Figure Showing Molecular Mechanism of Teprotumumab

Breakthrough Treatment for Thyroid Eye Disease

How does thyroid eye disease (TED) work?

Thyroid eye disease has many other names, including Graves’ eye disease, thyroid associated orbitopathy, Graves’ ophthalmopathy.

This review article authored by Dr. Shannon S. Joseph provides a comprehensive review of what we know and understand about the pathophysiology of thyroid eye disease.

In short, thyroid eye disease develops as a result of complex interactions amongst various molecules in the body including cell receptors, autoantibodies, immune cells, and other inflammatory molecules. These abnormal changes lead to the enlargement of the muscles and fat within the eye socket.

What are some symptoms of thyroid eye disease?

The eye socket is confined by rigid bony walls. When the muscles and fat within the eye socket are enlarged, the patients can develop prominent appearing eyes, abnormal positioning of the eyelids, inability to close the eyes, and double vision. Patients may also have redness and swelling of the eye and eyelids, as well as dryness, irritation, and tearing of the eyes. Severe TED can result in change and loss of vision.

The vast majority of TED patients also have Graves’ disease of the thyroid. However some patients can have normal or low thyroid levels. If your doctor suspects you may have TED, they may order blood work testing for certain antibodies, thyroid hormone levels, and imaging of your eye sockets if needed.

What are the risk factors associated with the development or worsening of TED?

The three main modifiable risk factors associated with the development or worsening of TED are smoking, diabetes mellitus, and abnormal thyroid function.

Smoking is the single most important risk factor for TED. Patients with Graves’ disease who smoke are 1. more likely to develop TED, 2. tend to have more severe disease and 3. are less responsive to treatment. Therefore, patients diagnosed with TED who are active smokers should quit as soon as possible.

Diabetes has been shown to be a risk factor associated with the development of TED-related optic nerve damage leading to vision loss. Therefore, diabetic patients diagnosed with TED should work with their PCPs/endocrinologists to ensure adequate blood sugar control.

Abnormal thyroid hormone levels is a risk factor for more severe TED. Patients who have abnormal thyroid hormone levels should work with their endocrinologists to restore and maintain normal thyroid function as soon as possible.

What are the treatment options for thyroid eye disease?

The treatment options for TED depends on multiple factors. One of the main factors for consideration is disease severity. Most patients have mild TED, and these patients can often improve spontaneously. The mainstay of treatment for mild TED is conservative, and can include artificial tears for eye lubrication, low salt diet and sleeping with head elevated to reduce swelling, and cold compress for comfort. Some patients who are selenium or Vitamin D deficient may benefit from supplementation. Smokers should stop smoking as this can lead to worsening disease. Patients should work with endocrinologists to normalize their thyroid hormone levels.

Patients with more severe disease may need any or a combination of medical and surgical treatments. Medical treatment options mainly include teprotumumab (Tepezza) and steroids. Surgical treatment options include orbital surgery, eye muscle surgery, and eyelid surgery. Other treatment options include orbital radiation. To achieve the best outcome, it is important to take a customized approach in developing treatment plans for each patient tailored to their needs.

What is Tepezza and how does it work?

Teprotumumab (Tepezza) is a human monoclonal antibody targeting against one of the key players in the development of TED: the IGF-1R. Extensive research has shown that blocking the IGF-1R pathway reduces the downstream effects of the two central players in TED: IGF-1R and TSHR. Therefore, teprotumumab (Tepezza) actually targets the underlying molecular mechanism (the root of the problem) in thyroid eye disease. This is what sets teprotumumab apart from other currently available treatment modalities for thyroid eye disease (steroid/radiation/surgery). The development of Tepezza is widely considered a major breakthrough in the treatment of TED.

Which patients could benefit from Tepezza?

Tepezza was approved by the FDA in January 2020. As a newer drug, we are still continuing to learn about its efficacy and safety. This review article co-authored by Dr.  Shannon S. Joseph provides a comprehensive review of what we know so far about the efficacy and safety of Tepezza. Here is a brief summary: 

What we learned from the two clinical trials
– The trials studied only a specific type of TED patients: those with active, moderate to severe disease who developed TED within 9 months prior, and have had no history of most other medical and surgical treatments.
– The trials showed that ~70-80% of patients responded to the treatment. These patients often had rapid improvement in eye prominence, inflammatory signs, and double vision.

What we learned since then:
– Recent case reports, including this article co-authored by Dr. Shannon S. Joseph, suggest patients with chronic TED or compressive optic neuropathy may also see improvement with teprotumumab.
– Further studies are needed to better understand the effect of teprotumumab in these patients.

What are the potential side effects & adverse reactions of Tepezza?

This review article co-authored by Dr. Shannon S. Joseph provides a comprehensive review of what we know so far about the efficacy and safety of Tepezza. Here is a brief summary: 

– Pregnancy and active pre-existing inflammatory bowel disease are contraindications for teprotumumab.
– The most common adverse events include muscle spasms, nausea, hair loss, diarrhea, fatigue, hearing impairment, and elevated blood sugar.
– Patients with pre-existing diabetes and pre-diabetes should have close monitoring of blood sugar.
– ~10% or more of patients reported hearing-related issues in the clinical trials. Subsequent case series show this percentage may be higher. Future studies are needed to better understand these observations. Patients at risk for hearing loss should get baseline and periodic audiograms should they choose to undergo treatment with Tepezza. 

Schedule a Consultation

Dr. Shannon S. Joseph is a board certified oculofacial plastic surgeon with extensive experience in thyroid eye disease.  Our practice serves patients in Southeastern Michigan with many patients who are from Birmingham, Bloomfield, West Bloomfield, Troy, Rochester, and the Rochester Hills areas. Dr. Joseph also frequently takes care of patients who travel from other parts of the country to see her. Do you have or think you may suffer from thyroid eye disease and would like a comprehensive evaluation and develop an customized treatment plan tailored specifically to you and your eyes? Contact us to schedule a consultation.