This condition does not meet the definition of a rare disease in the U.S. (fewer than 200,000 Americans). There may be forms of this condition that are rare. NORD posts this report because limited information is available about this condition and it may be underdiagnosed.
Last updated:
10/15/2026
Years published: 2020, 2024
NORD gratefully acknowledges Don Kikkawa, MD, Professor of Clinical Ophthalmology, Chief of the Division of Ophthalmic Plastic and Reconstructive Surgery and Vice Chairman at the University of California at San Diego (UCSD) Department of Ophthalmology and UCSD Shiley Eye Institute in La Jolla. Co-director of the UCSD Thyroid Eye Center and to Gioconda Alyea, MD (Brazil), MS, National Organization for Rare Disorders.
Thyroid eye disease (TED), also known as Graves’ orbitopathy or thyroid-associated ophthalmopathy, is an autoimmune inflammatory disorder. The immune system mistakenly attacks the tissues around the eyes (the orbit and periorbital tissues), causing swelling, pain, and changes in appearance and vision.1-6
TED most often occurs in people who have Graves’ disease and up to 40% of people with Graves’ disease develop TED. However, TED can also affect 3–5% of people with Hashimoto thyroiditis (an underactive thyroid condition) and even some people whose thyroid function is completely normal.1-6
The thyroid is a butterfly-shaped gland located at the base of the neck. The thyroid is part of the endocrine system, the network of glands that secrete hormones that regulate the chemical processes (metabolism) that influence the body’s activities as well as regulating the heart rate, body temperature and blood pressure. Graves’ disease is characterized by abnormal enlargement of the thyroid (goiter) and increased secretion of thyroid hormone (hyperthyroidism).
The disorder most commonly appears between the ages of 30 and 50, though it can occur at any age. It affects women far more often than men. In the United States, thyroid eye disease (TED), as a group, is not considered a rare disorder. However, certain variants of TED, including euthyroid Graves’ orbitopathy and Graves’ orbitopathy associated with thyroid dermopathy or acropachy, are considered rare. 1, 2, 5
The most common signs include upper eyelid retraction (present in over 90% of people with TED), bulging eyes (proptosis), swelling around the eyes, double vision (diplopia), and eye pain. In severe cases, pressure on the optic nerve, the nerve that carries visual information to the brain, can threaten sight. 4, 5, 7, 8
TED typically passes through an active inflammatory phase, lasting one to two years or more, before settling into a quieter phase. Even so, some problems such as proptosis and double vision often persist without treatment, and up to 50% of people are left with lasting effects.7, 9, 10
Effective treatments are available. These range from steroid medicines and targeted biologic therapies, including the FDA-approved medications teprotumumab and veligrotug, to surgery for more severe or lasting disease. Quitting smoking and keeping thyroid hormone levels well controlled are important steps that can reduce the risk of the disease getting worse. 2, 11-16
Although relatively infrequent, TED does not currently fulfill the main criterion for being defined as a rare disease, but several variants of the disease are considered rare diseases.
TED affects people in different ways, and symptoms can change over time. Doctors group the signs and the symptoms of TED into four main areas, inflammation, changes in appearance, problems with eye movement, and loss of vision. 4, 5, 7, 8
TED usually begins with an active inflammatory phase that lasts about 12–24 months or more. During this time, symptoms tend to worsen. 7, 9, 10 After this, there is a plateau phase and eventually a quieter (quiescent) phase, often within 18–24 months of onset. This pattern is sometimes called Rundle’s curve. Even after the active phase ends, problems such as having bulging eyes and double vision often remain and may not fully go away without treatment. More than half of the people with TED will have lasting effects. 7, 9-10
The most frequent signs and symptoms include: 4, 5, 7, 8
Early in the disease, people often notice: 4, 5, 7, 8
In severe cases, TED can progress to: 4, 5, 7, 8
Long-term effects can include persistent double vision, persistent proptosis, and, in rare cases, vision loss from optic nerve damage or corneal breakdown. Surgery is often needed to address significant lasting problems. 1, 3, 17
Certain factors are linked to a higher risk of serious complications and a worse outlook: 9, 15, 16, 18
TED is usually present in both eyes, but it can be asymmetric (which means that it is worse in one eye than the other) or, less commonly, affect only one eye. In some people, imaging scans show enlarged eye muscles even when there are no obvious symptoms. 5, 8
There are also differences between ethnic groups. Lower eyelid retraction is more common in Asian patients. The degree of proptosis and the ratio of women to men affected may also differ by population. 18
Effects on mental health and quality of life TED affects more than just vision and appearance. Studies have shown that people with TED have a higher rate of anxiety and depression than the general population. The disease can affect daily life both because of vision problems and because of changes in how a person looks. These emotional and psychological effects are an important part of the overall impact of TED.
TED is an autoimmune disease. This means the body’s immune system, which normally protects against infection, mistakenly attacks the body’s own tissues which, in this case, the tissues around the eyes. 1-6
The main factor in the development of TED is the thyroid-stimulating hormone receptor (TSHR), a protein found on cells of the thyroid gland that helps regulate thyroid function. TSHR is also present on certain cells within the eye socket (orbit). In people with TED, the immune system produces antibodies called TSH receptor antibodies (TRAb), which bind to these receptors and contribute to inflammation and changes in the tissues surrounding the eyes. 1-6
The inflammatory process involves immune cells and chemical signals that stimulate swelling and tissue expansion within the orbit. The muscles responsible for eye movement and the fatty tissue behind the eyes may become enlarged. Because the eye socket is surrounded by bone, this expansion can push the eyeballs forward, causing the characteristic bulging appearance known as proptosis. Inflammation and tissue changes can also contribute to eyelid retraction, restricted eye movement, and double vision. In severe cases, enlarged tissues can compress the optic nerve, potentially threatening vision. 4, 5, 7, 8
TED is most commonly associated with Graves’ disease, an autoimmune condition in which antibodies stimulate the thyroid gland to produce excessive thyroid hormones. However, TED can also occur in people with Hashimoto thyroiditis, another autoimmune thyroid disorder, or in individuals with normal thyroid function (euthyroid). Therefore, TED can develop even in people who have a normal thyroid gland. 1, 6
Several factors influence the risk of developing TED and the severity of the disease. Smoking is a well-established environmental risk factor associated with both the development and worsening of TED. Poorly controlled thyroid function and elevated TRAb levels are also associated with more severe disease. Although TED occurs more frequently in women, men and older individuals are more likely to develop severe manifestations and complications. 9, 15, 16, 18
Thyroid eye disease seems to affect all ethnic groups equally. The estimated prevalence is between 90 and 300/100,000 people. Although relatively infrequent, it does not fulfill the main criterion for being defined as a rare disease in the U.S. (The Orphan Drug Act of 1983 defined rare diseases as disorders affecting fewer than 200,000 Americans). However, several variants of the disease, namely, euthyroid Graves’ orbitopathy and Graves’ orbitopathy associated with thyroid dermopathy or acropachy are far below this threshold and can be considered rare diseases.
TED predominantly affects women, with an incidence of 16 per 100,000 women and 3 per 100,000 men per year. Males are more likely to have a severe form of the disease. It typically presents between the ages of 30 and 50, though it can occur at any age. Up to 40% of patients with Graves’ disease develop TED, but it may also be seen in 3–5% of those with Hashimoto thyroiditis or in euthyroid individuals. There is a genetic component to the disorder and people who have a family member with the disease or a family member with an autoimmune disease are at a greater risk of developing the disorder.
Diagnosing TED requires three things working together, a careful clinical assessment, blood tests, and imaging of the eye socket (orbit). 7, 8 A detailed history is an important part of the diagnostic process. Doctors will ask about when symptoms started, how quickly they have progressed, and whether risk factors such as smoking are present. 7, 8
A doctor will look for the characteristic signs of TED: upper eyelid retraction, bulging eyes (proptosis), swelling of the soft tissues around the eyes (periorbital edema), redness of the eye surface (conjunctival injection), and problems with the muscles that move the eyes (extraocular muscle dysfunction). 7, 8
To measure how active and how severe the disease is, doctors use structured scoring tools. The American Thyroid Association and the European Thyroid Association recommend either the Clinical Activity Score (CAS) or the VISA classification. A CAS score of 3 or more out of 7 indicates active disease, though a lower threshold may apply in Asian populations. Severity is judged by looking at the degree of soft tissue involvement, how far the eyes protrude (measured with a device called a Hertel exophthalmometer), how much eye movement is restricted, and whether there is a risk of sight-threatening complications, such as damage to the optic nerve (dysthyroid optic neuropathy, or DON) or breakdown of the cornea (the clear front surface of the eye). 7, 8
A full eye examination by an ophthalmologist (an eye specialist) is essential, both to assess TED completely and to rule out other conditions that can look similar. 7, 8
Blood tests Blood tests measure thyroid function, including TSH (thyroid-stimulating hormone), free T4, and free T3, and the level of TSH receptor antibodies (TRAb). TRAb results both support the diagnosis and serve as markers of how active the disease is. Another type of antibody, TPO antibodies, is not specific to TED, but may be helpful when TRAb results come back negative. 8, 24
A CT scan or MRI of the orbit is recommended when TED presents in an unusual way, affects only one eye, occurs in a person whose thyroid function is normal, or when DON is suspected. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI (Magnetic Resonance Imaging) is a non-invasive medical scan that uses strong magnetic fields and radio waves to create highly detailed, 3D images of the inside of the body.
Imaging looks for characteristic changes such as enlargement of the eye muscles (typically sparing the tendons at the ends of the muscles), crowding of tissues at the back of the eye socket (apical crowding), and expansion of the fatty tissue within the orbit. 8, 25
MRI is preferred when doctors want to measure how much active inflammation is present, while CT scanning gives better detail of the bony structures of the eye socket and is more useful for planning surgery. Imaging can also provide a baseline record for tracking changes over time and can guide management even after a diagnosis has already been established. 8, 25
Any other health conditions (systemic co-morbidities) should also be recorded. Because TED can change over time, repeat assessments are recommended to track how the disease is progressing and how well treatment is working. 7, 8
Affected people may undergo thyroid function tests to detect an underlying cause of thyroid eye disease such as Graves’ disease or hypothyroidism. These tests can detect elevated levels of thyroid hormones or antibodies in the blood.
Treatment of TED is guided by how active and how severe the disease is. A multidisciplinary team, typically including an endocrinologist (a hormone specialist) and an ophthalmologist (an eye specialist), works together to manage the condition. 2, 26, 27 Psychosocial support is essential as well as thyroid eye disease can cause noticeable changes in a person’s facial appearance that cannot be treated completely. Depression is common in individuals with the disorder and cosmetic changes can cause significant emotional distress and affect emotional well-being.
For every person with TED, the first steps are identifying and addressing risk factors. This means quitting smoking and bringing thyroid hormone levels back to normal. These steps are important regardless of how mild or severe the disease is. 26, 28
Local measures can ease day-to-day symptoms. Eye lubricants help with dryness and irritation. Prism lenses, special corrective lenses can reduce double vision (diplopia). Some people can wear an pathch to manage diplopia. Dark sunglasses can be used to help with sensitivity to light. For mild, active disease, selenium supplementation may also be beneficial, particularly in people living in regions with low selenium intake. 26, 28
Until recently, the main treatment for moderate-to-severe active TED was intravenous (given through a vein) glucocorticoids, typically a steroid medicine called methylprednisolone, given over 12 weeks for a total dose of 4.5 grams. Treatment is generally more effective during the active inflammatory phase of the disease. Studies have shown that a medicine called mycophenolate may be used alongside steroids to improve treatment outcomes. Another medicine, azathioprine, may be considered in selected cases, although evidence supporting its use is more limited. 2, 17, 26-28
FDA-approved biologic therapies
Newer treatments focus on a specific protein found on cells in the eye socket called the insulin-like growth factor-1 receptor (IGF-1 receptor). Two biologic medicines, meaning medicines made from living cells, that target this receptor are now approved by the U.S. Food and Drug Administration (FDA): 2, 11-13
Both are monoclonal antibodies, a type of medicine designed to block a very specific target in the body. In randomized clinical trials, both medicines have been shown to reduce eye bulging (proptosis), double vision (diplopia), and disease activity. Teprotumumab has also demonstrated benefits in some people whose disease has not responded to previous treatments. 2, 11-13
Monitoring is needed during treatment because side effects, including hearing impairment and high blood sugar (hyperglycemia), can occur. Proptosis can also return after treatment ends. 2, 11-13
Off-label biologic therapies
Two other biologic medicines are used off-label, meaning they are not FDA-approved specifically for TED but have been studied in this condition:
Radiation therapy directed at the eye socket (orbital radiotherapy) is reserved for select cases. It is often used together with glucocorticoids, particularly for people with active disease and worsening problems with eye movement (progressive strabismus) or double vision. It may also be considered as an additional treatment in selected cases of optic nerve damage (optic neuropathy). 17, 28
Surgery is considered when the disease threatens sight or when lasting problems remain after the active phase has settled. Sight-threatening optic nerve compression may require urgent treatment with high-dose intravenous glucocorticoids and, if necessary, orbital decompression surgery. Surgical options include: 4, 26, 31
Emerging therapies
Treatments targeting other pathways, including the TSH receptor (anti-TSH-R), a protein involved in antibody recycling (FcRn), and oral forms of IGF-1 receptor blockers, are currently under investigation and may further refine how TED is managed in the future. ¹¹⁻¹²
The European Group of Grave’s orbitopathy (EUGOGO) recommendations can be summarized as follows: 9
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials//
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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