Activity Of Thyroid-associated Ophthalmopathy Research Articles

T2 Relaxation Time in Extraocular Muscles of Patients with Mild Thyroid- Associated Ophthalmopathy: Comparing T2 Mapping With and Without Fat Suppression Using Different Measurement Methods.

This study aimed to compare the parametric value of T2 with and without fat suppression (FS) on T2 mapping for the evaluation of extraocular muscles (EOMs) in mild thyroid-associated ophthalmopathy (TAO). We prospectively recruited 44 consecutive patients with mild TAO seen between May 2020 and October 2022 and 26 healthy controls with no history of eye- or thyroid-related or other autoimmune diseases. Patients with mild TAO were subdivided into active and inactive groups based on their clinical activity scores. The T2 of each EOM was measured over a large and small area of interest on T2-mapping images with and without FS. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of T2 for detecting TAO activity. The T2 was significantly and heterogeneously higher in the active group than in the inactive and control groups (P < 0.05). FS-T2-mapping images had better signal display within and at the edges of the EOMs than those without FS. It was possible to observe high-signal aggregation visible in the periphery of some EOMs, and the central part showed relatively low signals. The maximum T2 measured in small or large areas with and without FS had good diagnostic efficacy for TAO activity, with that of no-FS being better (the area under the ROC curve of the maximum T2 measured in a small area and a large area without FS was 1.0 and 1.0 and P values of < 0.001 and < 0.001, respectively). Maximal T2 with or without FS can facilitate the early clinical detection of mild TAO activity. The maximum T2 in a small area can facilitate active staging of patients with mild TAO.

An ensemble deep learning diagnostic system for determining Clinical Activity Scores in thyroid-associated ophthalmopathy: integrating multi-view multimodal images from anterior segment slit-lamp photographs and facial images.

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. 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. 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. 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.

Correlation between choroidal vascularity and retrobulbar ocular blood flow changes and thyroid-associated ophthalmopathy activity: a cross-sectional study

ObjectiveTo evaluate the alterations in retrobulbar color Doppler imaging (CDI) parameters and retinal/choroidal optical coherence tomography angiography (OCTA) parameters and their association with the clinical activity and severity in thyroid-associated orbitopathy (TAO) patients.MethodsIn this study, the retrobulbar flow parameters including resistance index (RI), Pulsatile Index(PI), peak systolic velocity (PSV) and end diastolic velocity (EDV) in posterior ciliary artery (PCA), central retinal artery (CRA) and ophthalmic artery (OA) were determined by CDI. Moreover, the retina and choroidal vascularity including the superficial vessel density (SVD), deep vessel density (DVD), choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were determined by OCTA. All patients grouped as active TAO and inactive TAO based on Clinical activity score (CAS). We picked the severe eye among the subjects and compared all parameters between two groups. We analyzed the correlations among those parameters.ResultsThere was a significant difference in CAS score, proptosis value, ChT, LA, CVI between patients with active TAO and inactive TAO. In the active group, PSV and EDV of PCA were significantly higher than the inactive group. On logistic regression analysis, CAS was closely associated with PSV-PCA. On multiple linear regression, proptosis value was closely associated with ChT, LA, SA and CVI.ConclusionChoroidal vascularization and retrobulbar blood flow were concurrently higher in active TAO patients and several variables in choroid circulation was closely related to TAO clinical features.

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.

Image quality and evaluation ability of magnetic resonance imaging techniques for thyroid-associated ophthalmopathy: Dixon fat-suppression technique vs. spectral attenuated inversion recovery.

We aimed to compare two magnetic resonance imaging (MRI) techniques, Dixon and spectral attenuated inversion recovery (SPAIR) fat-suppression, in terms of image quality and suitability for evaluating thyroid-associated ophthalmopathy (TAO) lesion characteristics. This cross-sectional, retrospective study involved 70 patients with TAO (140 eyes) who underwent orbital coronal MRI examinations, including Dixon-transverse relaxation (T2)-weighted imaging (T2WI) and SPAIR-T2WI, between 2020 and 2022. We compared the fat-suppression quality and artifacts, noise (N), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal intensity ratio (SIR) of extraocular muscles (SIR-EOM) and lacrimal glands (SIR-LG), and TAO activity evaluation efficiency. Dixon-T2WI showed a higher frequency of better subjective image quality and suitability for evaluating the characteristics of TAO lesions (65.7% vs. 14.3%) than SPAIR-T2WI. Fat-suppression quality and artifact scores were lower for Dixon-T2WI than for SPAIR-T2WI (p < 0.001). The N, SNR, and CNR values, EOM-SIR, and LG-SIR were higher for orbital coronal Dixon-T2WI than for SPAIR-T2WI (all p < 0.001). Clinical activity scores (CASs) showed positive correlations with SIR. The correlation between EOM-SIR and LG-SIR of orbital coronal Dixon-T2WI with CAS was higher than that of SPAIR-T2WI (0.590 vs. 0.493, all p < 0.001; 0.340 vs. 0.295, all p < 0.01). EOM-SIR and LG-SIR of Dixon-T2WI yielded a higher area under the curve than SPAIR-T2WI for evaluating TAO activity (0.865 vs. 0.760, p < 0.001; 0.695 vs. 0.617, p = 0.017). Dixon-T2WI yields higher image quality than SPAIR-T2WI. Furthermore, it has a stronger ability to evaluate TAO inflammation than SPAIR, with higher sensitivity and specificity in active TAO staging.

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.

Turbo Gradient and Spin-Echo BLADE-DWI for Extraocular Muscles in Thyroid-Associated Ophthalmopathy

Purpose: To investigate feasibility and diagnostic performance of turbo gradient and spin-echo BLADE (proprietary name for Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction [PROPELLER] in Siemens MR systems)-diffusion weighted imaging (TGSE-BLADE-DWI) for depicting extraocular muscle (EOM) involvement and activity in thyroid-associated ophthalmopathy (TAO), and to compare TGSE-BLADE-DWI with readout-segmented echo-planar imaging (RESOLVE). Materials and methods: Thirty-five patients with identified TAO underwent the two DWI scans. Two radiologists visually scored the image quality of the two DWIs with respect to the susceptibility artifacts and geometric distortions on a three-point scale. The maximum size (Sizemax) of EOMs and corresponding ADCs (cADCs) of each patient were compared between the active and inactive phases. The clinical activity score (CAS) was used as a reference to assess the diagnostic performance of EOM ADCs for grading TAO activity. ROC analysis, Pearson correlation, and Wilcoxon signed-rank test were used for statistical analyses. Results: For scores of EOMs, the image quality of TGSE-BLADE-DWI was significantly higher than that of RESOLVE. There were no statistically significant differences between the AUCs of the two DWIs, Sizemax, or cADCs between the active and inactive phases. TGSE-BLADE-DWI ADCs were significantly higher than the RESOLVE ADCs in the right superior rectus, right lateral rectus, left superior rectus, and left inferior rectus. There were no statistically significant correlations between the cADC or Sizemax, and CAS. The highest AUC was 0.697 for RESOLVE and 0.657 for TGSE-BLADE-DWI. The best performing ADC threshold was 1.85 × 10-3 mm2/s with 85.7% sensitivity, 58.8% specificity and 66.67% accuracy for RESOLVE and 1.99 × 10-3 mm2/s with 79.0% sensitivity, and 55.6% specificity and 65.27% accuracy for TGSE-BLADE-DWI. Conclusion: Compared to RESOLVE, TGSE-BLADE-DWI provided improved image quality with fewer susceptibility artifacts and geometric distortions for EOM visualization and showed an equivalent performance in detecting active TAO.

Fibulin-1: a novel biomarker for predicting disease activity of the thyroid-associated ophthalmopathy.

This study was designed to investigate the association between fibulin-1(FBLN1) and thyroid-associated ophthalmopathy (TAO). The plasma FBLN1 levels were measured in 80 participants, including 30 active TAO patients, 25 inactive TAO patients, and 25 Graves disease (GD) patients without TAO using enzyme-linked immunosorbent assay (ELISA). TAO patients had significantly higher TRAb level than GD patients (p < 0.05). The active TAO patients consumed more tobacco and had higher CAS than inactive TAO patients (all p < 0.05). No significant differences were found in age, sex, and the level of FT3, FT4, and TSH between TAO and GD patients, and between the active and inactive TAO patients (all p > 0.05). The plasma FBLN1 level in TAO patients was higher than that in GD patients, and that in active patients was higher than that in inactive patients (all p < 0.05). Furthermore, the plasma FBLN1 level showed strong association with clinical activity score (CAS) of TAO (r = 0.67, p < 0.01). By receiver operator characteristic (ROC) curve analysis, FBLN1 demonstrated good efficiency for predicting disease activity at the cut-off value > 625.33 pg/ml with a sensitivity of 93.3% and a specificity of 88.0% (AUC:0.92, p < 0.01). The plasma FBLN1 levels correlated with TAO activity and a value >625.33 pg/ml was associated with active disease. Our results suggest that the plasma FBLN1 level could be a novel biomarker for predicting disease activity of TAO.

Detection and Correlation Analysis of Serum Uric Acid in Patients with Thyroid-Associated Ophthalmopathy.

Purpose To probe the property of serum uric acid in evaluating the activity of patients with thyroid-associated ophthalmopathy. Methods A total of 443 patients with TAO admitted to our hospital from March 2016 to February 2021 were selected for the observation group. Simultaneously, 443 healthy subjects were selected for the control group. The observation group was divided into the active group (n = 254) and the inactive group (n = 189) according to the clinical activity score (CAS). Besides, the patients were divided into mild group (n = 201), moderate severe group (n = 133) and extremely severe group (n = 109) based on the severity of TAO. Serum uric acid, free triiodothyronine (FT3), free thyroid hormone (FT4), thyrotropin stimulating hormone (TSH) and glycosylated hemoglobin (HbA1c) levels were detected and analyzed in each group. Results Serum UA, FT3, FT4, TSH and HbA1c in the active group were significantly enhanced than those in the other two groups (P < 0.05), and there was no significant difference between the inactive group and the control group (P > 0.05). In different disease severity groups, the serum UA level of patients in the active group was significantly promoted than that in the inactive group and control group (P < 0.05) and was decreased successively in extremely severe group, moderate severe group and mild group, with statistical significance (P < 0.05). Pearson's analysis showed that UA was positively correlated with FT3, FT4, and HbA1c (r = 0.652, P = 0.031; r = 0.571, P = 0.042; r = 0.737, P = 0.024), while was reversely correlated with TSH level (r = −0.137, P = 0.262). There was no correlation between UA and FT3, FT4, and HbA1c levels in the inactive group. UA detection showed the average sensitivity and specificity of TAO activity were 94.3% and 85.2%, respectively. There was no significant correlation between the severity of disease and serum UA in inactive patients (P = 0.135). There was a positive correlation between the severity of disease and serum UA in active patients (P = 0.005). Conclusion UA may be used as a laboratory indicator for quantitative clinical diagnosis of thyroid-associated ophthalmopathy (TAO) and as a parameter for the presence of TAO activity.

Bone marrow fibrocytes: villain or white knight in thyroid-associated ophthalmopathy?

We attempt to provide an historical perspective on progress made in understanding the pathogenesis of thyroid-associated ophthalmopathy (TAO), focusing on the roles of orbital fibroblasts (OF) in the diseased orbit (termed GD-OF) and how these cells differ from those residing in the healthy orbit. GD-OF comprise both residential OF and those apparently derived from CD34 + fibrocytes. CD34 + fibrocytes of the monocyte lineage putatively traffic to the TAO orbit from bone marrow. We believe that these fibroblastic cell populations dictate the activity and severity of TAO. Their impact on disease may be moderated by Slit2, a neuron axon guidance repellent synthesized by and released from residential CD34 - OF. Approximately 50% of patients with GD develop clinically meaningful TAO. Relatively few require systemic medical and surgical therapies, while milder disease can be managed with conservative, local care. Determining the intrinsic properties of GD-OF and their expression of Slit2 may explain why some patients with GD develop severe, vision-threatening TAO while others virtually escape any of its manifestations. Such insights should allow for improved and better-tolerated therapies. Identifying unique characteristics of fibrocytes and GD-OF subsets reveals their apparent roles in tissue activation, inflammation, and remodeling associated with TAO. Better understanding of these cells, their origins, behavior, and factors modulating their activities remains necessary for the development of more targeted, effective, and safe treatments.

Alterations in Spontaneous Neuronal Activity and Microvascular Density of the Optic Nerve Head in Active Thyroid-Associated Ophthalmopathy.

PurposeTo investigate changes in local spontaneous brain activity in patients with active thyroid-associated ophthalmopathy (TAO) and explore the relationship between such alterations and microvascular indices.MethodsThirty-six active TAO patients with active phase and 39 healthy controls (HCs) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI), neuropsychological tests, and ophthalmological examinations. The rs-fMRI-based fractional low-frequency fluctuation amplitude (fALFF) analysis methods were used to assess spontaneous brain activity in both groups. The structure (peripapillary retinal nerve fiber layer, pRNFL) and microvascular indices (the optic nerve head (ONH) whole image vessel density, ONH-wiVD, and peripapillary vessel density) were analyzed through optical coherence tomographic angiography imaging. The relationship between abnormal spontaneous brain activity and ophthalmological indices was analyzed using the Spearman’s rank correlation analysis.ResultsCompared with HCs, active TAO patients had increased fALFF in the right inferior temporal gyrus (R.ITG) and left posterior cingulate gyrus (L.PCC), but decreased fALFF in the right calcarine (R.CAL). The fALFF values in L.PCC were positively correlated with peripapillary vessel density, whereas fALFF values in R.CAL were negatively related to peripapillary vessel density.ConclusionsThis study demonstrates that changes in spontaneous brain activity of active TAO are accompanied by peripapillary microvascular variations. These results provide insights into the pathophysiological mechanisms of active TAO. In addition, the combination of fALFF values and peripapillary vessel density may be served as important references for better clinical decision making.

Multiparametric magnetic resonance imaging for differentiating active from inactive thyroid-associated ophthalmopathy: Added value from magnetization transfer imaging

PurposeTo investigate the feasibility of using magnetization transfer (MT) magnetic resonance imaging for evaluating patients with thyroid-associated ophthalmopathy (TAO), and determine its added value for differentiating active from inactive TAO and predicting clinical activity score (CAS), compared with conventional fat-saturated T2-weighted and diffusion-weighted imaging. MethodsOrbital MT, fat-saturated T2-weighted, and diffusion-weighted imaging of 60 prospectively enrolled consecutive patients with TAO was analyzed. Simplified histogram parameters (mean, max, min) of magnetization transfer ratio (MTR), signal intensity ratio (SIR), and apparent diffusion coefficient (ADC) at extraocular muscles were calculated for each orbit and compared between the active and inactive groups. ResultsIntraclass correlation coefficients of MTRs and SIRs were similar (0.802–0.963 vs 0.812–0.974, respectively), followed by those of ADCs (0.714–0.855). Patients with active TAO showed significantly lower MTRs and higher SIRs and ADCs than those with inactive TAO (P < 0.05). MTRmean achieved the highest area under the curve (AUC) of 0.868 for differentiating active from inactive group, followed by SIRmax (AUC, 0.836). MTRmean also demonstrated a higher and negative correlation with CAS (r = –0.614, P < 0.001) than MTRmax and MTRmin (r = –0.495, P < 0.001; r = –0.243, P = 0.007; respectively). Support vector machine-based analysis revealed that uniting MTRs could prosper concurrently added performance for disease activity differentiation and CAS prediction, compared with merely combining SIRs and ADCs (AUC, 0.933 vs 0.901; r = 0.703 vs. 0.673). ConclusionsMT imaging could potentially be used as a noninvasive method for differentiating the activity of TAO and predicting CAS, thereby offering added value to conventional SIR and ADC.

Correlation between Peripheral T Cell Subsets and the Activity of Thyroid-Associated Ophthalmopathy.

Introduction Thyroid-associated ophthalmopathy (TAO) is the most common orbital immunological disease in adults. T cells play an important role in the pathogenesis of TAO. However, our knowledge of the circulating T cell subsets in TAO is limited. Objective To investigate the circulating T cell subsets in TAO and the correlations between them and the activity of TAO. Methods Thirty-eight TAO patients (19 active and 19 nonactive) were enrolled. The absolute number and percentage of total lymphocytes, CD3+T cells, CD4+T cells, CD8+ T cells, CD3+CD4-CD8-T cells (DNT cells), and CD3+CD4+CD8+ T cells (DPT cells) in peripheral blood were measured by flow cytometer. Results TAO patients were divided into the active group and the nonactive group by the clinical activity score (CAS). The mean CAS was 4 ± 1.11 in the active group and 1.47 ± 0.61 in the nonactive group. No statistical differences were found in gender, age, and the levels of FT3, FT4, TSH, and TRAb between the two groups. The percentage of DNT cells was lower in the active group than in the non-active group, and it was negatively correlated with CAS (r = −0.349, P=0.032), but not the absolute number. The CD4/CD8 ratio, the absolute number and percentage of CD3+ T cells, CD4+ T cells, CD8+ T cells, and DPT cells did not differ between the two groups. ConclusionIn the present study, we found the percentage of DNT cells was significantly lesser in the active TAO than in the nonactive TAO, and it was negatively correlated with the activity of the TAO. It suggests that DNT cells may involve in the immunopathogenesis of TAO and can serve as a clinical biomarker of the disease activity.

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

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

Quantitative evaluation of activity of thyroid-associated Ophthalmopathy using short-tau inversion recovery (STIR) sequence

ObjectiveQuantitatively staging TAO using MRI remains limited. Our study aims to identify the cut-off signal intensity value for staging TAO using STIR sequence scan.MethodsBetween June 2018 and July 2020, a number of 51 patients with TAO (102 eyes) and 19 volunteer controls (38 eyes) were recruited. The clinical and biochemical parameters were measured in each patient. Disease activity was diagnosed based on the Clinical Activity Score (CAS). The signal intensities of extraocular muscles were scanned using short-tau inversion recovery (STIR) sequences from MRI.ResultsCompared to the inactive TAO patients and the controls, the signal intensity ratios (SIRs) of the superior rectus, inferior rectus, medial rectus, lateral rectus on STIR images were significantly increased in the active TAO patients. After adjustment for age and smokers, the SIRs of four extraocular muscles showed strong associations with CAS. By receiver operator characteristic (ROC) curve analysis, all four muscle SIRs demonstrated good efficiency for predicting disease activity [area under curve (AUC) 0.75–0.83, all P < 0.01]. The identified cut-off SIR values were further validated in a new group of TAO patients (30 eyes) enrolled between September 2020 and January 2021. The cut-off SIR value of > 2.9 in the inferior rectus showed optimal diagnostic value for staging the active TAO.Conclusionsthe signal intensity of extraocular muscles on STIR sequence was a good predictor for TAO activity. A cut-off SIR value of > 2.9 in the inferior rectus could be applied to evaluate the active stage of TAO.

The application of 99Tcm-DTPA orbital SPECT/CT in staging evaluation of thyroid associated ophthalmopathy

Objective: To explore the application value of 99Tcm-diethylenetriaminepentaacetic acid (DTPA) orbital single photon emission computed tomography/computed tomography (SPECT/CT) in staging evaluation of thyroid associated ophthalmopathy (TAO). Methods: A case-control study. A total of 40 patients with binocular TAO were recruited from May 2019 to December 2019 in the Second Hospital of Dalian Medical University. According to the clinical activity score (CAS) standard, 40 TAO patients were divided into the active group (15 cases) and the inactive group (25 cases), and 10 healthy volunteers were recruited as the control group. All subjects underwent 99Tcm-DTPA orbital SPECT/CT examination, and each subject's CAS, reading results and maximum standardized uptake value (SUVmax) were recorded. The Kruskal-Walis H test was used for the CAS comparison among the three groups. The analysis of variance was used for the SUVmax comparison among the three groups. The comparison between CAS and SUVmax before and after treatment was performed by paired samples Wilcoxon signed rank test and paired-sample t test, and Spearman correlation analysis was performed between SUVmax and CAS. The Kappa test was used to check the consistency between the reading result and CAS's judgment of TAO activity. The receiver operating characteristic curve was used to analyze the diagnostic value of the reading results and SUVmax for TAO. Results: The age difference among the three groups was not statistically significant, and the gender difference was not statistically significant (all P>0.05). The difference in CAS among the three groups was statistically significant (H=39.894; P<0.01). Patients with active TAO showed abnormal concentration and enhancement of nuclides in the orbital tissue, and the uptake of radionuclides was significantly increased, while patients with inactive TAO had a slight increase, and healthy volunteers had no significant or only mild uptake. The SUVmax of the active group (2.24±0.47) was highest, and that of the inactive group (1.57±0.43) was higher than the healthy control group (0.67±0.22). After pairwise comparison, there were statistical differences between groups (all P<0.05). According to Spearman correlation analysis, the SUVmax of all TAO patients was linearly, positively correlated with their CAS (r=0.753; P<0.05). In assessing the clinical activity of TAO, the reading results were consistent with CAS (Kappa value=0.737; P<0.05). Taking the reading results as the standard, the area under the receiver operating characteristic curve (AUC) of SUVmax was 0.992, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 86.70% and a specificity of 76.00%. Taking CAS results as the standard, the AUC of SUVmax was 0.853, and the threshold of SUVmax to distinguish between active and inactive periods was 1.850, with a sensitivity of 100.00% and a specificity of 87.50%. Five patients had inconsistent SUVmax and CAS. The CAS was ≥3, but the orbits did not show any inflammatory lesions in two of them; the CAS was<3, but the orbits showed inflammatory lesions in three of them. Thirteen active TAO patients with 99Tcm-DTPA orbital SPECT/CT showing significant accumulation of nuclides were given hormone shock therapy 12 times. After treatment, the CAS 2.00 (2.00) was lower than the pre-treatment 3.00 (1.50) score, and the difference was statistically significant (Z=-3.100, P<0.01). The SUVmax after treatment (1.60±0.20) was lower than the pre-treatment value (2.17±0.34), and the difference was statistically significant (t=10.197, P<0.01). Conclusion: 99Tcm-DTPA orbital SPECT/CT can relatively accurately determine the state of orbital inflammation in patients with TAO, and can be used as a useful supplement to evaluate the clinical activity of TAO, helping to guide clinical treatment. (Chin J Ophthalmol, 2021, 57: 830-836).

Evaluation of extraocular muscles in patients with thyroid associated ophthalmopathy using apparent diffusion coefficient measured by magnetic resonance imaging before and after radiation therapy.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease characterized by edema of extraocular muscles (EOMs). To characterize the inflammation of EOMs in patients with TAO before and after radiation therapy using apparent diffusion coefficient (ADC) and to analyze the correlation between ADC and clinical activity of TAO. The ADCs of superior rectus (SR), inferior rectus (IR), medial rectus (MR), and lateral rectus (LR) muscles were measured in 52 eyes of 26 patients with TAO before and three months after orbital radiation therapy. In addition, 38 eyes of 20 healthy volunteers were included. The clinical activity score (CAS) was evaluated. The ADC maps were reconstructed and measured on the coronal diffusion-weighted imaging (DWI) sequence and calculated in mm2/s. The mean ADCs of EOMs before treatment were 1.42 ± 0.23 in SR, 1.37 ± 0.23 in IR, 1.41 ± 0.21 in MR, and 1.28 ± 0.25 in LR. The mean ADCs after treatment were 1.27 ± 0.18, 1.22 ± 0.26, 1.30 ± 0.22, and 1.15 ± 0.21, respectively. The ADCs were significantly decreased after treatment (all P < 0.001). The ADCs of patients with TAO were significantly higher than those of controls. There was a statistically significant correlation between the mean ADCs and the CAS in each patient with TAO both before and after treatment (before: r = 0.520; P < 0.001; after: r = 0.625; P < 0.001). The ADC values of EOMs can be exploited as a quantitative indicator to evaluate the clinical activity and monitor the therapeutic responses of patients with TAO.

Detection of active and inactive phases of thyroid-associated ophthalmopathy using deep convolutional neural network

BackgroundThis study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations.MethodsA total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People’s Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks.ResultsNetwork A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021).ConclusionsThe deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.

Comparison of two regimens for patients with thyroid‑associated ophthalmopathy receiving intravenous methyl prednisolone: A single center prospective randomized trial

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.

The characteristics and clinical significance of serum TRAb IgG subtype in patients with thyroid associated ophthalmopathy

Objective To explore the distribution of serum TRAb IgG subtypes in patients with thyroid-associated ophthalmopathy(TAO) at different stages and its value in assessing TAO activity. Methods Forty-three patients with TAO, 30 patients with Graves′ disease (GD group), 19 patients with Hashimoto′s thyroiditis (HT group), and 50 healthy subjects (NC group)admitted to the First Affiliated Hospital of Zhengzhou University were collected from August 2018 to February 2019. According to the clinical activity score (CAS), the patients with TAO were further divided into the active period group (AP group, CAS≥3 points, 22 cases) and the inactive period group (IP group, CAS<3 points, 21 cases). The basic clinical data of subjects in each group were collected. The serum concentrations of FT3, FT4, TSH, thyroperoxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid-stimulating hormone receptor antibody (TRAb) were detected by chemiluminescence immunoassay and the binding rate in percentage (B) of serum TRAb IgG and IgG subtypes were detected by ELISA. The positive rate in each group and relative content of positive samples were compared. Results (1)Compared with HT group, the positive rates of IgG1 and IgG2 in TAO group and GD group were significantly decreased (P 0.05). (2)Compared with the IP group, IgG1(B) and the positive rates of IgG1 in the AP group were increased while IgG4(B) and the relative contents of IgG4 were reduced (P<0.05). (3)IgG1(B)was positively correlated with TAO activity (B=6.190, P=0.007), and higher IgG4(B)indicated more inclinations to the inactive period (B=-16.390, P=0.052). (4) The area under the curve of receiver operating characteristic (ROC) for TAO developing into active period assessed by activity rate was 0.859 (95%CI 0.746-0.973, P<0.05). When the activity rate was 4.29, the Jordon index showed the largest, with sensitivity of 81.8% and specificity of 81.0%. Conclusions Elevated levels of TRAb IgG1 in the patients with TAO indicate a tendency to active period, while elevated levels of TRAb IgG4 indicate a tendency to inactive period. The activity rate can provide a reference for assessing whether TAO is active or not. Key words: Thyroid-associated ophthalmopathy; IgG subtype; Clinical activity score