Featured speaker Raymond Douglas, MD, PhD (Cedars-Sinai Medical Center) |
On November 14, AEVR’s Decade of Vision 2010-2020 Initiative held its first-ever Thyroid Eye Disease (TED) Congressional Briefing. The event featured Raymond Douglas, MD, PhD, an oculoplastic surgeon who serves as Director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai Medical Center in Los Angeles. A clinician-scientist, his team researching TED and potential therapies has been funded through federal (National Eye Institute) and private sources. Joining Dr. Douglas was one of his patients Christine G., a small-business owner from California, who shared her experience with TED and its quality-of-life implications.
Dr. Douglas explained that TED, also called Graves’ ophthalmopathy or Graves’ Eye Disease, is an autoimmune disease that often occurs in individuals with Graves’ disease, which is caused by an overactive thyroid gland in a condition called hyperthyroidism. TED can occur in patients who already know they have thyroid disease–– about 80% of TED patients will present symptoms within 18 months of their Graves’ disease diagnosis––or it may be the first sign of Graves’ disease. While TED often occurs in individuals with hyperthyroidism, it is a distinct disease and treating hyperthyroidism may not resolve visual symptoms and changes. TED can be associated with a family history of the disease. Although it usually affects middle-age adults, it can occur at any age. Although females are affected more than males, it is usually more severe in males. Smoking can increase the risk of TED by 7-8 times and cause a longer “active” phase of the disease,
Patient representative Christine G. (center), joined by AEVR Executive Director James Jorkasky (left) and Dr. Douglas (right) |
In the “active” phase of TED, the main symptoms include inflammation and increased amounts of the tissue, muscles, and fat behind the eye (in the bony socket) causing the eyeballs to bulge out, a condition called proptosis. If the eye is pushed far enough forward, the eyelids may not close properly when blinking and sleeping, causing the cornea to become unprotected, dry, and damaged. The enlargement of the tissues and muscles of the eye may prevent it from properly working, which affects eye position (called strabismus) and movement, which can lead to diplopia, or double vision. In severe cases, the inflammation and enlargement of the tissues, muscles, and fat behind the eye compresses the optic nerve, which connects the eye to the brain, thereby causing vision loss.
Although medical therapy during the “active” phase of TED has included steroids, radiation, selenium supplements, and other immunomodulatory treatments, these have generally been ineffective in stopping the progression of the physiological changes in and around the eyes and may have their own side effects. As a result, most patients have sought surgical intervention during the “fibrotic” stage of the disease, which includes orbital decompression, extraocular muscle surgery, eyelid repositioning, and soft tissue draping. Dr. Douglas emphasized that often he can only operate on one eye at a time, therefore resulting in multiple surgeries for TED patients.
Since current treatments are ineffective, researchers have sought to identify the molecular pathways that lead to manifestation of the disease. They discovered that a protein, Insulin-like Growth Factor-1 Receptor (IGF-1R), is overexpressed in Graves’ disease and subsequently that a fully human monoclonal antibody called Teprotumumab inhibited IGF-1R 2 expression, blocking autoantibodies from attacking orbital cells, reducing inflammation, and preventing excessive cell growth/buildup behind the eye. In a series of safety and effectiveness clinical trials, Teprotumumab has been shown to be highly effective in reducing eye bulging and double vision and demonstrated a positive benefit-to-risk profile in treatment of TED with disease-modifying activity. A drug therapy version of Teprotumumab is currently under review by the Food and Drug Administration (FDA) as a first line agent in treating the “active” phase of TED, causing Dr. Douglas to comment that “the future is now” for the first effective TED treatment.
Christine related her experience with TED and how it became a significant challenge to her quality of life. Despite experiencing eye bulging and severe double vision, she has continued to run her business and engage in activities of daily living, such as swimming and biking. As a veteran of multiple surgeries, including one just three weeks before the Briefing, she discussed how she had to become her own advocate for proper treatment that has resulted in resolution of her double vision. She concluded by stating that, “I feel as though I have come out of a tunnel and into the light. And although I have dealt with the consequences of ‘active’ TED well before this new drug therapy, I am happy that others will not have to experience what I have.”
Kira Baldonado, left, and Sara Brown, right, both from Prevent Blindness, with Jeffrey Sherman, MD (Horizon Therapeutics) |
Randall Rutta of the American Autoimmune Related Diseases Association with Nora Wong, MPH of the National Eye Institute |