Abstracts of the EUGOGO Global TED Forum 2025

A01 Thyroid autoimmunity and TED

Colin Dayan

Thyroid Research Group, Cardiff University School of Medicine, Cardiff, UK

Correspondence: Colin Dayan Thyroid Research 2025, 18(s2):A01

Autoimmune thyroid disease is the commonest autoimmune condition. 5-10% of women have circulating antithyroid autoantibodies and over 40% have evidence of lymphocytic infiltration in the thyroid gland, with lower rates in men. The majority of autoimmune thyroid disease either does not impact thyroid function at all or results in subclinical hypothyroidism. Slow progression of subclinical hypothyroidism to overt disease - around 3-5% per year - has been documented but many cases remain subclinical. The main target antigens are well characterised (thyroglobulin Tg, thyroid peroxidase (TPO) and the TSH receptor, TSHR) with both T and B cell responses detectable. Levels of circulating autoantibodies are 100-1000x higher for Tg and TPO than for TSHR and TPO autoantibodies persist for years if not the patients lifetime. Graves disease results from the emergence of agonist antibodies to the TSH-receptor (TRAbs). Such agonist activity on a receptor is rare in autoimmune disease (although not unique). The link between Graves and TED appears to be TRAbs although it seems a subset of TRAbs are involved which are not present in all patients. Currently we do not have an assay for the “eye activity” and hence the relationship between TRAb levels and TED is imperfect. This presentation will review the role of TRAbs in TED and the role of TRAb measurements in clinical care.

A02 TED Immunology

Sijie Fang^1,2,3

¹Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai, China, ²Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai, China

Correspondence: Sijie Fang Thyroid Research 2025, 18(s2):A02

Thyroid eye disease (TED) is an organ-specific autoimmune disorder whose pathogenesis involves the synergistic action of T cells, B cells, myeloid cells, and other immune cells. Orbital fibroblasts (OFs), which highly express thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) on their surface, represent the core link in the immune imbalance of TED. Recent studies have demonstrated that, in addition to the classic T helper (Th) 1- and Th2-mediated inflammatory responses, Th17 cells can further induce orbital tissue remodeling, while cytotoxic T cells may be a critical factor contributing to tissue damage. TED-associated autoantibodies target the tightly bound “functional unit” of TSHR and IGF-1R, activate downstream signaling, promote OFs to release hyaluronic acid and inflammatory mediators, and induce their differentiation into orbital adipocytes, thereby forming a positive feedback loop. With the clinical application of biological agents targeting the neonatal Fc receptor (FcRN), interleukin (IL)-6R, and IGF-1R, it has become particularly important to clarify the mechanisms underlying the interaction between T cells and B cells via autoantibodies, cytokines, and co-stimulatory molecules. Myeloid cells secrete cytokines such as IL-6, tumor necrosis factor-α (TNF-α), and IL-23, which amplify the “crosstalk” between T cells and B cells and sustain the activation of OFs. Elucidating this complex immune-inflammatory network is expected to pave the way for novel approaches to the precise treatment of TED.

A03 Orbital Fibroblast Biology

Gina-Eva Görtz, Fahimeh Hashemi Arani, Mareike Horstmann, Anja Eckstein

Molecular Ophthalmology, University Hospital Essen, Essen, Germany

Correspondence: Gina-Eva Görtz Thyroid Research 2025, 18(s2):A03

Orbital fibroblasts (OFs) are central effector cells in the pathogenesis of Thyroid Eye Disease (TED). They exhibit remarkable functional plasticity and respond dynamically to immunological and metabolic stimuli by undergoing adipogenic or fibrotic differentiation. Within the orbit’s inflammatory microenvironment—shaped by hypoxia, cytokines, autoantibodies, and intercellular interactions—OFs undergo disease-relevant reprogramming.

Hypoxia plays a pivotal role by promoting VEGF secretion and adipogenic differentiation through HIF-1α activation. This effect is potentiated in smokers, correlating with more severe disease manifestations. OFs also interact closely with infiltrating immune cells, particularly macrophages, which under hypoxic conditions initiate proinflammatory signaling cascades, further accelerating fibroblast differentiation and tissue expansion.

Another key regulatory axis involves CD40 signaling, which induces the production of the bioactive lipid sphingosine-1-phosphate (S1P) in OFs. S1P enhances T cell recruitment into orbital tissue, thereby exacerbating local inflammation.

Additionally, functional crosstalk between the thyroid-stimulating hormone receptor (TSHR) and the insulin-like growth factor 1 receptor (IGF-1R) has been identified. This interaction synergistically amplifies hallmark features of TED, including inflammation, hyaluronan production, and adipogenesis. In our current study, we examine potential changes in IGF-1R expression in patients treated with or without radiotherapy to better understand its role in disease progression and treatment response.

We are also investigating the contribution of myofibroblasts in TED, comparing their fibrotic characteristics to those of OFs. The aim is to clarify their profibrotic potential and evaluate the therapeutic relevance of antifibrotic interventions.

Taken together, these findings underscore that OFs are not passive bystanders but active mediators of inflammation, remodeling, and fibrosis in TED. Targeted modulation of their signaling pathways holds promise for the development of personalized, mechanism-based therapies.

A04 Animal Models

Anja Eckstein¹, Gina Eva Görtz², Fahimeh Hashemi Arani², Mareike Horstmann², Erich Gulbins³, Paul Banga²

¹Ophthalmology, University Duisburg Essen, Essen, Germany, ²Molecular Ophthalmology, University Duisburg Essen, Essen, Germany, ³Molecular Biology, University Duisburg Essen, Essen, Germany

Correspondence: Anja Eckstein Thyroid Research 2025, 18(s2):A04

Animal models are essential for investigating the underlying mechanisms of disease and for testing potential therapies. Genetic immunization using a plasmid encoding the extracellular domain of the thyroid-stimulating hormone receptor (TSHR) induces a robust autoimmune response that closely mimics key features of human thyroid eye disease (TED). This model is now widely used to study the natural course of the disease and to evaluate new treatment strategies—both as monotherapies and in combination—at various stages of disease progression. Particularly valuable are settings that explore prevention, treatment of fully developed disease, and management of chronic stages.

TED exhibits variable phenotypes resulting from both inflammatory processes (immune cell infiltration and activation of orbital fibroblasts to secrete cytokines) and proliferative changes (adipogenesis—characterized in mice by browning of orbital fat—and fibrosis due to hyaluronan and extracellular matrix deposition). These pathological features can be thoroughly examined through histological analysis, omics technologies, and advanced imaging.

A major advantage of this animal model is the ability to assess not only local changes in the thyroid and orbit but also systemic immune responses, including immune cell activation in local lymph nodes and bone marrow. This is critical for developing therapies aimed at achieving long-lasting disease inactivation. Notable treatment studies have been conducted with Linsitinib (which halts TED and bone marrow activation), Maraviroc (primarily inhibiting adipogenesis), and Fingolimod (effective in preventing disease when administered early).

A05 TED and the Microbiome

Marian Ludgate

Thyroid Research Group, Cardiff University School of Medicine, Cardiff, UK

Correspondence: Marian Ludgate Thyroid Research 2025, 18(s2):A05

TED is an autoimmune condition most usually associated with hyperthyroid Graves’ disease (GD). Considerable progress has been made in understanding disease end-points, i.e. the orbital tissue remodeling which underpins disease. Less is known of events which trigger the loss of tolerance leading to autoimmunity; genetic susceptibility is implicated but environmental factors also participate. The gut microbiota composition varies with diet and has diverse functions, mainly mediated by short-chain fatty acids, including modulation of immune balance.

Murine models of TED/GD clearly support a role for the gut microbiota; disease-associated taxa were identified and induced disease could be ameliorated by antibiotic treatment but exacerbated by transfer of fecal material from TED/GD patients.

Studies in patients are more complex and display considerable geographic variation. Despite this, all studies have demonstrated reduced gut microbiota diversity and it is possible to begin definition of a microbiome signature. Of note, differential abundance of 15 genera (cases versus healthy controls) was most skewed in mild TED.

Microbiome studies in TED/GD are uniquely complicated by the interplay between the microbiota and thyroid hormones and/or therapeutic drugs. Future studies should include metagenomics (i.e., at species and strain levels) and microbial metabolites and would benefit from collaborations between teams in Europe, the USA and Asia.

Ludgate ME, Masetti G, Soares P. The relationship between the gut microbiota and thyroid disorders. Nat Rev Endocrinol. 2024 Sep;20(9):511-525. doi: 10.1038/s41574-024-01003-w. Epub 2024 Jun 21. PMID: 38,906,998.

A06 Thyroid Management in a changing landscape

Chrysoula Dosiou

Division of Endocrinology/Department of Medicine, Stanford University School of Medicine, Stanford, USA

Correspondence: Chrysoula Dosiou Thyroid Research 2025, 18(s2):A06

Graves’ disease (GD) is a systemic illness caused by thyroid stimulating immunoglobulins (TSI), with increased morbidity and mortality if untreated. While hyperthyroidism is its most common manifestation, extrathyroidal illnesses such as thyroid eye disease (TED) and pretibial myxedema cause significant disability. Therapies for GD since the 1940s - antithyroid drugs (ATDs), thyroidectomy and radioactive iodine - only address hyperthyroidism, not extrathyroidal manifestations. Recently, there has been a large shift towards ATDs as the preferred first-line therapy, from 53.9% in 2012 to 91.5% in 2023 in wordwide surveys to endocrinologists. Existing therapies still have significant limitations. About 50% of patients relapse after standard ATD therapy, while 50% of patients starting ATDs eventually require definitive therapy. Some patients suffer ATD side effects or cannot be adequately controlled. Definitive therapies cause permanent hypothyroidism requiring chronic levothyroxine. Long term ATDs (>2 years) have emerged as an alternative in relapsed patients or those at high initial risk of relapse, after studies have shown their safety and greater effectiveness compared to standard therapy. In addition, novel GD therapeutics are being developed targeting TSI and its target, the TSH receptor. FcRn inhibitors, approved for myasthenia gravis, block the recycling of IgG immunoglobulins, enhancing TSI clearance. Batoclimab has shown promise in early clinical trials in TED and is currently in phase 3 trial for GD, along with other FcRn inhibitors in development. TSHR blocking antibodies or small molecule antagonists are also being investigated, with K1-70, a TSHR blocking antibody showing efficacy against both hyperthyroidism and TED in a phase 1 trial. Such agents will be desirable in hyperthyroid patients with extrathyroidal GD manifestations and serve as alternatives for patients with side effects, relapse, or inadequate control on ATDs. This new era for GD will require an even tighter collaboration between endocrinologists and ophthalmologists for optimal disease management.

References

1. Villagelin D, Cooper DS, Burch HB. A 2023 international survey of clinical practice patterns in the management of Graves disease: a decade of change. J Clin Endocrinol Metab. 2024;109:2956–66.

2. Sjolin G, Holmberg M, Torring O, et al. The long-term outcome of treatment for Graves’ hyperthyroidism. Thyroid. 2019;29:1545–57.

3. Cooper DS. Long-term antithyroid drug therapy. Curr Opin Endocrinol Diabetes Obes. 2021;28:510–16.

4. Brito JP, Payne S, Singh Ospina N, et al. Patterns of use, efficacy, and safety of treatment options for patients with Graves’ disease: a nationwide population-based study. Thyroid. 2020;30:357–64.

5. Azizi F, Amouzegar A, Tohidi M, et al. Increased remission rates after long-term methimazole therapy in patients with Graves’ disease: results of a randomized clinical trial. Thyroid. 2019;29:1192–200.

6. Azizi F, Malboosbaf R. Safety of long-term antithyroid drug treatment? A systematic review. J Endocrinol Investig. 2019;42:1273–83.

7. Kahaly GJ, Dolman PJ, Wolf J, et al. Proof-of-concept and randomized, placebo-controlled trials of an FcRn inhibitor, Batoclimab, for thyroid eye disease. J Clin Endocrinol Metab. 2023;108:3122–34.

8. Furmaniak J, Sanders J, Sanders P, et al. TSH receptor specific monoclonal autoantibody K1-70(TM) targeting of the TSH receptor in subjects with Graves’ disease and Graves’ orbitopathy-results from a phase I clinical trial. Clin Endocrinol. 2022;96:878–87.

9. Stan M, Dosiou C. The evolving therapeutic landscape of Graves’ disease in adults: present and future. Eur Thyroid J. 2025;14:e250078.

A07 TED Biomarkers

Hans Olav Ueland^1,2

¹Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway, ²Department of Clinical Medicine, University of Bergen, Bergen, Norway

Correspondence: Hans Olav Ueland Thyroid Research 2025, 18(s2):A07

Thyroid eye disease (TED) affects about 40% of patients with Graves’ disease (GD), but sensitive and specific biomarkers for early detection, risk stratification, and monitoring are lacking. While TSH receptor autoantibodies (TRAb) are in clinical use, its diagnostic accuracy is limited. Several studies have investigated alternative biomarkers in blood, tear fluid and urine, but none have been validated in independent replication cohorts [1].

In 2022, a proteomic study exploring inflammation-related serum proteins in GD patients with and without TED identified elevated levels of macrophage colony-stimulating factor (CSF-1) and interleukin-6 (IL-6) in those with TED. However, these biomarkers did not demonstrate clear discriminatory power between the groups [2]. Notably, serum levels of fibroblast growth factor 21 (FGF-21) was elevated in GD patients that subsequently developed TED, suggesting its potential as a predictive biomarker. A recent study, on tear fluid, found increased levels of CD40 ligand (CD40L) and chemokine (C-C motif) ligand 2 (CCL2), as well as more ocular discomfort and impaired meibum quality in GD patients with TED compared to those without [3].

A metabolomic study from 2023, on tryptophan metabolism observed strong associations between kynurenine metabolites and GD, supporting Th1-mediated immune activity as the driving force in the GD pathogenesis [4]. In addition, a study of acylcarnitine profiles showed accelerated catabolism in GD with a shift in energy source from carbohydrates to fat [5].

In summary, although TRAb remains the only biomarker for TED in current clinical use, its diagnostic properties are limited. This underscores the need for continued research and validation of potential biomarkers. Moreover, integrating proteomic and metabolomic approaches could provide deeper insights into the pathogenesis of the disease.

References

1. Ueland, Hans Olav, et al. Molecular biomarkers in thyroid eye disease: a literature review. Ophthal Plast Reconstr Surg. 2023;39(6S):S19–S28.

2. Ueland, Hans Olav, et al. Novel inflammatory biomarkers in thyroid eye disease. Eur J Endocrinol. 2022;187(2):293.–300.

3. Neset, Mikael T, et al. Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease. Acta Ophthalmol. 2025. Ahead of publication.

4. Ueland, Hans Olav, et al. Systemic activation of the kynurenine pathway in Graves disease with and without ophthalmopathy. J Clin Endocrinol Metab. 2023;108(6):1290–7.

5. Neset, Mikael Thomassen, et al. Insight into the metabolic shifts in Graves’ hyperthyroidism: a study of acylcarnitine and lipid profiles. Eur Thyroid J. 2025;14(3).

A08 Definitive Treatment options: Radioiodine vs. Thyroidectomy

Karim Meeran

Endocrinology, Imperial College, London, UK

Correspondence: Karim Meeran Thyroid Research 2025, 18(s2):A08

Treatment of hyperthyroidism includes antithyroid drugs (which can be titration or block and replace), radioiodine or thyroidectomy. All these options have risks and benefits. Definitive treatment has the advantage of stabilizing thyroid function. Radioiodine is known to slightly increase the risk of worsening eye disease, but this risk is completely mitigated by prednisolone. Thyroidectomy has a lower risk of worsening eye disease, but has other risks including permanent hypoparathyroidism (resulting in severe hypocalcaemia that requires lifelong unpleasant treatment with large doses of calcium and vitamin D analogues) and vocal cord palsy. These risks are also low, but need to be considered before abandoning radioiodine.

With careful patient selection, and judicious use of prednisolone, radioiodone is an acceptable treatment in patients with TED.

A09 Managing Risk Factors

Miloš Žarković^1,2

¹Faculty of Medicine, University of Belgrade, Belgrade, Serbia, ²Thyroid Department, Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Belgrade, Serbia

Correspondence: Miloš Žarković Thyroid Research 2025, 18(s2):A09

Thyroid eye disease (TED) is a potentially sight-threatening autoimmune orbital disorder. Recent advances highlight the crucial role of managing risk factors in improving TED outcomes. Multiple factors contribute to TED risk and severity, including non-modifiable elements (male sex, older age, diabetes) and modifiable factors such as cigarette smoking, thyroid dysfunction, hypercholesterolemia, and exposure to radioactive iodine. High concentrations of thyrotropin receptor antibodies (TRAb) correlate with greater disease activity and severity. Among these, cigarette smoking is the most significant modifiable risk factor; it dramatically increases TED incidence and severity and impairs therapeutic response. Current guidelines strongly recommend smoking cessation. Similarly, both hyperthyroidism and hypothyroidism can exacerbate orbitopathy, making the achievement and maintenance of a stable euthyroid state an important preventive strategy. Early diagnosis and intervention are equally important–recognizing TED in its active phase and promptly controlling modifiable risks, combined with early immunomodulatory treatment of mild disease, can limit progression to disfiguring, severe stages. Timely diagnosis and intervention are vital; recognizing TED during its active phase and effectively managing modifiable risks, alongside early immunomodulatory treatment for mild cases, can prevent progression to severe and disfiguring stages of the disease. Thus, proactive risk factor management, early intervention, and a personalized, multidisciplinary approach are essential for improving clinical outcomes in patients with TED.

A10 Imaging in Thyroid Eye Disease

Kunwar Bhatia

Imaging, Imperial College Healthcare NHS Trust, London, UK

Correspondence: Kunwar Bhatia Thyroid Research 2025, 18(s2):A10

Imaging has several established and emerging roles in patients with known or suspected thyroid eye disease (TED).

Due to the presence of atypical clinical presentations of TED which can overlap with other orbital conditions, imaging has an initial role in supporting this diagnosis or suggesting alternative diagnoses. In this respect, a high clinical suspicion of TED mimics and appropriate imaging is required to avoid misdiagnosis.

In patients with TED, imaging provides both qualitative and semi-quantitative information with a particular focus on the posterior orbital structures that are sub optimally assessed by clinical evaluation alone. This includes the extra-ocular muscles, intraorbital fat, the orbital apex and optic nerve. Although CT and MRI can both provide dimensional (anatomic) information on the orbital soft tissues, MRI is far superior to CT in terms of permitting assessment of changes correlating with inflammation or oedema, which in turn may be surrogates for disease activity. Various MRI sequences including diffusion weighted imaging have been researched for their diagnostic utility, and the concept of a radiological activity score (RAS) has been proposed.

Some evidence suggests imaging may have diagnostic utility subgroup of TED patients with severe posterior orbital disease who are at risk of developing dysthyroid optic neuropathy.

Serial imaging has an important role in disease monitoring and can show changes associated with a reduction in inflammation as disease transitions to chronic stable phase. Imaging is likely to have a greater role in future clinical trials of novel antithyroid drugs and treatment paradigms.

A11 Occular Surface in TED

Andrea Kossler

Ophthalmology, Stanford University School of Medicine, Palo Alto, USA

Correspondence: Andrea Kossler Thyroid Research 2025, 18(s2):A11

Thyroid eye disease (TED) is associated with a high prevalence of ocular surface disease (OSD), estimated between 65% and 95%. While traditionally attributed to mechanical factors such as proptosis and corneal exposure leading to evaporative dry eye, recent evidence suggests an inflammatory etiology for OSD in TED. Previous findings indicate that lacrimal gland involvement plays a crucial role in TED, with enlargement correlated with disease severity. Additionally, alterations in tear film composition, including increased osmolarity and disrupted lipid layers, contribute to dry eye symptoms. This study delves into the molecular mechanisms underlying ocular surface changes by investigating the tear protein profiles of TED patients treated with Teprotumumab (TMB). The research builds upon proteomic studies indicating upregulation of inflammatory markers and downregulation of protective proteins in TED. However, no studies have yet assessed serial changes in the tear proteome after treatment with TMB. We conducted comprehensive proteomic analyses on tear samples collected from TED patients at three time points: before, during, and after teprotumumab compared to control patients. A significant number of proteins were identified (2,974 total), with 613 exhibiting differential expression between control and TED samples. Notably, proteins implicated in innate immunity, metabolism, and cell survival were depleted in the TED tear film compared to healthy control tears, suggesting that disruption of these processes contribute to the ocular surface phenotype of TED. Compared to controls, there were 168 proteins significantly upregulated in TED tears that were downregulated following treatment with TMB, and 286 proteins downregulated in TED tears that were restored following treatment with TMB, including proteins implicated in IGF regulation. Ocular surface disease appears to be multifactorial and incompletely treated with TMB. The insights gained from this research may help us understand the molecular underpinnings involved in TED and ultimately inform personalized therapeutic regiments to treat ocular surface and orbital disease for affected patients.

A12 Ocular hypertension in TED

Nicole Fichter¹, Jelena Juri Mandic²

¹Department of Ophthalmology, ADMEDICO Orbital Centre, Olten, Switzerland, ²Department of Ophthalmology, Medical School, University of Zagreb, Zagreb, Croatia

Correspondence: Nicole Fichter Thyroid Research 2025, 18(s2):A12

Epidemiologic data are scarce regarding elevated intraocular pressure (IOP) in TED patients in the sense of an ocular hypertension (OHT). But overall the prevalence of OHT in TED seems to be higher compared to the normal population. So far our guidelines do not contain recommendations when to start IOP lowering treatment (antiglaucomatous drug, AGD) in these patients. Thus, the decision is on an individual base and often patients are pre-treated with AGD once they consult a tertiary referral centre even if there are no signs of glaucomatous optic nerve damage. Any decision to treat or not to treat should outweigh the potential benefit of treatment (optic nerve protection) and possible side effects (e.g. ocular surface disease, costs of treatment). As this balancing act is often challenging this talk aims for a better understanding of pathophysiologic aspects of ocular hypertension in TED and to offer a guide for treatment decision.

A13 Thyroid Eye Disease (TED) Phases: Inflammatory Signs vs. Disease Progression

Peter Dolman

Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada

Correspondence: Peter Dolman Thyroid Research 2025, 18(s2):A13

In TED, both disease severity and phase are assessed for management and response to therapy.

Disease severity documents how different orbital tissues and functions are impacted and can direct therapy based on what works best for a particular catalogued change.

Disease phase: TED has a dynamic course represented by Rundle’s curve with disease severity plotted against time. The curve is biphasic with clinical features worsening and plateauing during the active/progressive phase, followed by an inactive/stable phase. Assessing the position along Rundle’s curve helps choice of management, with medications or radiotherapy offered during the progressive phase while surgery is delayed until the stable phase.

CAS (clinical activity score) is a 7-point score based on periocular inflammatory symptoms and signs. Three points are added for worsening vision, ductions or proptosis on follow-up. CAS presumes that periocular inflammation signals immunologic activity, like fever for pneumonia. Non-ophthalmologists can grade CAS and it has good positive predictive value for corticosteroid efficacy and is used in clinical trials. However, there is little proof that it predicts disease outcome, and has many false positives (including non-TED causes for high CAS) and false negatives (including individuals showing progression in TED despite low CAS).

Disease progression records the evolution of TED clinical features, with deterioration prompting medical intervention, stability favoring surgical therapy, and improvement suggesting response to therapy. The VISA classification measures four severity parameters (vision/inflammation/strabismus/appearance) and documents subjective and objective measures of progression for various ophthalmic measures. A focus group is standardizing progression criteria.

References

1. Mourits MP, Prummel MF, Wiersinga WM, et al. Clinical activity score as a guide in the management of patients with Graves’ Ophthalmopathy. Clin Endocrinol. 1997;47:9.

2. Dolman PJ. Evaluating graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012;26(3):229-4.

3. Dolman PJ. Grading severity and activity in thyroid eye disease. Ophthal Plast Reconstr Surg. 2016;34:S34–40.

4. Dolman PJ, Rootman J. VISA classification for Graves orbitopathy. Ophthal Plast Reconstr Surg. 2006;22(5):319-24.

A14 Hypothyroid and Euthyroid TED

Maria-Cristina Burlacu

Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

Correspondence: Maria-Cristina Burlacu Thyroid Research 2025, 18(s2):A14

Thyroid eye disease (TED) is commonly associated with hyperthyroid Graves’ Disease but can extend beyond the confines of hyperthyroidism. According to recent data, the prevalence of hypothyroid and euthyroid TED patients is 10.3% and 7.9% respectively, establishing these groups as clinically significant entities. While the underlying pathogenic mechanism remains uncertain, indirect evidence suggests that it may be unified across all thyroid states and driven by the thyrotropin receptor (TSHR) and signalling crosstalk between this primary antigen and the insulin-like growth factor-1 receptor (IGF-1R), both expressed on orbital fibroblasts. Clinically, euthyroid TED is generally milder and more often unilateral, with less impairment of quality of life and work ability compared to hyperthyroid and hypothyroid presentations. However, severe cases do exist. TSHR antibody titres are lower in euthyroid TED patients than in hyperthyroid TED patients, and euthyroid TED can be challenging to diagnose when TSHR antibodies are undetectable using standard laboratory assays. Long-term surveillance is mandatory, as about 25% of euthyroid patients will develop thyroid dysfunction within a mean period of two years following TED diagnosis. The management of euthyroid or hypothyroid TED is not dictated by thyroid function, but by the activity and severity of the eye disease, and is similar to that of the hyperthyroid form. Among the emerging therapies, the IGF-1R inhibitor teprotumumab has also proved efficient in treating euthyroid and hypothyroid TED, demonstrating a similar proptosis reduction and disease inactivation to that seen in hyperthyroid TED.

A15 Ethnic considerations in Thyroid Eye Disese/Graves Orbitopathy

Gangadhara Sundar, Blanche Lim

NUH Thyroid Eye Disease Service, Orbit & Oculofacial Surgery, Dept of Ophthalmology, National University Hospital, Singapore

Correspondence: Gangadhara Sundar Thyroid Research 2025, 18(s2):A15

TED is a global disease with a burden on humanity, challenging healthcare systems with significant effect on quality of life of afflicted individuals with indirect impact not just on the individuals, but also their families and thus society at large.

Etiologically, while most TED is related to Graves autoimmune hyperthyroidism, other associations include euthyroid disease, Hashimoto’s thyroiditis and other thyroid disorders.

TED is currently diagnosed and managed by standard guidelines predominantly studied and researched in western populations, primarily the Caucasians with some publications now addressing the disease, its manifestations in other ethnic groups e.g. the Chinese, Koreans, Indians, Middle east & the African populations. Current guidelines are universally applied globally, even in a diverse population with ethnic, geographic, social and cultural variations.

It is well known that certain unique characteristics play a role in diagnosis, prognosis and management. The presentation will share both current albeit limited evidence on geographic and ethnic variation in the incidence, prevalence of TED, clinical and radiologic characteristics with implications on early vs. late diagnosis, prognosis, management and outcomes of this disabling, disfiguring and potentially blinding disease. Given the multiethnic population in southeast asia, special emphasis will be laid on comparative differences between the East Asians, south Asians and Caucasians based on a single centre tertiary care referral multidisciplinary clinic at the National University Hospital, Singapore.

A16 Phenotypes in Thyroid Eye Disease - predictor to therapeutic response

Jimmy Uddin

Oculoplastics, Orbital, Moorfields Eye Hospital, London, UK

Correspondence: Jimmy Uddin Thyroid Research 2025, 18(s2):A16

The emergence and development of understanding different phenotypes of thyroid eye disease has progressed in the last 10 years.

We will discuss what phenotypic parameters can be measured and how they relate TED classification.

In particular, we will discuss the relevance of certain phenotypes and their value as a predictor to response with different therapeutics.

A17 Thyroid Eye Disease (TED) Mimickers: Diagnostic Challenges in Non-Thyroid Eye Causes of Orbital inflammation

Vickie Lee

Ophthalmology, Imperial College Healthcare NHS Trust, London, UK

Correspondence: Vickie Lee Thyroid Research 2025, 18(s2):A17

While TED is the most common cause of adult orbital inflammation, several other conditions can mimic, overlap, or coexist with it. Accurate diagnosis is crucial to avoid mismanagement. Ocular Myositis (OM) can be a heterogenous entity [1]. Non-idiopathic OM include paraneoplastic syndromes must be considered in cases of pre-existing malignancy. Drug-induced OM are associated with immune checkpoint inhibitors [2], bisphosphonates, and interferon. Infective OM include tuberculosis, Lyme disease, or herpetic viral infections. Ocular Myasthenia Gravis can co-exist with TED. Diagnostic delay is common, especially in patients with co-existing thyroid autoimmunity. Serological testing and single-fibre EMG aid diagnosis, though false negatives can occur in purely ocular forms [3]. Low flow Carotid-Cavernous Fistulas can be an elusive vascular masquerader. Time-of-flight Orbital MRI/MRA or catheter angiography enables elucidation [4]. Failure to recognise overlapping or secondary diagnoses may lead to inappropriate immunosuppression or missed opportunities for targeted treatment.

Other causes of orbital inflammation must be considered in patients with atypical, asymmetric, or treatment-refractory TED-like presentations. A multidisciplinary approach—including orbital imaging, neurophysiology, autoimmune and infectious investigations is essential. With increasing use of immunotherapies and expanding knowledge of paraneoplastic and iatrogenic syndromes, the differential for orbital inflammation continues to grow. Future research and registry data are needed to better characterise these overlapping entities.

References

1. McNab AA. Orbital inflammatory disease: a review. Clin Exp Ophthalmol. 2022;50(2):134–46.

2. Marino M, Latrofa F, Menconi F, et al. Role of checkpoint inhibitors in causing autoimmune ophthalmopathy. J Endocrinol Invest. 2022;45(7):1445–52.

3. Claytor B, Li Y. Challenges in diagnosing coexisting ocular myasthenia gravis and thyroid eye disease. Muscle Nerve. 2021 May;63(5):631–9. 10.1002/mus.27118. Epub 2020 Nov 27.

4. Balodis A, Kalējs VR, Migunova K. Bilateral low-flow type-D dural carotid-cavernous fistula: diagnosis and treatment with 3D time-of-flight magnetic resonance angiography. Am J Case Rep. 2024 Mar;20(25):e942833.

A18 IGF-1R Antagonists

Suzanne Freitag

Ophthalmology, Harvard Medical School, Boston, USA

Correspondence: Suzanne Freitag Thyroid Research 2025, 18(s2):A18

Teprotumumab has been available in the US for 5 years for the treatment of TED. This talk will show example cases demonstrating teaching points as well as review the literature on what has been learned during this interval. Attention will be paid to understanding the drug’s utility for various phenotypes of TED, the longitudinal efficacy of the drug, and an in-depth look at the side-effects of the drug.

A19 Teprotumumab: A Review of Efficacy & Longevity

Andrea Kossler

Ophthalmology, Stanford University School of Medicine, Palo Alto, USA

Correspondence: Andrea Kossler Thyroid Research 2025, 18(s2):A19

Purpose

This study compares the short- and long-term efficacy of intravenous methylprednisolone (IVMP) versus teprotumumab in treating active moderate-severe thyroid eye disease (TED).

Methods

A retrospective single-center study was conducted on active moderate-severe TED patients treated with IVMP or teprotumumab. Patients with less than 75% treatment adherence or less than 9 months of follow-up were excluded. Outcomes measured included proptosis reduction (PR), improvement in clinical activity score (iCAS), Gorman diplopia score (iGDS), and the need for TED-related surgery or additional medical treatments at post-treatment-completion (PTC) at 0, 6, 12, 18, and 24 months. The study also assessed disease resistance, progression, and reactivation rates.A retrospective single-center study was conducted on active moderate-severe TED patients treated with IVMP or teprotumumab. Patients with less than 75% treatment adherence or less than 9 months of follow-up were excluded. Outcomes measured included proptosis reduction (PR), improvement in clinical activity score (iCAS), Gorman diplopia score (iGDS), and the need for TED-related surgery or additional medical treatments at post-treatment-completion (PTC) at 0, 6, 12, 18, and 24 months. The study also assessed disease resistance, progression, and reactivation rates.

Results

Ninety-five patients were included, with 56 in the teprotumumab group and 39 in the IVMP group. At short-term follow-up (PTC-0M and -6M), teprotumumab exhibited superior efficacy, achieving mean PR of 3.50 vs. 0.77 mm (p<0.0001) and 2.91 vs. 1.29 mm (p = 0.001). iCAS improvement was significant at PTC-0M (4.04 vs. 2.59, p<0.0001), but not at PTC-6M (3.84 vs. 3.64, p = 0.255). The teprotumumab group required fewer additional medical therapies (p=0.026) and surgeries (p=0.038). The IVMP group had a higher rate of resistant/progressive disease (30.8%) compared to none in the teprotumumab group (p<0.001). At long-term follow-up (PTC-12M, -18M, -24M), no significant differences were observed in PR, iCAS, or the need for additional interventions. However, disease reactivation rates were higher in the teprotumumab group at PTC-12M (16.07% vs. none, p=0.010) and PTC-24M (30.4% vs. 5.1%, p=0.002).

Conclusion

While teprotumumab showed superior short-term efficacy in proptosis reduction and iCAS, long-term assessments indicated no significant differences between the two treatments, although higher disease reactivation rates were noted in the teprotumumab group. These findings suggest teprotumumab’s short-term benefits may not translate into long-term advantages over IVMP.

A20 Tocilizumab in thyroid eye disease (ted)

Ilaria Muller^1,2, D. Consonni², M. Marinò³, P. Limone⁴, S. Monti⁵, I. Campi⁶, N. Currò¹, M. Armenti², E. Crivicich², F. Crapella², M. Salvi¹

¹Fondazione Irccs cà granda, ospedale maggiore policlinico, milan, Italy ²University of Milan, Italy ³University of Pisa, Italy ⁴Ospedale Mauriziano, Turin, Italy ⁵Ospedale S. Andrea, Rome, Italy ⁶Istituto Auxologico, Milan, Italy

Correspondence: Ilaria Muller Thyroid Research 2025, 18(s2):A20

Objectives

In this trial (nct04876534) we compared the efficacy of tocilizumab (tcs) to methylprednisolone (mp) in improving thyroid eye disease (ted).

Methods

Endpoints: cas - 3 points (primary), proptosis (>2 mm), quality of life, diplopia and safety. 56 patients with active go (<9 months) were randomized to receive tcz (n. 28) or mp (n. 28). Tcz was administered iv in 4 monthly doses (8 mg/kg), while mp in 12 weekly doses (500 mg for 6 weeks, then 250 mg).

Results

Mean age, sex distribution and thyroid treatment were not different between the two groups. Mean baseline cas was 4.4 (±1.3) and 4.4 (±0.8), and proptosis in the study eye (more severe) was 25.2 and 25.5 mm, for patients randomized to tcz and mp, respectively. In the intention to treat analysis population, cas decreased in 75% and 79% of patients at 12 and 24 weeks, respectively, with tcz treatment compared to 36% and 29% with mp (p<0.003). At 36 and 48 weeks, 75% and 86% of patients after tcz, respectively, remained inactive (p<0.003). Proptosis decreased ≥2 mm in 61% of patients after tcz, compared to 29% after mp at 24 weeks (p<0.02). At 36 and 48 weeks proptosis responders were 57% and 61% after tcz and 18% and 25% after mp, respectively (p<0.01). The overall response (cas and proptosis) for tcz and mp was 54% and 11% at 36 weeks (p<0.01), and 61% and 18% at 48 weeks (p<0.01), respectively. No sae were reported, mp was discontinued in 2 patients due to allergic reaction. Quality of life (go-qol), improved after tcz compared to mp (p<0.01) for both appearance and visual function. Diplopia improved in 56 and 57% of patients at 12 and 24 weeks, respectively, after tcz and in 9% and 24% after mp (p<0.0005 and p<0.02, respectively).

Conclusions

Tcz is more effective than mp in inactivating go, but also improving proptosis (>60%), diplopia (>55%) and patients’ quality of life, at 48 months follow-up. Supported by roche italia to fondazione irccs cà granda, Milan, Italy.

A21 Autoantibodies to the TSH receptor - mechanisms of action and new therapeutics

Bernard Rees Smith

FIRS Laboratories, RSR Ltd, Cardiff, UK

Correspondence: Bernard Rees Smith Thyroid Research 2025, 18(s2):A21

Cryo-EM studies show that full length human TSH receptor (TSHR) is a monomer consisting of a leucine-rich repeat (LRR) domain (LRD), hinge region (HR) and transmembrane domain (TMD). Receptor autoantibodies (TRAb) bind to the ECD (LRD and HR) and usually act as agonists. Occasional patients have serum TRAb which block TSH and TRAb stimulation of the TSHR.

In the cell membrane, TSHR transitions between inactive and active states involving rotation of the LRD about the HR with the active state LRD further from the membrane.

Stimulating monoclonal autoantibody M22™ binds to the entire LRD (LRR 1-11) concave surface and cannot interact with inactive state receptor as this would result in a clash between antibody and membrane. No clash occurs when M22™ binds the active state and once bound M22™ holds the receptor in the active state resulting in prolonged activation. K1-18™, a different stimulating monoclonal autoantibody interacts with LRR 1-11 in a similar way to M22™.

Blocking type monoclonal autoantibody K1-70™ only interacts with LRR 1-7, positioning itself clear of the cell membrane when interacting with inactive or active receptor states. Once K1-70™ is bound binding of TSH and TRAb is prevented.

Monoclonal autoantibody 5C9™ interacts differently, binding the inactive conformation from LRR 3 to the HR. Its heavy chain CDR3 interacts with the HR locking the receptor in the inactive state causing inhibition of constitutive activity, of activating mutations activity and blocking receptor binding by TSH and TRAb.

A22 Adverse effects of the new targeted therapies

Marius Stan

Mayo Clinic, USA

Correspondence: Marius Stan Thyroid Research 2025, 18(s2):A22

We are fortunate to see a strong effort towards the development of new therapies for Graves’ disease and thyroid eye disease. Many agents will likely be studied for both entities. Some of them are at the stage of clinical use, while others are making their way through the different stages of clinical trials.

IGF-1 receptor blockers - these agents block growth hormone action and are associated with several adverse effects, most prominent for hyperglycemia, muscle cramps, fatigue, GI distress, and hearing changes.

FcRn inhibitors - these agents decrease total IgG significantly and thus increase the risk of infection. Some have also led to a decrease in albumin with subsequent increase in cholesterol values and development of edema.

IL6 blockers - these agents are potent inhibitors of inflammation, and they can lead to the reactivation of chronic infections. Severe allergic reactions or cytokine reactions have also been described.

TSH receptor blockers - these agents block the action of TSH and TSHR antibodies and have been well tolerated, but their mechanism of action is inevitably associated with hypothyroidism.

B cell depleters - these agents will induce sustained B-cell depletion for a number of months, thus increasing the risk of infection.

A number of other categories (small molecule antagonists to the TSH receptors, specific TRAb targeting and neutralizing molecules, protein degraders etc).

A23 Relapse after Targeted Therapies

Chrysoula Dosiou

Division of Endocrinology/Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

Correspondence: Chrysoula Dosiou Thyroid Research 2025, 18(s2):A23

The definition of relapse of thyroid eye disease (TED) following medical treatment is not standardized. Especially since the introduction of teprotumumab, multiple terms have been used to characterize worsening of disease after initial response. Follow-up of the OPTIC randomized controlled trial patients, that defined “disease flare” after teprotumumab therapy as proptosis increase of ≥2 mm or CAS increase by ≥2 points with a total CAS of ≥ 4, estimated it at 29% of initial proptosis responders at nearly a year following treatment completion. Data from observational studies, depending on the definition of relapse (any proptosis regression, ≥ 2 mm proptosis increase, ≥ 2-point CAS increase, either, or both) and the average follow-up of the study, have reported it in 26-59% of teprotumumab responders. Diplopia recurrence after teprotumumab has been observed in about half the responders at an average of 9 months. Relapse of TED after teprotumumab can manifest as worsening of either proptosis, diplopia, CAS, or a combination of these metrics. Timing differs from relapses after other existing medical therapies, occurring on average 7-12 months after treatment completion, with a number of recurrences after 1 year. Various predictors of relapse have been reported, including baseline CAS, dysthyroidism at the time of teprotumumab completion, and possibly high TSI/TRAb titers. Age was found to be a predictor of retreatment with teprotumumab. The above relapse rates compare with about a 30% rate of TED progression in RCTs using a composite outcome after intravenous steroids at 12 weeks after treatment and 57% rate of loss of 2 mm proptosis benefit/7% rate of loss of 2-point CAS improvement at 24 weeks after tocilizumab treatment in steroid-resistant patients. Data on treatment of teprotumumab relapses are very limited; a repeat course of teprotumumab or tocilizumab have been tried with success, while steroids seem less effective.

A24 Statins & Selenium

Michele Marino

University of Pisa, Italy

Correspondence: Michele Marino Thyroid Research 2025, 18(s2):A24

Statins

A role of cholesterol and of cholesterol-lowering medications in Graves’ Orbitopathy (GO) has recently emerged. A correlation between low-density lipoprotein cholesterol (LDL-Chol) and risk of GO has been reported. Furthermore, LDL-Chol seems to affect the course of GO and the response to intravenous glucocorticoids (ivGCs). Statins exert a protective role in preventing GO. Thus, statin treatment was found to reduce the risk of GO in patients with Graves’ hyperthyroidism. In addition, statins seem to be beneficial as an add-on therapy in patients with GO. Thus, in a randomized clinical trial, addition of oral atorvastatin to ivGCs improved the outcome of moderate-to-severe, active GO in hypercholesterolemic patients. Therefore, statins have both a preventive and a therapeutic role in GO, which be related to cholesterol-lowering, pleiotropic actions, and interaction with glucocorticoids.

Selenium

Based on the role of oxidative stress in GO pathogenesis, treatment with antioxidant agents, especially selenium, has been proposed. Tissue hypoxia and reactive oxygen species are involved in the changes that occur in fibroadipose orbital tissue and extraocular muscles. Selenium exerts an inhibitory action in terms of cell proliferation and release of hyaluronic acid in primary cultures of orbital fibroblasts. A randomized clinical trial conducted in patients with mild GO has provided evidence for a beneficial effect of selenium, although no data are available in more severe forms of GO. Thus, the use of selenium in the management of GO has been included in the clinical practice for patients with a mild eye disease.

A25 Immunomodulation Options - Should steroids have a role?

Mario Salvi

Graves’ Orbitopathy Center, Fondazione IRCCS Cà Granda, Milan, Italy

Correspondence: Mario salvi Thyroid Research 2025, 18(s2):A25

Glucocorticoids, preferably administered intravenously, have been shown to be effective as a first line therapy of active, moderate-severe TED/GO, based on EUGOGO 2021 guidelines. Dosing of methylprednisolone (MP) was tested in a large EUGOGO multicenter randomized clinical trial (159 patient) which showed that disease inactivation (decrease of the CAS) is generally observed in most patients with either 4.5–7.5 g cumulative dose, although the higher dose regimen is required to achieve some improvement on motility and overall severity. The 2022 ETA/ATA Consensus document has suggested MP treatment to target TED inactivation in moderate-severe disease or as first line in patients with dysthyroid optic neuropathy. Side effects are more frequently reported with doses exceeding 8.0 g per cycle of treatment, therefore higher doses should be reserved to patients with marked extraocular muscle dysfunction. Before administering MP, liver enzymes, viral markers for hepatitis, fasting serum glucose levels should be measured. Contraindications to therapy include active viral hepatitis and hepatic dysfunction, severe cardiovascular disease, uncontrolled hypertension or diabetes and untreated psychiatric disorders. Recent data from the MP arm of randomized trials of moderate-severe TED have shown that at 24 weeks a decrease of the CAS of 2 points is observed in about 75% of patients, and of 3 points in about 40% of patients with less than 30% of patients having a CAS of 0 or 1. Early GO deterioration or unresponsiveness after 6-8 weeks of IVGC may predict treatment failure and suggest alternative, second line therapies.

A26 When should we use RTX for TED?

Marius Salvi¹, Mario Salvi²

¹Endocrinology, Mayo Clinic, Rochester, USA, ²Endocrinology, University of Milan, Milan, Italy

Correspondence: Marius N. Stan Thyroid Research 2025, 18(s2):A26

Antibodies against TSHR are the pathogenic element in Graves’ disease and they are understood to play an important role in TED. Therefore, targeting the B-cells producing these antibodies was expected to be important in therapy. Preliminary open label case series have provided encouraging data for TED inactivation, without an impact on circulating TSHR autoantibodies. Two subsequent randomized clinical trials were performed that delivered contrasting results. One trial concluded that rituximab is equivalent to placebo, while the other one concluded a benefit for rituximab in comparison with IV methylprednisolone regarding control of inflammation. Comparing the two studies, it appears that the benefit is more likely to be present in patients with recent onset of disease and lower antibody titers. Currently the use of rituximab is considered to be a secondary choice in patients that have failed more established therapies.

A27 Triple therapy as medical decompression for low clinical activity score (CAS), progressive, Thyroid Eye Disease (TED)

Kelvin Kam Lung Chong^1,2,3,4, Kenneth Kai Hei Lai^1,2, Kenneth Chun Wah Wong⁵, Winnie Chiu Wing Chu⁶, Clement Chi Yung Tham^1,2,3,4, Calvin Chi Pui Pang¹

¹Ophthalmology and Visual Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, Hong Kong, ²Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, Hong Kong, ³-, Hong Kong Eye Hospital, Hong Kong, Hong Kong, ⁴Eye Centre, the Chinese University of Hong Kong Medical Centre, Hong Kong, Hong Kong, ⁵Clinical Oncology, Prince of Wales Hospital, Hong Kong, Hong Kong, ⁶Imaging and Interventional Radiology, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, Hong Kong

Correspondence: Kelvin Kam Lung Chong Thyroid Research 2025, 18(s2):A27

Aim

Prior studies reported suboptimal outcomes on combined immunosuppression (dual or triple therapies) for active, moderate-to-severe TED in Caucasian populations.

In this talk, we show that choosing the right.

1. patients using radiological rather than clinical activity (low-CAS progressive TED).

2. dosage of intravenous pulse methylprednisolone (IVMP).

3. dosages (from 360 mg bd to 720 mg mycophenolate bd) and.

4. types (from mycophenolate to sirolimus/rapamycin) of immunomodulatory drugs.

5. duration of oral immunomodulatory drugs (from 6 to 12 to 18 months).

6. simultaneous rather than sequential use of orbital RT during IVMP.

may achieve the effects of medical decompression, resulting in clinical, radiological, and serological improvements.

Methodology

Prospective, non-randomized case series in 2 referral centres.

Clinical, radiological (extraocular muscle EOM, area on coronal T1-weighted and inflammatory signal on STIR/T2-weighted fat suppressed MRI) and serological (TSH receptor antibodies, TRAb) parameters in patients with low-CAS recent (<12-month) onset, progressive TED received IVMP 4.5gm (for intractable diplopia) vs. 8gm (dysthyroid optic neuropathy (DON)) along with orbital RT and MMF or sirolimus for at least 12 months.

Results

Patients receiving triple therapy achieved significant improvement in vision, exophthalmos, diplopia, extraocular motility, MRI, and TRAb without recurrence 12 months after stopping immunomodulatory drugs. One patient developed radiation recall syndrome 6 weeks after orbital RT, requiring switching from sirolimus back to MMF. Elevated serum lipid, glucose, or leukopenia were either transient, managed with lipid-lowering agents, or a lower dosage of MMF/sirolimus.

Conclusion

Our encouraging results from triple combined immunosuppression demonstrated its safety, effectiveness, and potential as a cost-effective alternative for recent-onset, progressive TED with DON and/or intractable diplopia. Further randomized clinical trials, especially with emerging biologics, are thus warranted.

A28 Local Treatments in Graves Ophthalmopathy

Onur Konuk

Ophthalmology, Gazi University Medical School, Ankara, Türkiye

Correspondence: Onur Konuk Thyroid Research 2025, 18(s2):A28

Graves’ ophthalmopathy (GO), also known as thyroid-associated ophthalmopathy, commonly leads to eyelid retraction, orbital inflammation, and strabismus. Local and orbital injection therapies—including triamcinolone acetonide (TA) and botulinum toxin (BTX)—have emerged as valuable alternatives or adjuncts to systemic treatment, particularly when there are concerns of steroid intolerance, resistance, or significant side effects.

Local periorbital and subconjunctival injections of TA and BTX have demonstrated efficacy in rapidly alleviating upper eyelid retraction and reducing inflammatory signs in GO. Combining BTX-A with TA can hasten symptom improvement and minimize the total required steroid dose, enabling faster and more sustained resolution of lid retraction while reducing the risk of corticosteroid-related complications. Patients treated with both agents report rapid symptom relief (as early as one week), sustained effects up to several months, and a lower incidence of side effects such as steroid-induced glaucoma, compared to steroid alone.

Periorbital steroid injection (most notably triamcinolone acetonide) may decrease clinical activity scores, eyelid retraction, and exophthalmos, with additional benefit in controlling orbital inflammation. These outcomes have been observed both in moderate-to-severe active cases and when used as an alternative to systemic steroids in patients not suitable for systemic therapy. Complications are generally infrequent but may include transient intraocular pressure elevation, which often resolves with topical medication. When treating active strabismus associated with GO—especially restrictive strabismus due to extraocular muscle involvement—both orbital steroid injections and BTX have roles. Botulinum toxin is typically reserved for acute or residual strabismus, providing muscle relaxation and transient improvement in alignment; it is especially useful for those not suitable for surgery or as a bridge pending more definitive intervention.

In conclusion, local and orbital injections of triamcinolone and botulinum toxin represent effective strategies for managing eyelid retraction, orbital inflammation, and strabismus in Graves’ ophthalmopathy. These treatments allow for targeted symptom control, reduced systemic exposure, and flexibility as either primary treatments or adjuncts to surgery and systemic therapies. Continued research is needed to further refine indications, dosing strategies, and long-term efficacy in diverse clinical scenarios.

A29 The Role of Radiotherapy (XRT) for Thyroid Eye Disease (TED)

Peter Dolman

Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada

Correspondence: Peter Dolman Thyroid Research 2025, 18(s2):A29

Orbital radiotherapy is the oldest treatment for TED and works by targeting lymphocytes and orbital fibrocytes.

With standardized delivery, studies have found no increased risk of cataract, a single case of a secondary tumor, and 1% incidence of mild retinopathy in diabetics. This is safer than the significant systemic risks from corticosteroids and biologic agents.

Its role in therapy is controversial because of conflicting efficacy studies. This arises from the wide spectrum of disease outcomes, differing selection criteria in terms of severity and activity, and the lack of standardized outcomes.

Retrospective studies found XRT efficacy equal to corticosteroids (CS) for reducing soft tissue changes and superior in preserving ocular motility. Three randomized controlled studies (RCT) from Netherlands found that XRT was twice as effective at reducing inflammatory scores and motility compared to controls, and had a longer treatment duration compared with CS. On the other hand, a RCT study at the Mayo clinic found no benefit in proptosis, lid retraction or CAS scores between treated and untreated sides, while another study from UK found the addition of XRT to oral CS did not improve global orbital scores.

Large retrospective studies of its use in dysthyroid optic neuropathy (DON) have found that it could successfully reduce or delay the need for surgical intervention compared with CS alone. Another study found the addition of XRT to CS reduced the incidence of DON from 17% with CS alone to 0% for those treated with combination XRT/CS.

References

1. Donaldson SS et al. Supervoltage radiotherapy for Graves’ ophthalmopathy. J Clin Endocrinol Metab. 1973;37:276.

2. Gillis, et al. Secondary malignancy following radiotherapy for thyroid eye disease. Rep Pract Oncol Radiother. 2016;21.

3. Dolman PJ, et al. Orbital radiotherapy for thyroid eye disease. Curr opin ophthalmol. 2012;23:427–32.

4. Rajendram, et al. Combined immunosuppression and radiotherapy in thyroid eye disease (CIRTED). Lancet 2018;6:299.

5. Gold KG, Scofield S, Kazim M. Orbital radiotherapy combined with corticosteroid treatment for thyroid eye disease-compressive optic neuropathy. OPRS. 2018;34(2).

6. Shams PN, Dolman PJ, et al. Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease. Am J Ophthalmol. 2014 Jun;157(6):1299–305.

A30 DON Treatment: Conventional Challenges

Nicola Curro

Surgery, Fondazione IRCCS ca’ granda Ospedale Maggiore Policlinico, Milano, Milano, Italy

Correspondence: Nicola Curro Thyroid Research 2025, 18(s2):A30

Dysthyroid optic neuropathy (DON) is a potentially sight-threatening complication of Graves’ Orbitopathy (GO). It affects up to 3-5% of GO patients and its prevalence is estimated to be 0.18 per 10,000 population.

It is currently considered a complex clinical challenge, both in terms of diagnosis and treatment.

There are no guidelines regarding its diagnosis, which is not unfrequently late. There is consensus that DON can present with variable combinations of multiple clinical signs, not always present simultaneously. Visual function can be assessed by means of visual acuity (VA), colour sensitivity, relative afferent pupillary defect (RAPD), visual field (VF) and optic disc appearance. The tests most widely used in published literature are VA, VF, and RAPD. Recent papers reported that colour sensitivity assessment is a simple and highly sensitive method for the early diagnosis of DON. Ocular coherence tomography, CT scan and MRI of the orbit are useful for studying the anatomy of the optic nerve, of the orbital apex and of the extra-ocular muscles. Visual evoked potentials are a very sensitive method but difficult to apply in daily clinical practice. Other parameters like inflammatory and congestive signs may help in diagnosis and planning treatment.

Once DON is diagnosed, current clinical guidelines suggests intravenous treatment with very high dose of steroids. If acceptable clinical results are not achieved within 2 weeks, urgent surgical decompression of the orbit is considered necessary. However, there is no consensus regarding the dose and method of steroid administration, nor regarding the type of surgery, even though the medial wall is considered crucial. There are also no guidelines regarding pre- and post-treatment assessments. Some papers have reported the use of Rituximab, Tocilizumab and Teprotumumab for the treatment of DON but, of course, other studies are needed.

A31 Management of Dysthyroid Optic neuropathy: New paradigms

Juliette Abeillon - du Payrat

Endocrinology, Hospices Civils de Lyon, Lyon, France

Correspondence: Juliette Abeillon - du Payrat Thyroid Research 2025, 18(s2):A31

Dysthyroid optic neuropathy (DON) is a rare but sight threatening complication of Graves’ orbitopathy (GO) that can lead to permanent vision loss. Current guidelines recommend high-dose steroid treatment and, if unsuccessful, urgent surgical decompression of the optic nerve, and is effective in about 70% of DON patients.

New paradigms in GO treatment are emerging, with increasing data suggesting benefit of alternative medical treatments in DON:

• Monoclonal anti-IL6 antibody Tocilizumab was recently described as effective in DON, especially by Habroosh et al. in a cohort study of 13 patients, with a mean Visual acuity (VA) gain of 0.4 (p<0.002) (7 steroid resistant and 3 surgery resistant), two patients had recurrence of DON 9 months after, with remission after a second course of tocilizumab treatment, after a mean follow-up of 20months (12-35).

• IGF-1R monoclonal antibody inhibitor Teprotumumab is efficient on inflammation and orbit remodelling, but patients with DON have been excluded from placebo-controlled trials. Tamhankar et al. reviewed 24 patients from ten case series (including 10 patients from Sears et al.): 22 were steroid resistant and 9 surgery resistant. 88% had a significant improvement of DON, with a mean VA improvement of 3.7 lines (SD 3.7), occurring in 75% patients after 2 infusions. Follow up varies, and three patients had DON relapse during follow-up. A monocentric French study including 6 patients with steroid and surgery resistant DON showed recovery in 87.5% of affected eyes, persistant after a median follow-up of 73.8 weeks, with VA improvement in all patients (median 0.30 logMAR [0.24-0.42], after only one infusion in half patients. No patient relapsed with DON.

Tocilizumab and teprotumumab appear as very effective treatments of DON in pilot studies. Randomized trials and long-term follow-up are now needed to define precisely the place of biotherapies in DON management.

A32 Orbital Decompression (Conventional Challenges)

Marta Pérez-López

Orbit and Oculoplastic Unit, Ophthalmology, Hospital Universitario y Politécnico La Fe, Valencia, Spain

Correspondence: Marta Pérez-López Thyroid Research 2025, 18(s2):A32

Orbital decompression surgery is a safe and effective technique for the correction of exophthalmos and orbital congestion, which are characteristic features of thyroid eye disease. As with medical therapies, surgical techniques continue to evolve, aiming to achieve improved outcomes with fewer complications and better risk control. The challenges of orbital decompression surgery include achieving a reduction in proptosis that approximates the patient’s pre-disease baseline, ensuring symmetry, and minimizing the risk of new-onset diplopia—an adverse effect that may result from the expansion of the orbital space created during surgery. Minimally invasive approaches, the use of neuronavigation, and the removal of orbital fat in conjunction with bony orbital decompression provide effective reductions in proptosis. These techniques must be tailored to the individual patient’s needs and, when performed by experienced surgeons, are associated with a low risk of complications.

A33 Decision Making for Surgery following Treatment with Teprotumumab

Michael Kazim

Ophthalmology and Surgery, Columbia University, New York, USA

Correspondence: Michael Kazim Thyroid Research 2025, 18(s2):A33

The introduction of teprotumumab to the therapeutic armamentarium for TED has provided measurable benefits to both relief of exophthalmos and dysmotility. These appear to be afforded to both the acute and stable phases of the disease. The clinical benefits are however do not, in all cases, fully reverse the sequala of the disease, resulting in the need for surgical remediation of residual proptosis and diplopia and eyelid retraction. The published data suggests that the frequency of surgical procedures has not been significantly reduced by the application of teprotumumab although the magnitude of the procedures (degree of required decompression or amount/number of muscle recessions) may be diminished. An additional preoperative consideration for the post-teprotumumab treated patient is the timing for any procedure. This is informed by the current understanding of the rate of relapse (up to 50%) and the interval to relapse (12+months). These surgical planning considerations will be reviewed and a decision tree recommended.

A34 Strabismus Surgery - Aim for Symmetry

Anja Eckstein¹, Inga Neumann¹, Michael Oeverhaus¹, Ying Chen¹, Hinke Mareijke Jellema², Peerooz Saeed²

¹Ophthalmology, University Duisburg Essen, Essen, Germany, ²Ophthalmology, Amsterdam University medical Center, Amsterdam, Netherlands

Correspondence: Anja Eckstein Thyroid Research 2025, 18(s2):A34

Ocular motility impairment in Thyroid Eye Disease (TED) is typically restrictive, with affected muscles losing elasticity. Therefore, the treatment of choice is usually the recession of one or more muscles. Prior to surgery, it is crucial to evaluate available imaging studies. The orthoptic assessment should include the measurement of ocular ductions and squint angle, ideally in all nine gaze directions. Muscles with the most significant loss of elasticity should be addressed first. Smaller deviations can generally be corrected with single-muscle surgery, while larger deviations are limited by the arc of contact. Large esotropias, especially those occurring after medial decompression, can be corrected using an implant (e.g. Tutopatch) that elongates the muscle and helps preserve the arc of contact. Tutopatch may also be used in cases of bilateral marked elevation deficit, depending on the Incyclo-A pattern. Correction of vertical incomitance typically depends on cyclotorsion and the presence of an A- or V-pattern. If small vertical deviations remain after the initial surgery, oblique muscles can be recessed, again considering cyclotorsion and the A- or V-pattern.

A35 Strabismus Surgery Post-Teprotumumab

Madhura Tamhankar

Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA

Correspondence: Madhura Tamhankar Thyroid Research 2025, 18(s2):A35

Summary

The management of diplopia in thyroid eye disease (TED) patients is complex and involves both medical and surgical approaches. Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), has emerged as a breakthrough therapy for TED, particularly in moderate to severe cases. It reduces proptosis, improves extraocular muscle function, and alleviates diplopia by addressing the underlying inflammatory process and muscle fibrosis.

Although teprotumumab has shown promise in improving diplopia, strabismus surgery may still be needed for unchanged, persistent, or recurrent cases. Surgery timing is crucial, typically performed after disease stabilization and resolution of the inflammatory phase. The possibility of strabismus recurrence should also be considered.

This abstract will explore teprotumumab’s impact on diplopia resolution and its potential to reduce the need for surgery in TED patients. Measuring improvement in diplopia after teprotumumab is challenging due to variations in fusional capacity, age, type of misalignment, and other confounding factors in TED clinical trials.

Recent studies report variability in teprotumumab’s efficacy in treating TED-related strabismus, with some showing improvement and others indicating worsening or recurrence after treatment. Similarly, decreased extraocular muscle thickness has been linked to improved ocular motility, but its correlation with ocular alignment remains unreported.

Further investigations into the synergistic effects of teprotumumab and extraocular muscle surgery could provide an integrated approach to managing diplopia in TED patients.

A36 Eyelid Surgery in TED

Diego Strianese

Department of Neuroscience, University of Naples Federico II, Naples, Italy

Correspondence: Diego Strianese Thyroid Research 2025, 18(s2):A36

The pathogenesis of eyelid retraction in TED is multifactorial, involving a complex interplay of factors, including contraction of Müller’s muscle due to increased sympathetic tone, inflammation, subsequent fibrosis of eyelid retractors, as well as altered eyelid positioning relative to the proptotic globe. Eyelid retraction can lead to significant complications, including exposure keratopathy, dry eye, and cosmetic disfigurement. The primary aims of eyelid surgery in TED are to restore the normal anatomical position and function of the eyelids, alleviate ocular discomfort, and improve aesthetic appearance. Several techniques have been described for upper eyelid retraction repair which include: -Müllerectomy; Levator Recession; Graded Müller Muscle/Levator Recession; Blepharotomy; Transconjunctival injection of Botulinum toxin A; Periorbital injection of triamcinolone acetonide. For Lower Eyelid retraction repair Lateral Canthoplasty; Retractor Releas; Spacer Grafting; Midface Lift have been reported.Traditionally, eyelid repair in Thyroid Eye Disease (TED) is performed during the inactive phase, when inflammation has resolved and proptosis and strabismus issues have been addressed. However, certain subgroups of patients may require earlier intervention. Notably, individuals whose occupation involves extensive use of digital screens may experience ocular surface-related discomfort, necessitating prompt lid retraction repair to restore their functional ability. Another emerging subgroup that may benefit from early lid retraction repair comprises individuals whose profession relies heavily on their appearance on social media, where even minor changes can impact their earning potential. In such cases, eyelid retraction may be the sole manifestation of TED. To improve the quality of life for these patients, early lid retraction repair should be considered a viable option. Most procedures can be performed under local anesthesia, even in an office setting, allowing for a relatively quick recovery. While recovery times vary, most patients can resume daily activities within 1-2 weeks. Botulinum toxin injections may enable a rapid return to work, often within 24 h. Eyelid surgery in TED can significantly improve eyelid position, alleviate symptoms, and enhance cosmetic appearance. Nevertheless, potential complications, including over or under-correction, eyelid asymmetry, and exposure keratopathy, should be carefully discussed with patients, particularly those requiring early repair.

A37 Surgical Needs and Timing After Teprotumumab Therapy in patients with Thyroid Eye Disease (TED)

Andrea Kossler

Ophthalmology, Stanford University School of Medicine, Palo Alto, USA

Correspondence: Andrea Kossler Thyroid Research 2025, 18(s2):A37

Purpose

To evaluate the need for surgical intervention after teprotumumab therapy and to compare regression rates, characteristics, and surgical outcomes of TED patients undergoing surgery after treatment.

Methods

Three retrospective studies were analyzed. The first, a single-center study, compared the short and long-term surgical rehabilitation needs post-teprotumumab versus intravenous methylprednisolone (IVMP). The second study utilized TriNetX Analytics, comparing TED-related interventions, treatment burden, and care trajectories between teprotumumab and IVMP-treated patients. The third was a multicenter observational cohort study assessing postoperative regression rates in TED patients undergoing surgery within 180 days (G1) versus >180 days (G2) after teprotumumab infusion. Secondary outcomes included regression characteristics, required treatments, and orbital decompression proptosis reduction.

Results

Long-term follow-up revealed no significant difference between teprotumumab and IVMP groups regarding the need for additional treatments; however, teprotumumab patients required fewer surgeries per patient. Mean earliest time to surgery was comparable (teprotumumab: 12.73 ± 7.20 months; IVMP: 14.04 ± 7.84 months, p = 0.669). Surgical timing analysis post-teprotumumab showed no significant difference in regression rates between early and late surgery groups (G1: 20.8%, G2: 14.7%, p = 0.611). Patients undergoing late surgery (G2) experienced significantly higher Clinical Activity Scores during regression (6.1 vs. 4.2, p = 0.027) and a nonsignificant increase in proptosis (4.25 vs. 2.9, p = 0.298) compared to early surgery (G1). Both groups were equally likely to require repeat teprotumumab courses, though G2 required slightly more subsequent surgical procedures (p = 0.057).

Conclusions

Teprotumumab-treated TED patients demonstrated similar overall long-term rates of additional interventions compared to IVMP, however the number of surgeries per patient and overall treatment burden was less in teprotumumab treated patients. Additionally, the rate of post-op regression did not differ between earlier vs. delayed surgical intervention groups, however, earlier surgery may reduce severity, clinical impact, and subsequent surgical burden after regression.

A38 Optimising Outcome Measures in Thyroid Eye Disease (TED): Bridging the Gap Between Clinical Trials and Real-World Experience

Vickie Lee

Ophthalmology, Imperial College Healthcare NHS Trust, London, UK

Correspondence: Vickie Lee Thyroid Research 2025, 18(s2):A38

TED treatment has three central objectives: preserving or restoring vision, improving diplopia, and reversing disfigurement to enhance quality of life. Accurately measuring treatment efficacy across these domains remains a significant challenge. Clinician-reported outcomes (CRO) [1], Patient-reported outcomes (PRO), Surrogate or biomarker outcomes (SO), and composite outcomes (CO) each have limitations and susceptibility to bias.

CROs are affected by inter- and intra-observer, patient, and equipment variation [2]. PROs eg GO-QOL [3] and Bahn-Gorman scores may diverge from CROs, influenced by patient expectations, psychological state, and social factors. For example, a symmetrical 2 mm reduction in proptosis may be clinically meaningful but not perceptible to the patient, especially for asymmetrical TED. Similarly, improved duction measurements may move diplopic images closer together worsening subjective diplopia.

MRI-based diffusion weighted imaging (DWI) show promise in identifying active inflammation [4]. Serum and tear-based biomarker outcomes are increasingly explored as SO [5]. CO lack standardisation across historical randomised trials, complicating comparisons between corticosteroids [6,7], rituximab [8,9], mycophenolate [10] azathioprine & radiotherapy [11]. More recent IGF-1R inhibition trials have more uniform outcome definitions facilitating comparisons. One trial study on long-term efficacy of teprotumumab showed 82% of patients not requiring retreatment at 99 weeks [12]. However real-world data highlight higher relapse rates [12], a significant incidence of hearing loss, an adverse event underrepresented in trial data [14] but improved systemic safety over steroid treatment [15].

We propose integrating minimally clinically important difference (MCID) thresholds, visual field indices, and ocular surface disease measures into routine assessment. A standardised Radiological Activity Score (RAS) and a Global TED Patient Registry are urgently needed to document longitudinal real-world outcomes and align them with trial endpoints.

References

1. Bartalena L, Wiersinga WM. Proposal for standardization of primary and secondary outcomes in patients with active, moderate-to-severe graves’ orbitopathy. Eur Thyroid J. 2020 Dec;9(Suppl 1):3–16. 10.1159/000510700.

2. Perros P, Žarković M, Pearce SH, Razvi S, Kolli H, Dickinson AJ. Inter-observer variability of clinical activity score: assessments in patients with thyroid eye disease. Am J Ophthalmol. 2023 Aug;252:94–100.

3. Terwee CB, Gerding MN, Dekker FW, et al. Development of a disease specific quality of life questionnaire for patients with Graves’ ophthalmopathy: the GO-QOL. Br J Ophthalmol. 1998;82(7):773–9.

4. George NM, Feeney C, Lee V, Avari P, Ali A, Madani G, Lingam RK, Bhatia KS. Extraocular muscle Diffusion Weighted Imaging as a quantitative metric of posterior orbital involvement in thyroid associated orbitopathy. Insights Imaging. 2024 Aug 1;15(1):183.

5. Ueland HO, Neset MT, Methlie P, Ueland GÅ, Pakdel F, Rødahl E. Molecular biomarkers in thyroid eye disease: a literature review. Ophthalmic Plast Reconstr Surg. 2023 Dec 1;39(6S):S19-S28.

6. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab. 2005;90:5234–40.

7. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G, Azzolini C, Boboridis KG, Mourits MP, Soeters MR, Baldeschi L, Nardi M, Currò N, Boschi A, Bernard M, von Arx G; European Group on Graves’ Orbitopathy. Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab. 2012 Dec;97(12):4454–63.

8. Stan MN, Garrity JA, Carranza Leon BG, Prabin T, Bradley EA, Bahn RS. Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015;100:432–41.

9. Salvi M, Vannucchi G, Currò N, Campi I, Covelli D, Dazzi D, et al. Efficacy of B-Cell.

10. Targeted therapy with rituximab in patients with active moderate to severe.

11. Graves’ orbitopathy: a randomized controlled study. J Clin Endocrinol Metab. 2015;100:422–31.

12. 10 Kahaly GJ, Riedl M, König J, Pitz S, Ponto K, Diana T, et al. Mycophenolate plus.

13. methylprednisolone versus methylprednisolone alone in active, moderate-to-.

14. severe Graves’ orbitopathy (MINGO): a randomised, observer-masked, multicentre.

15. trial. lancet Diabetes Endocrinol 2018;6:287–98.

16. Dayan CM, Stratton IM, Taylor PN, et al. Randomised controlled trial of intravenous methylprednisolone and oral mycophenolate in moderate to severe thyroid eye disease (CIRTED): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020;8(4):287–98.

17. Kahaly GJ, Subramanian PS, Conrad E, Holt RJ, Smith TJ. Long-term efficacy of teprotumumab in thyroid eye disease: follow-up outcomes in three clinical trials. Thyroid. 2024 Jul;34(7):880–9. 10.1089/thy.2023.0656.

18. Kahaly GJ, Subramanian PS, Conrad E, Holt RJ, Smith TJ. Long-term efficacy of teprotumumab in thyroid eye disease: follow-up outcomes in three clinical trials. Thyroid. 2024 Jul;34(7):880–9. 10.1089/thy.2023.0656.

19. Sears CM, Azad AD, Sears JJ, et al. Real-world safety of teprotumumab: rates of hearing-related adverse events higher than reported in clinical trials. Thyroid. 2023;33(3):366–72.

20. Lo JE, Freitag SK, Liu CY, Barbesino G, Sheng-Kai Ma K. Long-term cardiovascular, renal, and safety outcomes of teprotumumab versus systemic glucocorticoids in thyroid eye disease: a target trial emulation. Ophthalmology. 2025 May 19:S0161–6420(25)00310–0.

A39 New Quality of Life Assessments

Katharina A Ponto^1,2

¹Ophthalmology, Gutenberg University Medical Centre, Mainz, Germany, ²Ophthalmology/ Oculoplastic Surgery, Dardenne Eye Hospital, Bonn, Germany

Correspondence: Katharina A Ponto Thyroid Research 2025, 18(s2):A39

Thyroid Eye Disease (TED) has profound effects on patients’ quality of life (QoL), impacting not only visual function but also appearance, self-perception, and mental well-being. In recent years, the importance of QoL as a treatment goal has gained significant recognition, extending beyond traditional measures of disease activity or severity.

This presentation provides an overview of current tools used to assess QoL in TED, including the GO-QoL and TED-QoL questionnaires, and discusses their validation, limitations, and evolving role in clinical and research settings. Emerging data from real-world studies and clinical trials underscore the need to integrate patient-reported outcomes more systematically into treatment planning and evaluation.

New perspectives highlight the psychological burden of TED, the discrepancy between clinical severity and subjective distress, and the need to address factors like anxiety, fatigue, and disfigurement-related distress. The talk will also explore recent developments in digital health, including the use of electronic Patient-Reported-Outcome-Measures and mobile tools to track QoL over time.

Together, these insights point toward a more patient-centered, multidimensional approach to TED care, where QoL is not only measured—but actively targeted—in clinical practice.

A40 Medical research surveys in TED

Tomasz Bednarczuk¹, Maria-Cristina Burlacu ²

¹Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland, ²Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

Correspondence: Tomasz Bednarczuk Thyroid Research 2025, 18(s2):A40

Medical research surveys collect data on health issues such as disease prevalence, treatment effectiveness, and patient outcomes. They are vital for advancing healthcare research and improving patient care. Two previous European Group on Graves’ Orbitopathy (EUGOGO)/European Thyroid Association (ETA) surveys (1998, 2006) revealed significant regional differences in treatment recommendations, deficiencies in the quality of care, and ongoing shortcomings in TED management. Improving clinician training, increasing patient access to specialist multidisciplinary centres, and publishing practical guidelines were suggested solutions to improve the management of TED. Since then, EUGOGO have released TED management guidelines (2008, 2016 and 2021), and a joint consensus statement from American Thyroid Association (ATA) and ETA has been developed (2022) to support clinicians treating TED patients. The most recent survey of ATA and ETA members (2022) still found significant geographic variation among clinicians in the delivery of care and choice of treatment. One fundamental reason behind this practice variation was likely the regional difference in drug availability and coverage. Moreover, clinicians’ concerns about TED management demanded ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.

Over the past two decades, many European medical centres have implemented early access to multidisciplinary specialist clinics involving both endocrinologists and ophthalmologists. These EUGOGO Combined Thyroid Eye Clinics provide a good setting for patient-centred care, using standardised assessments and tailored ophthalmologic and endocrinologic treatments according to current knowledge depending on the patients’ individual needs. Conducting additional questionnaires at EUGOGO centers can provide valuable insights into experienced practices and opinions on TED management where evidence-based medicine is limited.

A41 Establishing a Global Registry for Graves Orbitopathy: Advancing Scientific Knowledge Through Multicenter Academic Collaboration

Michael Oeverhaus, Inga Neumann, Karim Al-Ghazzawi, Ying Chen, Anja Eckstein

Ophthalmology, University Hospital Essen, Essen, Germany

Correspondence: Michael Oeverhaus Thyroid Research 2025, 18(s2):A41

Graves orbitopathy (GO), an autoimmune inflammatory disorder of the orbit, poses significant diagnostic and therapeutic challenges due to its heterogeneous presentation and variable clinical course. Despite advances in understanding the disease’s pathophysiology, the lack of standardized, large-scale, and longitudinal data has impeded the analysis especially of off-label treatments. This abstract outlines the establishment and implementation of a global, multicenter registry dedicated to patients with GO, coordinated through a consortium of university-affiliated medical centers led by EUGOGO centers. The registry systematically collects anonymized clinical, biochemical, imaging, therapeutic, and outcome data using harmonized protocols aligned with international consensus statements.

The primary aim is to facilitate large-scale observational studies and longitudinal analyses to identify disease phenotypes, prognostic markers, and treatment outcomes across diverse populations. Secondary objectives include enabling real-world evidence generation, fostering translational research, and supporting clinical trial recruitment through phenotype stratification. Preliminary data indicate significant interregional variability in disease severity, treatment strategies, and healthcare access, underlining the need for harmonized clinical pathways.

By leveraging the combined academic expertise and data-sharing capacities of university centers worldwide, this registry represents a critical infrastructure for the advancement of GO research. It also serves as a model for collaborative, cross-border disease surveillance and precision medicine development in rare or complex autoimmune disorders.

Rapid Fire Abstracts

A42 Artificial Intelligence in Thyroid Eye Disease Patient Management: Innovations and Applications

Mirco Armenti¹, Beatrice Dazzi¹, Ilaria Muller^1,2, Nicola Currò^2,3, Claudio Guastella^2,4, Giovanna Mantovani^1,2, Mario Salvi²

¹Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy, ²Graves Orbitopathy Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy, ³Ophthalmology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy, ⁴Specialistic Surgical Sciences, Otolaryngology and Head and Neck Surgery, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy

Correspondence: Mirco Armenti Thyroid Research 2025, 18(s2):A42

Thyroid Eye Disease (TED) is a complex extrathyroidal manifestation of Graves’ disease requiring accurate, longitudinal clinical monitoring. This project investigates the integration of artificial intelligence (AI) into TED management via the Salus platform, aimed at enhancing the efficiency and consistency of patient care.

The system includes two main components: (1) automated extraction of structured clinical data from unstructured medical records using Large Language Models (LLMs), and (2) a clinical console that enables visualization and longitudinal tracking of thyroid and ophthalmologic parameters.

A pilot study was conducted on 10 TED patients, each with five sequential visits at 12-week intervals, totaling 50 clinical encounters and generating over 100 medical documents. Structured parameters extracted included CAS scores, proptosis measurements, GOQoL assessments, thyroid function tests, and TSH receptor antibodies. The system successfully structured over 300 clinical datapoints, allowing for improved tracking of disease progression.

Preliminary internal validation indicates reliable extraction of clinically relevant information, supporting faster and more consistent review of patient data. Formal quantitative evaluation is planned as part of ongoing system validation.

Beyond clinical utility, the Salus console also facilitates standardized data collection, enabling the creation of structured databases for research purposes. This project represents a promising advance in the deployment of AI tools to enhance both clinical care and research in complex endocrinological disorders.

A43 Molecular Insights into Thyroid Eye Disease via Untargeted Lipidomics and Metabolomics in a TSHR Mouse Model

Fahimeh Hashemi¹, Mareike Horstmann¹, Erich Gulbins², Anke Daser³, Anja Eckstein¹, Gina-Eva Görtz¹

¹Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany, ²Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany, ³Department of Oto-Rhino-Laryngology, University of Duisburg-Essen, Essen, Germany

Correspondence: Fahimeh Hashemi Thyroid Research 2025, 18(s2):A43

Objectives

Thyroid eye disease (TED) is a complex manifestation of Graves’ disease (GD), an autoimmune disorder driven by thyroid-stimulating autoantibodies (TSAb) targeting the thyrotropin receptor (TSHR). The molecular mechanisms underlying TED remain poorly understood. To explore the role of lipid and metabolite dysregulation, we applied untargeted lipido-metabolomics to a mouse model of TED.

Methods

Mice were immunized with the pTriEx1.1Neo-human TSHR A-subunit plasmid to induce TED or with the pTriEx1.1Neo-β-Gal plasmid as a control. Orbital tissues were harvested from both groups for lipid and metabolite extraction. Analyses were performed using UHPLC-QTOF mass spectrometry, and data were processed in MetaboAnalyst v6.0.

Results

Lipidomics revealed significant alterations in lipid profiles between TED and control groups, particularly in triglycerides (TGs), diglycerides (DGs), and ceramides. Heatmap analysis highlighted clear distinctions, suggesting that TSHR immunization disrupts lipid metabolism. Pathway analysis of metabolomics data identified changes in folate biosynthesis, lysine degradation, and proline metabolism, with increased levels of hydroxyproline and sepiapterin.

Conclusions

Our findings suggest that elevated TGs may reflect adipogenesis in the orbit, contributing to TED pathophysiology. The detection of ceramides with very long-chain fatty acids (≥C24), rare in mammals, hints at a possible microbial component in TED. Notably, hydroxyproline upregulation implicates fibrotic remodeling in endocrine orbitopathy (EO). These molecular signatures offer potential as biomarkers and therapeutic targets. Further validation using human samples is warranted to establish their clinical relevance and clarify their role in TED pathogenesis.

A44 Dissecting Orbital Immune Landscapes in Graves’ Orbitopathy: Single-Cell Transcriptomics, Multi-Omics Integration and Multi-Method Validation

Yuanping Hai^1,2, Qintao Ma ¹, Yongbo Duan ³, Haixiong Chen⁴, Lan liu¹, Yi Wang ⁵, Jie Shen¹, George Kahaly²

¹Department of Endocrinology and Metabolism, the Eighth Affiliated Hospital of Southern Medical University (The First PE, Foshan, China, ²Molecular Thyroid Research Lab, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany, ³Department of Ophthalmology, the Eighth Affiliated Hospital of Southern Medical University (The First PE, Foshan, China, ⁴Department of Radiology, the Eighth Affiliated Hospital of Southern Medical University (The First PE, Foshan, China, ⁵Department of Ophthalmology, Peking University Third Hospital, Beijing, China

Correspondence: Yuanping Hai Thyroid Research 2025, 18(s2):A44

Background

Graves’ Orbitopathy (GO) is an autoimmune disorder characterized by immune infiltration, fibroblast activation, and tissue remodeling. The cellular and molecular heterogeneity underlying disease progression remains unclear.

Methods

We performed single-cell RNA sequencing of orbital tissues from patients with active-severe and inactive-mild GO and healthy controls. Bioinformatic tools including SCENIC, Milo, and high-dimensional weighted gene co-expression network analysis (hdWGCNA) were used to identify transcriptional changes, cellular subtypes, and regulatory networks. Key cellular subtypes and molecules were validated by bulk RNA sequencing, multiplex immunofluorescence, immunofluorescence, immunohistochemistry, western blotting, and in vitro functional validation.

Results

We identified seven major cell types, mainly involved in orbital fibroblasts (OFs), endothelial cells, T cells, and B cells. Notably, we performed an in-depth analysis of OFs, the central effector cells, and revealed their stage-specific alterations. Active GO was marked by elevated expression of inflammatory and fibrotic genes, while inactive GO featured adipogenic and metabolic pathways. SCENIC and hdWGCNA analyses identified key transcription factors and GO-associated gene modules. Among three OF subsets, the CD34CXCL14 population was significantly enriched in active GO and promoted fibrosis. T and NK cell subsets showed enhanced activation and cytokine expression in active GO, while inflammatory endothelial and macrophage populations contributed to the proinflammatory microenvironment.

Conclusions

This study provides a high-resolution single-cell landscape of GO, highlighting dynamic cellular reprogramming and key profibrotic subsets. CXCL14CD34OFs may serve as potential therapeutic targets for fibrotic remodeling in GO.

A45 External Validation of a Machine Learning System for Detecting Active Thyroid Eye Disease Using Facial Images in a Spanish Cohort

Kyubo Shin¹, Jaemin Park¹, JaeSang Ko^1,2, Jin Sook Yoon²

¹R&D Division, THYROSCOPE INC., Ulsan, South Korea, ²Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea

Correspondence: Kyubo Shin Thyroid Research 2025, 18(s2):A45

Purpose

The Clinical Activity Score (CAS) is widely used to assess thyroid eye disease (TED) activity but is subject to variability depending on the evaluator’s experience. This study aimed to externally validate a machine learning (ML)-based software that classifies TED as active (CAS ≥ 3) or inactive using digital facial images, comparing its performance with photo-based evaluations by general ophthalmologists and an oculoplastic specialist.

Methods

A total of 1,118 facial images from 140 TED patients treated at a Spanish tertiary center were analyzed. The reference CAS was determined by an oculoplastic specialist through in-person evaluation. The ML system’s sensitivity, specificity, accuracy, and F1 score were assessed and compared to photo-based evaluations by the three physicians.

Results

ML system achieved an F1 score of 0.77 (95% CI: 0.74–0.81), sensitivity of 80.5%, and specificity of 87.8%. The general ophthalmologists’ photo-based evaluation yielded an F1 score of 0.61, sensitivity of 55.9%, and specificity of 90.2%. The oculoplastic specialist’s photo-based assessment had an F1 score of 0.72, sensitivity of 59.0%, and specificity of 98.2%.

Conclusions

This ML-assisted system demonstrated high diagnostic accuracy for detecting active TED in an external Spanish cohort. Its performance surpassed that of a general ophthalmologist and approximated expert-level evaluations, supporting its potential as a consistent and scalable tool for TED activity assessment. Notably, these results were achieved without any model training on Spanish patient data, suggesting that further improvement is possible through future model refinement using diverse population datasets.

A46 An effective and cost-effective steroid sparing approach to Thyroid Eye Disease

Robert Nutt, Kavita Aggarwal, Aoife Naughton, Johnathan Norris

Oxford Eye Hospital, Oxford University Hospitals Trust, Oxford, UK

Correspondence: Robert Nutt Thyroid Research 2025, 18(s2):A46

Background/Aim

First-line treatment for active thyroid eye disease (TED) in many centres involves a large steroid load and up to 12 hospital visits, bringing significant side-effect risks, health care costs and burden to patients. We aim to evaluate the efficacy and cost-effectiveness of a steroid-sparing TED protocol which is less burdensome to health providers and patients.

Methods

A retrospective, single-centre consecutive case series of patients with active TED treated with rituximab (100mg), with typically 1-2 doses of IVMP (250mg) by the Oxford Joint Thyroid Eye Clinic. Additional steroid-sparing agents (Methotrexate or mycophenolate) were administered if clinically indicated. VISA clinical activity score (VCAS), VISA severity score (VSS) and TSH-receptor antibody (TRAB) levels were monitored at baseline and subsequent visits. We also compare the average total cost of a treatment course with the standard IVMP treatment.

Results

59 patients (18 male; 41 female) were included. Mean VCAS improved from 5.35 to 3.5 at initial follow-up, and 0.55 by latest follow up (p<0.001). VSS also significantly improved from 11.4 to 3.3/20 by late follow up (p<0.001). Mean number of hospital visits was 1.9 (range 1-4), compared to 12 for the standard IVMP course. Calculating drug and day case visit costs (£446 in our Trust), the mean cost of our treatment course is £1505.6 compared to £5467.2 for a 12-week IVMP course.

Conclusions

Low-dose rituximab with 250mg to 500mg IVMP is an effective alternative to standard IVMP treatment which saves many hospital visits and approximately £4000 per treatment course.

A47 Triglycerides as a Predictor of Activity and Severity in Thyroid Eye Disease: A Multicenter Study

Hyeong Ju Byeon¹, Jungyul Park², JaeSang Ko³, Jin Sook Yoon³

¹Ophthalmology, Gangnam Severance Hospital, Seoul, South Korea, ²Ophthalmology, St.Mary’s Hospital, Seoul, South Korea, ³Ophthalmology, Severance Hospital, Seoul, South Korea

Correspondence: Hyeong Ju Byeon Thyroid Research 2025, 18(s2):A47

Background

This study investigated the association between dyslipidemia and thyroid eye disease (TED) activity and severity using a multicenter dataset from South Korea.

Methods

A retrospective, multicenter study included adult patients (aged ≥19 years) with TED and elevated thyroid autoantibody levels, including thyroid-stimulating immunoglobulin (TSI) >140% and TSH-binding inhibiting immunoglobulin (TBII) >1.5 IU/L. Patients previously treated with systemic steroids were excluded. TED activity was defined by a Clinical Activity Score, and severity was categorized as mild or marked based on the NOSPECS classification. Logistic regression analyses identified associations between lipid profiles and TED activity/severity. Subgroup analysis excluded statin users. Receiver operating characteristic curves determined optimal TG cutoff values.

Results

Of 330 patients (71.3% women; mean age, 45.7 ± 13.2 years), elevated TG levels was independently associated with TED activity (odds ratio [OR] = 1.005, 95% CI: 1.001–1.008, P = 0.011) and severity (OR = 1.004, 95% CI: 1.001–1.007, P = 0.014). Optimal TG cutoff values were 104 mg/dL for active TED and 108 mg/dL for marked severity. These associations remained consistent in non–statin users with similar cutoff values. Elevated intraocular pressure and smoking were significantly associated with increased disease severity. Subgroup analysis excluding statin users revealed significant associations of total cholesterol and LDL cholesterol with TED activity.

Conclusions

Elevated TG levels are significantly associated with TED activity and severity, highlighting the potential clinical value of measuring TG for risk stratification and disease management. Further studies should explore whether TG-lowering interventions improve TED outcomes.

A48 Depression, anxiety and stress in the Belgian patient suffering from Graves Orbitopathy

Virginie G.S. Ninclaus^{1, 2}, Eloïse Ruysschaert², Emmelien Lauwerier³, Geert Crombez³, Bart P. Leroy^{1, 2}, Bruno Lapauw^{2, 4}

¹Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium, ²Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium, ³Department of Clinical-Experimental and Health Psychology, Ghent University, Ghent, Belgium, ⁴Department of Endocrinology, Ghent university Hospital, Ghent, Belgium

Correspondence: Virginie G.S. Ninclaus Thyroid Research 2025, 18(s2):A48

Graves’ Orbitopathy (GO) significantly impacts patients’ quality of life, involving physical symptoms and psychosocial distress. There are reports of increased psychological burden, potentially including severe outcomes. The objective of this study was to investigate depression, anxiety and stress in patients with active GO, and possible mediators thereof, compared with healthy controls.

Materials & methods

We included 34 patients of the Ghent University hospital with active GO (CAS 3 and more) and 39 sex- and age-matched healthy controls. Subjects completed a survey consisting demographic questions and the 21-question version of the Depression Anxiety Stress Scale (DASS2).

Results

We found significant more depression, anxiety and stress in the GO group compared to the healthy control group.

Conclusions

GO patients suffer from more depression, anxiety and stress compared to healthy controls of the same sex and age. In further analysis, we will explore if and how differences in clinial parameters and differences in coping strategies explain differences in health outcome.

A49 Paediatric Thyroid Eye Disease: Clinical Experience from a quaternary referral centre

Mustafa Al-Asady¹, Li Yen Goh¹, Jimmy Uddin¹

¹Adnexal Department, Moorfields Eye Hospital, London, UK

Correspondence: Mustafa Al-Asady Thyroid Research 2025, 18(s2):A49

Thyroid eye disease (TED) is an autoimmune condition in children, typically associated with Graves’ disease. Compared to adults, paediatric TED tends to be milder with fewer vision-threatening complications. This study describes the phenotypic features and management of paediatric TED cases at a quaternary centre in the UK.

Methods

A retrospective review of patients aged 0–17 years diagnosed with TED at Moorfields Eye Hospital between 2000 and 2023 was conducted. Data on demographics, thyroid status, ophthalmic findings, neuroimaging, and treatment were analysed. Disease activity and severity were assessed using European Group on Graves’ Orbitopathy (EUGOGO) guidelines and clinical activity score (CAS) criteria.

Results

TED onset occurred at a median age of 13 years; 81% were female. Most had hyperthyroid Graves’ disease (89%) and mild TED at presentation (87%). Common features included proptosis (75%) and eyelid retraction (37%). No cases of optic neuropathy or sight-threatening disease were recorded. Four patients had active TED, and five underwent orbital decompression for quality-of-life reasons. Systemic steroids were used in two cases, with no use of radiotherapy or biologics. Neuroimaging showed extraocular muscle enlargement in 37%.

Conclusions

This study highlights the clinical experience of managing paediatric TED at a quaternary referral centre. Paediatric TED is generally milder than adult TED, with fewer severe complications. Early recognition and conservative management are often sufficient, though steroid-sparing agents and biologics offer promising alternatives.

Rapid Fire and Poster Winner

A50 Incidence of Thyroid Eye Disease and Surgical Interventions in Patients with Graves’ disease treated with Antithyroid medication, Radioiodine, or Thyroidectomy – A Nationwide Registry-Based Cohort Study

¹Lena Boulakh¹, Jonas L. Isaksen², Steffen Heegaard^1,3,4, Helena Buch Hesgaard^5,6, Jørgen Kim Kanters^2,7, Birte Nygaard^3,8, Henrik Enghousen Poulsen^{3,9, 10}, Peter Bjerre Toft^1,3, Christina Ellervik^3,11,12, Andrea Kossler¹³

¹Ophthalmology, Rigshospitalet-Glostrup, Copenhagen, Denmark, ²Of Experimental Cardiology + Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark, ³Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, ⁴Department of Pathology, Rigshospitalet-Glostrup, Copenhagen, Denmark, ⁵Insitute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden, ⁶Department of Ophthalmology, Sahlgrenska University Hospital, Gothenburg, Sweden, ⁷Center of Biosignal Research, University of California, San Francisco, USA, ⁸Department of Endocrinology, Herlev-Gentofte Hospital, Copenhagen, Denmark, ⁹Department of Endocrinology, Bispebjerg Fredriksberg Hospital, Copenhagen, Denmark, ¹⁰Department of Cardiology, Nordsjaellands Hospital, Copenhagen, Denmark, ¹¹Department of Clinical Biochemistry, Zealand University Hospital, Koge, Denmark, ¹²Department of Laboratory Medicine, Harvard Medical School, Boston Children’s Hospital, Boston, USA, ¹³Department of Ophthalmology, Standford University, School of Medicine, Palo Alto, USA

Correspondence: Lena Boulakhz Thyroid Research 2025, 18(s2):A50

Purpose

To provide the real-life incidence of thyroid eye disease (TED) in Graves’ disease (GD) patients according to antithyroid medication as monotherapy or followed by radioactive iodine (RAI) or thyroidectomy, and to study the incidence of decompression and strabismus surgery in GD patients diagnosed with TED.

Methods

In this nation-wide registry-based study, data were extracted from nationwide registries, between 2004 and 2022 including all Danish residents. Each hospital visit, treatment, and surgery performed at a hospital in Denmark is registered.

Results

A total of 24,091 GD patients were included(81.5%women): 96.0% received antithyroid medication, 11.6% received additional RAI, and 6.3% underwent thyroidectomy in addition to medical treatment. Throughout a median follow-up of 7.4 years [IQR: 2.9-13.3], 1,267 (5.3%) patients developed TED. The 1-year incidences of TED were 3.2% in the antithyroid medication only group, 1.1% in the RAI group, and 2.5% in the thyroidectomy group. The 7-year TED incidences were 5.3%, 3.4%, and 4.0%, respectively. The incidence rates for decompression surgery were 2.7% after one year and 5.9% after 7 years, while rates for strabismus surgery were 1.9% after one year and 7.4% after seven years.

Conclusion

This study is the first to provide real-life incidence data on TED in patients with GD based on treatment decisions as actually provided rather than assigned according to research protocol. The results can be utilized to understand the disease course and burden of GD and TED, informing healthcare planning, evaluating current treatment guidelines, and providing patients with relevant information on the complications of GD and TED.

Poster Prize Winner Abstracts

A51 Real world effectiveness of Mycophenolate-sodium therapy in patients at risk with Graves’ orbitopath

Michael Oeverhaus^1,2, Julius Sander¹, Karim Al-Ghazzawi¹, Nikolaos Bechrakis¹, Ying Chen¹, Inga Neumann¹, Anja Eckstein¹

¹Ophthalmology, University Hospital Essen, Essen, Germany, ²Praxis Dres. Oeverhaus, Germany

Correspondence: Michael Oeverhaus Thyroid Research 2025, 18(s2):A51

Purpose

Patients with active, moderate-to-severe Graves’ orbitopathy require immunosuppressive treatments to reduce inflammation and morbidity. Since 2021 EUGOGO lists Mycophenolate-sodium (MPS) as first-line-treatment, which lead to a change in treatment regimens. In our center MPS was administered mainly for patients at risk for deterioration (e.g. unstable thyroid function, smoker etc.) or as second-line treatment. To augment the limited data we analyzed our real-world cohort retrospectively.

Methods

We analyzed all consecutive patients of our tertiary referral center (2019-2023) with a complete data set, who either received MPS simultaneously with intravenous methylprednisolone (IVMP), or after a first course of IVMP.

Results

We evaluated the data of 172 patients. Ninety-five were eligible for analysis. Clinical Activity Score showed a significant decrease between baseline (BL) and primary endpoint 6 months (3.9±0.9 vs. 2.4±1.4, p<0.0001). Inactivation was achieved in 60% of all patients at 6 months and in 77% at 12 months. Deviation, motility, upper eye lid retraction and proptosis showed no significant changes after 6 months. TSH-receptor-antibody-levels (TRAb) showed a significant decrease at 3 and 6 months (p<0.0001). 10.5% developed DON. Multiple logistic regression showed a significant influence of irradiation after BL for inactivation (OR 6.18, 95% CI: 1.08 to 48.99).

Discussion

The effect of MPS is limited. Although inactivation is most often achieved, the severity of the disease in form of fibrosis (lid retraction, motility) and proptosis is not reversed. Further rehabilitative surgery is needed and patients should still be closely monitored for DON. Other immunosuppressants seem to be more effective (e.g. Tocilizumab) even in IVMP resistant GO. Randomized controlled studies are needed to further elucidate this topic.

A52 Assessment of quality of life (QOL) by baseline factors among patients with Thyroid Eye Disease (TED)

Amina Malik¹, Sarah Bray², Margarita Ochoa-Maya², Christina Giannopoulou², sun Kim², Haridarshan Patel², George J Kahaly³

Correspondence: Amina Malik Thyroid Research 2025, 18(s2):A52

¹Oculoplastic & Reconstructive Surgery, Houston Methodist Eye Associates, Houston, USA, ²Amgen Inc., Thousand Oaks, USA, ³Department of medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

Introduction

TED can alter vision and physical appearance impacting QOL. Graves Ophthalmopathy Quality of Life Questionnaire (GO-QOL) data in patients with active TED was assessed for impact on daily activities.

Method

This post-hoc analysis included baseline data from 3 teprotumumab trials (Phase2[NCT01868997], OPTIC[NCT03298867] and OPTIC-J[RCT2031210453]) of active TED. GO-QOL scores (visual function[VF] and appearance[AP]) were assessed (higher scores=better QOL). Response frequency for individual questions were evaluated (1=seriously limited, 2=little limited, 3=not at all limited) in daily activities, appearance, and social interactions.

Responses were assessed by sex/age, and by anxiety/depression history from Phase 2 and OPTIC.

Results

163/225(72%) patients from all 3 studies were female, mean(SD) age was 50.7(12.7) years. Baseline AP and VF scores were 59.7 and 67.0, respectively. Most common limitations reported in VF were reading (68%) and watching TV (62%), and in AP were appearance (96%), self-confidence (67%), and avoiding photos (64%).

Females reported higher impairment than males in AP (55.4vs70.9) and VF scores (66.0vs69.8), with lower scores for masking appearance changes (1.9vs2.5), avoiding photos (1.8vs2.4), and effect on self-confidence (1.9vs2.3).

Younger <50years) had lower AP scores vs. older (>65years) patients (56.8vs70.3) and lower scores for appearing less in photos (1.8vs2.4), masking appearance changes (1.9vs2.4) and influence on self-confidence (2.0vs2.3); VF scores were 69.6 and 64.4, respectively.

30/171(17.5%) Phase 2/OPTIC patients reported anxiety/depression; these patients had lower VF (57.7vs65.8), AP (45.3vs59.5), and scores for feeling hindered (1.7vs2.2), effect on self-confidence (1.5vs2.0), and feeling socially isolated (2.2vs2.5) versus those without anxiety/depression.

Conclusion

Female patients, younger individuals, and those with anxiety/depression reported greater QOL impairment, underscoring the necessity of recognizing and addressing TED’s psychosocial impact.