Overview

Thyroid eye disease (TED) is an autoimmune eye disorder, also known as Graves’ eye disease. It is an inflammatory disorder that affects the tissue around the eyes, causing inflammation (swelling and redness).¹ It is typically associated with autoimmune diseases such as hyperthyroidism, an overactive thyroid gland, and those who have Graves’ disease.

TED has two distinct phases, acute/active and chronic/inactive. The active phase can range from 6 months to two years, or longer, before the inflammation subsides.² During this time, symptoms may appear, varying from mild to severe. When it is severe, it can cause permanent damage and scarring to your eyes, with lasting cosmetic and vision changes.

TED may also be referred to by several other names. Ophthalmopathy and Orbitopathy are two other terms for eye disease. Your healthcare provider may also describe TED as:

• Thyroid ophthalmopathy
• Thyroid-associated orbitopathy (TAO)
• Thyroid orbitopathy
• Graves’ ophthalmopathy (GO)
• Graves’ orbitopathy
• Graves’ eye disease
• Opthalmopathy
• Orbitopathy

Causes of thyroid eye disease

The exact causes of TED are not yet fully known and understood. Thyroid eye disease is an autoimmune disease, meaning your body’s immune system mistakenly attacks your thyroid and eye tissues. An overactive thyroid gland, such as in Graves’ disease, is the most common cause, with one in three people with Graves’ disease developing TED³. But other autoimmune thyroid diseases, like Hashimoto’s disease, can also cause it. Though rare, even people with an underactive or normal thyroid function can develop TED.

In these diseases, your immune system creates antibodies that mimic thyroid hormones and attach to thyroid hormone receptors. These receptors are commonly found within your thyroid itself, but some are found in the tissues behind your eyes. This means the same antibodies that affect your thyroid can also affect your eyes.

Thyroid eye disease risk factors

Factors that can increase the risk of developing thyroid eye disease are:

• Being female, females assigned at birth are five times more likely to get Graves’ disease and TED, typically between the ages of 30-50 years old
• Having Graves’ disease – TED affects 25-50% of people with Graves'
• Abnormal thyroid hormone levels – low or high thyroid hormone levels can contribute to TED
• Radioiodine (radioactive iodine, RAI) - RAI therapy is a standard treatment for Graves’ disease to treat hyperthyroidism. But it may contribute to TED or make it worse
• Smoking - significantly raises the risk of developing TED by two to eight times.⁴ Smoke exposure also makes you more likely to have more severe symptoms that last longer. The best thing you can do is quit smoking if you have Graves’ or know you have abnormal thyroid levels, to lower the chance of getting TED

Symptoms of thyroid eye disease

Inflammation of the fat and muscle tissue surrounding and behind the eyes can lead to scar tissue formation, which may cause changes to the eyes, such as: 

• Eye bulging (proptosis)
• Eye irritation
• Dry or teary eyes
• Inflamed and swollen eyelids (blepharitis)
• Frequent blinking
• Headaches and eye pain
• Double vision (diplopia)
• A feeling of grittiness in the eye
• Sensitivity to light (photophobia)
• Difficulty moving your eyes and eyes that do not work together

Symptoms normally affect both eyes, but sometimes symptoms may only be present in one eye.¹

Complications of TED:

Most cases are mild, where the appearance and vision changes caused by TED generally improve after the active phase is over. In severe cases, scarring can prevent the tissues around your eyes from healing and returning to the shape they were before. Parts of your eyes that affect your vision may also be permanently damaged. In these cases, surgery may be required.¹

Lasting changes to appearance may include:

• Eyelid retraction
• Protruding eyes
• Baggy eyes
• Red eyes

Lasting changes to vision may include:

• Blurry vision
• Double vision
• Severe vision loss

Diagnosing thyroid eye disease

A healthcare provider, such as an ophthalmologist, will be able to diagnose thyroid eye disease by doing a physical eye exam. They’ll be able to examine both your eyelids and eyes, checking for TED symptoms, such as bulging eyes, watery and red eyes, and eyelids that do not close properly.

If your healthcare provider thinks that you have thyroid eye disease, they will then refer you to a TED eye specialist and order blood tests, which may include a thyroid stimulating immunoglobulin (TSI) test and a thyroid stimulating hormone (TSH) tests, to check if your thyroid antibodies levels and hormone levels are too high or too low.⁵

Your TED eye specialist will also need to know your medical history, such as if you have a thyroid condition or if you are a smoker, and if anyone else in your family has a history of TED or thyroid problems.

Other tests your provider may request include:¹

• Ultrasound of the eyes
• Magnetic resonance imaging (MRI) scan
• Computed tomography (CT) scan

Management and treatment of thyroid eye disease

TED can be managed and treated with a combination of supportive treatments and various pharmacological medications, or in some more severe cases, surgery.

Supportive care options for TED include:⁶

• Eye drops
• Scleral lenses
• Vision aids such as special corrective glasses or eye patches
• Selenium deficiency supplements.

The main pharmacologic treatments for TED include:

• Corticosteroids
• Immunosuppressants
• Biologic therapies

Corticosteroids

Corticosteroids (also called glucocorticoids) are commonly used to reduce inflammation in TED and work by suppressing the immune response. The two main corticosteroids are intravenous (IV) corticosteroids and oral corticosteroids.

Intravenous corticosteroids such as methylprednisolone are typically reserved for moderate to severe cases or when there is a risk of vision loss. They are usually given as weekly infusions over 12 weeks. Side effects include liver damage. However, studies show that approximately 70% of responses are positive, indicating that they are more effective than oral steroids.⁷

Oral corticosteroids, such as prednisone, may be prescribed at high doses initially, followed by a gradual tapering schedule. While corticosteroids can be effective, with studies showing a 60% favourable response, long-term use carries risks, such as high blood sugar, osteoporosis, weight gain, Cushing syndrome, and increased susceptibility to infections. Therefore, patients on prolonged steroid therapy require monitoring for side effects and may need additional treatments, such as bone-protective medications, to counteract complications.⁷

Immunosuppressants

Immunosuppressants work by reducing immune system activity and target immune-mediated inflammation more directly, preventing further damage to the eye tissues. Mycophenolate mofetil (MMF) and cyclosporine are the most common drugs used to help control TED in this category. They are both administered orally, either through tablets, capsules, or solutions.

MMF works by inhibiting the production of antibodies and the proliferation of T-cells and C-cells (our immune cells) responsible for inflammation. Studies have shown that MMF is most effective when given every day for 24 weeks and used alongside corticosteroids such as methylprednisolone which improves eye symptoms and reduces the need for higher steroid doses.⁸

Cyclosporine suppresses specific immune cells called T-cells by inhibiting calcineurin, a protein that activates these T-cells. Cyclosporine is most beneficial when combined with oral corticosteroids such as prednisone, especially in patients who do not respond to steroids alone.⁸

However, immunosuppressants carry risks, such as immunosuppression, and 

increase the risk of infection, liver toxicity, and kidney damage. Patients receiving these medications require close monitoring through regular blood tests to ensure safety and effectiveness. 

 Biologic therapies

Biologic therapies are a newer treatment option for TED, designed to target specific immune pathways involved in the disease and work by targeting monoclonal antibodies. 

The first FDA-approved biologic for TED, Teprotumumab (Tepezza), was approved in 2020 for use in the US . It works by blocking the insulin-like growth factor-1 receptor (IGF-1R), a protein that contributes to inflammation and eye protrusion. Clinical trial studies have shown that teprotumumab significantly reduces eye bulging in most patients, with improvements seen as early as six weeks. A total of eight doses are administered via an intravenous infusion every three weeks.⁹

Studies found that over 70% of patients administered with Tepezza had reductions in eye protrusions. Although effective with a more targeted action and fewer side effects than other treatments, teprotumumab still has potential side effects, including muscle spasms, nausea, fatigue, hearing problems, and increased blood sugar levels. Tepezza also cannot be administered to pregnant women or women wanting to conceive and for six months after treatment due to possible risks to fetal development⁹. Other biologics, such as rituximab and tocilizumab, are currently being investigated for TED, but further research is needed before they become widely available treatment options.¹⁰

Summary

Thyroid eye disease is an autoimmune disease that affects the tissues surrounding the eyes, causing inflammation. The condition is linked to Graves’ disease and those with abnormal thyroid hormone levels. The main symptoms experienced are eye protrusion, swollen eyelids, and eye irritation. Mild cases can be treated with medication, however, severe cases can lead to permanent scarring in and around the eyes. Thyroid eye disease is rare and needs to be diagnosed by a specialist as early on as possible. If you are experiencing any TED symptoms, please consult your healthcare practitioner as soon as possible for further advice.