Thyroid Eye Disease
Synonyms
Graves' ophthalmopathy, Graves' orbitopathy, thyroid-associated orbitopathy, TAO, TED, Graves’ eye disease,Overview
Thyroid eye disease (TED) is characterized by progressive inflammation and damage to tissues around the eyes, especially extraocular muscle, connective and fatty tissue. TED has an active disease phase in which progressive inflammation, swelling and tissue changes occur. This phase is associated with a variety of symptoms including pain, a gritty feeling in the eyes, swelling or abnormal positioning of the eyelids, watery eyes, bulging eyes (proptosis) and double vision (diplopia). The active phase can last anywhere from approximately 6 months to 2 years. This is followed by an inactive phase in which the disease progression has stopped. However, some symptoms such as double vision and bulging eyes can remain. In some people, cosmetic changes and significant disability can develop. Although uncommon, in severe instances, vision loss can occur. Thyroid eye disease is an autoimmune disorder. An autoimmune disorder is one in which the body’s adaptive immune system, which protects the body from infectious or other foreign substances, mistakenly attacks healthy tissue instead. Treatment includes reversing hyperthyroidism, specific medications, supportive measures and in some patients, surgery.
Thyroid eye disease most commonly occurs as part of Graves’ disease, which is an autoimmune disease that affects the thyroid and often the skin and eyes. 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). Less often, thyroid eye disease can occur in people who have or have had an overactive thyroid (hyperthyroidism) or in individuals with an underactive thyroid (hypothyroidism) such as people who have a disorder called Hashimoto thyroiditis.
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
Symptoms
The signs and symptoms can vary greatly from one person to another. Eye symptoms can range from mild to severe. For some individuals, the symptoms can lead to pain, disfigurement of the eye socket and, eventually, potentially threaten eyesight. The disorder can vary greatly in expression. For some people, the disorder remains little changed for many years, while for others it will worsen or slightly improve. Occasionally people experience repeated episodes of worsening (exacerbations) of the disease, and improvement of the disease (remission).
Initial symptoms include redness, irritation and discomfort of the eyes and eyelids. Dry eyes and pain when moving the eyes may also occur. Eyelid retraction is also common which is when the upper eyelid is positioned too high and/or the lower eyelid too low thus exposing the eye. The most noticeable symptom can be exophthalmos or proptosis, which means that the eyes bulge or protrude outward out of the eye socket. Bulging of the eyes can cause a person to appear as if they are constantly ‘staring’.
Additional symptoms and signs can include blurred vision, double vision (diplopia), misalignment of the eyes (strabismus), chronic bloody eyes, white area of eye inflamed, constant, watery eyes due to the excess formation of tears, swelling near the upper and lower eyelids, an intolerance of bright lights and difficulty moving the eyeballs.
Causes
Thyroid eye disease is an autoimmune disorder, which means that a problem with the body’s adaptive immune system that protects the body from infectious or other foreign substances, mistakenly attacks health tissue instead. The immune system normally produces specialized proteins call antibodies. Antibodies react against foreign materials (e.g. bacteria, viruses, toxins) in the body to destroy them. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. Specific antibodies are created in response to specific materials or substances. A substance that stimulates an antibody to be produced is called an antigen.
The exact underlying process by which thyroid eye disease occurs is not fully understood. In individuals with Graves’ disease, the immune system creates an abnormal antibody called thyroid-stimulating immunoglobulin. This antibody mimics the function of thyroid-stimulating hormone, which is normally produced by the pituitary gland. These abnormal antibodies also affect the cells surrounding the eyes causing the symptoms associated with the disorder. Researchers think that the affected eye tissue contains proteins that appear similar to proteins of the thyroid gland and the antibodies mistakenly target these proteins. Patients often also have overexpression of a protein called insulin-like growth factor 1 receptor (IGF-1R), and this is thought to play a significant role in the development of the disorder. However, not everyone with thyroid eye disease has these immune system abnormalities suggesting that other abnormal antibodies or other factors can cause thyroid eye disease in some people. Researchers are still investigating the underlying cause of the disorder.
Diagnosis
A diagnosis of thyroid eye disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Certain symptoms that occur in thyroid eye disease are often obvious and can lead to a diagnosis upon a physical examination. Some affected individuals have reported that their eyes “didn’t feel right” before symptoms of the disease began.
Individuals suspected of having thyroid eye disease will undergo a complete eye examination. This may include measuring the degree of proptosis (eye bulging) using a device called an exophthalmometer. This small device enables an eye doctor to measure how far forward the eyes have moved (displacement).
Clinical Testing and Workup
In moderate to severe disease, a specialized imaging technique called computerized tomography (CT) scanning may be used to assess whether the optic nerve is compressed by inflamed, enlarged muscles in the eye. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Regular eye tests may be given to assess a person’s clarity of vision (visual acuity).
Affected individuals 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
Treatment may require the coordinated efforts of a team of specialists, general internists, physicians who specialize in diagnosing and treating eye disorders (ophthalmologists) including eye doctors with experience treating thyroid eye disease, physicians who specialize in diagnosing and treating disorders of the hormone system (endocrinologists), psychologists and other healthcare professionals may need to systematically and comprehensively plan treatment. Psychosocial support is essential as well.
In 2020, the U.S. Food and Drug Administration (FDA) approved teprotumumab trbw (Tepezza), the first approved drug indicated to treat thyroid eye disease. Teprotumumab inhibits (or blocks) the activity of the protein insulin-like growth factor-1, which is believed to a play as significant role in the development of the disorder. Affected individuals have shown significant improvement in proptosis, double vision and overall quality of life when taking teprotumumab.
In affected individuals who have underlying Graves’ disease, treatment includes reversing hyperthyroidism. Treating hyperthyroidism of Graves’ disease is important, but will not improve symptoms of thyroid eye disease.
Some individuals with mild thyroid eye disease may be treated with supportive measures such as dark sunglasses to treat sensitivity to light, ointments, artificial tears and/or prisms that are attached to glasses. Prisms can help correct double vision. Some people may wear an eyepatch to manage double vision.
Individuals with moderate-to-severe disease may receive corticosteroids, which are drugs that reduce inflammation and swelling, but do not affect diplopia and proptosis. Prednisone is a common corticosteroid that is used to treat individuals with thyroid eye disease.