The way it used to be... in thyroid eye disease

Thyroid eye disease (sometimes referred to as TED or Graves' eye disease) is a type of autoimmune disease that occurs in certain patients, not all patients, with autoimmune thyroid disease where the body's immune cells attack thyroid cells but also the tissues around the eye (the orbit). Scientists currently believe this is because the orbital tissues contain proteins that are similar to those in the thyroid gland.

Thyroid eye disease was first described by Robert Graves, an Irish physician who recognized the association of hyperthyroidism and exophthalmos [bulging eyes] in 1835.

“The immune cells attack the fat and the fibroblasts in the extraocular muscles surrounding the eye, even around the eyelids, and cause the increase in expansion of the fat and the muscle size, pushing the eye forward, causing proptosis,” Raymond Douglas, MD, PhD, director of the orbital and thyroid eye disease program at Cedars-Sinai Medical Center, said.

Thyroid eye disease causes inflammation of the orbital tissues and can cause a number of different symptoms such as:

• Red eyes

• Itchy eyes

• Dry eyes

• Watery eyes

• Bulging eyes

• Double vision

"Over time, some symptoms, like red eyes, may improve or go away. But because of scarring, other symptoms, like eye bulging or double vision, may remain. It’s also possible for new symptoms to appear and for existing symptoms to get worse, this is called a flare." (from Tepezza.com)

There is one symptom that unmistakably points to the diagnosis of TED, and that is double vision upon waking.

“Almost nothing gives you double vision when you first wake up. If practitioners asked that one question, they would detect more early TED,” she said. “Ask patients if they experience double vision or blurring when they look at their cell phone when they first wake up. It typically goes away over 20 to 30 minutes.”

Dr. Kimberly Cockerham, M.D. on Healio.com

“They [the body's immune cells] will also attack the tissues around the eyes, causing eyelid retraction and inflammation, or just some very significant facial changes.” Dr. Douglas goes on to say. "The expansion of orbital muscles can also stretch and compress the optic nerve."

During my residency training at the University of Maryland in the early 2000s, I had several patients with severe thyroid eye disease that are tragic and unforgettable. In particular, I had one patient who had severe proptosis [eye bulging] where one eye was blinded by his disease. The orbital swelling was so severe that even with the use of high dose systemic steroids that the optic nerve had been essentially choked to death on one side and he was at risk of losing the other eye also. I assisted my oculoplastics attending for his orbital decompression surgery to save the vison in his remaining eye. Despite a successful operation that saved the vision in the one remaining eye, he still had difficulty closing his eyelids and needed to put ointment on at night to prevent the eyes from drying out. He remained on high dose steroids for many months that caused him to exhibit uncharacteristic violent, angry outbursts towards his concerned and caring family.

Some of the other severe thyroid eye disease patients in the past could require not only this kind of orbital decompression surgery, but subsequent double vision (strabismus surgery) and then eyelid surgery for the inability to close the eyelids (lagophhalmos surgery). Each of these surgeries are major surgeries usually requiring general anesthesia and the risks that go along with this. Surgical rehabilitation from thyroid eye disease can be a long, arduous process for the patient and their families that often takes more than a year.

From start to finish, the process of surgery can take 9 months or longer.

“You generally want to wait 4 to 6 months after each of these surgeries to get stability,” Allen said. “You want to make sure they are completely healed before you continue. If there is a patient who has orbital issues as well as strabismus and eyelid involvement, you are potentially looking at over a year of rehabilitation.”

Consequently, surgery is not an option for every patient, and the risks and benefits need to be weighed individually for each patient, Douglas said.

“Many patients are afraid of surgery because of the complications, and it doesn’t always fix things completely,” he said.

Dr. Richard Douglas from Healio.com May 26, 2021

Things have changed a lot since the FDA approved teprotumumab (Tepezza), an IGF-1R blocking antibody, in January 2020. Dr. Richard Lindstrom's December 10, 2023 Perspective article provides a poignant perspective on the recent development and use of the breakthrough pharmcologic therapy Tepezza. "The impact of Tepezza on the quality of life of TED patients is another modern-day miracle of the innovation cycle." The cost of the treatment is high currently "about $400,000 ... requiring eight intravenous injections over 24 weeks." However, in the past, for our moderate to severe patients, no amount of time, money or surgery could get these patients back to their baseline. The cost to patients will depend on combination of factors including insurance coverage and company-supported access program. Amgen recently purchased Horizon Therapeutics PLC, the maker of Tepezza in October 2023, for $27.8 billion. Costs will continue to evolve as our understanding of the disease improves and even newer therapies emerge. Currently, the goal of most eye care professionals is to identify TED patients at an early stage, "allowing effective treatment before vision-threatening or psychological side effects occur."

Articles references in this blog post:

• What is Thyroid Eye Disease? on Tepezza.com

• Thyroid eye disease managed jointly by ophthalmologists and endocrinologists on Healio.com published June 1, 2021

• Treatment for thyroid eye disease enters new era, shows potential for brighter future on Healio.com published December 7, 2023.

• Ophthalmologists need to play early role in diagnosing thyroid eye disease on Healio.com published December 10, 2023

• Amgen completes acquisition of Horizon Therapeutics PLC press release published October 6, 2023