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The Battle of the Bulge

Pathogenesis & Treatments of Thyroid Eye Disease by Jillian Webster

Although the ultimate causes of thyroid eye disease (TED) are not completely understood, there are significant correlations between genetic, environmental, and nutritional factors, as well as the location of TSH receptors of IGF1 receptors. For example, Graves’ disease — an autoimmune disease that causes an overactive thyroid, as well as demographics, may be correlated to the development of TED. In the future, this condition will hopefully be treated prophylactically. This and other topics about thyroid eye disease were discussed by Dr. Sathyadeepak Ramesh from Wills Eye Hospital in Pennsylvania, USA, during a webinar organized by CyberSight in November last year.

Understanding TED’s pathophysiology

According to a study by Ardley et. al., heredity may be a gateway into early detection of TED. Dr. Ramesh highlighted that there is evidence of genetic heritability of one of the early signs of TED — lid retraction. In a Punnett square presented by Dr. Ramesh, he showed that there are correlative characteristics in genetics regarding the experience of TED, especially in females.

As well as genetics, the patient’s environment can also contribute to the development of TED. Patients with Graves’ disease are at much greater risk of developing TED. Although the inheritability of Graves’ disease is still debated, the attributes shown in the study display some correlation.

Diet and other lifestyle choices may also be correlated to the risk of developing TED. Tobacco smokers with Graves’ disease are at the highest risk of developing it, with the risk diminishing if the patient stops smoking. Those with the least risk are patients who have never smoked tobacco and maintain a healthy body.

A well-balanced diet is also a way to prevent many diseases, including TED. Dr. Ramesh referenced studies that may suggest a correlation between the presence of selenium, vitamin D, and other micronutrients, and the reduction in TED-related inflammation. He recommended regular ingestion of a multivitamin combined with a complete diet for dietary prevention.

TED’s clinical and medicinal manifestations

molecular biological level. The disease is characterized by thyrotropin (TSH) receptors triggering antibodies that attach to other TSH receptors and cause stimulation of stem cells. Those cells can then grow into a multitude of different cells that then lead to orbital staining by thyroid receptors, inflammation, dryness of the eye, as well as several psychosocial impacts. Medical professionals should consider the individual case of each patient and look for ways to prevent the disease from occurring.

If prevention is not possible, then there are a number of treatments available, depending on the stage of the disease and the comfort of the patient. A study highlighted by Dr. Ramesh looks at five patients from the onset of TED to quiescence. The study reports that TED continues in a curve fashion over the course of 18 months. Because of this research, ophthalmologists and endocrinologists can make accurate predictions regarding the progression of TED.

According to Dr. Ramesh, TED has four clinical manifestations. The most common is eyelid retraction and occurs in 90% of cases. This is caused by inflammation in the levator palpebrae muscles surrounding the eyeball. It can be noticeable by pressure in the orbit that can cause discomfort or dryness of the eye. It can also cause significant physical changes. TED can not only affect the appearance of the orbital area but also to the lips, and cheeks — which can be a concern for patients.

Common optical symptoms of TED are proptosis (or displacement of the eye), congestion, and a feeling of ache in the orbit or the cranium. The most extreme orbital symptom is mild to severe optic nerve inflammation.

Treatment options

Ocular surface disease is another clinical manifestation of TED. It can be divided into two types: inactive and active cases. Active cases are marked by severe inflammation of the eyelid as well and corneal staining. Treatment for active cases is usually topical steroids. Inactive cases normally do not display eyelid or cortical staining. However, the patient may find it hard to blink completely and might experience eye dryness. The treatment for an inactive case may be artificial tears or surgery.

Steroids can help with inflammation. If the patient is bothered, then do a decompression on a stable patient. However, Dr. Ramesh suggests surgery for inactive TED.

Surgical procedures are not the only treatment for TED. As mentioned before, Dr. Ramesh recommends a balanced diet in combination with a multivitamin to help prevent TED in all patients, especially those who may be prone to the disease.

In addition, many recent clinical trials have received mixed reviews from the medical community. The most notable is one on teprotumumab. This FDA-approved drug and the only one approved for the treatment of TED, not only reduces symptoms but also modifies the disease, altering the length and severity of its active phase.

Topical and intravenous steroids may also be beneficial for individuals suffering from TED-related inflammation. Steroid application is useful in alleviating swelling and pain. However, it does not modify the disease itself. Orbital radiation is also a treatment that has produced some controversy. Dr. Ramesh said some researchers believe in the therapeutic abilities of this practice and some disagree. However, he does not recommend orbital radiation until orbital decompression has been performed.

Surgery is the preferred method of treatment by Dr. Ramesh. He recommends orbital decompression after a patient has already had a reduction in inflammation due to steroid therapy. This procedure involves removal of bone in order to relieve the pressure from the orbital tissue. This procedure also has positive psychosocial outcomes. Orbital decompression not only can improve double vision due to orbital pressure but it can also allow for the physician to recreate the face of the patient before affliction with the disease.

Prevention is key

Currently, treatment is aimed at improvement and stopping progression. However, in the future, molecular therapy will be used as a permanent solution before complications become permanent. These current treatments will not only help but also revert fibrosis. Prevention of fibrosis is key, but in the future, there will be a medication that will reserve this very difficult aspect of TED.

During the CyberSight webinar, ophthalmologists peer into the future of TED treatment.

Editor’s Note:

The CyberSight Lecture on Thyroid Eye Disease: Past, Present and Future was held on November 19, 2020. Reporting for this story took place during the event.