By Alon Kahana, MD, PhD (University of Michigan)
What Is Graves’ eye disease or Thyroid eye disease?
Graves’ disease 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 inflamed thyroid gland can enlarge (“goiter”) and excess hormone changes metabolism and affects 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. 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 (euthyroid) or low (hypothyroid), 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 blood stream (for example, TSI – thyroid stimulating immunoglobulin). The components of the disease affecting the thyroid gland versus the eyes have common causes, but evolve separately and each must be treated separately.
- 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
- A feeling of pressure in the eye sockets
- Double vision
- Loss of vision
- Loss of perception of bright colors
The symptoms described above 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.
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 become overly exposed and dry, leading to ulceration, or the optic nerve may be damaged from compression by scarred muscles or by stretching from eye protrusion. Either of these devastating complications 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 thyroid eye disease (also known as Graves’ ophthalmopathy), the eyes bulge forward and/or the eyelids retracts to some degree. Many patients with mild thyroid eye disease will experience spontaneous improvement over the course of two to three years, once the thyroid endocrine disease is treated. Many patients also adapt to the abnormality and learn to compensate. Severe ophthalmopathy usually affects approximately 10% of patients. It is caused by inflammation of the muscles and orbital fat, which causes them to swell. As they swell, the muscles and fat can scar in the swollen state, push the eye forward, stretch the optic nerve, and press on the nerve in the orbital apex. Pressure or stretching of the nerve can cause permanent vision loss. Scarring of the muscles can also lead to double vision because the muscles can no longer work well together. In some patients, eye protrusion makes it difficult for the lids to close properly and the cornea becomes exposed and vulnerable. 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.
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. In addition, it is critically important that the thyroid hormone levels are stabilized. Unstable thyroid hormone levels – either too much or too little – is associated with worsening eye disease. Low vitamin D and selenium levels may also be associated with worse thyroid eye disease.
Tests and Diagnosis
If your doctor suspects that 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 hormone by the thyroid gland, radioactive iodine to eliminate hormone-producing cells, or 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, disease activity, scarring, and visual loss not readily apparent to the patient may otherwise go unnoticed and cause permanent changes.
There is good evidence to suggest that radioactive iodine treatment poses significant risks to worsening thyroid eye disease. The presence of significant eye disease is a relative contraindication to radioactive iodine treatment. Even with mild or no eye disease, treatment with oral steroids at the time of radioactive iodine treatment is usually indicated, to reduce the risks to the eye.
Following thyroid ablation, with radioactive iodine or thyroidectomy surgery, it is critically important to treat the resultant hypothyroid state rapidly. Following surgery, this means initiating treatment within a week of total thyroidectomy. Following radioactive iodine treatment, this usually means rechecking thyroid levels at 6 weeks post treatment and reassessing frequently (every 4-8 weeks) until thyroid hormone levels stabilize with treatment.
There is also conflicting evidence on the role of prolonged methimazole use in the development of thyroid eye disease. Methimazole does not treat the underlying problem, which is the auto-immune disease directed against thyroid gland antigens. Methimazole only treats the resultant hyperthyroid endocrine state. European studies suggest that prolonged methimazole treatment does not increase the risk of thyroid eye disease, but the studies were limited to patients with no underlying eye disease. American studies suggest that in the presence of some eye disease, prolonged methimazole treatment is a significant risk factor for worsening disease. This is also our anecdotal experience at the University of Michigan. We typically recommend endocrine stabilization with methimazole followed by definitive treatment with either radioactive iodine or thyroidectomy surgery, depending on the rest of the clinical picture (including severity of the eye disease).
Eye Disease 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 optic neuropathy, but sometimes it can also helpful in reducing orbital congestion, redness, pain, and eye exposure.
Scientists at the Kellogg Eye Center and elsewhere are actively involved in studying the biology of thyroid eye disease and developing new treatment approaches. At your evaluation, please ask your doctors about any new discoveries or treatment protocols that you might qualify for.
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.
REMINDER: It is critically important to stop smoking in order to reduce the severity and duration of thyroid eye disease!
Written by Alon Kahana, MD, PhD