Illustration of Proptosis
This story is part of a series on the current progression in Regenerative Medicine. This piece is part of a series dedicated to the eye and improvements in restoring vision.
In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.
Thyroid eye disease (TED) is an autoimmune disorder that causes inflammation of the muscles and tissues around the eyes. This can lead to proptosis or bulging of the eyes, diplopia or double vision, and a significant reduction in the patient’s quality of life. TED is most often connected to Graves’ disease.
In this autoimmune condition, the thyroid gland overproduces hormones. Still, it can also occur in patients with Hashimoto’s thyroiditis or as a result of radiation therapy to the head and neck.
What is Thyroid Eye Disease?
Thyroid eye disease can be explained simply by saying that it is a disease where autoantibodies target specific eye cells, causing them to bulge out and compress the optic nerve. This can lead to vision problems and even blindness in severe cases.
In more detail, the immune system produces autoantibodies that activate specific receptors. These receptors then trigger the release of cytokines, which are chemical messengers that cause inflammation and fibrosis in the eye tissues. As a result of this inflammation, the extraocular muscles become inflamed and swollen, leading to a range of symptoms, including proptosis or bulging of the eyes, double vision, and exposure keratopathy.
Proptosis occurs due to the swollen muscles pushing the eyeball forward, leading to an abnormal eye protrusion. Double vision and exposure keratopathy can occur due to the abnormal position of the eyeball caused by the swollen muscles. Exposure keratopathy is when the cornea, the transparent outer layer of the eye, becomes dry and damaged due to inadequate protection from the eyelid.
Current Common Treatments
Currently, the mainstay of treatment for TED is glucocorticoids, such as prednisone or methylprednisolone, powerful anti-inflammatory drugs that can help reduce swelling and inflammation. However, these drugs can also cause significant side effects, including weight gain, mood changes, and increased risk of infection.
In addition to glucocorticoids, doctors may also recommend other treatment options based on the severity of the condition and the patient’s needs. Radiotherapy, which uses high-energy radiation to target the tissues in and around the eyes, can effectively reduce inflammation and swelling. Immunosuppressants, such as mycophenolate or azathioprine, may also suppress the immune system and prevent further damage to the eye tissues.
In some cases, surgery may be necessary to correct the position of the eyes or to reduce pressure on the optic nerve. This can involve decompression surgery to remove bone from around the eyes or to remove fat from behind the eyes to create more space. In rare cases, doctors may recommend orbital radiotherapy, which is a type of radiation therapy that targets the eye socket to reduce inflammation and swelling.
A Novel Treatment for Thyroid Eye Disease
Teprotumumab, a fully human monoclonal antibody, is a novel treatment option for TED. Its mechanism of action involves binding to and blocking the activity of IGF-1 R, preventing the activation of fibroblasts and thereby reducing inflammation and fibrosis. This medication was approved by the FDA in January 2020 for the treatment of active TED based on the results of two randomized, double-masked, placebo-controlled, parallel-group, multicenter trials.
A recent study published in the International Journal of Ophthalmology reviewed the efficacy and safety of teprotumumab for the treatment of TED, incorporating data from three clinical trials involving 341 patients. The analysis found that teprotumumab was significantly more effective than a placebo in reducing proptosis, or the protrusion of the eyes, in both the intention-to-treat and per-protocol populations. Patients treated with teprotumumab also showed improvements in diplopia response, overall response, and the clinical activity score, a measure of disease activity. Additionally, patients receiving teprotumumab experienced more significant gains in proptosis and quality of life than those receiving a placebo.
Despite these positive outcomes, the analysis also revealed that patients treated with teprotumumab are at a higher risk of adverse events, including serious complications such as muscle spasms and gastrointestinal reactions. However, these side effects were generally tolerable and manageable in clinical trials.
The Future of Thyroid Eye Disease
The findings on teprotumumab as a treatment for TED are highly promising, with evidence indicating that it may offer a safer and more efficient alternative to glucocorticoids. Although the studies analyzed had relatively short follow-up periods and small sample sizes, these limitations do not negate the potential benefits of teprotumumab.
Indeed, future research should prioritize examining this treatment’s long-term safety and efficacy by studying patients’ experiences with chronic-inactive TED. Additionally, identifying biomarkers that predict response to treatment is a crucial avenue for advancing our understanding of TED and optimizing treatment outcomes. These areas of study offer significant potential for improving patient outcomes and increasing medical knowledge.
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