Thyroid Eye Disease Symptoms Research Articles

6822 Proptosis Improvement with Teprotumumab is Independent of Race, Ethnicity, Gender and Age from Three Global Randomized, Double-Masked, Placebo-Controlled Trials of Patients with Acute Thyroid Eye Disease (TED)

Abstract Disclosure: G.J. Kahaly: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. S.T. Wester: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Immunovant, Lassen. Research Investigator; Self; Amgen Inc, Sling Therapeutics, Immunovant. C.Y. Liu: Other; Self; royalties from Wolters Kluwers Health. H. Kate: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. E. Conrad: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. R.J. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Y. Hiromatsu: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. Introduction: Thyroid eye disease (TED) produces orbital tissue expansion, inflammation, proptosis (eye bulging) and diplopia (double vision), causing eye pain and appearance/visual changes. Teprotumumab, an insulin-like growth factor-1 receptor inhibitor, significantly improved signs and symptoms of TED in three placebo-controlled trials in patients with high inflammation. Here, we report pooled proptosis response in patient subgroups. Methods: Patients ≥18 years old from three placebo-controlled trials, two in the US and EU (NCT01868997, NCT03298867) and one in Japan (OPTIC-J; jRCT2031210453), with Graves’ disease and recent onset (≤9 month duration) active TED (Clinical activity score, CAS≥4, ≥3 for OPTIC-J) were included. Patients received eight infusions of teprotumumab or placebo over 21 weeks, with the final study visit at Week 24 (three weeks after final dose). Observed proptosis response, defined as ≥2 mm improvement from baseline in study eye without deterioration ≥2 mm in fellow eye at Week 24, versus placebo is reported by tobacco use (yes/no), race (White or Asian), and age (<65/≥65). Cochran-Mantel-Haenszel tests compared teprotumumab and placebo subgroups. Results: Of 111 teprotumumab and 114 placebo patients, 68.5% (76) and 76.3% (87) were female, respectively; mean (SD) age 50.3 (12.4) and 51.1 (13.1) years, respectively; mean (SD) TED duration 5.49 (2.32) and 5.98 (2.40) months, respectively; and 78.4% (87) and 73.7% (84) were never/former smokers, respectively. In the overall population, 80.2% (89/111) of teprotumumab patients and 14.0% (16/114) of placebo patients had a proptosis response (P<.0001). At Week 24, 70.8% (17/24) of teprotumumab and 23.3% (7/30) placebo smokers were proptosis responders; in non-smokers, 82.8% (72/87) of teprotumumab and 10.7% (9/84) placebo patients were proptosis responders (P<.0001 for both). In White patients, 78.9% (56/71) of teprotumumab and 15.8% (12/76) of placebo patients were proptosis responders; in Asian patients, 90.0% (27/30) of teprotumumab and 10.0% (3/30) of placebo patients were responders (P<.0001 for both). In patients <65 years, 79.2% (76/96) teprotumumab patients and 13.4% (13/97) placebo patients were responders; in patients ≥65 years, 86.7% (13/15) teprotumumab and 17.6% (3/17) placebo were responders (P<.0001 for both). Conclusions: Subgroup analysis of proptosis response by tobacco use, race, and age showed that teprotumumab treatment led to significantly higher proptosis response versus placebo in all groups. Public Presentation: 6/1/2024

Efficacy and Systemic Effects of a Single Deep Orbital Triamcinolone Injection for Thyroid Eye Disease.

Orbital steroid injections offer a potential therapeutic avenue for managing Thyroid Eye Disease (TED). This study aimed to assess the effectiveness and potential systemic impacts of a single deep orbital triamcinolone injection in TED patients. In a prospective investigation conducted from January 2021 to March 2023, patients diagnosed with TED were enrolled. Inclusion criteria encompassed a Clinical Activity Score (CAS) of ≥3, extraocular muscle inflammation, and upper eyelid retraction. A total of 1 mL of triamcinolone acetonide (40 mg/mL) was administered posterior to the orbital septum at both the medial and lateral aspects of both the upper and lower eyelids. Parameters, including CAS, margin-reflex distances (MRD1 and MRD2), intraocular pressure (IOP), ocular motility (Hess area ratio [HAR%]), exophthalmometry, extraocular muscle size, and blood and urinary indices, were evaluated before and at 2 and 4 weeks after a single injection. Analysis included 28 patients (23 women, 5 men; mean age (SD): 38.7 (11.1) years), representing 56 eyes. Following the injection at 4 weeks, the mean CAS and MRD1 significantly decreased by 2 points and 0.8 mm, respectively. There was a 4.5% increase in HAR%, and extraocular muscle size decreased by 4 to 15.3 mm². Neutrophil count, C-reactive protein, and thyroid antibodies significantly decreased. No severe adverse ophthalmic or systemic effects, including IOP increases or liver damage, were observed. Bilateral single orbital triamcinolone injections provided relief from TED symptoms through both direct effects on orbital soft tissue and systemic effects by decreasing antibody reactions.

Phasing and continuity of the treatment of thyroid eye disease in patients with Graves' disease

According to modern concepts, thyroid eye disease (TED) is an independent progressive autoimmune disease of the organ of vision, closely associated with the autoimmune pathology of the thyroid gland (TG), (ICD code - H06.2, proptosis in case of impaired thyroid function E05.0). TED treatment is a long step-by-step process, including immunosuppressive therapy, radiation therapy of the orbits and surgical treatment.TED is a multidisciplinary problem. A patient with thyrotoxicosis clinic and TED symptoms will be taken to an endocrinological clinic for normalization of thyroid hormones and treatment of thyrotoxicosis complications. At the same time, under thesupervision of an ophthalmologist, TED diagnostics and treatment will be carried out. Teamwork is of utmost importance because the effectiveness of TED treatment will depend on the speed of achieving a stable euthyroid state, the accuracy of determining the TED activity and severity, and the presence of complications requiring surgical treatment.There are two main phases in the TED development. In the first phase of active inflammation, an increase in the symptoms of TED occurs, then a plateau phase follows, when the symptoms of activity persist but do not progress, then the symptoms regress and the process becomes inactive, while visual disturbances and cosmetic defects may persist. Determining the TED activity is very important from a clinical point of view, because the choice of treatment and tactics of patient management depend on the inflammation activity.We describe a clinical case of phasing treatment of TED complicated by optic neuropathy and movement disorders in a patient with Graves' disease, resistant to immunosuppressive therapy with glucocorticoids and requiring deep lateral bony orbital decompression.

Concurrent pretibial myxedema and thyroid eye disease following mRNA COVID-19 vaccine in a patient with history of Graves’ disease

A 70-year-old female had a history of thyroid surgery for benign nodules and Graves’ disease. Following mRNA COVID-19 vaccination, she presented Graves’ orbitopathy and pretibial myxedema. Symptoms of thyroid eye disease and thyroid dermopathy improved after 500-mg methylprednisolone infusions.

SAT466 Inactive Thyroid Eye Disease Patient Journey

Abstract Disclosure: K. Cockerham: Consulting Fee; Self; Horizon Therapeutics plc, Viridian. T.J. Smith: Consulting Fee; Self; Horizon Therapeutics plc, Viridian, Lundbeck. Other; Self; US patents covering the use of IGF-1 receptor inhibitors in TED which are held by UCLA and the Lundquist Institute. E. Conrad: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. R.J. Holt: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. Objective: Limited long-term data are available on US patients with thyroid eye disease (TED). From an online survey conducted in January 2020 of patients who were assessed by their healthcare providers (HCPs) as having inactive TED, 100 patients (age 45.2 ± 7.6 years, 47% female) with current non-inflammatory/inactive TED were identified with an average duration of 2.7 years after active TED diagnosis.1 Here we examined the journey of these TED patients from active/inflammatory to inactive/non-inflammatory disease status. Methods: We collected patient demographics, diagnoses and symptom prevalence over time, number of HCPs seen, and treatments from an online survey conducted in January 2020. Results: Of 100 patients, 98 had a diagnosis (Dx) of thyroid autoimmunity. Active TED was typically diagnosed within 2.2 years of the thyroid Dx (N=98), approximately 2.1 years after first eye symptoms with an average of 5.7 TED symptoms while visiting a mean of 2 HCPs between first TED symptoms and Dx. Mostly ophthalmologists (69%), endocrinologists (49%), and primary care physicians (PCP; 45%) were consulted. By the time TED was assessed as inactive/non-inflammatory (2.7 years after active TED diagnosis1), patients typically visited 2 different HCP specialties within the past year (ophthalmologists 61%, endocrinologists 51%, and PCP 32%) and were experiencing 3.4 TED symptoms with an average of 19.7 ± 31.7 visits/year (median: 6 visits/year, range: 1-160 visits/year) and 2 prescribed medications for TED. Over-the-counter eyedrops (50%) and pain relievers (ibuprofen/naproxen [41%] and acetaminophen [33%]) were the most commonly used for inactive TED patients. Prescription eyedrops (27%) and topical steroids (22%) were also commonly used in inactive TED. Oral and intravenous steroids were used in 8% and 3%, respectively. Among the 27% of patients with any surgical TED procedure, orbital decompression (14/27; 52%, mean age 38) and strabismus surgery (8/27; 30%) were the most commonly performed. Discussion/Conclusion: From this analysis, patients with active/inflammatory TED typically experience ∼ 3 years of symptoms, HCP visits, and treatments prior to inactive TED diagnosis. TED diagnosis is often delayed in the US. Approximately 5 years elapse from first TED eye symptoms. This and other recent data1 indicate that inactive TED is typically symptomatic, and patients continue to experience impaired quality of life, requiring specialized care/medication for symptom management.

Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series

BackgroundTeprotumumab 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 presentationWe 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.ConclusionsTeprotumumab 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.

SAT-500 Response to Tocilizumab Retreatment in Refractory Thyroid Eye Disease

Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported.Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal < 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100.Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed.

Immunotherapies for thyroid eye disease.

Thyroid eye disease is a complex autoimmune disorder which causes substantial morbidity. It can result in orbital disfigurement, double vision, and visual loss. Consequently, it has a substantial negative effect on quality of life, mental health, and socioeconomic status. Most signs and symptoms of thyroid eye disease (TED) can be explained by the expansion of the orbital contents. Steroids are the mainstay of treatment in TED. However, recurrence may occur once steroids are withdrawn. Furthermore, in most cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required to reduce disfigurement, double vision, and to preserve vision. Therefore, novel, causal, and more efficacious treatment strategies are warranted. In the last decade, the pathophysiology of TED has also been revised with the identification of new potential therapeutic targets. Recent clinical trials have shown that considerable benefit may be derived from the addition of antiproliferative agents (e.g., mycophenolate sodium) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab (anti-IGFR) which appears to substantially reduce proptosis, rituximab (anti-CD20) which reduces inflammation and tocilizumab (anti-IL-6) which potentially benefits both of these parameters. This short review summarizes the recent research developments in this area.

Oral Montelukast and Cetirizine for Thyroid Eye Disease

To study the efficacy of oral montelukast, a cysteinyl leukotriene receptor antagonist, in combination with cetirizine, a histamine-1 receptor antagonist, in the treatment of thyroid eye disease. Patients considering surgical correction of eyelid retraction for inflammatory symptoms of thyroid eye disease were offered a preoperative medical regimen of oral montelukast/cetirizine. Exclusion criteria included prior use of oral montelukast (i.e., for seasonal allergy or asthma), compressive optic neuropathy, severe ophthalmopathy requiring systemic corticosteroids, and orbital and/or muscle surgery. A 6-week course of oral cetirizine (10 mg every morning) and oral montelukast (10 mg every evening) was administered and patients subjectively rated their ocular surface dryness, tearing, itching, injection, eyelid swelling, eyelid retraction, double vision, proptosis, and visual clarity, at baseline, after 3 weeks and 6 weeks of medical therapy, and after 3 weeks off of the medications. Six of the 12 patients recruited for the study reported a subjective improvement in tearing, dryness, and itching. Less effect on diplopia and proptosis was noted after 6 weeks of medical therapy. Two of the patients who did not report response chose to proceed with eyelid retraction surgery and both had evidence of mast cell infiltration in their Müller muscle specimens. The response observed in this open-label trial suggests that oral montelukast and cetirizine may be an effective medical regimen for patients with thyroid eye disease who experience mild to moderate orbital congestion and inflammation.