Review

Thyroid eye disease: What’s the latest?

Ashley B. Vincent, DO, Alexander R. Engelmann, MD, Catherine J. Hwang, MD and Christian Nasr, MD
Cleveland Clinic Journal of Medicine November 2025, 92 (11) 693-701; DOI: https://doi.org/10.3949/ccjm.92a.25043

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ABSTRACT

Thyroid eye disease (TED) is an inflammatory autoimmune condition now recognized as being associated not only with Graves hyperthyroidism but also with euthyroidism and hypothyroidism. A high index of suspicion is required to diagnose TED and to recognize sight-threatening disease. Care is best provided in a multidisciplinary setting among primary care clinicians, endocrinologists, and ophthalmologists. This review summarizes the pathophysiology, risk factors, clinical presentation, and activity and severity evaluation of TED as well as the most recent advances in its treatment.

KEY POINTS

  • Several factors increase the risk of developing TED, but cigarette smoking is the most important modifiable risk factor.

  • Treatment is determined by the clinical activity score, the European Group on Graves’ Orbitopathy disease severity assessment, and impact on daily life.

  • Vision-threating dysthyroid optic neuropathy is the most severe manifestation of TED, and it requires urgent intervention.

Thyroid eye disease (TED), also known as Graves or thyroid-associated orbitopathy, is an inflammatory autoimmune disorder that affects orbital and periorbital tissues. Robert J. Graves (1796–1853) gave the first contemporary description of thyroid-associated orbitopathy; however, in the book The Canon of Medicine (Arabic: al-Qānūn fiāl-t.ibb), Ibn Sina (980–1037), known in the West as Avicenna, was possibly the first to describe the condition of protuberant eyes and swollen neck in patients who seemed to be affected by thyrotoxicosis. More recently, there has been better understanding of the pathophysiology of this condition, which has led to innovative insights into its treatment.1

See related editorial, page 702

TED is most known for its association with Graves disease, but it can also occur in patients with euthyroidism or hypothyroidism. It has a pooled prevalence of 27% in North American patients with Graves disease,2 with 85% of patients developing TED within 18 months of Graves onset.3 The incidence of TED is thought to be decreasing for several reasons, including improved detection and treatment of hyperthyroidism; recognition that radioactive iodine treatment is a major risk factor; and a reduction in cigarette smoking, which is the most prominent modifiable risk factor.3

This review outlines TED’s pathophysiology, risk factors, clinical presentation, treatment options based on disease activity and severity, and when surgery might be indicated.

PATHOPHYSIOLOGY IS DRIVEN BY ORBITAL FIBROBLASTS

TED is characterized by inflammation and remodeling of orbital tissue, resulting in enlargement of the extraocular muscles and expansion of the retrobulbar fat and connective tissue compartment.4 This process is caused by autoimmune, environmental, and immunologic factors that lead to uncontrolled activation and proliferation of orbital fibroblasts.

The key effector cells in TED are the CD34+ fibroblasts, which are derived from circulating fibrocytes, cells that promote wound healing at sites of tissue injury and possess proinflammatory properties.5,6 Orbital fibroblasts in patients with TED can express thyroid-stimulating hormone (TSH) receptors.6 In addition, insulin-like growth factor (IGF) 1 receptors are overexpressed on orbital fibroblasts, B cells, and T cells in individuals with TED. TSH receptors and IGF-1 receptors form a functional complex that, when activated, facilitates CD34+ fibroblast infiltration into the orbit, followed by release of inflammatory cytokines (including interleukin 16), adipogenesis, hyaluronan production, and chemokine secretion. The release of chemokines facilitates lymphocyte trafficking into the orbit, leading to further differentiation of fibroblasts into adipocytes and scar-forming myofibroblasts.4–6

RISK FACTORS

There are nonmodifiable and modifiable factors that increase a person’s risk for developing TED.

Nonmodifiable

These risk factors include older age (unimodal peak between ages 50 and 59), female sex (although more severe disease occurs in males), and genetic predisposition.7 The highest prevalence is in Black individuals (0.12%), followed by White (0.11%), Asian (0.07%), and Hispanic (0.05%) individuals; however, the racial and ethnic variations may be related to differences in orbital anatomy and genetics.7

Modifiable

Cigarette smoking is the most important modifiable risk factor because it not only increases the risk of developing TED but is also associated with a more severe disease course and may lead to a decreased or delayed treatment response.3 Cigarette smoking is thought to increase the risk of TED by causing hypoxia and generating reactive oxygen species.8 Current smoking is a greater risk than cumulative pack-year history.3

Radioactive iodine treatment for hyperthyroidism also increases the risk of developing TED and can worsen preexisting TED in the months after treatment.9 Tissue damage caused by radioactive iodine releases antigens, which may exacerbate the autoimmune process and result in TED.10 Certain patients have a higher risk of developing TED or experiencing worsening TED after radioactive iodine treatment, including those who are smokers, have high thyroid-stimulating immunoglobulin or TSH receptor antibody levels, or have uncontrolled hyperthyroidism.10

Selenium deficiency may also increase the risk of developing and worsening TED.11 The average North American diet is generally selenium sufficient, but in Europe and other regions with less selenium-rich diets, this consideration is important.12

High serum total and low-density lipoprotein cholesterol levels are reported in patients with TED.3 It has been reported that patients with hypercholesterolemia who use statins have a decreased risk of developing TED.13 However, it is unclear whether this decreased risk is due to the anti-inflammatory effect of statins or the proinflammatory actions of cholesterol, and whether statins will effectively treat or prevent TED.

NATURAL HISTORY AND CLINICAL PRESENTATION

The natural history of TED that was described by Rundle and Wilson14 in 1945 is still widely accepted today. The initial active inflammatory phase, during which patients experience progressive inflammation and tissue expansion, can last from 6 to 36 months, depending on smoking status.15 In the brief static phase, the disease will stabilize as inflammation subsides. TED then improves during the inactive fibrotic phase, which typically occurs 18 to 24 months after onset, but symptoms may persist.3 Recurrent TED has been described in 15.7% of patients, and mostly occurs within the first 10 years after the initial episode.15

Patients with TED present with a range of ocular signs and symptoms that reflect the pathogenesis described previously. Most patients have bilateral disease; however, asymmetric and unilateral cases can occur.3 Common signs and symptoms include the following16,17:

  • Proptosis (bulging eyes)

  • Eyelid retraction

  • Diplopia (double vision)

  • Periorbital edema

  • Conjunctival redness

  • Ocular dryness or grittiness

  • Excessive tearing

  • Photophobia

  • Eye pain.

Eyelid retraction and proptosis are the most common TED symptoms (pooled prevalence 57% for both), followed by diplopia due to restricted extraocular muscle movement and swelling.2

Dysthyroid optic neuropathy

Patients with severe TED require urgent intervention, and can present with vision-threatening corneal breakdown, globe subluxation, or dysthyroid optic neuropathy.16 Dysthyroid optic neuropathy is the most severe manifestation of TED, and it is caused by compression of the optic nerve at the orbital apex due to extraocular muscle swelling, which can result in permanent vision loss.18 In rare cases, it can be caused by stretching of the nerve because of proptosis.16

About 5% of patients with TED may progress to dysthyroid optic neuropathy.19 Specific risk factors include increasing age, male sex, and heavy smoking. Patients with type 1 diabetes mellitus are at higher risk due to diabetic vasculopathy.18 Patients with dysthyroid optic neuropathy may have the following initial symptoms:

  • Reduced visual acuity

  • Reduced color vision (assessed with pseudoisochromatic plates)

  • Presence of an afferent pupillary defect

  • Visual field reduction (tested with static perimetry).

Diagnostic imaging may show apical crowding (see below), increased extraocular muscle volume, increased superior ophthalmic vein diameter, and proptosis.18,20

IMAGING AND LABORATORY TESTING

Imaging is not mandatory for patients with bilateral TED, but it should be considered in unilateral or asymmetric cases, for preoperative orbital surgery evaluation,12 or to assess for apical crowding as a risk factor for dysthyroid optic neuropathy18 (Figure 1). Computed tomography or magnetic resonance imaging will reveal tissue expansion of extraocular muscles, orbital fat, and lacrimal glands. Noncontrast computed tomography of the orbits is the preferred imaging modality because it is relatively inexpensive, increasingly available, and already used during preoperative evaluation for decompression surgery.16 Magnetic resonance imaging, however, has better soft-tissue resolution and can show muscle edema on T2-weighted images, which may improve identification of acute inflammation.18

Figure 1
Figure 1

Orbital contrast computed tomography in a patient with dysthyroid optic neuropathy due to thyroid eye disease. (A) Axial view shows apical crowding in the left orbit. The enlarged medial rectus (*) and lateral rectus (red arrow) are compressing the optic nerve (blue arrow). (B) Posterior coronal view of the globe shows apical crowding in the left orbit (red arrow) compared with the right orbit (blue arrow).

OS = left globe

Although proptosis is most readily detected with an exophthalmometer in the clinical setting, it can also be seen on both computed tomography and magnetic resonance imaging. The cutoffs for proptosis measurement vary among racial and ethnic groups owing to differences in ocular anatomy, but a measurement of 22 mm or greater or an asymmetry between eyes greater than 2 mm is defined as pathologic.20

Imaging may also help exclude differential diagnoses (discussed below) as extraocular muscle enlargement in TED appears fusiform and the tendons are not involved.16 The order of extraocular muscle involvement is inferior, medial, superior, and then lateral recti; the oblique muscles are the least likely to be enlarged.16,20 Repeat imaging is generally not required unless patients have new signs or symptoms.16

Laboratory evaluation for TED includes thyroid function tests and autoantibody titers. There are 2 antibody evaluation methods: measuring all immunoglobulins targeting TSH receptor antibodies (thyrotropin-binding inhibitory immunoglobulin test) and the thyroid-stimulating immunoglobulin assay.21

OTHER CONDITIONS WITH SIMILAR CLINICAL FEATURES

There are several conditions that can cause bilateral or unilateral proptosis and be mistaken for TED. These conditions include infectious, inflammatory, malignant, and infiltrative diseases.

Orbital myositis is an inflammatory process involving the extraocular muscles that most commonly affects women in their 30s.22 Patients often present with acute unilateral orbital and periorbital pain, diplopia, proptosis, swollen eyelids, and conjunctival hyperemia; visual acuity is typically not affected. Although orbital myositis and TED share symptoms of severe inflammation, TED tends to have a more insidious onset. Both TED and orbital myositis respond to glucocorticoid therapy, so it cannot be used to differentiate the conditions.22

Orbital cellulitis is characterized by an infection posterior to the orbital septum most commonly due to adjacent spread from the sinuses, trauma to the skin, or hematogenous spread in patients with bacteremia.17 Patients may present with extraocular motility restriction, conjunctival injection (red eyes), and signs of optic nerve compromise. Computed tomography of the orbits reveals orbital fat stranding, proptosis, extraocular muscle inflammation, and evidence of sinus involvement. Management includes urgent broad-spectrum intravenous (IV) antibiotics and frequent ophthalmologic evaluations.17

Immunoglobulin G4–related orbital disease is a fibroinflammatory systemic disorder characterized by elevated serum immunoglobulin G4 levels.17 Patients present with bilateral proptosis and eyelid swelling, and often have lacrimal gland involvement.23 Visual disturbance, extraocular motility restriction, and inflammatory symptoms are uncommon. Immunoglobulin G4–related orbital disease affects women and men equally at a median age of 59.23

Sarcoidosis is a systemic inflammatory disease that can affect the eye and its supporting structures, and ocular involvement can be the initial presenting symptom in 20% to 30% of patients.17 Biopsy of the involved orbital tissue can definitively diagnose sarcoidosis; however, if a biopsy cannot be completed, then chest radiography showing hilar adenopathy may assist in diagnosis.22

Lymphoma is the most common malignancy of the ocular adnexa.17 Patients with ocular lymphoma may present with unilateral or bilateral proptosis, diplopia, periorbital swelling, ptosis, vision changes, and systemic B symptoms (fever, night sweats, and unexplained weight loss). The most common subtypes are extranodal marginal zone B-cell lymphoma and diffuse large B-cell lymphoma. Biopsy and histopathologic analysis confirm the diagnosis.17

Nonspecific orbital inflammation, also known as orbital pseudotumor or idiopathic orbital inflammation, is characterized by inflammation of orbit.17 Its cause is unknown. Computed tomography and magnetic resonance imaging will show tendon involvement, which can help to differentiate it from TED. Treatment consists of systemic steroids, and, in refractory cases, external beam radiation and immunomodulatory agents.17

TREATMENT IS BASED ON DISEASE ACTIVITY AND SEVERITY

Management of TED requires an individualized approach that involves lifestyle measures, local treatments, pharmacologic therapies, and, in some cases, surgery. The 2022 American Thyroid Association and the European Thyroid Association16 consensus statement on the management of thyroid eye disease and the 2021 European Group on Graves’ Orbitopathy12 (EUGOGO) clinical practice guidelines for medical management of Graves orbitopathy recommend specific treatments determined by disease activity and severity, symptoms, impact on the patient’s daily living and quality of life, and risk to vision.

Treating hyperthyroidism

Restoring and maintaining euthyroidism is associated with TED stabilization and improvement. Patients with Graves hyperthyroidism can be treated with antithyroid drugs, radioactive iodine, or total thyroidectomy.24 However, current evidence suggests that the use of antithyroid drugs or thyroidectomy do not alter the disease course of mild TED, whereas radioactive iodine treatment can worsen or cause de novo TED. Immunosuppression with glucocorticoids is recommended both as prophylaxis and for treating radioactive iodine–induced TED.10

Local treatment for all patients

Local treatment of TED includes management of dry eyes and surface inflammation. Dry eyes may be due to incomplete blinking or change in blinking rate, inadequate tear distribution and excess tear evaporation from a widened palpebral fissure, and decreased tear production from the inflammatory process of TED.25,26 Patients should be treated with artificial tears during the day.12 While sleeping, ophthalmic gels or ointments and taping the eyelids or wearing swimming goggles are recommended, depending on the degree of lagophthalmos (inability to close eyelids completely) and other symptoms. Elevating the head at night helps decrease edema.16

Patients should be counseled to quit smoking and to avoid secondhand smoke.24

Assessing disease activity and severity

Treatment decisions are based on assessment of clinical activity, severity, duration, and the orbital components involved. The clinical activity score (CAS) is a simple, validated scoring system used to assess disease activity.12 The CAS has 7 items based on commonly seen TED signs and symptoms. A score of 3 or higher indicates active disease. On follow-up assessment, a 10-item CAS that includes 3 additional points for worsening proptosis, motility, and visual acuity is used for monitoring change over time (Table 1).12,16

View this table:
TABLE 1

Clinical activity score assessment for thyroid eye disease activity

Disease severity assessment determines whether there is an immediate or future threat to vision. EUGOGO27 classifies disease severity as mild, moderate-to-severe, and sight-threatening TED based on the presence of features described in Table 2.

View this table:
TABLE 2

European Group on Graves’ Orbitopathy thyroid eye disease classification and severity features

Mild TED

The goal of mild TED treatment is to improve quality of life, promote remission, and prevent progression. Treatment includes the local interventions discussed above and a single course of sodium selenite 100 μg twice daily for 6 months.11 Treatment duration is limited to 6 months due to available evidence and risk of selenium toxicity.16 It is unclear whether selenium supplementation in selenium-sufficient areas provides this same benefit.

Patients with mild TED generally do not experience a significant impact on quality of life or symptoms that necessitate pharmacologic or surgical intervention, and can often be treated with watchful waiting.

Moderate-to-severe TED

Several medical therapies are used to treat moderate-to-severe TED. For patients with active disease, the goal of therapy is to shorten the active phase and achieve remission.

IV glucocorticoids are the first-line therapy in moderate-to-severe active TED without significant soft-tissue involvement (eg, proptosis or diplopia). The general dosing regimen is IV methylprednisolone 500 mg once weekly for 6 weeks, and then 250 mg once weekly for 6 weeks.28 Treatment with IV glucocorticoids has been shown to improve CAS by 3 points in 77% of patients.16 It is less clear if soft-tissue changes like proptosis and diplopia respond to IV glucocorticoids. Potential adverse effects of IV glucocorticoids were more likely at higher cumulative doses.28

Teprotumumab, an inhibitory human monoclonal antibody that targets the IGF-1 receptor on orbital fibroblasts, has proven beneficial in patients with active moderate-to-severe TED and soft-tissue involvement, including proptosis and diplopia. In the OPTIC (Treatment of Graves’ Orbitopathy [Thyroid Eye Disease] to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study) trial,29 83% of patients with active TED treated with IV teprotumumab every 3 weeks for 8 doses (10 mg/kg first dose, 20 mg/kg subsequent doses) had a reduction in proptosis of 2 mm or greater, compared with 10% in the placebo group, with a number needed to treat of only 1.36. Patients treated with teprotumumab also had greater improvements in CAS, diplopia, and quality-of-life scores.

The OPTIC-X (Treatment of Graves’ Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study) trial30 studied OPTIC trial participants who experienced a flare after teprotumumab treatment, and reported that 62.5% of patients responded when re-treated with teprotumumab. Of the 5 patients who did not initially respond to teprotumumab, 2 responded after re-treatment.30

Adverse effects of teprotumumab include gastrointestinal symptoms and worsening of inflammatory bowel disease, muscle cramps and pain, alopecia, fatigue, hyperglycemia, and hearing loss (in up to 10%).31 Hyperglycemia occurs due to teprotumumab’s inhibitory action on IGF-1 receptors, which reduces feedback inhibition of growth hormone secretion and results in increased glucose production and insulin resistance.

IGF-1 is also important for inner-ear hair cell survival because it promotes the cell cycle and inhibits apoptosis. It is speculated that, by inhibiting IGF-1 receptors on inner-ear hair cells, prosurvival signaling is diminished, leading to hearing impairment.31 Thus, patients should have a baseline audiogram before teprotumumab is initiated. Approximately 65% of patients who experience hearing loss while on teprotumumab have a return to baseline hearing after discontinuation.32 It is important to note that sensorineural hearing loss has been reported in as many as 23.5% of patients with Graves disease who have not been treated with teprotumumab.33

Teprotumumab should be avoided in patients age 18 and younger due to insufficient safety data16 and during pregnancy due to possible effects on fetal growth.31

The reported long-term response rate after treatment with teprotumumab is around 33%, with proptosis regression in 65% of eyes, leading many clinicians to reconsider the clinical usefulness of a medical therapy that is costly (approximately $360,000 in 202334) and has significant adverse effects.34,35 In a multicenter retrospective study conducted in the United States, 24% of patients who received teprotumumab required re-treatment; older age was the only significant predictor of re-treatment.36

Rituximab may be used in patients with active moderate-to-severe TED who do not respond to or cannot tolerate IV glucocorticoids.16 A monoclonal anti-CD20 antibody, rituximab is used to treat some lymphomas and autoimmune conditions. It binds to CD20 receptors on B cells and results in B-cell depletion and decreased production of pathogenic antibodies.37,38 Rituximab has shown efficacy in decreasing CAS in patients who were previously treated with IV glucocorticoids but not in treatment-naïve patients with TED.16 Because rituximab has little to no effect on proptosis or diplopia, it is not recommended for patients with soft-tissue involvement.

Tocilizumab is an interleukin 6 receptor blocker that is used to treat rheumatoid arthritis, and is thought to work by inhibiting interleukin 6 expressed by orbital fibroblasts and reducing inflammation.39 In a randomized controlled trial, tocilizumab failed to show improvement in soft-tissue involvement,16,40 but in a real-world study of 54 patients, 78% reported reduction in proptosis and 68% had diplopia improvement.16,41 Therefore, tocilizumab can be considered for patients who are intolerant or who have not responded to IV glucocorticoid therapy. Adverse effects include risk of severe infections, hepatotoxicity, and anaphylaxis.16

Mycophenolate mofetil alone or in combination with IV glucocorticoids vs IV glucocorticoids alone for TED has been studied in 2 randomized controlled trials.16 Reported improvements in some outcomes included inactivation (CAS reduction), proptosis reduction, and increased eye motility. There was a tendency toward lower rates of adverse effects in the mycophenolate mofetil treatment groups compared with IV glucocorticoids alone. Only one of the studies reported fewer relapses after combination therapy with mycophenolate mofetil and IV glucocorticoids.28

The EUGOGO12 clinical practice guidelines recommend mycophenolate mofetil with IV glucocorticoids as first-line therapy for patients with TED. However, the American Thyroid Association and the European Thyroid Association16 task force did not find the data on mycophenolate mofetil sufficiently convincing.

Orbital radiation therapy has been used to treat TED for several decades, and seems to work by depleting lymphocytes and fibrocytes in orbital tissue.16 Different studies have reported variable outcomes, which may be due to the inclusion criteria and study settings. One retrospective study, however, showed that in patients with active disease, orbital radiation therapy combined with IV glucocorticoids had a favorable effect on ocular motility vs IV glucocorticoids alone, and none of the patients developed dysthyroid optic neuropathy after an average follow-up of 3.2 years.16,42

Historically, the dosing used is 20 Gy administered to the orbit in 10 daily fractions.16 Modifications of this treatment plan (lower dose or more fractions) seem to work as well.43 Orbital radiation therapy should be avoided in patients younger than 3518 and is relatively contraindicated in patients with severe hypertension or diabetes mellitus due to an increased risk of retinal vascular disease.16

Sight-threatening TED

Sight-threatening TED, an emergency that requires immediate recognition and treatment due to the risk of irreversible vision loss, can be caused by dysthyroid optic neuropathy, severe corneal breakdown, or rarely globe subluxation.12 Owing to optic nerve compression, IV glucocorticoids are recommended as first-line therapy for patients with dysthyroid optic neuropathy. In one study, improved visual acuity was reported in 5 of 9 patients treated with pulse IV methylprednisolone.44 The recommended regimen is IV methylprednisolone 500 to 1,000 mg daily for 3 consecutive or alternate days.45 If a patient fails to respond to treatment, urgent orbital decompression is recommended.

When dysthyroid optic neuropathy is due to optic nerve stretching caused by proptosis, surgical decompression is indicated as this condition rarely responds to medical therapy.16

Patients with dysthyroid optic neuropathy who require orbital decompression may also need adjuvant medical or orbital radiation therapy to inactivate TED. Currently, there is limited evidence to support alternative therapies for dysthyroid optic neuropathy; however, teprotumumab and tocilizumab are under investigation.45

WHEN SHOULD SURGERY BE CONSIDERED?

Surgical intervention in the acute phase of disease is indicated only for treating irreversible sight-threatening complications because eyelid, extraocular muscle, and orbit surgery during the active phase has the potential to cause inflammation to flare. The 2 main surgical options include permanent tarsorrhaphy for exposure keratopathy (severe dryness of the cornea leading to breakdown of the corneal surface) and optic nerve decompression for dysthyroid optic neuropathy.12 If surgical intervention is warranted for either of these reasons, a patient’s disease may be considered active enough to require use of IV glucocorticoids, teprotumumab, or other pharmacologic therapies.12

Once a patient’s TED has been quiescent for 4 to 6 months, surgical treatment may be considered and must occur in sequence after the patient is euthyroid.16 The first step is treating proptosis with orbital decompression surgery, if indicated, to remove bone and expand orbital volume.46 Next, surgery to correct strabismus may help improve alignment; however, many patients may still require prism glasses to achieve single vision. The final step is adjusting eyelid position by either lowering a retracted eyelid or raising a ptotic one. Some patients may subsequently elect to undergo cosmetic surgery to correct disease-related changes to their facial appearance.46

If these surgeries are performed out of order, the progress made with a previous surgery may be undone. Surgery can result in substantial improvements in quality of life for patients with TED due to better visual function and perceived appearance.47

MULTIDISCIPLINARY APPROACH IS NEEDED

Evaluating and treating TED requires a multidisciplinary approach among clinicians from multiple specialties, including primary care, endocrinology, and ophthalmology (general, neuro-ophthalmology, or oculoplastic), to optimize patient outcomes.24 These established multidisciplinary teams improve time to diagnosis and treatment of TED.48

Clinicians must maintain a heightened awareness of TED, including sight-threatening TED, and be able to discern the disease stage and activity by using the scoring systems discussed earlier. The roles of these clinicians overlap considerably and have the same goal: achieving euthyroidism in patients and avoiding treatment that may increase the risk of TED development or progression, starting medical therapy appropriate for the stage and disease activity while closely monitoring for adverse effects, and determining whether surgery is indicated.

Audiologists, smoking cessation clinics, or psychologists may also be helpful to patients.

CONCLUSION

Although TED was first described a millennium ago, effective management remains a challenge. Surgery has been a last resort for a century, and Rundle and Wilson’s observation on the course of TED holds true in most but not all cases. However, in the past decade, with better understanding of the pathophysiology of TED, medical therapies have been developed that target specific pathways or receptors involved in the disease.

Success in controlling TED is sometimes short-lived, with reactivation haunting patients and clinicians, leading to as-yet unanswered questions. Are we interrupting the course of the disease and the activity picks up where it left off after we discontinue treatment? Should we perhaps learn from our immunology colleagues and treat continuously with smaller doses, given at shorter intervals, and for a longer period? What about combination therapy? One thing we do know for sure is that patients with TED have hope.

DISCLOSURES

Dr. Nasr has disclosed being an advisor or review panel participant for Horizon Therapeutics and Nevro Corporation. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

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