BACKGROUND: Selenium is a trace element crucial for thyroid function, and has potential therapeutic benefits in Graves\' orbitopathy (GO). Therefore, we aim to evaluate its efficacy and safety in GO patients to provide valuable insights into its role as a therapeutic option for this condition.
METHODS: Systematic review and meta-analysis.
METHODS: GO Patients treated with selenium compared to placebo.
METHODS: Clinical activity score (CAS), Graves\' orbitopathy quality of life (GO-QOL), eye symptoms and signs, and adverse events.
RESULTS: Out of 1684 records screened, four randomised controlled trials were included. Selenium was superior at 6 months in lowering the CAS (MD = -1.27, 95% confidence interval [CI] [-1.68, -0.85], p < .0001]), improving total GO-QOL (RR = 2.54, 95% CI [1.69-3.81], p < .00001), and improving the visual and the psychological functioning scores (MD = 10.84, 95% CI [4.94-16.73], p = .003), (MD = 12.76, 95% CI [8.51-17.00], p < .00001) respectively. Similarly, it significantly improved these outcomes at 12 months. It also showed a significant decrease in the palpebral aperture at 6 months (MD = -1.49, 95% CI [-2.90, -0.08], p = .04). However, no significant differences were observed in proptosis, soft tissue involvement, ocular motility, and adverse effects.
CONCLUSIONS: Selenium is effective in reducing CAS and improving the palpebral aperture and GO-QOL in patients with GO. Additionally, it is safe and has promising therapeutic implications. However, further research is needed to validate its long-term efficacy and safety.

UNASSIGNED: Manifestations of thyroid-associated ophthalmopathy (TAO) vary greatly. Few tools and indicators are available to assess TAO, restricting personalized diagnosis and treatment.
UNASSIGNED: To identify an aptamer targeting thyroid-stimulating hormone receptor (TSHR) and utilize this aptamer to evaluate clinical activity in patients with TAO.
UNASSIGNED: An aptamer targeting TSHR was developed by exponential enrichment and systematic evaluation of TSHR ligands. After truncation and optimization, the affinity, equilibrium dissociation constant, and serum stability of this aptamer were evaluated. The affinity of the TSHR-targeting aptamer to isolated fibrocytes was assessed, as was aptamer internalization by fibrocytes. The mechanism of binding was determined by molecular docking. The correlation between disease manifestations and the percentage of TSHR-positive cells was assessed by correlation analysis.
UNASSIGNED: The aptamer TSHR-21-42 was developed to bind to TSHR, with the equilibrium dissociation constant being 71.46 Kd. Isolated fibrocytes were shown to bind TSHR-21-42 through TSHR, with its affinity maintained at various temperatures and ion concentrations. TSHR-21-42 could compete with anti-TSHR antibody, both for binding site to TSHR and uptake by cells after binding. In addition, TSHR-21-42 could bind to leukocytes in peripheral blood, with this binding differing in patients with TAO and healthy control subjects. The percentage of TSHR-positive monocytes, as determined by binding of TSHR-21-42, correlated positively with clinical activity score in patients with TAO, indicating that TSHR-21-42 binding could assess the severity of TAO.
UNASSIGNED: This aptamer targeting TSHR may be used to objectively assess disease activity in patients with TAO, by evaluating the percentages of TSHR positive cells in peripheral blood.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Background: We previously developed a machine learning (ML)-assisted system for predicting the clinical activity score (CAS) in thyroid-associated orbitopathy (TAO) using digital facial images taken by a digital single-lens reflex camera in a studio setting. In this study, we aimed to apply this system to smartphones and detect active TAO (CAS ≥3) using facial images captured by smartphone cameras. We evaluated the performance of our system on various smartphone models and compared it with the performance of ophthalmologists with varying clinical experience. Methods: We applied the preexisting ML architecture to classify photos taken with smartphones (Galaxy S21 Ultra, iPhone 12 pro, iPhone 11, iPhone SE 2020, Galaxy M20, and Galaxy A21S). The performance was evaluated with smartphone-captured images from 100 patients with TAO. Three ophthalmology residents, three general ophthalmologists with <5 years of clinical experience, and three oculoplastic specialists independently interpreted the same set of images taken under a studio environment and compared their results with those generated by the smartphone-based ML-assisted system. Reference CAS was determined by a consensus of three oculoplastic specialists. Results: Active TAO (CAS ≥3) was identified in 28 patients. Smartphone model used in capturing facial images influenced active TAO detection performance (F1 score 0.59-0.72). The smartphone-based system showed 74.5% sensitivity, 84.8% specificity, and F1 score 0.70 on top three smartphones. On images from all six smartphones, average sensitivity, specificity, and F1 score were 71.4%, 81.6%, and 0.66, respectively. Ophthalmology residents\' values were 69.1%, 55.1%, and 0.46. General ophthalmologists\' values were 61.9%, 79.6%, and 0.55. Oculoplastic specialists\' values were 73.8%, 90.7%, and 0.75. This smartphone-based ML-assisted system predicted CAS within 1 point of reference CAS in 90.7% using facial images from smartphones. Conclusions: Our smartphone-based ML-assisted system shows reasonable accuracy in detecting active TAO, comparable with oculoplastic specialists and outperforming residents and general ophthalmologists. It may enable reliable self-monitoring for disease activity, but confirmatory research is needed for clinical application.

UNASSIGNED: Thyroid eye disease (TED; also known as thyroid - associated orbitopathy, Graves ophthalmopathy) is an autoimmune inflammatory disease which presents in typical signs and symptoms such as deep orbital pain, chemosis with or without caruncular edema, unilateral or bilateral proptosis, eyelid retraction, eyelid edema or erythema, restrictive strabismus and compressive optic neuropathy.
UNASSIGNED: The aim of this study was to investigate the role of thermal camera in the assessment of thyroid eye disease (TED) activity compared to the Clinical Activity Score (CAS) scale, exophthalmometry values, and thyroid hormone and antibody levels.
UNASSIGNED: A total of 50 patients participated in this cross-sectional study of whom 29 were in the active phase of TED according to the sum on CAS scale and 21 patients in the inactive phase. The Flir E8® thermal camera was used to measure the temperature of the orbital area and the values were compared with the CAS scale, exophthalmometry values and thyroid hormone and antibody levels.
UNASSIGNED: Higher values of temperature (p>0.0001), CAS score (p>0.0001), exophthalmometry (p=0.022), FT4 (p=0.0176) and TRAb (p=0.0091) were found in patients in the active phase of TED. Temperature of orbital area showed statistically significant positive correlation with CAS scale (p=0.0001), exophthalmometry values (p=0.0022) and anti-TPO levels (p=0.019).
UNASSIGNED: Thermal camera showed higher values of the temperature of the orbital area in patients in the active phase of the disease and positively correlated with the CAS scale, exophthalmometry findings and anti-TPO levels.

UNASSIGNED: The aim of this study was to assess intraocular inflammation in patients with active and inactive Graves\' ophthalmopathy (GO) using an aqueous laser flash meter and to assess its relationship with thyroid hormones, antibodies, and clinical activity score (CAS).
UNASSIGNED: Forty patients (29 females and 11 males) were included in the study. The patients were divided into two groups according to CAS; patients with CAS <3 (inactive) were included in Group 1 and patients with CAS ≥3 (active) were included in Group 2. The laser flare meter was used to measure the flare of aqueous humor. Each patient\'s ocular findings, thyroid hormone, and antibody levels were also recorded.
UNASSIGNED: The mean age of patients was 46.88±11.79 years in Group 1 and 44.50±12.59 years in Group 2 (p=0.555). The mean CAS was 0.88±0.65 in Group 1 and 3.57±0.85 in Group 2 (p<0.001). The mean aqueous flare was 6.5±2.2 ph/ms in Group 1 and 7.0±6.4 ph/ms in Group 2 (p=0.73). Hertel exophthalmometry, intraocular pressure (IOP), antithyroglobulin antibody, and thyroid stimulating hormone receptor antibody (TRAb) levels were similar in both groups (each p>0.05). There was no correlation between aqueous flare value and CAS, Hertel exophthalmometry, IOP, thyroid hormone, and antibody levels (each p>0.05). There was a significant correlation between CAS and antibody levels (each p<0.05).
UNASSIGNED: Flare values that are not much above the normal range may be an indication that intraocular inflammation is not elevated in GO patients. This suggests that the damage to the blood-aqueous barrier in these patients is not severe enough to increase intraocular inflammation.

Thyroid eye disease (TED) can be difficult to manage. The range of available treatments is expanding rapidly; however, cost is a concern and some patients do not respond. The Clinical Activity Score (CAS) was devised as a measure of disease activity and a potential predictor of response to anti-inflammatory treatment. Despite the widespread use of the CAS, inter-observer variability has not been investigated. The aim of the study was to determine the inter-observer variability of the CAS in patients with TED.
Prospective reliability analysis.
Nine patients with a spectrum of clinical features of TED were assessed by 6 experienced observers on the same day. Agreement among the observers was analyzed using the Krippendorff alpha.
The Krippendorff alpha for the total CAS was 0.532 (95% CI = 0.199-0.665), whereas alpha values for the individual components of the CAS varied between 0.171 (CI = 0.000-0.334) for lid redness and 0.671 (CI = 0.294-1.000) for spontaneous pain. Assuming that a CAS value ≥3 implies suitability of the patient for anti-inflammatory treatment, the calculated Krippendorff alpha for agreement among assessors on whether treatment should be given or not given was 0.332 (95% CI = 0.0011-0.5862).
This study has shown unreliable inter-observer variability in total CAS and most individual CAS components, thus highlighting the need for improving the performance of the CAS or seeking other methods to assess activity.

BACKGROUND: The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment.
METHODS: This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12 weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12 weeks after intravenous (IV) GC therapy initiation, and 2 months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured.
RESULTS: The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2 months. The thyroid-stimulating hormone receptor antibody level decreased until 12 weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126 days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2 months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78 days.
CONCLUSIONS: Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.

Graves ophthalmopathy (GO) occurs in 25-50% cases of Graves disease. Most cases are just mild, only 5% represents eye threatening diseases. About 5-10% of cases could be euthyroid and 10% hypothyroid, respectively. All patients with GO should be assessed for activity (clinical activity score - CAS) and severity of the disease. Essential conditions of the successful treatment are well controlled thyroid dysfunction, smoking cessation and to refer patients with moderate to severe and sight threatening GO to specialized thyroid eye centers as soon as possible. Local therapy to maintain wet eye (lubricants) and supplementation of selenium deficiency is adequate in mild cases of GO. In cases of moderate to severe and sight threatening GO, administration of intravenous glucocorticoids in thyroid eye centers is first line treatment and a combination with mycophenolate or radiotherapy could be considered. When the first-line treatment fails or a contraindication/intolerance to them is present, non-steroid immunosuppressive drugs (mycophenolate, ciclosporin), rituximab, or radiotherapy could be considered. In rare cases of sight threatening GO urge surgical orbital decompression or tarsorrhaphy is warranted.

UNASSIGNED: Clinical experience regarding the fluctuations of the refractive error of the eye during the different stages of Graves\' ophthalmopathy observed through outpatient clinic frequent check-ups points towards an underestimated and often overlooked problem. Published data about it are sparse. The clinical manifestations of Graves\' ophthalmopathy can be understood from the perspective of \"compartment syndrome\" and literature implies how such changes can affect the refractive error and consequently, the visual acuity. The purpose of the study was to explore how the clinical activity score of Graves\' ophthalmopathy affects refractive error and visual acuity.
UNASSIGNED: The study was prospective and observational, including 60 eyes of 30 patients with clinically active Graves\' ophthalmopathy. All the patients were monitored and evaluated over a period of 36 months by the clinical activity score, spherical equivalent and visual acuity. All the observed parameters were statistically analyzed.
UNASSIGNED: The mean values of spherical equivalent and visual acuity throughout the observed period showed continuous fluctuation. Repeated measure analysis of variance showed statistically significant differences in visual acuity and spherical equivalent over the observed period. There was a statistically significant positive correlation between visual acuity and clinical activity score. The correlation between spherical equivalent and clinical activity score was also positive but not statistically significant.
UNASSIGNED: A decrease in the clinical activity score is either the result of a spontaneously resolving course of Graves\' ophthalmopathy or a consequence of treatment, so lowering in fluctuation of refractive error and improved visual acuity may be associated with a reduction in orbital inflammation.