RARE DISEASE
Euthyroid Graves orbitopathy
Euthyroid Graves orbitopathy
Euthyroid Graves orbitopathy
Synonyms: Euthyroid Graves ophthalmopathy
Synonyms: Euthyroid Graves ophthalmopathy
Synonyms: Euthyroid Graves ophthalmopathy
Drug discovery
2
drugs
With orphan designations
Overview
Euthyroid Graves orbitopathy (EGO) is a rare variant of thyroid eye disease characterized by orbital inflammation (proptosis, diplopia, eyelid retraction) without current or past thyroid dysfunction. Diagnosis relies on clinical features, orbital imaging, and exclusion of mimics like IgG4-related disease. While euthyroid, 9-15% develop thyroid dysfunction over time. TRAb levels may be low or absent initially but often emerge later [1][4][12]. Misdiagnosis is common due to frequent asymmetrical presentation [7][12].
Categories: rare developmental anomalies during embryogenesis, rare ophthalmic disorders
Research Papers
791 drug discovery papers about Euthyroid Graves orbitopathy, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
791 drug discovery papers about Euthyroid Graves orbitopathy, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-08 | Ultrasound-guided thermal ablation in patients affected by Graves' disease: a systematic review and meta-analysis.
Ultrasound-guided thermal ablation (U-GTA) techniques, including radiofrequency ablation (RFA) and microwave ablation (MWA), have recently been proposed as minimally invasive alternatives to surgery or radioiodine (RAI) therapy for patients with Graves' disease (GD) who are unresponsive to antithyroid drugs. However, evidence supporting its effectiveness and safety remains limited. A PubMed/MEDLINE, Web of Science, and Scopus research updated until January 31, 2026, was performed. The review question was: What is the euthyroidism rate (outcome) one year after U-GTA (intervention) in Graves' disease (population)? Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the prevalence with corresponding 95% confidence intervals. Four studies comprising 82 patients (88% female) were included in the analysis. Approximately 2.4% of patients required levothyroxine replacement after U-GTA. Thyroid volume significantly decreased following treatment, and baseline thyroid volume was identified as a predictor of relapse in one study. A transient increase in anti-TSH receptor antibodies was observed one month after U-GTA, followed by a subsequent decline. No worsening or new onset of Graves' orbitopathy was reported. Post-procedural adverse events occurred in 6.1% of patients and were transient. At 12 months, pooled euthyroidism rate was 67.0% (95% CI 54-78), with low heterogeneity (I² = 0%). U-GTA appears to induce biochemical remission in approximately two-thirds of selected patients with persistent or relapsed GD, with a favourable short-term safety profile and preservation of thyroid function in most cases. However, remission rates remain lower than those typically reported for definitive surgical treatment, and current evidence is limited to small, non-randomized studies with relatively short follow-up. Larger prospective comparative trials with standardized protocols are required to define the role of U-GTA within current management strategies for GD.
2026-04-01 | Thyroid Eye Disease: Current Perspectives in Pathogenesis, Risk Factors, and Management
Thyroid eye disease (TED), also referred to as Graves’ orbitopathy or thyroid-associated ophthalmopathy, is an autoimmune inflammatory disorder of the orbit that most often accompanies hyperthyroidism due to Graves’ disease. This review summarises current understanding of its immunopathogenesis, including the role of autoantibodies against the thyroid-stimulating hormone receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R), the subsequent activation of orbital fibroblasts, cytokine-mediated inflammation, glycosaminoglycan deposition and fibrosis. The clinical spectrum ranges from mild ocular surface irritation to sight-threatening dysthyroid optic neuropathy — and the classification systems (e.g., CAS, VISA, EUGOGO) used to assess disease activity and severity. Key modifiable risk factors such as smoking, uncontrolled thyroid status, micronutrient deficiencies (selenium, iron, iodine), dyslipidaemia, and vitamin D deficiency are reviewed. We present management strategies from achieving euthyroidism and risk-factor control, to supportive care (lubrication, eyelid taping) and medical therapies — from high-dose intravenous methylprednisolone to immunosuppressants (mycophenolate, azathioprine) and novel biologics such as teprotumumab (anti-IGF-1R), rituximab (anti-CD20) and tocilizumab (anti-IL-6R). Surgical options (orbital decompression, strabismus correction, eyelid surgery) for disfiguring or sight-threatening disease are discussed. Finally, we highlight future directions including biomarker development and personalised, mechanism-based therapy. Early recognition and intervention, along with risk factor modification and targeted treatments, may improve functional and psychosocial outcomes in TED.
2026-01-28 | Euthyroid Graves' Ophthalmopathy With Negative Antibodies (EGONA): A Comprehensive Case-Based Review.
Euthyroid Graves' ophthalmopathy with negative antibodies (EGONA) is a rare form of thyroid eye disease. This literature review aims to establish the different presentations seen in the cases of euthyroid Graves' ophthalmopathy with negative antibodies. Despite the thyroid levels being normal, the mechanism by which EGONA causes eye disease is the same as the classical Graves' ophthalmopathy. Proper diagnosis relies mainly on clinical signs and imaging of the eye. A systematic search of PubMed, PubMed Central, and ScienceDirect was conducted with no date restrictions. Articles were included if they were English-language case reports describing patients with euthyroid ophthalmopathy and negative thyroid antibodies during initial presentation, with full-text availability and a documented clinical course. Data from nine articles (12 cases) were extracted, focusing on presentation, management, and outcomes. Treatments include corticosteroids, anti-thyroid medication, and surgery. Prognosis varied between those who developed thyroid imbalances and the presence of antibodies later down the course.
2026-01-06 | Periphlebitis of the Superior Ophthalmic Vein in Noninflammatory Thyroid Eye Disease
A 32-year-old female with euthyroid Graves’ disease presented with right-sided proptosis, first noticed 3 months prior to consultation. Although she was euthyroid, her thyroid-stimulating receptor antibodies were positive. An orbital CT scan, requested by her general ophthalmologist, demonstrated an inflammatory lesion involving the right superior muscle complex. On examination, visual acuity was 20/20 in OU. Margin reflex distances were 7 mm in the OD and 5 mm in the OS (panel A). Hertel exophthalmometry measured 22 mm in OD and 14 mm in OS (panel B). No clinical inflammatory signs were detected, with both VISA (vision, inflammation, strabisumus and appearance) and CAS (clinical activity score) inflammation scores graded as zero in OU. Intraocular pressure was asymmetric, measuring 19 mm Hg in the proptotic eye and 12 mm Hg in OS. Fundus examination was normal in OU. Axial T1-weighted postcontrast magnetic resonance imaging of the orbits with fat saturation revealed periphlebitis of the right superior orbital vein, characterized by a poorly defined, enhancing inflammatory process surrounding the vein (panel C). Color Doppler ultrasonography showed reduced flow velocity in OD (3.8 cm/s vs. 5.97 cm/s in OS) (panel D). Periphlebitis of the superior orbital vein is a rare manifestation of thyroid eye disease, usually associated with the active form of the orbitopathy. The present case highlights that superior orbital vein periphlebitis in thyroid eye disease may reduce orbital venous flow without the classic conjunctival signs of venous impedance or clinical signs of disease activity.FIG.
2025-11-04 | Assessing the Role of Tocilizumab in the Treatment of Thyroid Eye Disease: A Retrospective Single Centre Analysis.
Due to the variable course of thyroid eye disease (TED), treatment should be tailored to disease severity, individual risk factors, and clinical course. This study is based on a retrospective analysis at the orbital centre of the University Eye Clinic Essen and evaluates the efficacy of the IL-6 receptor blocker tocilizumab as a second-line therapy in patients with therapy-refractory TED. After approval of cost coverage, 20 patients were treated with tocilizumab over a mean period of 4.8 ± 2.7 months. The following parameters were assessed: sex, age, underlying thyroid disease, disease activity and severity, prior therapies, visual acuity, intraocular pressure, eyelid position, exophthalmos, monocular excursions, strabismus/diplopia, levels of TSH receptor antibodies (TRAb), and adverse events. The female-to-male ratio was 3 : 1. Mean patient age was 58.2 ± 8.5 years. The majority (90%, n = 18) had Graves' disease; one patient had primary hypothyroidism and one was euthyroid. All patients had previously failed various treatment regimens (median cumulative steroid dose 4.6 g [1.5 - 7.5 g], 55% mycophenolate, 65% orbital apex radiation, 20% balanced orbital decompression). Among 17 patients with detectable TRAb at baseline, mean antibody levels decreased by 48.4%. A reduction of at least 30% was achieved in 70.6% of these patients (n = 17). A decrease in the Clinical Activity Score (CAS) by ≥ 2 points was observed in 70% of cases. The mean inflammation score (maximum 20 points per patient) decreased from 8.8 ± 3.9 to 3.4 ± 2.4. The effect on exophthalmos was moderate: mean reduction was 0.9 ± 1.8 mm (range - 6 mm to + 3 mm). A decrease of ≥ 2 mm was documented in 25% of patients, whereas an increase was noted in 12.5% (0.5 to 3 mm). Improvement in ocular motility was documented in 22.5% of patients, while 10% showed deterioration. This cohort exclusively included therapy-refractory patients, some with protracted disease. The significant reduction in inflammation and particularly in TRAb levels, as a biomarker of disease activity, demonstrate the efficacy of tocilizumab in this highly selected population. Tocilizumab may therefore be an important treatment option for patients with high antibody levels and predominantly inflammatory disease manifestations. Further studies are warranted to evaluate whether it reduces the risk of relapse after successful treatment with an IGF-1 receptor blocker.
2026-08-08 | Ultrasound-guided thermal ablation in patients affected by Graves' disease: a systematic review and meta-analysis.
Ultrasound-guided thermal ablation (U-GTA) techniques, including radiofrequency ablation (RFA) and microwave ablation (MWA), have recently been proposed as minimally invasive alternatives to surgery or radioiodine (RAI) therapy for patients with Graves' disease (GD) who are unresponsive to antithyroid drugs. However, evidence supporting its effectiveness and safety remains limited. A PubMed/MEDLINE, Web of Science, and Scopus research updated until January 31, 2026, was performed. The review question was: What is the euthyroidism rate (outcome) one year after U-GTA (intervention) in Graves' disease (population)? Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the prevalence with corresponding 95% confidence intervals. Four studies comprising 82 patients (88% female) were included in the analysis. Approximately 2.4% of patients required levothyroxine replacement after U-GTA. Thyroid volume significantly decreased following treatment, and baseline thyroid volume was identified as a predictor of relapse in one study. A transient increase in anti-TSH receptor antibodies was observed one month after U-GTA, followed by a subsequent decline. No worsening or new onset of Graves' orbitopathy was reported. Post-procedural adverse events occurred in 6.1% of patients and were transient. At 12 months, pooled euthyroidism rate was 67.0% (95% CI 54-78), with low heterogeneity (I² = 0%). U-GTA appears to induce biochemical remission in approximately two-thirds of selected patients with persistent or relapsed GD, with a favourable short-term safety profile and preservation of thyroid function in most cases. However, remission rates remain lower than those typically reported for definitive surgical treatment, and current evidence is limited to small, non-randomized studies with relatively short follow-up. Larger prospective comparative trials with standardized protocols are required to define the role of U-GTA within current management strategies for GD.
2026-04-01 | Thyroid Eye Disease: Current Perspectives in Pathogenesis, Risk Factors, and Management
Thyroid eye disease (TED), also referred to as Graves’ orbitopathy or thyroid-associated ophthalmopathy, is an autoimmune inflammatory disorder of the orbit that most often accompanies hyperthyroidism due to Graves’ disease. This review summarises current understanding of its immunopathogenesis, including the role of autoantibodies against the thyroid-stimulating hormone receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R), the subsequent activation of orbital fibroblasts, cytokine-mediated inflammation, glycosaminoglycan deposition and fibrosis. The clinical spectrum ranges from mild ocular surface irritation to sight-threatening dysthyroid optic neuropathy — and the classification systems (e.g., CAS, VISA, EUGOGO) used to assess disease activity and severity. Key modifiable risk factors such as smoking, uncontrolled thyroid status, micronutrient deficiencies (selenium, iron, iodine), dyslipidaemia, and vitamin D deficiency are reviewed. We present management strategies from achieving euthyroidism and risk-factor control, to supportive care (lubrication, eyelid taping) and medical therapies — from high-dose intravenous methylprednisolone to immunosuppressants (mycophenolate, azathioprine) and novel biologics such as teprotumumab (anti-IGF-1R), rituximab (anti-CD20) and tocilizumab (anti-IL-6R). Surgical options (orbital decompression, strabismus correction, eyelid surgery) for disfiguring or sight-threatening disease are discussed. Finally, we highlight future directions including biomarker development and personalised, mechanism-based therapy. Early recognition and intervention, along with risk factor modification and targeted treatments, may improve functional and psychosocial outcomes in TED.
2026-01-28 | Euthyroid Graves' Ophthalmopathy With Negative Antibodies (EGONA): A Comprehensive Case-Based Review.
Euthyroid Graves' ophthalmopathy with negative antibodies (EGONA) is a rare form of thyroid eye disease. This literature review aims to establish the different presentations seen in the cases of euthyroid Graves' ophthalmopathy with negative antibodies. Despite the thyroid levels being normal, the mechanism by which EGONA causes eye disease is the same as the classical Graves' ophthalmopathy. Proper diagnosis relies mainly on clinical signs and imaging of the eye. A systematic search of PubMed, PubMed Central, and ScienceDirect was conducted with no date restrictions. Articles were included if they were English-language case reports describing patients with euthyroid ophthalmopathy and negative thyroid antibodies during initial presentation, with full-text availability and a documented clinical course. Data from nine articles (12 cases) were extracted, focusing on presentation, management, and outcomes. Treatments include corticosteroids, anti-thyroid medication, and surgery. Prognosis varied between those who developed thyroid imbalances and the presence of antibodies later down the course.
2026-01-06 | Periphlebitis of the Superior Ophthalmic Vein in Noninflammatory Thyroid Eye Disease
A 32-year-old female with euthyroid Graves’ disease presented with right-sided proptosis, first noticed 3 months prior to consultation. Although she was euthyroid, her thyroid-stimulating receptor antibodies were positive. An orbital CT scan, requested by her general ophthalmologist, demonstrated an inflammatory lesion involving the right superior muscle complex. On examination, visual acuity was 20/20 in OU. Margin reflex distances were 7 mm in the OD and 5 mm in the OS (panel A). Hertel exophthalmometry measured 22 mm in OD and 14 mm in OS (panel B). No clinical inflammatory signs were detected, with both VISA (vision, inflammation, strabisumus and appearance) and CAS (clinical activity score) inflammation scores graded as zero in OU. Intraocular pressure was asymmetric, measuring 19 mm Hg in the proptotic eye and 12 mm Hg in OS. Fundus examination was normal in OU. Axial T1-weighted postcontrast magnetic resonance imaging of the orbits with fat saturation revealed periphlebitis of the right superior orbital vein, characterized by a poorly defined, enhancing inflammatory process surrounding the vein (panel C). Color Doppler ultrasonography showed reduced flow velocity in OD (3.8 cm/s vs. 5.97 cm/s in OS) (panel D). Periphlebitis of the superior orbital vein is a rare manifestation of thyroid eye disease, usually associated with the active form of the orbitopathy. The present case highlights that superior orbital vein periphlebitis in thyroid eye disease may reduce orbital venous flow without the classic conjunctival signs of venous impedance or clinical signs of disease activity.FIG.
2025-11-04 | Assessing the Role of Tocilizumab in the Treatment of Thyroid Eye Disease: A Retrospective Single Centre Analysis.
Due to the variable course of thyroid eye disease (TED), treatment should be tailored to disease severity, individual risk factors, and clinical course. This study is based on a retrospective analysis at the orbital centre of the University Eye Clinic Essen and evaluates the efficacy of the IL-6 receptor blocker tocilizumab as a second-line therapy in patients with therapy-refractory TED. After approval of cost coverage, 20 patients were treated with tocilizumab over a mean period of 4.8 ± 2.7 months. The following parameters were assessed: sex, age, underlying thyroid disease, disease activity and severity, prior therapies, visual acuity, intraocular pressure, eyelid position, exophthalmos, monocular excursions, strabismus/diplopia, levels of TSH receptor antibodies (TRAb), and adverse events. The female-to-male ratio was 3 : 1. Mean patient age was 58.2 ± 8.5 years. The majority (90%, n = 18) had Graves' disease; one patient had primary hypothyroidism and one was euthyroid. All patients had previously failed various treatment regimens (median cumulative steroid dose 4.6 g [1.5 - 7.5 g], 55% mycophenolate, 65% orbital apex radiation, 20% balanced orbital decompression). Among 17 patients with detectable TRAb at baseline, mean antibody levels decreased by 48.4%. A reduction of at least 30% was achieved in 70.6% of these patients (n = 17). A decrease in the Clinical Activity Score (CAS) by ≥ 2 points was observed in 70% of cases. The mean inflammation score (maximum 20 points per patient) decreased from 8.8 ± 3.9 to 3.4 ± 2.4. The effect on exophthalmos was moderate: mean reduction was 0.9 ± 1.8 mm (range - 6 mm to + 3 mm). A decrease of ≥ 2 mm was documented in 25% of patients, whereas an increase was noted in 12.5% (0.5 to 3 mm). Improvement in ocular motility was documented in 22.5% of patients, while 10% showed deterioration. This cohort exclusively included therapy-refractory patients, some with protracted disease. The significant reduction in inflammation and particularly in TRAb levels, as a biomarker of disease activity, demonstrate the efficacy of tocilizumab in this highly selected population. Tocilizumab may therefore be an important treatment option for patients with high antibody levels and predominantly inflammatory disease manifestations. Further studies are warranted to evaluate whether it reduces the risk of relapse after successful treatment with an IGF-1 receptor blocker.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Euthyroid Graves orbitopathy, including 1 approved therapy.
2 orphan drug designations for Euthyroid Graves orbitopathy, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
teprotumumab | antibodies | FDA | 2013-05-06 | 2020-01-21 | Horizon Therapeutics Ireland DAC |
salmeterol xinafoate/fluticasone propionate | small molecules | FDA | 2009-10-29 | — | Lithera, Inc. |
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