive TAO patients exhibited significantly lower ALFF values in the right calcarine (Calcarine_R) and left postcentral gyrus (Postcentral_L). Active TAO patients also showed significantly higher ALFF values in the left caudate nucleus (Caudate_L) and increased fALFF values in the superior lobe of the right cerebellum (Cerebelum_Crus1_R). Moreover, both active and inactive TAO patients demonstrated decreased FC within the left postcentral gyrus (Postcentral_L) compared to HCs. Additionally, active TAO patients exhibited lower FC compared to inactive TAO patients. The ALFF values in the Calcarine_R of active TAO patients positively correlated with disease duration (r = 0.5892, p = 0.0049) and the Hamilton Anxiety Rating Scale (HARS; r = 0.5377, p = 0.0119). Furthermore, the ALFF value in the Calcarine_R of inactive TAO patients negatively correlated with visual functioning (r = -0.5449, p = 0.0072), while the ALFF values in the Caudate_L of active TAO patients positively correlated with visual functioning (r = 0.6496, p = 0.0014). We found that the Caudate_L and Cerebelum_Crus1_R related to motor control and coordination in active TAO patients exhibit significant compensatory mechanisms; whereas, the Calcarine_R and Postcentral_L related to visual and somatosensory cortices show varying degrees of impairment. Our findings complement the functional neural mechanism of TAO.

T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy

ABSTRACT Background Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20–30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. Objectives To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. Design and methods Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. Results Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. Conclusions Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2.

The aim of this study was to investigate the microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMC) of thyroid-associated ophthalmopathy (TAO) patients and to explore the molecular mechanisms of MicroRNA-376b (miR-376b) in the pathogenesis of TAO. PBMCs from TAO patients and healthy controls were analyzed by miRNA microarray to screen for the significantly differentially expressed miRNAs. The miR-376b expression in PBMCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The downstream target of miR-376b was screened by online bioinformatics, and detected by qRT-PCR and Western blotting. Compared with normal controls, 26 miRNAs were significantly different in PBMCs of TAO patients (14 miRNAs were down-regulated and 12 miRNAs were up-regulated). Among them, miR-376b expression was significantly decreased in PBMCs from TAO patients compared to healthy controls. Spearman correlation analysis revealed that miR-376b expression in PBMCs was significantly negatively correlated with free triiodothyronine (FT3), and positively correlated with thyroid-stimulating hormone (TSH). MiR-376b expression was obviously reduced in 6T-CEM cells after triiodothyronine (T3) stimulation compared to controls. MiR-376b mimics significantly decreased hyaluronan synthase 2 (HAS2) protein expression and the mRNA expression of intercellular cell adhesion molecule-1 (ICAM1) and tumor necrosis factor-α (TNF-α) in 6T-CEM cells, whereas miR-376b inhibitors markedly elevated HAS2 protein expression and gene expression of ICAM1 and TNF-α. MiR-376b expression in PBMCs was significantly decreased in PBMCs from TAO patients compared with the healthy controls. MiR-376b, regulated by T3, could modulate the expression of HAS2 and inflammatory factors. We speculate that miR-376b may be involved in the pathogenesis of TAO patients by regulating the expression of HAS2 and inflammatory factors.

Botulinum Toxin Type A Injection for Correction of Upper Eyelid Retraction in Thyroid-Associated Ophthalmopathy.

Upper lid retraction (ULR) is the most common and earliest symptom in thyroid-associated ophthalmopathy (TAO) patients. Surgical correction is effective for ULR in stable diseases. However, non-invasive treatment is also required for the TAO patient in active phase. Here, we reported a complex case with TAO and unilateral ULR simultaneously. The patient had a history of progressive ptosis in the left eyelid and underwent anterior levator aponeurotic-Muller muscle resection to correct the ptosis. However, the patient gradually developed bilateral proptosis and ULR, mainly in the left eyelid. The patient was finally diagnosed with TAO with left ULR. Then, the patient was treated with botulinum toxin type A (BTX-A) injection in the left eyelid. The effect of BTX-A treatment started 7 days after injection, peaked at one month, and lasted for approximately 3 months. This study highlighted the therapeutic effect of BTX-A injection for the treatment of ULR-related TAO.

The outcomes of endoscopic orbital decompression combined with fat decompression for thyroid-associated ophthalmopathy

PurposeTo present the clinical features of thyroid-associated ophthalmopathy (TAO) with different CT types, and to report the outcomes of endoscopic orbital decompression combined with fat decompression (EOD-FD).Patients and methodsThirty-four patients with TAO who underwent EOD-FD between December 2020 and March 2022 in the Ophthalmology Department of Li Huili Hospital Affiliated with Ningbo University, were included in this retrospective interventional case series. Patients were categorized into two groups based on the results of computerized tomography (CT) scans: muscle expansion type and fat hyperplasia type.ResultsThirty-four TAO patients (55 eyes) were included in this study, and the mean age was 38.62 years (range 22–60 years). The average eye protrusion (EP) reduced from preoperative 23.20 mm to postoperative 19.66 mm (p < 0.0001). Mean intraocular pressure (IOP) decreased from 20.11 mmHg at baseline to 17.29 mmHg postoperatively (p < 0.0001), with a reduction of 2.84 mmHg (14.12%). Twenty cases of muscle expansion and fourteen cases of fat hyperplasia were definite by CT imaging. The mean IOP in the muscle expansion group was higher than that in the fat hyperplasia group (p < 0.05). Elevated intraocular pressure (IOP) occurred in 23 eyes (36.11%), and it was associated with extraocular muscle involvement, gender, and EP. In 3 cases of impaired vision, the mean best corrected visual acuity (VA) improved from 0.4 preoperatively to 0.84 postoperatively (p < 0.01). There were 8 cases with visual field (VF) damage and/or corneal epithelium damage, and all these damages were reversible.ConclusionIn this study, we describe the clinical features and experience of EOD-FD in patients with TAO. EOD-FD is an effective technique in reducing IOP and proptosis, with a low incidence of postoperative diplopia.

Decreased macular choriocapillaris in thyroid-associated ophthalmopathy: focusing on chorioretinal folds with and without optic disc edema.

The aim of this study was to evaluate the vessel density (VD) of the macular choriocapillaris (CC) and retina in thyroid-associated ophthalmopathy (TAO) patients with chorioretinal folds (CRFs) with and without optic disc edema (ODE) and the correlations of these characteristics with visual function. This was a cross-sectional study. Twenty TAO patients with CRFs (35 eyes) and 20 normal subjects (normal group, 40 eyes) were recruited at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from March 2018 to October 2022. Then, CRF patients were divided into two groups, the ODE and non-ODE groups (NODE), based on the presence or absence of ODE. All the patients underwent optical coherence tomography angiography (OCTA) and the VD of the macular CC and retina was computed. The correlation of VD and visual function was analyzed. Compared with the normal group, the macular whole-image VD in the retinal superficial layer (SLR-mwiVD: 49.82 ± 3.38 in the normal group, 42.44 ± 5.40 in the NODE group, and 42.51 ± 5.37 in the ODE group), deep layer (DLR-mwiVD: 51.05 ± 6.23 in the normal group, 45.71 ± 6.66 in the NODE group, and 46.31 ± 5.48 in the ODE group), and CC (CC-mwiVD: 70.23 ± 2.47 in the normal group, 68.04 ± 3.73 in the NODE group, and 63.09 ± 6.51 in the ODE group) was decreased in the NODE (all p < 0.05) and ODE group (all p < 0.01). There was no difference in these parameters except CC-mwiVD between the ODE and NODE groups. The CC-mwiVD in the ODE group (63.09 ± 6.51) was significantly reduced compared with that in the NODE group (68.04 ± 3.73, p = 0.004). All these VD parameters were negatively correlated with BCVA, VF-PSD, and P100 latency and positively associated with VF-MD, P100 amplitude, and HRR scores (all p < 0.05). There was a significant decrease in the VD of the macular CC and retina of patients with CRFs with or without ODE, which was correlated with visual dysfunction. The VD of the macular CC in CRF patients with ODE was significantly reduced compared with that in the NODE group, but similar results were not observed in the retina.

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.

Therapeutic outcomes of mycophenolate mofetil and glucocorticoid in thyroid-associated ophthalmopathy patients.

To analyze the efficacy of mycophenolate mofetil (MMF) and glucocorticoid administration in patients with thyroid-associated ophthalmopathy (TAO). Sixty patients with moderate to severe TAO treated in Jingzhou Central Hospital from January 2022 to June 2022 were selected and enrtolled in this study. The subjects were divided into experimental group (n=30) and control group (n=30) based on the random number table method. Glucocorticoid pulse therapy was provided in the control group, while MMF was given in the experimental group on the basis of Control group. Clinical activity score (CAS), quality of life (QOL), visual acuity, eyelid fissure width, intraocular pressure, and degree of exophthalmos were observed at the time of admission and at the 12th week and 24th post-treatment weeks. We compared the immune function (TRAb, IL-6, and CD4+/CD8+) of the two groups pre-treatment and 24 weeks post-treatment, and evaluated the clinical therapeutic effect. The clinical effective rates at 12 and 24 weeks in the experimental group were higher (73.3% and 83.3%) than those in the control group (46.7% and 60.0%) (P <0.05). After 12 weeks of treatment, patients' CAS scores, and bilateral lid fissure width decreased and right eye visual acuity increased in the control group compared with those before treatment (P < 0.05); further, after 24 weeks of treatment, patients' QOL scores and bilateral visual acuity increased and CAS scores, bilateral lid fissure width and proptosis decreased compared with those before treatment, and patients' QOL scores, CAS scores and bilateral proptosis improved more than those at 12 weeks of treatment (P <0.05). Additionally, greater improvements were observed in the patients' QOL and CAS scores, and proptosis after 24-week treatment than after 12-week treatment (P<0.05). In the experimental group, the QOL score and binocular visual acuity increased, whereas the CAS score, intraocular pressure, lid width, and proptosis decreased after 12 weeks of treatment as compared to the values of these parameters in the pre-treatment period (P < 0.05); after 24 weeks of treatment, greater improvements were established in the ocular-related indexes improved compared to the pre-treatment period and after 12 weeks of treatment (P < 0.05). After 12 weeks of treatment, the patients in the experimental group had more considerable improvements in the right visual acuity, right intraocular pressure, and left lid fissure width than the control group (P < 0.05); at 24 weeks of treatment, patients in the experimental group had greater improvements in the QOL score, bilateral visual acuity, intraocular pressure, bilateral lid fissure width, and bilateral proptosis than the control group (P < 0.05). No significant differences were found in the values of TRAb, IL-6, and CD4+/CD8+ between the two groups before treatment (P>0.05); the values of TRAb, IL-6, and CD4+/CD8+ in the experimental group was significantly lower than those before treatment and in the control group after 24weeks of treatment. (P>0.05). No statistically significant difference was observed in the incidence of liver damage and menstrual disorders between the two groups during the 24 weeks of treatment (P>0.05). The combination of oral MMF and glucocorticoid shock therapy is an effective drug for the treatment of patients with moderately active TAO.