UNASSIGNED: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder that principally targets the central nervous system, specifically the spinal cord and optic nerves. NMOSD is often associated with thyroid pathologies such as Graves\' disease or Hashimoto\'s thyroiditis. Thyroid eye disease (TED) is an autoimmune condition characterized by inflammation and hypertrophy of the extraocular muscles. Dysthyroid optic neuropathy (DON), a critical complication of TED, may lead to irreversible visual loss. We report a case of DON complicated by NMOSD.
UNASSIGNED: We report a case of an autoimmune disease presenting as DON in a 44-year-old Japanese woman with a history of Graves\' disease, who experienced reduced visual acuity and orbital pain. Brain magnetic resonance imaging disclosed hypertrophy of the rectus muscles, compressing the optic nerve bilaterally. Consequently, she was diagnosed with DON and underwent three courses of steroid semi-pulse therapy and left orbital decompression surgery, alleviating optic nerve compression. Nevertheless, the visual prognosis remained poor. A subsequent serological test showed positive for aquaporin-4 antibody. Treatment with satralizumab, an interleukin-6 receptor monoclonal antibody, was initiated in conjunction with steroids to suppress the autoimmune response and reduce NMOSD relapse risk. Following this treatment, no NMOSD recurrences were reported.
UNASSIGNED: This case highlights the necessity of considering the possible coexistence of DON and NMOSD in patients with autoimmune diseases.

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.

OBJECTIVE: Thyroid eye disease (TED) negatively impacts quality of life. TED occurs predominantly in Graves\' disease (GD). Teprotumumab improves TED but concern for hearing adverse events (AEs) has emerged. Hearing dysfunction is reported in thyroid autoimmune disease but the background prevalence in GD/TED without teprotumumab remains uncertain.
OBJECTIVE: To quantify ear-related diagnostic codes/hearing AEs in GD, TED, and patients receiving teprotumumab by examining medical claims and clinical trials.
METHODS: Deidentified claims for ear/labyrinth-related ICD-10 codes (KOMODO®) were examined in GD patients without TED, and TED patients without/with teprotumumab treatment. Hearing AE incidence/severity was evaluated in teprotumumab clinical trials. Graves\' Ophthalmopathy QOL (GO-QOL) scores were compared in teprotumumab TED trial patients without/with hearing AEs.
RESULTS: GD (469,720), TED (38,566) and teprotumumab-treated (967) patients were identified in the claims database. Ear-related codes (including those not specific for hearing) occurred in 24% GD, 33% TED, and 32% teprotumumab-treated patients. \"Sensorineural hearing loss bilateral\" was most frequent: 32,961/469,720 (7%) GD, 4,279/38,566 (11.1%) TED, and 104/967 (10.8%) teprotumumab patients. Pre-teprotumumab use,165 (17.1%) patients had ear-related codes while 98 (10.1%) had new ear-related codes post-treatment.Eight teprotumumab oncology trials revealed 8.1% (51/633) had Ear/Labyrinth Disorders with 2.1% (13) considered study-drug-related and 3.8% (24) hearing impairment/tinnitus-related AEs, with 1.3% (8) considered teprotumumab-related. Similar rates occurred in TED trials.GO-QOL improved in teprotumumab-treated patients without/with hearing AEs. Incidence/severity was consistent across patients with chronic and acute TED.
CONCLUSIONS: These analyses indicate similar occurrence of hearing claims in patients with GD/TED alone as following teprotumumab treatment. Future analyses of incremental hearing risk from teprotumumab should utilize a priori study designs accounting for background hearing dysfunction in patients with GD/TED.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group.
METHODS: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy.
RESULTS: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05).
CONCLUSIONS: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) involves cerebral vasculature constriction and dilation. While the exact pathophysiology of RCVS is still not fully understood, there are multiple etiological factors suggested to be implicated in triggering RCVS. We report two RCVS cases potentially linked to teprotumumab. Case 1: A 59-year-old female with Graves\' eye disease (GED) developed leg weakness and headache after initiating teprotumumab, and neuroimaging studies revealed multifocal cerebral vasospasm (CVS). Verapamil mitigated vasospasm and the patient overall improved. Case 2: A 71-year-old female with GED developed thunderclap headache two months after starting teprotumumab, with subarachnoid hemorrhage (SAH) and CVS revealed on neuroimaging studies. The patient improved on verapamil and was discharged without deficits.
CONCLUSIONS: The temporal correlation between teprotumumab initiation and RCVS\'s symptom onset raises concern for the potential involvement of teprotumumab in triggering RCVS via disrupting cerebrovascular modulation. Further research is needed to investigate this proposed association.

OBJECTIVE: It is commonly taught that thyroid eye disease (TED) causes enlargement of the extraocular muscles (EOMs) in the following descending order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus (LR), superior oblique (SO) and inferior oblique (IO). However, with recent literature challenging this notion, we aimed to compare EOM volumes in our cohort of TED patients.  Methods: We conducted a retrospective, non-randomized case-control study. Twenty-eight orbits from 28 unique patients with TED who had high-resolution CT scans were compared to 31 normal orbits, all from a single academic institution. Orbital soft tissues were manually segmented using ITK-SNAP 3.8.0 (http://itksnap.org), and soft tissue volumes of the control and TED orbits were compared using independent-sample t-tests.
RESULTS: Of the TED orbits, 54% of SR/levator palpebrae superioris complex volumes (SRC) and 50% of IR volumes were greater than two standard deviations above the normal orbit average. Compared to controls, the mean SRC volume in TED subjects was 2.3 times enlarged, followed by the IR (2.1 times), SO (1.8 times), MR (1.7 times), LR (1.6 times), IO (1.6 times), and orbital fat (1.4 times) (p < 0.01 for all).  Conclusions: Our findings suggest that contrary to previous teaching, the SRC may be the most severely affected in TED.

OBJECTIVE: The clinical activity score (CAS) and European severity scale (ESS) are established clinical tools to assess thyroid eye disease (TED) but are limited in terms of subjectivity and their reliability in non-Caucasian individuals, and can underestimate significant disease in the posterior orbit. Preliminary data from pilot studies have shown that diffusion-weighted imaging (DWI) using extraocular muscle (EOM) apparent diffusion coefficient (ADC) measurements may provide complementary information in TED. This study expands on previous research to assess for correlations between clinical scores and EOM-ADCs in stratifying disease activity and severity in a large patient cohort from an ethnically diverse population.
METHODS: A retrospective review of TED clinics between 2011 and 2021 identified 96 patients with a documented CAS and ESS and an orbital MRI that included DWI. From regions of interest manually placed on EOM bellies, the highest ADC was computed for each patient and analysed for correlations and associations with CAS and ESS using Spearman Rank correlation and Mann-Whitney U tests, and any potential discriminatory cut-offs using Receiver Operator Curve analyses. A p-value < 0.05 indicated statistical significance.
RESULTS: EOM-ADCs showed a positive association with CAS (p ≤ 0.001). EOM-ADCs were higher in sight-threatening compared to mild disease (p ≤ 0.01). A cut-off of 995 mm2/s achieved AUC = 0.7744, equating to 77% sensitivity and 67% specificity for discrimination between mild-moderate and sight-threatening disease.
CONCLUSIONS: EOM-ADCs correlate with higher scores of disease severity and activity in TED. Besides providing quantitative data to support clinical tools, EOM-ADC cut-offs may identify patients at risk of developing sight-threatening diseases.
UNASSIGNED: This study critically evaluates the limitations of conventional clinical assessment tools for TED and demonstrates the utility of DWI scans with ADC measurements in identifying active disease, offering valuable insights to advance clinical radiology practice.
CONCLUSIONS: Conventional tools for TED assessment have subjective limitations. ADCs from non-echoplanar diffusion-weighted imaging correlate with clinical activity. Non-echoplanar diffusion-weighted imaging offers quantitative assessment to aid clinical practice reliability.

Thyroid Eye Disease (TED) is a debilitating autoimmune condition often associated with thyroid dysfunction, leading to significant ocular and orbital morbidity. This review explores recent advancements in the management of TED, focusing on both medical and surgical innovations. The introduction of Teprotumumab, the first FDA-approved drug specifically for TED, marks a pivotal development in medical therapy. Teprotumumab targets the insulin-like growth factor-1 receptor (IGF-1R), effectively reducing inflammation and tissue remodeling. Clinical trials demonstrate its efficacy in reducing proptosis and improving quality of life, making it a cornerstone in the treatment of active, moderate-to-severe TED. Surgical management remains critical for patients with chronic TED or those unresponsive to medical therapy. Advancements in orbital decompression surgery, including image-guided and minimally invasive techniques, offer improved outcomes and reduced complications. Innovations in eyelid and strabismus surgery enhance functional and cosmetic results, further improving patient satisfaction. The management of TED necessitates a multidisciplinary approach involving endocrinologists, ophthalmologists, oculoplastic surgeons, radiologists, and other specialists. This collaborative strategy ensures comprehensive care, addressing the diverse aspects of TED from thyroid dysfunction to ocular health and psychological well-being. Future directions in TED treatment include emerging pharmacological therapies targeting different aspects of the disease\'s pathophysiology and advanced surgical techniques aimed at enhancing precision and safety. This review underscores the importance of a personalized, multidisciplinary approach in managing TED, highlighting current advancements, and exploring potential future innovations to improve patient outcomes and quality of life.

OBJECTIVE: Thyroid eye disease (TED) is the most common orbital disease in adults. Ocular motility restriction is the primary complaint of patients, while its evaluation is quite difficult. The present study aimed to introduce an artificial intelligence (AI) model based on orbital computed tomography (CT) images for ocular motility score.
METHODS: A total of 410 sets of CT images and clinical data were obtained from the hospital. To build a triple classification predictive model for ocular motility score, multiple deep learning models were employed to extract features of images and clinical data. Subgroup analyses based on pertinent clinical features were performed to test the efficacy of models.
RESULTS: The ResNet-34 network outperformed Alex-Net and VGG16-Net in prediction of ocular motility score, with the optimal accuracy (ACC) of 0.907, 0.870, and 0.890, respectively. Subgroup analyses indicated no significant difference in ACC between active or inactive phase, functional visual field diplopia or peripheral visual field diplopia (p > 0.05). However, in the gender subgroup, the prediction model performed more accurately in female patients than males (p = 0.02).
CONCLUSIONS: In conclusion, the AI model based on CT images and clinical data successfully realized automatic scoring of ocular motility in TED patients. This approach potentially enhanced the efficiency and accuracy of ocular motility evaluation, thus facilitating clinical application.

This study aims to investigate the changes in ocular biomechanical factors in patients with inactive thyroid eye disease (TED) who undergo orbital decompression surgery. This observational prospective study include 46 eyes of 31 patients with inactive TED undergoing orbital decompression at a tertiary university hospital from October 2021 to September 2023. All participants underwent a full ophthalmic examination, and a biomechanical examination was performed using corvis ST at baseline, 1 month, and 3 months postoperatively. The study participants had a mean age of 45 ± 11.6 years, and 58.1% of them were female. The second applanation time (A2T) increased from baseline to postoperative month 1 and continued to increase to postoperative month 3 (P < 0.001). The first applanation velocity (A1V), highest concavity (HC) peak distance, and pachymetry parameters also increased from postoperative month 1 to postoperative month 3 (P = 0.035, P = 0.005, and P = 0.031, respectively). The HC time increased from baseline to postoperative month 3 (P = 0.027). Other changes were statistically insignificant. The P-values were adjusted according to biomechanically corrected intraocular pressure (bIOP). Baseline Hertel significantly influenced A2 time (P < 0.001). Our findings suggest that ocular biomechanical parameters may change following decompression surgery in patients with inactive TED. Specifically, an increase in A2T, A1V, and HC peak distance suggests a decrease in corneal stiffness, although the increased HC time contradicts this. It is recommended to postpone keratorefractive or intraocular lens implantation surgeries until corneal biomechanics stabilize after decompression surgery for optimal results.