Graves’ orbitopathy, also known as thyroid eye disease (TED), is an autoimmune condition in which immune cells attack the thyroid gland, which in turn responds by secreting an excess amount of thyroid hormone.
As a result, the thyroid gland enlarges and excess hormones change metabolism and affect the function of the heart, brain and other organs. The hyperthyroid state is characterized by fast pulse/heartbeat, palpitations, increased sweating, high blood pressure, irritability, fatigue, weight loss, heat intolerance, and loss of hair and alterations in hair quality. At times, people in the hyperthyroid state can be diagnosed with a psychiatric disorder, such as bipolar or manic disorder, while in fact they have a side effect of hyperthyroidism.
The eyes are particularly vulnerable to thyroid disease, because the immune system that attacks the thyroid gland often also targets the eye muscles and connective tissue within the eye socket (orbit). The skin is also affected, but to a lesser degree in most patients. The immunologic attack on the tissues of the orbit results in scarring of the orbital tissues, enlargement of the eye muscles, and expansion of the fat compartment that is present to protect the eye. The exact trigger for thyroid eye disease is not known, but the orbital tissues likely share some antigenic features with the thyroid gland. In addition, the orbital tissues contain receptors and enzymes that respond to changes in thyroid hormone levels. Eye symptoms can range from mild to severe, but only 10-20% of patients have vision-threatening disease.
Thyroid eye disease can also be present when the level of thyroid hormone in the blood is normal or low, depending on the degree of glandular stimulation caused by the immune attack and by the amount of thyroid gland destruction present at the time of diagnosis. However, most patients with eye symptoms have abnormal hormone levels that are accompanied by specific antibodies in the bloodstream. The components of the disease affecting the thyroid gland versus the eyes have common causes, but evolve separately and must each be treated separately.
Symptoms of Thyroid Eye Disease
These symptoms may not necessarily mean that a person has thyroid eye disease. However, if you experience these symptoms, contact your eye doctor for a complete examination to evaluate for this common eye condition.
- Swelling (edema) of the eyelids and tissue around the eye
- A constant stare
- Eyelid retraction
- Dry eyes or a sensation of grit or irritation to the eye
- Watering and redness of the eyes
- Sensitivity to light
Disease Progression
When the immune system attacks the muscles and other ocular tissues in the eye socket, the swelling and scarring resulting from the inflammation can cause the symptoms and signs noted above. In severe cases, the transparent window of the eye (cornea) may ulcerate, or the optic nerve may be damaged, either of which may result in a permanent loss of vision if not treated appropriately. Corneal damage is often due to a combination of the eyes bulging forward and eyelid retraction from eyelid tissue scarring, leading to exposure of the cornea from poor lid closure (see below). Optic nerve damage is due to thickened, inflamed and/or scarred muscles impinging on the optic nerve at the back of the socket (apex), just as the nerve exits the orbit to enter the brain (see below).
In most patients who develop Graves’ ophthalmopathy, the eyes bulge forward or the eyelid retracts to some degree. Many patients with mild to moderate Graves’ ophthalmopathy will experience spontaneous improvement over the course of two to three years or will adapt to the abnormality and learn to compensate. Severe ophthalmopathy will affect approximately 10% of patients. It is caused by inflammation of the muscles, which causes them to swell. As they swell, the muscles can scar in the swollen state, push the eye forward, and press on the nerve in the orbital apex. Scarring of the muscles can lead to double vision and even compression of the optic nerve, causing loss of vision. In some patients, eye protrusion makes it difficult for the lids to close properly and the cornea becomes exposed and vulnerable. When the optic nerve is compromised, progressive and irreversible vision loss can occur. Rarely, orbital swelling may precipitate glaucoma that can also affect the optic nerve. Surgical intervention is often required in order to save or restore adequate visual function.
Risk Factors
Approximately one million Americans are diagnosed with Graves’ disease each year. Women are much more likely than men to get Graves’ disease, but both men and women can develop thyroid eye disease. Cigarette smokers are at significantly increased risk to develop the eye disease, and when they do, often have more severe and prolonged activity that threatens vision. Patients who have vitamin D deficiency are more likely to develop thyroid eye disease. Furthermore, treatment with radioactive iodine, unstable thyroid hormone levels, and/or high levels of anti-thyroid antibodies, are all important risk factors for the development of thyroid eye disease.
Tests and Diagnosis
If your doctor suspects you have an overactive or underactive thyroid gland, your thyroid function must first be evaluated and treated appropriately by an internist trained in doing so. Treatments include medications to suppress the production of hormones by the thyroid gland, radioactive iodine to eliminate hormone-producing cells, and surgery to remove the thyroid tissue. In most cases, replacement thyroid hormone is required following the natural course of the Graves’ autoimmune attack on the thyroid gland or following effective treatment.
Once your thyroid function is treated and returned to normal, the eye disease must be monitored as it often continues to progress. Eye involvement must be evaluated on a continuing basis by an ophthalmologist during the active phase of the disease and, if necessary, treated. Although symptoms often resolve on their own, activity, scarring, and visual loss not readily apparent to the patient may otherwise go unnoticed and cause permanent changes.
Treatment and Drugs
Treatment for thyroid eye disease generally occurs in two phases. The first phase involves treating the active eye disease. This active period can last from a few months to as many as three years. Smoking lengthens the period of activity. Treatment during the active phase of the disease focuses on preserving sight and the integrity of the cornea as well as providing treatment for double vision when it interferes with daily functioning and becomes bothersome.
Most patients experience relief from dry eyes by using artificial tears throughout the day and gels or ointments at night. Some patients also use eye covers at night or tape their eyes shut to keep them from becoming dry if the eyelids do not close properly. Dryness occurs because the lids are retracted and cannot blink properly, because the tear-producing glands have been affected by the autoimmune process and aren’t functioning well, and/or because the forward bulging of the eyes prevents them from being completely covered by the lids. In some cases, acute swelling causing double vision or loss of vision may be treated for a limited time with oral prednisone. However, prednisone given for more than a few weeks at the dosages required to suppress the autoimmune inflammation always causes bothersome and dangerous side-effects that may become severe. In patients who respond to prednisone, a short course of intravenous (IV) steroids (methylprednisolone) may provide symptomatic improvement with fewer side effects than oral prednisone; this is referred to as an IV steroid pulse. Surgical decompression can also be used during the active phase, most often to relieve progressive damage to the optic nerve (optic neuropathy), but sometimes it can also helpful in reducing orbital congestion, redness, pain, and eye exposure.
A newly FDA-approved drug, teprotumumab (Tepezza®, Horizon Therapeutics), has been shown to be effective in the majority of patients with active thyroid eye disease, i.e. patients who experience eye redness, pain with eye movement, worsening proptosis, and/or worsening diplopia. Teprotumumab is given by eight IV infusions over 24 weeks. It is very expensive, and requires insurance pre-authorization, but can be a very good option for some patients.
Once the disease achieves remission and the thyroid hormone levels are stabilized, treatment can focus on restoring function and correcting unacceptable changes that persist after the ocular conditions of the active phase have stabilized, such as bulging eyes (proptosis), double vision (diplopia), and eyelid malposition. Treatment at this point is typically surgical, and needs to proceed in a predetermined order: orbital surgery first to correct the proptosis (orbital decompression), followed by eye muscle surgery to correct the diplopia, followed by eyelid surgery to improve eyelid closure and corneal protection.
It is critically important to stop smoking in order to reduce the severity and duration of thyroid eye disease!