Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

Interrater reliability of photographic assessment of thyroid eye disease using the VISA classification.

PURPOSE: To determine the interrater reliability (IRR) of thyroid eye disease (TED) photographic assessment using the VISA classification. To assess whether a VISA grading atlas improves ophthalmology trainees' performance in photographic assessment of TED. METHODS: A prospective, partially randomized, international study conducted from September 2021 to May 2022. Online study invitation was emailed to a volunteer sample group of 68 ophthalmology college accredited consultants and trainees, and 6 were excluded from the study. Participants were asked to score 10 patient photographs of TED using only the inflammation and motility restriction components of the VISA classification. IRR was compared between groups of practitioners by their level of experience. A clinical activity grading atlas was randomized to 50% of the ophthalmology trainees. RESULTS: Overall rater ICC was 0.96 for inflammation and 0.99 for motility restriction. No statistically significant difference in IRR between rater groups was identified. Trainees with a grading atlas had the highest IRR for inflammation (ICC = 0.95). Each subcomponent of the inflammation and motility restriction components of VISA classification had an ICC considered good to excellent. The mean overall rater score was 4.6/9 for inflammation and 3.5/12 for motility restriction. For motility restriction there was a reduced mean score variance among all raters when scoring photographs with more severe motility restriction. CONCLUSION: IRR using the inflammation and motility restriction components of the VISA classification was excellent. A VISA grading atlas improved trainee performance in grading inflammation.

Assessment of risk of obstructive sleep apnea with thyroid eye disease and its activity.

PURPOSE: To evaluate the association between obstructive sleep apnea (OSA) and thyroid eye disease (TED) and its effect on disease activity. METHODS: A prospective case-control study was conducted from January 2020 to March 2022. All TED patients (group A) were clinically evaluated. The activity of thyroid eye disease was calculated based on the clinical activity score (CAS), and grading of severity was done according to the EUGOGO classification. All TED patients (group A) were screened for OSA using the Snoring Tired Observed Pressure (STOP)-Bang survey. Age- and gender-matched control group patients (group B) without TED were screened for OSA. RESULTS: One hundred TED patients and 138 control patients without TED were included in the respective groups. Sixty-two (62%) patients in group A and 48 (34.78%) patients in group B were having high risk of OSA, and this difference was statistically significant (P = 0.001). Further, in group A patients, on univariate analysis, TED activity was significantly associated with a high risk of OSA (P = 0.009). On multivariate logistic regression analysis, OSA also showed significant association with TED activity (odds ratio [OR]: 4.14, 95% confidence interval [CI]: 1.11-18.85 at 10% level; P = 0.05). CONCLUSION: Our study showed that OSA is significantly associated with TED disease and its activity. However, no significant association was found between OSA and severity of the disease.

Assessment of retinal and choroidal vessel density and nerve fibre layer thickness changes after orbitotomy in patients with severe non-active thyroid orbitopathy: a prospective study.

PURPOSE: To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression. METHODS: Eighteen patients (25 eyes) with severe not active not compressive (NANC) TED who were candidates for decompression surgery for cosmetic reasons were included in this study, and a 3 × 3 mm macular scan was used to measure vessel density and RNFL thickness. Whole macular vessel density in its superficial, deep and choriocapillaris layers was evaluated. The following data were extracted for each of layers: superior and inferior hemispheres, fovea, parafoveal vessel density, its superior and inferior hemispheres, and temporal, superior, nasal and inferior quadrant. RESULTS: The mean RPC increased postoperatively, which was statistically significant in small vessels of peripapillary area (p-value = 0.045). The mean RNFL thickness decreased after surgery and it was statistically significant in the peripapillary (p-value = 0.032) and Inferior-Hemifield area (p-value = 0.036). The choriocapillaris changes were significant in Superior-Hemifield (p-value = 0.031) and Fovea (p-value = 0.03). CONCLUSION: Thyroid-associated orbitopathy patients have a tendency to decrease vascular density and correlated with disease activity more than stage of orbitopathy. There was not a strong and even discrepant result in linkage of RNFL thickness and other optic nerve function tests and TED patient status and it is needed to do studies with more epidemiologic power and same methodology of study to be more comparable.

Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Computer aided volumetric assessment of orbital structures in patients with Graves' orbitopathy: correlation with serum thyroid antiperoxidase antibodies and disease activity.

INTRODUCTION: Graves' disease is an autoimmune disorder. Goiter and Graves' orbitopathy are frequently seen clinically. It would be helpful for the diagnosis, grading, prognosis, and treatment of this condition if it was possible to find serum biomarkers to establish a connection between the plasma levels of these compounds and orbital changes. METHODS: A retrospective study was performed by revising the medical records of 44 patients with Graves' orbitopathy and 15 controls. The Osirix software (Pixmeo, Geneva, Switzerland) was used for manual orbital measurements. Plasma levels of Graves' orbitopathy substances were obtained in the analytical review of the patients. RESULTS: A greater muscle volume was observed in patients with Graves' orbitopathy in relation to the control group (p < 0.001). The clinical activity score (CAS) was associated to total muscle mass (p = 0.013) and retrorbital fat (p = 0.048). Our results indicated a direct relationship between serum concentrations of anti-thyroid peroxidase antibodies and inferior rectus thickening (p = 0.036); however, we did not observe a positive correlation between other muscle volumes and serum concentrations of various thyroid-related substances. CONCLUSIONS: This study is the first that uses Osirix measurement software to manually assess orbital features in patients with Graves' orbitopathy. These measurements were compared to the outcomes of tests performed in a laboratory. Among several serum biomarkers, anti-thyroid peroxidase appears to be a reliable biomarker that correlates positively with inferior rectus muscle thickness in patients with thyroid eye disease. This may help to improve the management of this disease.

Thyrotropin Receptor Autoantibody Assessment in Thyroid Eye Disease: Does the Assay Type Matter?

PURPOSE: Thyroid receptor antibodies can quantify thyroid eye disease activity, predict outcomes and aid timing of interventions. The type and generation of assay is frequently unspecified, complicating meta-analyses. To determine the clinical and biochemical relationships between a second-generation thyrotropin receptor-binding inhibition antibody (TRAb) immunoassay, detecting stimulatory and blocking antibodies, with the thyroid stimulating immunoglobulin (TSI) bridging immunoassay detecting the stimulatory component only. METHODS: Retrospective review of 100 consecutive patients attending a regional specialist service. For each patient and visit, both a TRAb and TSI were performed, and a clinical activity score (CAS) recorded. RESULTS: A significant positive correlation between TRAb and TSI (rho = 0.828, p < 0.01) but a weaker correlation between the assays and CAS (TRAb: rho = 0.439, p < 0.01; TSI: r = 0.357, p < 0.01) were found. In 10% of the episodic data, patients had a TRAb level that was disproportionately high (39.41 ± 52.84 IU/L), compared to their TSI levels (9.53 ± 12.10 IU/L) with a higher-than-average CAS (2.47 ± 1.78; range, 0-5). Within 12 months of diagnosis, a significant positive correlation between CAS and TRAb (rho = 0.503, p < 0.01) as well as between CAS and TSI (rho = 0.329, p < 0.01) were found. In patients with a diagnosis over 12 months, the correlation with CAS for both TSI and TRAb were Spearman rank correlation coefficient of 0.347 (p < 0.01) and 0.327 (p < 0.01), respectively. CONCLUSIONS: TRAb and TSI correlate strongly and to a lesser extent with the CAS. For most patients, TRAb can be replaced with the more economical TSI. TRAb also correlates better with newly diagnosed, more active patients than TSI. In a subset of patients, blocking antibodies may play a significant pathogenic role, requiring different treatment and monitoring. Further studies are required to investigate this relationship.

Assessment of the levels of interleukin-17 and interleukin-38 in thyroid-associated ophthalmopathy patients.

PURPOSE: The objective of the study was to analyse the levels of IL-17 and IL-38 in the samples of unstimulated tears, orbital adipose tissues, and sera of patients diagnosed with active forms of TAO. The correlation of the levels of IL-17 and IL-38 with clinical activity score (CAS) was scrutinized. METHODS: A study was conducted at the Kazakhstan Scientific Research Institute of Eye Diseases (Almaty city, Kazakhstan). Study participants (n = 70) were sub-divided into 3 groups: (1) a group of patients diagnosed with active TAO (n = 25), (2) a group of patients with an inactive form of TAO (n = 28), and (3) a "control group" (patients diagnosed with orbital fat prolapse, n = 17). All patients underwent a clinical assessment and diagnostics. The activity of the disease and its severity were assessed using the CAS and NOSPECS scales. Thyroid function tests were performed, including the study of the levels of thyroid-stimulating hormone, triiodothyronine, free thyroxine, and antibodies to the thyroid-stimulating hormone receptor. IL-17 and IL-38 levels in non-stimulated tear samples, orbital tissue, and patients' sera were measured using commercial ELISA kits. RESULTS: The results showed that the number of former smokers prevailed among patients with active TAO (48%) in comparison with patients with inactive TAO (15.4%), p = 0.001. The concentration of IL-17 significantly increased in the samples of non-stimulated tears, adipose tissues of the orbit and sera of patients with active forms of TAO. The level of IL-38 was reduced in all types of samples (p ≤ 0.05). The results of a histological study of orbital adipose tissues in the group of patients with an active form of TAO showed the presence of focal infiltration with lymphocytes, histiocytes, plasma cells, severe sclerosis and vascular plethora. We observed an association between the CAS of patients with active TAO and the level of IL-17 in sera (r = 0.885; p = 0.001). On the contrary, a negative correlation was detected for the level of IL-38 in sera. CONCLUSIONS: The results highlighted the systemic effect of IL-17 and the local effect of IL-38 in TAO. We observed a significant increase in the production of IL-17, and a decrease in IL-38 in samples of sera and unstimulated tears (the active form of TAO). Our data indicate a correlation of IL-17 and IL-38 levels with the clinical activity of TAO.

Quantitative assessment of the intraorbital segment of the optic nerve in patients with thyroid orbitopathy using diffusion tensor imaging.

BACKGROUND: It is difficult to detect optic nerve changes in patients with thyroid-associated ophthalmopathy (TAO) before the development of optic neuropathy. PURPOSE: To detect changes in the intraorbital segment of the optic nerve in patients with TAO using diffusion tensor imaging (DTI) and determine any correlations with disease severity. MATERIAL AND METHODS: A total of 74 participants (17 normal, 22 mild, and 35 moderate-severe TAO) were organized to be given 3-T DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) for the orbital segments of their optic nerves. All underwent ophthalmological examinations for visual acuity, intraocular pressure, exophthalmos, and fundoscopy, and were assessed based on the Clinical Activity Score (CAS). Univariate analysis of variance and Pearson's correlation coefficients were carried out. RESULTS: Patients with moderate-to-severe TAO had significantly lower FA values and higher MD values (P < 0.05). FA values were negatively correlated with CAS but had no obvious correlations with the degree of exophthalmos. MD values had no obvious correlations with CAS or the degree of exophthalmos. CONCLUSION: DTI parameters of the intraorbital optic nerves were significantly altered in moderate-to-severe patients before onset of clinical optic nerve dysfunction and may, therefore, be used as an imaging biomarker for assessing the disease.

Utility Assessment of Moderate to Severe Thyroid Eye Disease Health States.

Importance: Thyroid eye disease (TED) results in varying degrees of proptosis and diplopia negatively affecting quality of life (QoL), producing possibly substantial visual changes, disfigurement, and disability. Objective: To determine the association of varying TED severities with QoL in a non-TED population by assessing health state utility scores. Design, Setting, and Participants: This qualitative study, conducted from April 20, 2020, to April 29, 2021, assessed health states for active, moderate-severe TED, and values were elicited using time trade-off methods. Six health states of varying severity were determined from 2 placebo-controlled clinical trials (171 patients with TED and clinical activity score ≥4, ±diplopia/proptosis) and refined using interviews with US patients with TED (n = 6). Each health state description was validated by interviews with additional TED patient advocates (n = 3) and physician experts (n = 3). Health state descriptions and a QOL questionnaire were piloted and administered to a general population. Visual analog scales (VASs) were also administered to detect concurrence of the findings. Main Outcomes and Measures: TED health state utility scores and whether they differ from one another were assessed using Shapiro-Wilk, Kruskal-Wallis, pairwise Wilcoxon rank sum, and paired t tests. Results: A total of 111 participants completed time trade-off interviews. The mean (SD) utility value was 0.44 (0.34). The lowest (worse) mean utility value was observed in the most severe disease state (constant diplopia/large proptosis) with 0.30 (95% CI, 0.24-0.36), followed by constant diplopia/small proptosis (0.34; 95% CI, 0.29-0.40), intermittent or inconstant diplopia/large proptosis (0.43; 95% CI, 0.36-0.49), no diplopia/large proptosis (0.46; 95% CI, 0.40-0.52), and intermittent or inconstant diplopia/small proptosis (0.52; 95% CI, 0.45-0.58). The highest (best) mean value, 0.60 (95% CI, 0.54-0.67), was observed for the least severe disease state (no diplopia/small proptosis). Conclusions and Relevance: These findings suggest that patients with active, moderate-severe TED may have substantial disutility, with increasing severity of proptosis/diplopia more likely to have detrimental associations with QoL. These health state scores may provide a baseline for determining QoL improvement in these TED health states (utility gains) treated with new therapies.

Application of artificial intelligence in the assessment of thyroid eye disease (TED) - a scoping review.

Background: There is emerging evidence which suggests the utility of artificial intelligence (AI) in the diagnostic assessment and pre-treatment evaluation of thyroid eye disease (TED). This scoping review aims to (1) identify the extent of the available evidence (2) provide an in-depth analysis of AI research methodology of the studies included in the review (3) Identify knowledge gaps pertaining to research in this area. Methods: This review was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). We quantify the diagnostic accuracy of AI models in the field of TED assessment and appraise the quality of these studies using the modified QUADAS-2 tool. Results: A total of 13 studies were included in this review. The most common AI models used in these studies are convolutional neural networks (CNN). The majority of the studies compared algorithm performance against healthcare professionals. The overall risk of bias and applicability using the modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool led to most of the studies being classified as low risk, although higher deficiency was noted in the risk of bias in flow and timing. Conclusions: While the results of the review showed high diagnostic accuracy of the AI models in identifying features of TED relevant to disease assessment, deficiencies in study design causing study bias and compromising study applicability were noted. Moving forward, limitations and challenges inherent to machine learning should be addressed with improved standardized guidance around study design, reporting, and legislative framework.

MRI in the assessment of thyroid-associated orbitopathy activity.

Management of patients with thyroid-associated orbitopathy (also called Graves' disease) is dependent on the assessment of the disease activity. Evaluation of disease activity is based on ophthalmological examination. Magnetic resonance imaging (MRI) is an auxiliary method that may help quantify the activity and is also helpful in obtaining anatomical information concerning muscle thickness, exophthalmos, or optic neuropathy. We present a review of MRI techniques of the orbits with emphasis on the evaluation of disease activity. The most convincing seems to be the group of T2-weighted techniques such as conventional T2 weighting, T2 relaxometry, and T2 mapping. Dynamic contrast-enhanced MRI is another promising method.

Therapy With Intravenous Methylprednisolone Pulses Is Associated With Loss of Bone Microarchitecture in Trabecular Bone Score -Assessment Among Patients With Moderate-to-Severe Graves' Orbitopathy: A Pilot Study.

Background: Therapy with intravenous glucocorticoids (GCs) is associated with various side effects, however, the impact on bone remains elusive. Trabecular bone score (TBS) is a diagnostic tool providing information on bone microarchitecture based on images obtained from dual-energy X-ray absorptiometry. We investigated the influence of the intravenous methylprednisolone (IVMP) pulse administration on TBS in patients with moderate-to-severe Graves' orbitopathy (GO). Methods: Fifteen patients with GO were treated with 12 IVMP pulses (6x0.5g, 6x0.25 g on a weekly schedule). They received supplementation with 2000 IU of vitamin D and 1.0 g of calcium throughout the study period. TBS was assessed at baseline and after last IVMP pulse. To determine the difference between values at baseline and after treatment the least significant change (LSC) methodology was used. We compared pre- and posttreatment mean TBS values. Results: We found a significant decrease of TBS in 5 out of 15 (33%) patients. Mean TBS value decreased becoming 2.4% lower than at baseline (p<0.05). Conclusions: IVMP pulse therapy exerts negative effect on bone microarchitecture in TBS assessment. The analysis of the clinical risk factors for osteoporosis and the evaluation of bone mineral density and TBS should be considered before initiating IVMP therapy.

Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management.

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.

Assessment of serum dipeptidyl peptidase-IV levels in autoimmune thyroid disease.

OBJECTIVE: Decreased serum dipeptidyl peptidase-IV (sDPPIV) levels have been reported in patients with autoimmune diseases. However, few studies have analyzed the association between sDPPIV levels and autoimmune thyroid disease (AITD). This study aimed to evaluate the association between sDPPIV levels and three types of AITD: Graves' disease (GD), Graves' ophthalmopathy (GO), and Hashimoto's thyroiditis (HT). METHODS: Patients newly diagnosed with GD (n = 65), GO (n = 22), and HT (n = 27) and healthy individuals (n = 30) were recruited. Clinical characteristics and thyroid function data were collected. sDPPIV was measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls (786.3 ± 46.95), patients with GD and GO had significantly lower sDPPIV levels (662.2 ± 38.81 and 438.4 ± 31.78). Additionally, sDPPIV levels were negatively associated with antithyroid peroxidase antibody (r = -0.20) and antithyroglobulin antibody (r = -0.19), but there was no significant relationship between thyroid hormone and sDPPIV levels. GO cases were divided by proptosis with and without muscle thickening; sDPPIV levels were lower in the muscle thickening group than those in the without muscle thickening group. Logistic regression analysis showed that sDPPIV was negatively correlated with GO and GD. CONCLUSIONS: sDPPIV concentrations were abnormal in patients with GD and GO, and reduced sDPPIV expression may be involved in the progression of GO and GD.

Neural network-based method for diagnosis and severity assessment of Graves' orbitopathy using orbital computed tomography.

Computed tomography (CT) has been widely used to diagnose Graves' orbitopathy, and the utility is gradually increasing. To develop a neural network (NN)-based method for diagnosis and severity assessment of Graves' orbitopathy (GO) using orbital CT, a specific type of NN optimized for diagnosing GO was developed and trained using 288 orbital CT scans obtained from patients with mild and moderate-to-severe GO and normal controls. The developed NN was compared with three conventional NNs [GoogleNet Inception v1 (GoogLeNet), 50-layer Deep Residual Learning (ResNet-50), and 16-layer Very Deep Convolutional Network from Visual Geometry group (VGG-16)]. The diagnostic performance was also compared with that of three oculoplastic specialists. The developed NN had an area under receiver operating curve (AUC) of 0.979 for diagnosing patients with moderate-to-severe GO. Receiver operating curve (ROC) analysis yielded AUCs of 0.827 for GoogLeNet, 0.611 for ResNet-50, 0.540 for VGG-16, and 0.975 for the oculoplastic specialists for diagnosing moderate-to-severe GO. For the diagnosis of mild GO, the developed NN yielded an AUC of 0.895, which is better than the performances of the other NNs and oculoplastic specialists. This study may contribute to NN-based interpretation of orbital CTs for diagnosing various orbital diseases.

Extraocular Muscle Volumetry for Assessment of Thyroid Eye Disease.

BACKGROUND: In this study we evaluate the diagnostic accuracy of extraocular muscle volumetry in detecting thyroid eye disease and to compare the results with simple measurements of maximal medial rectus (MR) diameter. METHODS: Cross-sectional study that included 47 eyes of 47 patients with thyroid eye disease and 47 healthy controls. Patients underwent slitlamp examination and imaging consisting of computed tomography scans. Image segmentation and volume measurements were performed by 2 independent researchers. Intraobserver and interobserver reliability testing was also conducted. RESULTS: Total extraocular muscle volume was 7.31 ± 1.88 cm3 and medial volume was 2.38 ± 0.73 cm3 in the study group. In this group, the maximum measured diameter of the MR was 6.67 ± 0.35 mm. MR volume was statistically associated with maximum MR diameter (r = 9.78; P < 0.001). Both MR volume and maximum MR diameter measurements showed good predictive efficacy as shown using receiver operator characteristic curve analysis. CONCLUSIONS: Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.

Echographic Assessment of Extraocular Muscle Response to Teprotumumab.

PURPOSE: To evaluate extraocular muscle response to teprotumumab using orbital echography in thyroid eye disease. METHODS: This retrospective study included adult thyroid eye disease patients with pre- and post-teprotumumab orbital echography. Data collected included: age, Hertel measurements, clinical activity score, Gorman diplopia scores, ocular motility, and recti muscle diameters measured by echography. The patient's more proptotic eye before treatment initiation was designated as the study orbit. Ocular motility was assessed by totaling the ductions in all 4 cardinal directions. Orbital echography was obtained pre- and post-treatment to assess response of extraocular muscle diameters. RESULTS: Six patients with a mean age of 67 years were included. There was a mean improvement in proptosis of 4.3 mm in the study eye with 11/12 orbits showing improvement in globe position ( p < 0.05). All patients had a decrease in clinical activity score with a mean reduction of 2.5. Four patients had an improvement in Gorman diplopia score. Ocular motility in the study orbits improved by a total mean of 26.9° ( p < 0.05). Mean total extraocular muscle diameter was reduced from 27.4 to 23.4 mm ( p < 0.001). On average, superior recti were largest pre- and post-treatment, followed by inferior, medial, then lateral recti. However, inferior recti showed the greatest reduction of 23% ( p < 0.02). CONCLUSIONS: Orbital echography demonstrated extraocular muscle reduction in all patients after teprotumumab, correlating with improved clinical activity score, ocular motility, and proptosis. Orbital echography is a safe and cost-effective imaging alternative to monitor therapeutic response to teprotumumab.

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

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

Orbital decompression for thyroid eye disease: surgical treatment outcomes in endocrinological assessment.

INTRODUCTION: Surgical orbital decompression involves removal of one or more of the orbital bony walls in order to gain space for overgrown muscles and adipose tissue, which results in a reduction in pressure on the eye. This observational study aims to perform an endocrinological assessment of the surgical treatment outcomes of thyroid eye disease (TED) patients before and after orbital decompression. MATERIAL AND METHODS: This retrospective study included 51 TED patients (84 orbits) who underwent endoscopic orbital decompression (EOD) or balanced orbital decompression. The effect of surgical treatment was evaluated via the clinical activity score (CAS), and modified NOSPECS and EUGOGO classification. RESULTS: Before orbital decompression, the average CAS index was 3.83 ± 1.86 points, whereas the modified NOSPECS score was 3.31 ± 0.97 points. After surgical intervention, the values were as follows: 2.07 ± 1.84 points for CAS and 2.5 ± 0.97 points for modified NOSPECS. The EUGOGO classification before surgery showed that Graves' orbitopathy (GO) was mild, moderate to severe, and sight-threatening in 1%, 25%, and 74% of the orbits, respectively. After surgery, GO was determined to be mild, moderate to severe, and sight-threatening in 24%, 57%, and 19% of the orbits, respectively. Statistical analysis was performed using the R 3.6.2 statistical environment. Inference about the statistical reliability of the parameter was made by calculating the mean and the 95% credibility interval (CI). CONCLUSIONS: The severity of TED decreased after orbital decompression. The CAS, and modified NOSPECS and EUGOGO classification showed a statistically reliable postoperative reduction. The drop in activity of the disease after orbital surgery requires careful follow-up.