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This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice.

Thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy, is an autoimmune disorder caused due to a complex interplay between autoantigens including the thyroid-stimulating hormone receptor and the insulin-like growth factor-I receptor. TED is characterized by progressive proptosis or diplopia. This systematic review aimed to compare the efficacy of the newer monoclonal antibody – teprotumumab and intravenous methylprednisolone (IVMP) in TED patients. We performed a systematic review of previously published studies from 2013 to June 2023. A total of 329 articles were screened; among them, 111 non-duplicate publications were identified. After the screening of titles and abstracts, 156 publications were excluded; then, another 47 published papers were excluded after the full-text screening. The remaining 15 eligible studies were included in this systematic review. The majority of studies used either teprotumumab alone or in combination with others. Among 15 studies, eight studies used teprotumumab in TED patients, whereas remaining 7 studies used a standard treatment regimen. This systematic review provides an overview of the existing treatment options using monoclonal antibody – teprotumumab and IVMP in TED patients. The overall assessment provides a finding that antibody – teprotumumab is is a good choice compared to conventional IVMP for providing better outcomes in patients with TED.

This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid eye disease (TED) treatment has been recently revolutionized with the approval of teprotumumab, a targeted insulin growth factor 1 receptor (IGF1R) inhibitor. To date, teprotumumab is the only FDA-approved drug for treating TED. In this article, we would like to temper the current enthusiasm around IGF1R inhibitors. Methods: critical review of the literature by independent academic practitioners. Results: several questions should be raised. First, "how an orphan drug has become a blockbuster with annual sales exceeding $1 billion?" Teprotumumab infusions are expensive, costing about USD 45,000 for one infusion and USD 360,000 for eight infusions in a 75 kg patient. Teprotumumab approval was based on two randomized clinical trials investigating active (clinical activity score ≥ 4) TED patients. Despite this, teprotumumab was approved by the FDA for "the treatment of TED" without distinguishing between active and inactive forms. The second question is as follows: "how can a new drug, compared only to a placebo, become the new standard without being compared to historically established gold standard medical or surgical treatments?" Teprotumumab has never been compared to other medical treatments in active TED nor to surgery in chronic TED. Up to 75% of patients may experience proptosis regression after treatment discontinuation. Finally, ototoxicity has emerged as a potentially devastating side effect requiring frequent monitoring. Investigation into the long-term side effects, especially in women of childbearing age, is also warranted. Conclusions: Teprotumumab is undoubtedly a major treatment option in TED. However, before prescribing a drug, practitioners should assess its benefit/risk ratio based on the following: (i) evidence-based medicine; (ii) their empirical experience; (iii) the cost/benefit analysis; (iv) the long-term outcomes and safety profile. [ABSTRACT FROM AUTHOR]

PurposeTo explore if orbital fat-to-muscle ratio (FMR) is predictive of whether surgical decompression or teprotumumab leads to greater proptosis reduction in thyroid eye disease (TED).MethodsA single-center retrospective cohort study comparing surgical decompression with teprotumumab according to FMR. All TED patients completing an 8-dose course of teprotumumab between January 2020 and September 2022 and all patients undergoing bony orbital decompression from January 2017 to December 2019 were included. Subjects were excluded if they were

Thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy, is an autoimmune disorder caused due to a complex interplay between autoantigens including the thyroid-stimulating hormone receptor and the insulin-like growth factor-I receptor. TED is characterized by progressive proptosis or diplopia. This systematic review aimed to compare the efficacy of the newer monoclonal antibody - teprotumumab and intravenous methylprednisolone (IVMP) in TED patients. We performed a systematic review of previously published studies from 2013 to June 2023. A total of 329 articles were screened; among them, 111 non-duplicate publications were identified. After the screening of titles and abstracts, 156 publications were excluded; then, another 47 published papers were excluded after the full-text screening. The remaining 15 eligible studies were included in this systematic review. The majority of studies used either teprotumumab alone or in combination with others. Among 15 studies, eight studies used teprotumumab in TED patients, whereas remaining 7 studies used a standard treatment regimen. This systematic review provides an overview of the existing treatment options using monoclonal antibody - teprotumumab and IVMP in TED patients. The overall assessment provides a finding that antibody - teprotumumab is is a good choice compared to conventional IVMP for providing better outcomes in patients with TED. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Thyroid eye disease (TED) is a disfiguring autoimmune disease characterized by changes in the orbital tissues and is caused by abnormal thyroid function or thyroid-related antibodies. It is the ocular manifestation of Graves' disease. The expression of thyroid-stimulating hormone receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1 R) on the cell membrane of orbital fibroblasts (OFs) is responsible for TED pathology. Excessive inflammation is caused when these receptors in the orbit are stimulated by autoantibodies. CD34+ fibrocytes, found in the peripheral blood and orbital tissues of patients with TED, express immune checkpoints (ICs) like MHC II, B7, and PD-L1, indicating their potential role in presenting antigens and regulating the immune response in TED pathogenesis. Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, it can also lead to the occurrence of TED in some instances, suggesting the abnormality of ICs in TED. This review will examine the overall pathogenic mechanism linked to the immune cells of TED and then discuss the latest research findings on the immunomodulatory role of ICs in the development and pathogenesis of TED. This will offer fresh perspectives on the study of pathogenesis and the identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

BackgroundTeprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries.MethodsAll AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.ResultsA total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0–92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women.ConclusionThis study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.

Introduction: Thyroid eye disease (TED) is a rare condition involving autoimmune-mediated inflammation of the orbit and periocular structures, which can result in many debilitating symptoms. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor 1 receptor, is gaining popularity for the treatment of TED. In fact, owing to its efficacy and side effect profile, some recommend that it be considered as a first-line therapy for patients with TED. While teprotumumab is often chosen due to its efficacy and relatively favorable side effect profile compared to other treatments, there is a known risk of hyperglycemia with this mechanism of action, which is well described through clinical trials in the oncology literature. Though all cases in the clinical trial study of teprotumumab were mild, there is growing evidence that its effect on blood sugar can be more profound. Case Presentation: We present a case of a well-controlled, recently diagnosed type 2 diabetic placed on teprotumumab for treatment of TED who developed life-threatening hyperglycemia. The case report provides evidence of hyperglycemic risk, as it highlights a patient’s significant increase in hemoglobin A1C to 15.4 in addition to elevated serum glucose of 954 mg/dL while receiving teprotumumab. Conclusion: This case of severe hyperglycemia accentuates the need for more diligent, if not universal, glucose monitoring during teprotumumab treatment.

Introduction: In 2020, teprotumumab became the first FDA-approved treatment for thyroid eye disease (TED). In clinical trials, hyperglycemia had been described as mild and controlled with medication. We present a case that occurred in 2020 of a 67-year-old male with TED and pre-existing glucose intolerance, who was hospitalized with severe hyperglycemia (1,059 mg/dL) after three doses of teprotumumab. Case Presentation: This patient’s HbA1c was in the pre-diabetic range (6.3%) 6 months prior to initiating teprotumumab. After three doses, the patient was hospitalized with hyperosmolar hyperglycemic nonketotic syndrome and an HbA1c of 11.7%. He was diagnosed with type 2 diabetes mellitus and treated with insulin aspart mixed 70/30. He remained on this regimen for 14 months with an A1c of 6.0%. He then self-discontinued the insulin, with an A1c 4 months later measuring 5.5%. The patient’s latest HbA1c approximately two and a half years after hospitalization was 6.1% on no medications. Conclusion: It appears that teprotumumab was a trigger for this transient case of diabetes, and detecting those that have underlying glucose intolerance ahead of time is important. We recommend blood glucose levels for patients with pre-diabetes prior to and ideally in the first few days after each infusion, to help determine patients at a greater risk for adverse hyperglycemic outcomes. A glucometer may be valuable for patients to self-monitor while on teprotumumab. If fasting blood glucose is ≥126 mg/dL or non-fasting glucose is >200 mg/dL, patients should be referred for further diabetes assessment and possible treatment initiation.

Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.

Purpose: We present a case of rapid improvement in symptoms of thyroid eye disease and amelioration of worsening peripheral edema and acropathy with infusion of teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor. Observations: A 66 year old female with history of Hashimoto thyroiditis developed progressive thyroid eye disease (TED), peripheral edema, and acropathy attributable to acute Graves disease. Her signs and symptoms, refractory to oral steroid and diuretic therapy, rapidly improved following a standard dosing regimen of teprotumumab (one infusion 10 mg/kg then seven infusions 20 mg/kg) to resolution. Conclusions & importance: Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, is the first medication approved by the FDA for use in TED. Teprotumumab may contribute to the treatment of extraocular manifestations of Graves disease, chief among these peripheral soft tissue manifestations.

Thyroid eye disease (TED) is an inflammatory condition involving the periocular and orbital soft tissues, affecting most commonly patients with hyperthyroid disorders. Traditional treatments used for the active phase of the disease range from conservative lubrication for mild symptoms to systemic immunomodulating drugs for moderate-to-severe symptoms. Teprotumumab (Tepezza) is a monoclonal antibody with an inhibitory effect on insulin-like growth factor 1 and is the first Food and Drug Administration (FDA) approved targeted medical therapy for reducing the inflammatory signs and symptoms associated with TED. Two large multicenter, randomized, double-masked, placebo-controlled trials have confirmed the efficacy and safety of teprotumumab in patients with active, moderate-to-severe TED. Recent reports and publications have also demonstrated the efficacy of teprotumumab in a wider range of patients. In this review, we summarize the clinical features and pathophysiology of TED, disease course, and traditional management methods. We further detail the development of teprotumumab, the founding studies that brought it to its FDA approval, adverse events profile, and ongoing as well as future investigations. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid eye disease (TED) is a rare condition involving autoimmune-mediated inflammation of the orbit and periocular structures, which can result in many debilitating symptoms. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor 1 receptor, is gaining popularity for the treatment of TED. In fact, owing to its efficacy and side effect profile, some recommend that it be considered as a first-line therapy for patients with TED. While teprotumumab is often chosen due to its efficacy and relatively favorable side effect profile compared to other treatments, there is a known risk of hyperglycemia with this mechanism of action, which is well described through clinical trials in the oncology literature. Though all cases in the clinical trial study of teprotumumab were mild, there is growing evidence that its effect on blood sugar can be more profound. Case Presentation: We present a case of a well-controlled, recently diagnosed type 2 diabetic placed on teprotumumab for treatment of TED who developed life-threatening hyperglycemia. The case report provides evidence of hyperglycemic risk, as it highlights a patient's significant increase in hemoglobin A1C to 15.4 in addition to elevated serum glucose of 954 mg/dL while receiving teprotumumab. Conclusion: This case of severe hyperglycemia accentuates the need for more diligent, if not universal, glucose monitoring during teprotumumab treatment. [ABSTRACT FROM AUTHOR]

Introduction: In 2020, teprotumumab became the first FDA-approved treatment for thyroid eye disease (TED). In clinical trials, hyperglycemia had been described as mild and controlled with medication. We present a case that occurred in 2020 of a 67-year-old male with TED and pre-existing glucose intolerance, who was hospitalized with severe hyperglycemia (1,059 mg/dL) after three doses of teprotumumab. Case Presentation: This patient's HbA1c was in the pre-diabetic range (6.3%) 6 months prior to initiating teprotumumab. After three doses, the patient was hospitalized with hyperosmolar hyperglycemic nonketotic syndrome and an HbA1c of 11.7%. He was diagnosed with type 2 diabetes mellitus and treated with insulin aspart mixed 70/30. He remained on this regimen for 14 months with an A1c of 6.0%. He then self-discontinued the insulin, with an A1c 4 months later measuring 5.5%. The patient's latest HbA1c approximately two and a half years after hospitalization was 6.1% on no medications. Conclusion: It appears that teprotumumab was a trigger for this transient case of diabetes, and detecting those that have underlying glucose intolerance ahead of time is important. We recommend blood glucose levels for patients with pre-diabetes prior to and ideally in the first few days after each infusion, to help determine patients at a greater risk for adverse hyperglycemic outcomes. A glucometer may be valuable for patients to self-monitor while on teprotumumab. If fasting blood glucose is ≥126 mg/dL or non-fasting glucose is >200 mg/dL, patients should be referred for further diabetes assessment and possible treatment initiation. [ABSTRACT FROM AUTHOR]

Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P < 0.001; phase 2 study) and proptosis responder rate as defined by a reduction of 2 mm or more in proptosis (83% vs. 10%; P < 0.001; phase 3 study). In both studies, treatment with teprotumumab compared with placebo achieved a significant mean reduction of proptosis (-3.0 mm vs. -0.3 mm, phase 2 study; -3.32 mm vs. -0.53 mm, phase 3 study) and CAS (-4.0 vs. -2.5, phase 2 study; -3.7 vs. -2.0, phase 3 study). Teprotumumab also resulted in a greater proportion of patients with a final CAS of 0 or 1, higher diplopia responder rate, and a larger improvement in the Graves' Ophthalmopathy Quality of Life overall score. More than half of patients (62%, phase 2 trial; 56%, phase 3 trial) who were primary end point responders maintained this response at 51 weeks after the last dose of therapy. The most common adverse events reported with teprotumumab included muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (13%), fatigue (10%), hearing impairment (10%), and hyperglycemia (8%). Teprotumumab is contraindicated for those with inflammatory bowel disease and who are pregnant. Although the current dosing regimen has proven effective for TED, dose-ranging studies including variable concentrations, infusion frequencies, and durations of teprotumumab therapy in the setting of TED have not been performed.

IntroductionClassification of thyroid eye disease (TED) is largely based on guidelines developed in Europe and North America. Few studies have investigated the presentation and treatment of TED in Black populations. The objective is to examine the manifestations of TED in secondary and tertiary care center-based populations with a significant proportion of Black patients.Materials and methodsRetrospective chart review identifying patients with a reported race/ethnicity and a presenting clinical diagnosis of TED at Kings County Hospital and SUNY Downstate Medical Center and affiliated clinics from January 1, 2010 through July 31, 2021. Main outcome measures include age of disease onset, sex, smoking status, insurance status, postal code of residence, clinical exam features, number of follow-up visits, length of follow-up, and treatments received.ResultsOf the 80 patients analyzed, 49 were Black (61.2%) and 31 were White (38.8%). Between Black and White patients, there were differences in the mean age of presentation (48.1 [range 21-76] vs 56.8 [range 28-87] years, P=0.03), insurance status (51.0% vs 77.4% private insurance, P=0.02), and mean follow up length among those with multiple visits (21.6 [range 2-88] vs 9.7 [range 1-48] months, P=0.02). The distribution of EUGOGO scores were not significantly different between Black and White patients. On initial presentation, fewer Black patients had chemosis (OR 0.21, 95% CI, 0.08 to 0.57, P=0.002), and caruncular swelling (OR 0.19, 95% CI, 0.06 to 0.59, P=0.002) compared to White patients. During the overall disease course, fewer Black patients had subjective diplopia (OR 0.20, 95% CI, 0.07 to 0.56, P=0.002), chemosis (OR 0.24, 95% CI, 0.09 to 0.63, P=0.004), and caruncular swelling (OR 0.18, 95% CI, 0.07 to 0.51, P=0.001) compared to White patients. Black patients received oral steroids (42.9% vs 67.7%, P=0.03), intravenous steroids (18.4% vs 16.1%, P=0.8), orbital decompression surgery (16.7% vs 6.5%, P=0.19), and teprotumumab (22.9% vs 22.6%, P=0.99) at similar rates.DiscussionBlack patients presented with fewer external exam findings suggestive of active TED compared to White patients, but the rate of compressive optic neuropathy and decompression surgery were similar in the two groups. These differences may be due to disease phenotypes, which warrant further study.

PURPOSE: To report the first case of a patient with chronic thyroid eye disease (TED) treated with teprotumumab. OBSERVATIONS: A 50-year-old female with a 3-year history of Graves disease presented with bilateral exophthalmos greatest on the left side. She was followed for 2 years with stable proptosis measurements (23mm OD, 28mm OS). Her clinical activity score (CAS) was 1 and there were no examination findings reflective of active inflammation. The patient underwent systemic treatment with teprotumumab and despite chronic TED and low CAS, she had notable improvement in proptosis (18mm OD, 22mm OS) and decrease in extraocular muscle volume as noted on orbital imaging. CONCLUSION AND IMPORTANCE: This case report suggests that teprotumumab may be used in patients with chronic TED and low CAS. Improvement in the proptosis and reduction in extraocular muscle volume suggest that teprotumumab may alter disease course even in patients with inactive or quiescent TED.

Progress in the management of thyroid eye disease (TED) has bee n slow for many decades. The recent introduction of teprotumumab (TEP) in the t herapeutic arena for TED has had a major impact in view of its efficacy, particularly with respect to its ability to reduce proptosis. However, the high cost of TEP, limited ava ilability to patients outside the USA, and the lack of data on cost-effectiveness are significant barriers to improving the care of patients with TED globally. Recent guidan ce from authoritative professional organisations deliver different perspectives on the role of TEP in the routine management of patients with TED, underscoring the complexities of interpreting the evidence. The advance that TEP undoubtedly represents in managi ng TED effectively has highlighted inequities faced by patients and uncertainties abou t appropriate metrics of efficacy. Professional organisations have an important role addre ssing these problems. Future studies need to focus on optimising the measurement of o utcomes and on assessing cost-effectiveness.

Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.

IntroductionThyroid eye disease (TED) is an immune-mediated disorder associated with a heterogenous array of manifestations that may unfavorably impact vision and quality of life. As understanding of this entity’s complex pathogenesis has evolved, so have therapies with novel molecular targets offering promise for improved patient outcomes.ResultsEmerging immunologic therapies for the management of thyroid eye disease have diverse mechanisms of actions and routes of administration. Different conventional and biological immunosuppressive agents have been studied as mediators of the autoimmune and autoinflammatory pathways in thyroid eye disease. Teprotumumab – an anti-IGF-1R monoclonal antibody that has recently emerged as a first-line therapy for active, moderate-to-severe TED – has demonstrated statistically significant improvements in proptosis, diplopia, clinical activity score, and quality of life compared to placebo. Currently under investigation are several other agents, with varying administration modalities, that aim to inhibit IGF-1R: VRDN-001 (intravenous), VRDN-002 or VRDN-003 (subcutaneous), lonigutamab (subcutaneous), and linsitinib (oral). Tocilizumab, a monoclonal antibody of interleukin 6, has played a role in the management of multiple autoimmune and inflammatory conditions and may offer promise in TED. Another incipient biologic target for TED management is the neonatal Fc receptor, inhibition of which has potential to decrease recycling of immunoglobulin and antibody levels; agents addressing this target including monoclonal antibodies as well as antibody fragments. Finally, hypolipidemic agents may play a role as mediators of TED-associated inflammation.ConclusionAmong the agents under investigation that aim to decrease ocular morbidity associated with TED are agents that IGF-1R, interleukin 6, and the neonatal Fc receptor. The management of TED continues to expand with novel immunologic approaches for disease therapy.

INTRODUCTION: HIV fourth-generation assay, designed for the detection of HIV p24 antigen along with anti-HIV antibodies of both immunoglobulin M and immunoglobulin G type against HIV 1 and HIV 2 viral antigens, have helped in the early detection of HIV infection and supports in minimizing the transmission risk in the acute phase of infection. The objective of this study was to evaluate the analytical and clinical performance of HIV fourth-generation assay based on enhanced chemiluminescence technology. MATERIALS AND METHODS: The analytical performance of the assay was evaluated in terms of accuracy, precision, limit of detection, type of sample (serum vs. plasma), cross-reactivity (with other transfusion transmissible infections markers), and interference (with endogenous substances). Proficiency control material included kit-controls, archived known positive donor samples, third-party controls, and World Health Organization (WHO)/National Institute for Biological Standards and Controls (NIBSC, MHRA, UK) controls. The clinical performance was evaluated using routine donor and patient samples received during the study period. RESULTS: HIV fourth-generation assay showed reliable and reproducible results measured in terms of coefficient of variation % with kit-controls, archived known positive donor samples, third-party controls, and WHO international standards for anti-HIV 1 and 2 antibodies, HIV1 p24 antigens and HIV2 p26 antigen controls. The analytical sensitivity of the HIV fourth-generation assay was found to be 0.1 IU/mL of HIV1 p24 antigen control and there was no cross-reactivity or interference observed. In the clinical performance of the assay, HIV fourth-generation assay showed reliable performance in both donor and patient samples. CONCLUSION: HIV fourth-generation assay meets the requirements for its use as a screening assay for HIV infection based on the analytical and clinical performance of the assay. [ABSTRACT FROM AUTHOR]

Purpose: We report histopathologic orbital tissue analysis from three patients with thyroid eye disease (TED) – active, chronic, and post-teprotumumab to better characterize orbital cellular populations in these varying states of TED. Observations: Orbital tissues in TED demonstrate minimal lymphocytic infiltration in fat and Mueller's muscle. Following teprotumumab treatment, the tissues were devoid of lymphocytes with only perivascular cuffs of T-lymphocytes remaining in orbital fat. Conclusions and importance: In active TED, post-teprotumumab treatment, and in quiescent TED, orbital fat may not show significant inflammatory infiltration. More work is warranted to characterize specific cellular effects of teprotumumab and other biologics.

Backgrounds: The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking. We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs. Methods: To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase, Cochrane Library, CBM, CNKI, Wan-Fang and ICTRP databases. The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies. The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS), the improvement of proptosis and diplopia improvement, and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses. Results: A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab). TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX. TCZ was the highest probability of safety, followed by RTX and TMB. Conclusions: Based on the best available evidence, TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials, indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition, the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established, and it is encouraging that the treatment paradigm for GO may change in the future. This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA) (27). [ABSTRACT FROM AUTHOR]

Spiral ganglion neurons (SGNs) connect cochlear hair cells with higher auditory pathways and their degeneration due to drug toxicity (ototoxicity) contributes to hearing loss. This study aimed to identify drug classes that are negatively correlated with the transcriptome of regenerating SGNs. Human orthologs of differentially expressed genes within the regenerating neonatal mouse SGN transcriptome were entered into CMap and the LINCS unified environment and perturbation-driven gene expression was analyzed. The CMap connectivity scores ranged from 100 (positive correlation) to −100 (negative correlation). Insulin-like growth factor 1/receptor (IGF-1/R) inhibitors were highly negatively correlated with the regenerating SGN transcriptome (connectivity score: −98.87). A systematic literature review of clinical trials and observational studies reporting otologic adverse events (AEs) with IGF-1/R inhibitors identified 108 reports (6141 treated patients). Overall, 16.9% of the treated patients experienced any otologic AE; the rate was highest for teprotumumab (42.9%). In a meta-analysis of two randomized placebo-controlled trials of teprotumumab, there was a significantly higher risk of hearing-related (pooled Peto OR [95% CI]: 7.95 [1.57, 40.17]) and of any otologic AEs (3.56 [1.35, 9.43]) with teprotumumab vs. a placebo, whether or not dizziness/vertigo AEs were included. These results call for close audiological monitoring during IGF-1-targeted treatment, with prompt referral to an otolaryngologist should otologic AEs develop. [ABSTRACT FROM AUTHOR]

Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease that is closely related to thyroid dysfunction. It is one of the most common orbital diseases in adults with complex clinical manifestations. As the disease progresses, it may manifest as proptosis, diplopia, exposure keratitis, corneal ulceration and compressive optic neuropathy, leading to irreversible visual impairment or even blindness. The treatment is lack of specificity and only focuses on clinical symptomatic treatment, the efficacy is uncertain. It is currently a problematic area of ophthalmology. Clinical first-line drug treatment is based on glucocorticoids. Second-line treatments, such as immunosuppressants and radiotherapy, all them have certain limitations. With the in-depth and comprehensive understanding of the disease, a variety of new targeted drugs represented by teprotumumab and rituximab have been developed for the pathogenesis of TAO. Their excellent roles in relieving inflammation and controlling the disease are the future research direction. In this paper, the current status and research progress of conservative treatment of TAO will be reviewed.

Abstract Background Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab’s effect on intraocular pressure. Case presentation We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman. The diagnosis of thyroid eye disease was based on increased redness, swelling, and excessive tearing; abnormal proptosis, lid retraction, and diplopia measurements were also taken during physical examination. Intraocular pressure in primary, lateral gaze, and upgaze was documented. There was significant (p = 0.0397) improvement of primary gaze eye pressure from pre-teprotumumab infusions (baseline) to completion of the treatment course. Conclusions Teprotumumab significantly decreased the intraocular pressure for patients during the duration of the study. Teprotumumab is a novel medication that is approved for the primary treatment of thyroid eye disease in both acute and chronic thyroid eye disease. Previous treatments used to treat thyroid eye disease include glucocorticoids, radiotherapy, or orbital decompression surgery; however, these treatments all have significant limitations. Teprotumumab is an effective noninvasive alternative for decreasing symptoms of thyroid eye disease and, as shown, also lowers intraocular pressure. However, teprotumumab should not be used as a substitute for glaucoma medications; its ability to lower intraocular pressure may be in addition to lowering periorbital pressure and retro-orbital pressure.

Mizuki Tagami,1 Shigeru Honda,1 Atsushi Azumi2 1Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan; 2Ophthalmology Department and Eye Center, Kobe Kaisei Hospital, Kobe, Hyogo, JapanCorrespondence: Mizuki Tagami, Department of Ophthalmology and Visual Science, Graduate School of Medicine, Osaka City University, 1-5-7 Asahimachi, Abeno-ku, Osaka-shi, 545-8586, Japan, Tel/Fax +81-6-6645-3867, Email tagami.mizuki@med.osaka-cu.ac.jpAbstract: Dysthyroid optic neuropathy (DON) is a potentially sight-threatening eye disease associated with Graves’ orbitopathy (GO). DON is not common in GO patients, reportedly occurring in only about 5% of patients. The pathogenesis of severe DON is considered to involve both muscular nerve strangulation and impaired blood flow. There is some objective grading of physical examination findings and the severity of GO, including a clinical activity score (CAS) and EUropean Group On Graves’ Orbitopathy (EUGOGO), but no specialized protocol completely characterizes DON. Most clinicians have decided that the combination of clinical activity findings, including visual acuity, color vision, and central critical fusion frequency, and radiological findings, including magnetic resonance imaging (MRI), can be used to diagnose DON. MRI has the most useful findings, with T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences enabling detection of extraocular changes including muscle and/orbital fat tissue swelling and inflammation and, therefore, disease activity. The first-choice treatment for DON is intravenous administration of steroids, with or without radiotherapy. Unfortunately, refractoriness to this medical treatment may indicate the need for immediate orbital decompression within 2 weeks. Especially in the acute phase of DON, thyroid function is often unstable, and the surgeon must always assume the risk of general anesthesia and intra- and post-operative management. In addition, there are currently many possible therapeutic options, including molecular-targeted drugs. The early introduction and combination of these immunomodulators, including Janus kinase inhibitors and insulin-like growth factor-1 receptor antibody (teprotumumab), may be effective for GO with DON. However, this is still under investigation, and the number of case reports is small. It is possible that these options could reduce systemic adverse events due to unfocused glucocorticoid administration. The pathophysiology of DON is not yet fully understood, and further studies of its treatment and long-term visual function prognosis are needed.Keywords: Graves’ orbitopathy, orbital decompression, dysthyroid optic neuropathy, magnetic resonance imaging, MRI, visual outcome, teprotumumab, Janus kinase inhibitors

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.

Thyroid eye disease (TED), an autoimmune inflammatory disorder of the orbit, presents with a potential array of clinical sequelae. The pathophysiology behind TED has been partially characterized in the literature. There remain certain elusive mechanisms welcoming of research advances. Disease presentation can vary, but those that follow a characteristic course start mild and increase in severity before plateauing into an inactive phase. Diagnosis and evaluation include careful physical examination, targeted laboratory work up, appropriate imaging studies, and tailored treatment regimens. Special consideration may apply to certain populations, such as pediatric and pregnant patients. [ABSTRACT FROM AUTHOR]

We report a 51‐year‐old woman with thyroid eye disease and biopsy‐proven pretibial myxedema that was subsequently treated with teprotumumab with improvement. [ABSTRACT FROM AUTHOR]

Graves' orbitopathy (GO) is an orbital autoimmune disorder and the main extrathyroidal manifestation of Graves' disease, the most common cause of hyperthyroidism. GO affects about 30% of Graves' patients, although fewer than 10% have severe forms requiring immunosuppressive treatments. Management of GO requires a multidisciplinary approach. Medical therapies for active moderate‐to‐severe forms of GO (traditionally, high‐dose glucocorticoids) often provide unsatisfactory results, and subsequently surgeries are often needed to cure residual manifestations. The aim of this review is to provide an updated overview of current concepts regarding the epidemiology, pathogenesis, assessment, and treatment of GO, and to present emerging targeted therapies and therapeutic perspectives. Original articles, clinical trials, systematic reviews, and meta‐analyses from 1980 to 2021 were searched using the following terms: Graves' disease, Graves' orbitopathy, thyroid eye disease, glucocorticoids, orbital radiotherapy, rituximab, cyclosporine, azathioprine, teprotumumab, TSH‐receptor antibody, smoking, hyperthyroidism, hypothyroidism, thyroidectomy, radioactive iodine, and antithyroid drugs. Recent studies suggest a secular trend toward a milder phenotype of GO. Standardized assessment at a thyroid eye clinic allows for a better general management plan. Treatment of active moderate‐to‐severe forms of GO still relies in most cases on high‐dose systemic—mainly intravenous—glucocorticoids as monotherapy or in combination with other therapies—such as mycophenolate, cyclosporine, azathioprine, or orbital radiotherapy—but novel biological agents—including teprotumumab, rituximab, and tocilizumab—have achieved encouraging results. [ABSTRACT FROM AUTHOR]

To compare the effects of different treatment modalities on active, moderate‐to‐severe Graves' orbitopathy (GO). We searched PubMed and Embase for randomized controlled trials published up to 30 Nov 2020, of different modalities for the treatment of active, moderate‐to‐severe GO. We performed Bayesian network meta‐analyses. This study is registered with PROSPERO (CRD42020166287). Fifteen RCTs were identified. Network meta‐analysis showed that in comparison with placebo, teprotumumab, mycophenolate plus intravenous glucocorticoids (IVGCs), mycophenolate, rituximab, azathioprine, IVGCs, orbital radiotherapy, oral glucocorticoids (OGCs) were effective treatments (ordered from most effective to least effective). Teprotumumab was more efficacious in reducing proptosis than IVGCs. No significant difference in changes in diplopia grade was recorded between teprotumumab, rituximab, orbital radiotherapy and IVGCs. Low (4.5–5 g), middle (6 g) and high (7–8 g) cumulative doses of IVGCs were shown to be more effective than OGC in improving the overall response rate, but the very low‐group (<3 g) seemed to have a lower risk of adverse events. We found that teprotumumab offered the highest level of efficacy in terms of the overall response rate and was more efficacious in reducing proptosis than IVGCs. With regard to different dosages of IVGCs, the cumulative dose of 4.5–5 g of IVGCs seems to be the most appropriate schedule in terms of efficacy and safety outcomes. Due to the limited number of patients treated with teprotumumab and the lack of comparison with other effective therapeutics, teprotumumab might not become the standard first‐line therapy for active, moderate‐to‐severe GO. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine changes in intraocular pressure (IOP) in patients with thyroid eye disease (TED) following teprotumumab. MATERIALS AND METHODS: A retrospective review of 17 patients with TED who received teprotumumab between January 2020 and September 2021 was conducted. IOP, extent of proptosis, and clinical activity score were reviewed at baseline and at 6 weeks, 12 weeks, and 24 weeks for patients undergoing teprotumumab treatment. The primary outcome measure was change in IOP, while secondary outcome measures included changes in proptosis and clinical activity score. RESULTS: Of the 17 patients (34 eyes) with TED who were treated with teprotumumab, the mean age was 50.5 years, and 15 (88%) were female. The mean baseline IOP was 20 mm Hg (range 13-28), and the mean baseline clinical activity score was 3.8 (range 0-6). Of the 34 eyes examined at baseline, examinations were repeated in 16 at 6 weeks, 26 at 12 weeks, and 8 at 24 weeks. At week 6 of treatment, mean IOP decreased by 4.9 mm Hg (P < 0.0001). At week 12 of treatment, mean IOP decreased by 4.6 mm Hg (P < 0.0001). Mean IOP was decreased at last record of follow-up by 4.9 mm Hg (P < 0.0001). CONCLUSION: Among patients with TED, teprotumumab treatment was associated with a reduction in IOP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab's effect on intraocular pressure.Case Presentation: We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman. The diagnosis of thyroid eye disease was based on increased redness, swelling, and excessive tearing; abnormal proptosis, lid retraction, and diplopia measurements were also taken during physical examination. Intraocular pressure in primary, lateral gaze, and upgaze was documented. There was significant (p = 0.0397) improvement of primary gaze eye pressure from pre-teprotumumab infusions (baseline) to completion of the treatment course.Conclusions: Teprotumumab significantly decreased the intraocular pressure for patients during the duration of the study. Teprotumumab is a novel medication that is approved for the primary treatment of thyroid eye disease in both acute and chronic thyroid eye disease. Previous treatments used to treat thyroid eye disease include glucocorticoids, radiotherapy, or orbital decompression surgery; however, these treatments all have significant limitations. Teprotumumab is an effective noninvasive alternative for decreasing symptoms of thyroid eye disease and, as shown, also lowers intraocular pressure. However, teprotumumab should not be used as a substitute for glaucoma medications; its ability to lower intraocular pressure may be in addition to lowering periorbital pressure and retro-orbital pressure. [ABSTRACT FROM AUTHOR]

Abstract Background On 21st January 2020, the FDA approved Tepezza (teprotumumab-trbw) for the treatment of active Graves’ orbitopathy (GO) in adults. This approval was based on positive results from two multinational randomised double-blind placebo-controlled clinical trials. Discussion This article discusses the outcomes of those trials and the potential role of teprotumumab in altering current treatment paradigms in Graves’ orbitopathy. Future challenges are explored, including the need to confirm its disease-modifying effect, to establish its optimal position in the treatment pathway, and to define the appropriate subset of patients who would benefit from its use. Conclusions The results from these two large clinical trials have shown teprotumumab to have remarkable effects on multiple clinical outcomes in GO, particularly in its ability to reverse proptosis. It may herald a new era in the treatment of thyroid eye disease and could offer an alternative to surgery and its associated complications. Additional studies will continue to shape the treatment of GO and define the role of teprotumumab within the treatment paradigm.

Thyroid associated ophthalmopathy (TAO) is a common extra-thyroid clinical manifestation of Graves’ disease. It is an inflammatory disease of the eye and orbital tissues. Up to one-third of pediatric Graves’ disease patients could be diagnosed with TAO. The symptoms can be variable with remissions and exacerbations of pediatric Graves’ disease, which has negative effects on the quality of life in children. Teprotumumab is a fully human IgG1κ type monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), and was approved for the treatment of TAO as a “breakthrough therapy” by the FDA in 2020. Nevertheless, the safety and effectiveness have not been established in pediatric patients. IGF-1R plays an important role in human development, which raises concerns of developmental toxicity. As presented in the pharmacology review report, juvenile monkeys were tested in two separate repeated-dose toxicity studies and no NOAEL was identified. Teprotumumab affected the growth, thymus, spleen and decreased the bone growth. Younger animals seemed to be more sensitive to the effects on normal growth and normal thymus. Hearing impairment posed additional risk to the potential pediatric use, especially for school-age children. Considering the nature of the target, Teprotumumab should not be used empirically in children. More efforts would be made for the further development of teprotumumab for pediatric use.

Purpose: To report the case of a patient with reactivated, refractory thyroid eye disease (TED) treated with teprotumumab. Observations: A 51-year-old female with a 16-year history of thyroid eye disease previously treated with orbital decompression and multiple eyelid surgeries presented in a recurrent flare of the disease. The disease recurrence was refractory to intravenous steroid therapy and only partially responsive to oral steroid therapy, and the patient developed dysthyroid optic neuropathy in the right eye with decreased visual acuity and color vision. Clinical activity score was 8/10 and proptosis measurements were 27 mm OD and 26 mm OS. The patient underwent treatment with eight infusions of teprotumumab coinciding with a low taper of oral prednisone and experienced resolution of dysthyroid optic neuropathy, decrease of clinical activity score to 1, and dramatic improvement in proptosis (17 mm OD, 17 mm OS) and extraocular muscle size on imaging. Thirty weeks after completion of teprotumumab and 2 weeks after the second dose of the COVID vaccine, she experienced another flare and subsequently underwent bilateral orbital decompressions. Conclusion: This case report suggests teprotumumab may be used in patients with reactivation of longstanding thyroid eye disease. Reduction of extraocular muscle size and improvement in proptosis suggest teprotumumab may be disease-modifying even in advanced cases.

Purpose: Describe five cases of long-standing, active thyroid eye disease that responded to treatment with teprotumumab. Observations: Five patients with a greater than 9-month-history of thyroid eye disease, including two patients who had previously failed orbital radiotherapy, received eight doses of teprotumumab. All five patients, including those with a history of orbital radiotherapy, achieved a proptosis reduction of at least 2 mm in each eye as well as a Clinical Activity Score reduction of at least 2 points. In addition, all cases of diplopia improved and all but one case of lagophthalmos improved. Conclusions and Importance: Teprotumumab may be a safe and efficacious therapy for active thyroid eye disease that is of longer duration than previously studied in clinical trials, as well as disease refractory to orbital radiotherapy. In addition to robust improvement in proptosis and Clinical Activity Score, data from this series suggests diplopia and lagophthalmos may also respond to teprotumumab. Further study of teprotumumab is needed, but in the meantime these results may encourage providers to consider teprotumumab for their patients with long-standing or previously treated disease.

Background: Long-duration thyroid eye disease (TED) may present with persistent proptosis despite the absence of inflammatory symptoms, and treatment options have been limited to surgical intervention. Recently, teprotumumab, a monoclonal antibody, has garnered interest as a non-surgical option to reduce proptosis in such cases. This systematic review investigates the impact of teprotumumab on reducing proptosis in long-duration TED. Methods: A search was conducted across major online databases, and data were aggregated from observational studies, clinical trials and case series. Nine studies met the inclusion criteria. Cumulative and weighted effect measures were synthesized. The biases and limitations of each study were assessed. Results: Existing evidence shows teprotumumab to be highly efficacious in reducing proptosis in chronic TED; however, there are significant limitations in the quality of existing evidence. The cumulative meta-analysis reveals a mean proptosis reduction of 3.05 ± 0.54 mm across 182 orbits from nine studies, and the weighted meta-analysis shows a mean reduction of 2.69 ± 0.53 mm across 172 orbits from eight studies. Discussion: While existing clinical studies are open to bias and intrinsically limited, the meta-analysis dilutes the risk of bias by weighting more precise evidence, providing the highest quality evidence to date. Further research is essential to understand teprotumumab's long-term efficacy and comparative advantages over surgical options. These findings have significant implications for treating persistent proptosis in patients with long-duration TED, potentially offering a non-surgical alternative where options were previously limited., Competing Interests: Disclosures: Nicholas Householder and Coby Ray have no financial or non-financial relationships or activities to declare in relation to this article., (© Touch Medical Media 2024.)

Pretibial myxedema (PTM), also called thyroid dermopathy, is a dreaded and potentially debilitating manifestation of thyroid disease, more commonly Graves’ disease, which can occur at any time over the course of the disease. No substantial long-term therapies have been able to target the condition, and management has typically been supportive (eg, compression socks, weight loss), with courses of moderateintensity steroids. Teprotumumab has been approved for the management of thyroid eye disease (TED), and it is believed that the 2 share a similar pathophysiology likely related to type 1 insulin-like growth factor receptor, which may explain why some patients have also experienced improvement in PTM. Here we present a patient who received 8 doses of teprotumumab for TED who, over the course of management and into follow-up, experienced significant improvement in her pretibial myxedema. The patient noted considerable improvement in quality of life and ability to perform daily activities. We present this case to consider further investigation into the utilization of teprotumumab for thyroid disease–related PTM in patients with impaired quality of life. [ABSTRACT FROM AUTHOR]