Thyroid Eye Disease

Thyroid eye disease (TED) is an autoimmune condition that is most associated with Graves’ disease (90%).  Less commonly, patients with TED can have Hashimoto’s disease (4%) or normal thyroid function (6%).

Of all patients with Graves’ disease, approximately 20 – 50% will go on to develop TED.  Thyroid eye disease is more common in women, though disease tends to be more severe in men. The average age of onset for TED is between 30 and 50 years old.

In the majority of cases, signs and symptoms of TED occur within 18 months of the diagnosis of thyroid dysfunction. The diagnosis of TED is typically based on characteristic clinical findings, though imaging and laboratory tests can be helpful in some circumstances.

Clinical Features

The characteristic symptoms of Graves’ eye disease feature the inflammation of the eye tissues. The eyes are painful, red and watery – particularly in sunshine or wind. The covering of the eye is inflamed and swollen.

The lids and tissues around the eyes are swollen with fluid. The eyeballs bulge out of their sockets. Because of eye muscle swelling, the eyes are unable to move normally and there may be blurred or double vision. Some patients have decreased colour vision as well.

On examination, it can be seen that the eyes are pushed out of their sockets. This can be measured using an instrument called an “exophthalomometer.”

Laboratory Tests

Patients commonly note eye irritation, burning, tearing, sensitivity to light, redness, pain on eye movements and/or an ache behind the eye. In some instances, patients will note double vision or vision loss.

Perhaps the most characteristic sign of TED is upper eyelid retraction. Expansion of the muscle and fat within the eye socket result in more prominent/bulgy appearing eyes, referred to as proptosis.  In some instances, the movement of the eye becomes restricted because of changes in the eye muscles, and this results in double vision. On occasion, the optic nerve can become compressed or inflamed, resulting in decreased visual acuity, limited visual field and abnormal color vision. This is referred to as dysthyroid optic neuropathy (DON) and needs to be treated in an expedited fashion.

Laboratory Tests

The diagnosis of TED is not based on a specific laboratory or imaging test, but rather a constellation of the signs and symptoms above. Sometimes antibody levels will be measured to provide information about the activity of TED, but this is not always needed.

Natural History

Thyroid eye disease is often considered in two stages: active and inactive. The active stage is characterized by inflammation and progressive signs/symptoms. In most patients, the active stage lasts 12 – 18 months, but smoking has been shown to both increase the severity of disease and extend the duration of activity.  It is strongly encouraged that individuals stop smoking.

The inactive stage of TED is characterized by stable features with fewer signs of inflammation.  Many changes that happen during the active stage can persist, including changes in the eyelid and eyeball position (eyelid retraction and proptosis) and double vision from limitation of extraocular motility.

Treatment

The first step is ensuring that hyperthyroidism is appropriately treated, as poorly controlled thyroid levels can have negative effects on overall health and have been associated with worse eye disease.  Even when the thyroid is well controlled, the eye disease can progress, and thus separate treatments can be necessary.

Treatment of TED is generally guided by disease stage (active vs inactive) and grade (mild, moderate or severe). For patients with active, mild disease, conservative measures are generally recommended.  Selenium supplementation (100 mcg by mouth twice per day) has been found to be beneficial in this group of patients and is generally well tolerated. Lubrication with artificial tears and ointment can also make the eyes feel more comfortable.  Cool compresses and salt restriction can be helpful if puffiness and swelling around the eyes are bothersome.  For patients with more severe disease (active stage, moderate or severe grade) additional treatment may be indicated.  In some instances, this involves intravenous steroids, or other immunosuppresants including rituximab or tocilizumab. More recently teprotumumab, an IGF1 receptor antibody, was FDA approved for use in this group of patients. This medication is not currently available in Canada; however, many more similar medications in this class are currently being investigated.

For patients who have transitioned into the inactive stage of disease, the focus of treatment becomes rehabilitation. In this stage, surgery can be done to address the remaining stigmata of the disease. This may involve eye socket surgery (orbital decompression) to make the eyes less bulgy, eye muscle surgery to improve the double vision, eyelid surgery to decrease the retraction, or a combination thereof. 

 

Updated in May 2024 by Kelsey A. Roelofs, MD, Department of Ophthalmology, University of Alberta, from the original text written by: Irving B. Rosen, MD., FRCS(C), FACS,  and Paul G. Walfish CM, MD, FRCP(C), FACP, FRSM.