Thyroid-associated Orbitopathy Patients Research Articles

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.

Ultrasound Examination of the Orbit in Patients With Thyroid- Associated Orbitopathy – Examination Guide and Recommendations for Everyday Practice. A Review

The purpose of this study is to present the possibilities and benefits of ultrasonography (US) of the orbit in the diagnosis and treatment of thyroid-associated orbitopathy (TAO). Methods: US examination of the orbit is an essential addition to clinical and laboratory examination in TAO patients. Nevertheless, it is often neglected in clinical practice or indicated with delay. Based on previously published studies and our experience with the diagnosis and treatment of TAO patients, we aim to highlight the clear benefit of US examination of the orbit and oculomotor muscles, not only for correct TAO diagnosis but also in the monitoring of the disease over time. However, knowledge of the drawbacks and limitations of this method is also essential, as we shall point out. It is always necessary to remember that US examination must be evaluated in connection with the clinical findings. A detailed recommendation for US examination of the extraocular muscles and the orbit based on our experiences with diagnosing and treating TAO patients in daily practice is also included. Conclusion: According to our experience, US examination of the orbit is an excellent and irreplaceable tool for timely TAO diagnosis and further disease monitoring. However, considerable examiner experience and detailed knowledge of the clinical and ultrasound manifestations of TAO are essential.

Differentially expressed genes in orbital adipose/connective tissue of thyroid-associated orbitopathy.

Thyroid-associated orbitopathy (TAO) is a disease associated with autoimmune thyroid disorders and it can lead to proptosis, diplopia, and vision-threatening compressive optic neuropathy. To comprehensively understand the molecular mechanisms underlying orbital adipogenesis in TAO, we characterize the intrinsic molecular properties of orbital adipose/connective tissue from patients with TAO and control individuals. RNA sequencing analysis (RNA-seq) was performed to measure the gene expression of orbital adipose/connective tissues of TAO patients. Differentially expressed genes (DEGs) were detected and analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified by the Cytoscape plug-in, cytoHubba. We validated several top DEGs through quantitative real-time polymerase chain reaction (qRT-PCR). We identified 183 DEGs in adipose tissue between TAO patients (n=3) and control patients (n=3) through RNA sequencing, including 114 upregulated genes and 69 downregulated genes. The PPI network of these DEGs had 202 nodes and 743 edges. PCR-based validation results of orbital adipose tissue showed multiple top-ranked genes in TAO patients (n=4) are immune and inflammatory response genes compared with the control individual (n=4). They include ceruloplasmin isoform x3 (CP), alkaline tissue-nonspecific isozyme isoform x1 (ALPL), and angiotensinogen (AGT), which were overrepresented by 2.27- to 6.40-fold. Meanwhile, protein mab-21-like 1 (MAB21L1), phosphoinositide 3-kinase gamma-subunit (PIK3C2G), and clavesin-2 (CLVS2) decreased by 2.6% to 32.8%. R-spondin 1 (RSPO1), which is related to oogonia differentiation and developmental angiogenesis, was significantly downregulated in the orbital muscle tissues of patients with TAO compared with the control groups (P=0.024). Our results suggest that there are genetic differences in orbital adipose-connective tissues derived from TAO patients. The upregulation of the inflammatory response in orbital fat of TAO may be consistent with the clinical phenotype like eyelid edema, exophthalmos, and excess tearing. Downregulation of MAB21L1, PIK3C2G, and CLVS2 in TAO tissue demonstrates dysregulation of differentiation, oxidative stress, and developmental pathways.

Comparison of Three Methods of Tonometry in Patients With Inactive Thyroid-Associated Orbitopathy

Introduction: Intraocular pressure (IOP) measurement in patients with thyroid-associated orbitopathy (TAO) can be difficult and misleading, particularly in patients with diplopia and eye deviation (esotropia or hypotropia). However, when measuring IOP, it is also necessary to pay sufficient attention to TAO patients without diplopia in primary gaze direction and without motility disorder that might not be readily apparent. Purpose: The aim of this study was to evaluate the accuracy of measurement of intraocular pressure (IOP) using three different types of tonometers: the rebound tonometer (iCARE), the Goldmann applanation tonometer (GAT) and the non-contact airpuff tonometer (NCT) in patients with inactive TAO. Materials and Methods: A total of 98 eyes of 49 adult patients with TAO were examined. The study group included 36 females and 13 males, with an age range of 19–70 years and a median age of 55.0. All the patients had evidence of thyroid disease, a history of mild to moderate TAO, no clinical signs or symptoms of active disease, and no diplopia in direct gaze direction. In addition to a comprehensive eye examination, all the patients underwent measurement of intraocular pressure with three tonometers: NCT, iCARE, and GAT. The measurements with these three devices were compared. Results: The mean IOP was 18.1 ± 2.4 mmHg (range 13–25 mmHg) with GAT, 22.3 ±5.0 mmHg (range 13–35 mmHg) with NCT, and 18.0 ±2.4 mmHg (range 13.3–26 mmHg) with iCARE. The mean difference between the GAT and iCARE measurements (using the Bland-Altman analysis) was -0.1 ±1.16 mmHg (limits of agreement -2.4 to 2.1). The mean difference between the GAT and NCT measurements was 4.2 ±3.6 mmHg (limits of agreement -2.8 to 11.2). The mean difference between the iCARE and NCT measurements was -4.3 ±3.7 mmHg (limits of agreement -11.6 to 2.9). No significant difference was found between GAT and iCARE (p = 1.000). However, there was a significant difference between GAT and NCT (p < 0.0001), as well as between iCARE and NCT (p < 0.0001). Conclusions: In patients with TAO, NCT significantly overestimates IOP values compared to the GAT and ICare. By contrast, the iCARE rebound tonometer provides IOP measurements comparable to the gold standard GAT in these patients.

Computed Tomography and Magnetic Resonance Imaging of the Orbit in the Diagnosis and Treatment of Thyroid-Associated Orbitopathy – Experience from Practice. A Review

The purpose is to acquaint readers with the contribution of imaging methods (IMs) of the orbit, specifically computed tomography (CT) and magnetic resonance imaging (MRI), in the diagnosis of thyroid-associated orbitopathy (TAO). Methods: IMs of the orbit are an indispensable accessory in the clinical and laboratory examination of TAO patients. The most frequently used and probably most accessible method is an ultrasound examination of the orbit (US), which, however, has a number of limitations. Other methods are CT and MRI. Based on the published knowledge implemented in our practice and several years of experience with the diagnosis and treatment of TAO patients, we would like to point out the benefits of CT and MRI in the given indications: visualisation of the extraocular muscles, assessment of disease activity, diagnosis of dysthyroid optic neuropathy and differential diagnosis of other pathologies in the orbit. Our recommendation for an ideal MRI protocol for disease activity evaluation is also included. Conclusion: IMs play an irreplaceable role not only in the early diagnosis of TAO, but also in the monitoring of the disease and the response to the applied treatment. When choosing a suitable IM for this diagnosis, a number of factors must always be taken into account; not only availability, cost and burden for the patient, but especially the sensitivity and specificity of the given method for the diagnosis of TAO.

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.

To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression. 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 × 3mm 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. 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). 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.

FACTORS ASSOCIATED WITH THYROID ASSOCIATED ORBITOPATHY DUE TO GRAVES’ DISEASE

Background: Thyroid associated orbitopathy (TAO) is the principal extrathyroidal manifestation of Graves’ disease (GD). TAO is described as chronic inflammation of orbital and periorbital tissue. Environmental risk factors variably influence development of TAO and risk factors vary with ethnicity and geographical region. Aims: To evaluate the clinical factors for TAO in patients with GD. Setting and Design: This was a hospital-based cross-sectional study done on consecutive 76 newly diagnosed patients of GD documented by thyroid 99mTechnetium-pertechnetate scan. Materials and Methods: Patients were subjected to complete clinical workup and thyroid profile. The diagnosis of TAO was based on the criteria of Bartley and Gorman. Fifty two TAO patients were compared with twenty four non TAO patients (controls) for risk. Statistical Analysis Used: All analyses were performed with SPSS software (version 21.0). Results: TAO was present in 52 (68%) of patients with GD. TAO was bilateral in 50 (96%) of patients. Majority of patients had mild orbitopathy 34 (65.4%) and none of the patients showed any signs of sight-threatening disease. Clinical activity score (CAS) was active in 13.5% of the study group. There was significant female preponderance in TAO. Current smoking increased the risk of TAO (P = 0.023). Total triiodothyronine (T3) and mean intraocular pressure (IOP) in primary and upward gaze was significantly elevated at baseline in TAO patients. Braley’s sign was seen in 30.7% of patients with TAO and in 8.3% of patients in the control group (P = 0.033). Current smoking, total T3 > 4ng/dl and differential IOP > 6 mmHg were found to be associated with risk of TAO. Conclusion: TAO was clinically inactive and of mild severity in most cases. This study identified current smoking, total T3 > 4 ng/dl and differential IOP > 6 mmHg as risk factors for TAO.

Neural network application for assessing thyroid-associated orbitopathy activity using orbital computed tomography

This study aimed to propose a neural network (NN)-based method to evaluate thyroid-associated orbitopathy (TAO) patient activity using orbital computed tomography (CT). Orbital CT scans were obtained from 144 active and 288 inactive TAO patients. These CT scans were preprocessed by selecting eleven slices from axial, coronal, and sagittal planes and segmenting the region of interest. We devised an NN employing information extracted from 13 pipelines to assess these slices and clinical patient age and sex data for TAO activity evaluation. The proposed NN’s performance in evaluating active and inactive TAO patients achieved a 0.871 area under the receiver operating curve (AUROC), 0.786 sensitivity, and 0.779 specificity values. In contrast, the comparison models CSPDenseNet and ConvNeXt were significantly inferior to the proposed model, with 0.819 (p = 0.029) and 0.774 (p = 0.04) AUROC values, respectively. Ablation studies based on the Sequential Forward Selection algorithm identified vital information for optimal performance and evidenced that NNs performed best with three to five active pipelines. This study establishes a promising TAO activity diagnosing tool with further validation.

Macular microvasculature in patients with thyroid-associated orbitopathy: a cross-sectional study

PurposeThe aim of this study was to evaluate macular blood flow in patients with thyroid-associated orbitopathy (TAO) as compared to healthy subjects. The inflammatory nature of the disease, as well as the vascular congestion caused by the increase in the volume of orbital soft tissue and extraocular muscles, rationalize the assessment of retinal blood flow changes in these patients.MethodsThis is a cross-sectional study with the convenience sampling method. Macular flow density was assessed using optical coherence tomography angiography (OCTA) and compared between patients with TAO and healthy individuals. We also compared macular flow density in two subgroups of patients based on clinical activity score (CAS).ResultsEighty–five cases, including 30 healthy individuals and 55 patients with TAO, participated. The foveal avascular zone (FAZ) area was significantly larger in the patient group than in the control. Patients with active TAO with CAS 3 or more had significantly larger FAZ areas than those with CAS less than 3 (p = 0.04).ConclusionWe showed that the FAZ area is larger in active TAO patients and can be considered a possible candidate feature for monitoring disease activity and thyroid-associated vasculopathy.

Efficacy and Safety of 6-Weekly versus 12-Weekly Intravenous Methylprednisolone in Moderate-to-Severe Active Thyroid-Associated Ophthalmopathy.

To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25-74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves' disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/-ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups.

Clinical Significance of Corneal Striae in Thyroid Associated Orbitopathy.

To elucidate the clinical implications of corneal striae (CS) in thyroid associated orbitopathy (TAO) patients. In this cross-sectional study, the presence of CS was confirmed after topical fluorescein staining on a slit lamp for consecutive treatment-naive TAO patients. Orbital parameters, including margin reflex distances, lagophthalmos, exophthalmos, intraocular pressure and radiological measurements, were compared between eyes with and without CS. The largest cross-sectional areas of each rectus muscle were measured by segmenting the T1-weighted (T1W) magnetic resonance images (MRI). The logistic regression analyses were used to evaluate the associations between CS and orbital parameters and rectus muscle measurements. Fifty-three consecutive TAO patients (presenting age 46.47 ± 14.73 years, clinical activity score 1.77 ± 1.25) who had unilateral CS were enrolled. In univariate analysis, both the degree of lagophthalmos and the area of the levator palpebrae superioris-superior rectus complex (LPS/SR) on T1W MRI were significantly larger in CS eyes compared to eyes without CS (p < 0.05). Multivariate analyses showed that CS in TAO patients were significantly associated with the degree of lagophthalmos (OR = 1.75, 95% CI: 1.18-2.61, p < 0.05) and LPS/SR area (OR = 19.27, 95% CI: 1.43-259.32, p < 0.05) but not with the other parameters. CS could predict LPS/SR enlargement and larger lagophthalmos in TAO (p < 0.05). The largest cross-sectional areas of LPS/SR and inferior rectus were positively correlated with clinical activity scores (p < 0.05). The presence of CS in TAO eye is significantly associated with LPS/SR enlargement and worse lagophthalmos. CS might be evaluated further as a potential ocular surface biomarker to identify upper lid and LPS/SR involvement in TAO.

Perspectives on Antibody-Based Thyroid-Associated Orbitopathy Treatments

Thyroid-associated orbitopathy (TAO) is a disfiguring and in severe cases debilitating autoimmune disease that has been the subject of much recent drug development and investigation. This condition is characterized by an acute inflammatory phase followed by a resolving, cicatricial phase. There has been a search to find an effective agent to address the acute inflammatory phase of this disease, which would hopefully minimize end stage disfigurement, overall morbidity, and the need for surgery. The advent of antibody-based immunologic therapies has shown promise in this regard. Herein we discuss the current biologic therapeutic landscape, including agents targeting the insulin-like growth factor-1 receptor (IGF-1R, teprotumumab) and the interleukin-6 receptor (IL-6R, tocilizumab), and provide additional insight and opinion from our group practice that is highly experienced in treating a large number of TAO patients. Notably, though teprotumumab is effective, and we regularly prescribe this agent with good success, we feel that tocilizumab should be regarded as another first-line therapy that may be a more appropriate choice for certain patients with active inflammatory TAO.

Machine learning-assisted system using digital facial images to predict the clinical activity score in thyroid-associated orbitopathy

Although the clinical activity score (CAS) is a validated scoring system for identifying disease activity of thyroid-associated orbitopathy (TAO), it may produce differing results depending on the evaluator, and an experienced ophthalmologist is required for accurate evaluation. In this study, we developed a machine learning (ML)-assisted system to mimic an expert’s CAS assessment using digital facial images and evaluated its accuracy for predicting the CAS and diagnosing active TAO (CAS ≥ 3). An ML-assisted system was designed to assess five CAS components related to inflammatory signs (redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and/or plica, and conjunctival edema) in patients’ facial images and to predict the CAS by considering two components of subjective symptoms (spontaneous retrobulbar pain and pain on gaze). To train and test the system, 3,060 cropped images from 1020 digital facial images of TAO patients were used. The reference CAS for each image was scored by three ophthalmologists, each with > 15 years of clinical experience. We repeated the experiments for 30 randomly split training and test sets at a ratio of 8:2. The sensitivity and specificity of the ML-assisted system for diagnosing active TAO were 72.7% and 83.2% in the test set constructed from the entire dataset. For the test set constructed from the dataset with consistent results for the three ophthalmologists, the sensitivity and specificity for diagnosing active TAO were 88.1% and 86.9%. In the test sets from the entire dataset and from the dataset with consistent results, 40.0% and 49.9% of the predicted CAS values were the same as the reference CAS, respectively. The system predicted the CAS within 1 point of the reference CAS in 84.6% and 89.0% of cases when tested using the entire dataset and in the dataset with consistent results, respectively. An ML-assisted system estimated the clinical activity of TAO and detect inflammatory active TAO with reasonable accuracy. The accuracy could be improved further by obtaining more data. This ML-assisted system can help evaluate the disease activity consistently as well as accurately and enable the early diagnosis and timely treatment of active TAO.

Glucocorticoid therapy reduces ocular hypertension in active moderate-severe thyroid-associated orbitopathy

PurposeOcular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This study investigates this in moderate-severe active TAO.MethodsSixty-eight patients with active moderate-severe TAO were recruited, 49 of whom were treated with 12-week GC therapy.The clinical and biochemical parameters were collected.Treatment outcomes were evaluated after GC therapy.ResultsThe prevalence of OHT was 44.85% in moderate-severe active TAO patients,including 81.97% of mild hypertension, 13.11% of moderate hypertension and 4.92% of severe hypertension.Clinical and biochemical parameters had no significant difference between OHT patients and non-OHT patients,such as age, sex distributions, smoking status, the kind and the duration of thyroid disease,the duration of eye symptoms and the level of FT3,FT4,TSH, TR-Ab, and Tpo-Ab, Tg-Ab(all P > 0.05).After GC therapy,the intraocular pressure(IOP) in OHT eyes decreased significantly (P < 0.05), while IOP in non-OHT eyes remained unchanged (P > 0.05).There was no significant difference in CAS and the effective rate of GC therapy between OHT eyes and non-OHT eyes (P > 0.05).ConclusionIn moderate-severe active TAO, the prevalence of OHT was 44.85%, most of which were mild hypertension.OHT was relieved by GC therapy,which had no effect on the efficacy of GC therapy.Our results will enhance physicians' confidence in GC therapy.

Improvement of Ocular Surface Disease by Lateral Tarsoconjunctival Flap in Thyroid-Associated Orbitopathy Patients with Lid Retraction.

There is a high incidence of ocular surface disease (OSD) in thyroid-associated orbitopathy (TAO) patients as a result of incomplete eyelid closure and chronic inflammatory eyelid status. This study was performed to evaluate the efficacy of a lateral tarsoconjunctival flap (LTF) in improving OSD in TAO patients from the perspective of correcting eyelid closures. As a study design, TAO patients were enrolled in this study to evaluate OSD perioperatively before they were scheduled for LTF surgery. Additional lid surgery was also recorded. The outcome was evaluated with perioperative OSD measurements and tear inflammatory mediators at baseline and one month and three months postoperatively. As a result, 42 patients (5 male, 37 female) underwent LTF surgery, and 13 patients received medial pretarsal support with collagen grafts. Eleven patients underwent blepharotomy, and 6 patients received Botox injections for upper lid retraction. The mean age of the participants was 46.4 years old, and the mean follow-up period was 10.6 months. Their clinical activity score (CAS) at the time of the operation was 2.1. Dry eye parameters, such as ocular surface disease index, tear breakup time, Schirmer’s I test score, and meibomian gland dropout were all significantly improved 3 months postoperatively. Tear osmolarity and inflammatory mediators in tear fluid, such as IL-6, IL-8, IL-18 and MCP-1, were also significantly improved after the procedures. After the surgery, all complications were mild and temporary. As a conclusion, LTF could provide TAO patients with both lid retraction correction and improvement of ocular surface disorders. Dry eye parameters significantly improved 3 months postoperatively. This method can serve as an alternative treatment option for lid correction in TAO patients.

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy.

BackgroundThyrotropin receptor autoantibodies (TSH-RAb) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO.Methods87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cellbased bioassay.ResultsCompared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001).ConclusionsIn patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays.

Evaluation of macular blood flow after intermittent intravenous infusion of high-dose corticosteroids (pulse therapy) in patients with thyroid-associated orbitopathy (TAO) using angio-OCT

PurposeThe aim of this study is to evaluate the changes in macular blood flow index (BFI) in patients with moderate to severe thyroid-associated orbitopathy (TAO) before and after pulse therapy and their relationship with clinical features and disease activity using angio-OCT technology.MethodsWe analyzed twenty-four eyes. Every patient underwent a complete eye examination and angio-OCT analysis (OCT Topcon ImageNet 6; DRI OCT Triton, Topcon Corporation) before (T0) and two months (T2) after pulse therapy. We analyzed macular vascular blood flow in four angiographic levels: superficial plexus (SP), deep plexus (DP), external retina (ER), and choriocapillaris (CC). We used the clinical activity score (CAS) score to define TAO as moderate or severe.ResultsMacular BFI significantly increased at T2 in the DP, ER, and CC (p < 0.01). CAS score (5.8 ± 0.8 vs. 3.9 ± 0.9, p < 0.01) and Hertel exophthalmometry values (22.6 ± 2.3 mm vs. 21.2 ± 2,5 mm, p < 0.01) improved for all patients at T2 compared T0. Mean IOP increased from 13.3 ± 2.8 mmHg to 14.3 ± 2.1 mmHg (p < 0.01). No correlation was found between CAS score and macular BFI in all the analyzed levels.ConclusionsPulse therapy treatment can change macular BFI. In particular, two months alter pulse therapy, all the patients show an increase in macular vascular blood flow in each angiographic level. According to our results, angio-OCT analysis of the macular BFI may be a useful tool in the follow-up of TAO patients after pulse therapy.

The Role of TPOAb in Thyroid-Associated Orbitopathy: A Systematic Review

ABSTRACT Introduction Thyroid-associated orbitopathy (TAO) is one of the most common autoimmune inflammatory disorders of the orbit. The presence of anti-thyroid antibodies is believed to play a role in the pathogenesis and clinical status of the TAO patients. Herein, we review the usefulness of TPOAb as a biomarker for TAO. Methods A systematic search in MEDLINE library was conducted. Results: Twenty studies were included. TPO is expressed in orbital tissues, and the polymorphism rs11675434 SNP has proven to be associated with clinically evident TAO. Studies in pediatric patients have shown a positive correlation between high TPOAb levels and TAO. In contrast, results in adults are inconsistent. Some studies imply a protective role of TPOAb, yet the majority did not find any association. Some authors have suggested an implication of TPOAb in the pathophysiology of TAO in TRAb-negative patients. Conclusions The role of TPOAb in TAO remains unclear and controversial.

Differentiation between thyroid-associated orbitopathy and Graves' disease by iTRAQ-based quantitative proteomic analysis.

Graves’ ophthalmopathy, also known as thyroid‐associated orbitopathy (TAO), is the most common inflammatory eye disease in adults. The most common etiology for TAO is Graves’ disease (GD); however, proteomic research focusing on differences between GD and TAO is limited. This study aimed to identify differentially expressed proteins between thyroid‐associated orbitopathy (TAO) and GD. Furthermore, we sought to explore the pathogenesis of TAO and elucidate the differentiation process via specific markers. Serum samples of three patients with TAO, GD, and healthy controls, respectively, were collected. These samples were measured using the iTRAQ technique coupled with mass spectrometry. Differentially expressed proteins in TAO and GD were identified by proteomics; 3172 quantified proteins were identified. Compared with TAO, we identified 110 differential proteins (27 proteins were upregulated and 83 were downregulated). In addition, these differentially expressed proteins were closely associated with cellular processes, metabolic processes, macromolecular complexes, signal transduction, and the immune system. The corresponding functions were protein, calcium ion, and nucleic acid binding. Among the differential proteins, MYH11, P4HB, and C4A were markedly upregulated in TAO patients and have been reported to participate in apoptosis, autophagy, the inflammatory response, and the immune system. A protein–protein interaction network analysis was performed. Proteomics demonstrated valuable large‐scale protein‐related information for expounding the pathogenic mechanism underlying TAO. This research provides new insights and potential targets for studying GD with TAO.

Risk factors for thyroid-associated orbitopathy due to Graves' disease

Background: Thyroid-associated orbitopathy (TAO) is the principal extrathyroidal manifestation of Graves' disease (GD). TAO is described as chronic inflammation of orbital and periorbital tissue. Environmental risk factors variably influence the development of TAO and risk factors vary with ethnicity and geographical region. Aims: To evaluate the clinical factors for TAO in patients with GD. Setting and Design: This was a hospital-based cross-sectional study done on consecutive 76 newly diagnosed patients of GD documented by thyroid 99mtechnetium-pertechnetate scan. Materials and Methods: Patients were subjected to a complete clinical workup and thyroid profile. The diagnosis of TAO was based on the criteria of Bartley and Gorman. Fifty-two TAO patients were compared with 24 non-TAO patients (controls) for risk. Statistical Analysis Used: All analyses were performed using SPSS software (version 21.0). Results: TAO was present in 52 (68%) of patients with GD. TAO was bilateral in 50 (96%) patients. Majority of the patients had mild orbitopathy (34, 65.4%) and none of the patients showed any signs of sight-threatening disease. Clinical activity score was active in 13.5% of the study group. There was significant female preponderance in TAO. Current smoking increased the risk of TAO (P = 0.023). Total triiodothyronine (T3) and mean intraocular pressure (IOP) in primary and upward gaze were significantly elevated at baseline in TAO patients. Braley's sign was seen in 30.7% of patients with TAO and in 8.3% of patients in the control group (P = 0.033). Current smoking, total T3 >4 ng/dl, and differential IOP >6 mmHg were found to be associated with the risk of TAO. Conclusion: TAO was clinically inactive and of mild severity in most cases. This study identified current smoking, total T3 >4 ng/dl, and differential IOP > 6mmHg as risk factors for TAO.