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
789 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:
789 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:
2026-01-06 | 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.
2025-11-03 | The role of mycophenolate mofetil in the therapy of thyroid eye disease.
Thyroid eye disease (TED) is an autoimmune disorder that can threaten vision loss. In 90% cases, it is related to Graves' disease, and in 10% cases, it occurs with euthyroidism or with chronic autoimmune thyroiditis. It is the leading cause of orbital pathology in adults. The TED treatment remains challenging for clinicians, particularly in moderate-to-severe or sight-threatening forms of the disease. One-third of TED patients experience a relapse despite the corticosteroids as a first-line treatment. Some patients show poor response or even no response to the treatment. There are many adverse effects associated with chronic use of intravenous methylprednisolone (IVMP). There is a need for new, efficient therapeutic methods, such as immunomodulating drugs like mycophenolate mofetil (MMF). This paper describes the role and potential efficiency of MMF application in TED by its direct action on TED pathogenic mechanisms. The introduction of MMF in the second-line treatment helps decrease the level of clinical symptoms and the risk of chronic complications, while causing only a small number of adverse events. Nevertheless, it should be noted that there are no unified guidelines available for consolidating treatment focused on maintaining remission after the first dose of IVMP. Moreover, clinical knowledge on the use of MMF application in TED is still limited, and further research is needed. Nonetheless, the available evidence is promising and MMF may play a vital role in future therapeutic strategies.
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.
2025-11-03 | The role of mycophenolate mofetil in the therapy of thyroid eye disease.
Thyroid eye disease (TED) is an autoimmune disorder that can threaten vision loss. In 90% cases, it is related to Graves' disease, and in 10% cases, it occurs with euthyroidism or with chronic autoimmune thyroiditis. It is the leading cause of orbital pathology in adults. The TED treatment remains challenging for clinicians, particularly in moderate-to-severe or sight-threatening forms of the disease. One-third of TED patients experience a relapse despite the corticosteroids as a first-line treatment. Some patients show poor response or even no response to the treatment. There are many adverse effects associated with chronic use of intravenous methylprednisolone (IVMP). There is a need for new, efficient therapeutic methods, such as immunomodulating drugs like mycophenolate mofetil (MMF). This paper describes the role and potential efficiency of MMF application in TED by its direct action on TED pathogenic mechanisms. The introduction of MMF in the second-line treatment helps decrease the level of clinical symptoms and the risk of chronic complications, while causing only a small number of adverse events. Nevertheless, it should be noted that there are no unified guidelines available for consolidating treatment focused on maintaining remission after the first dose of IVMP. Moreover, clinical knowledge on the use of MMF application in TED is still limited, and further research is needed. Nonetheless, the available evidence is promising and MMF may play a vital role in future therapeutic strategies.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles 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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