by Kristen Monaco, Staff Writer, MedPage Today September 15, 2022

Making an initial call of thyroid eye disease (TED) can be difficult, but once the diagnosis has been made, settling on the right treatment requires attention to several factors.

"Treatment options for TED depend on the severity of the disease," said Terry J. Smith, MD, of Kellogg Eye Center at the University of Michigan in Ann Arbor. He added that most cases of TED only require local, supportive care in the form of eye drops, eye gel, and protection against wind and strong light.

For patients with more severe disease, typical treatments include systemic steroids, radiotherapy (RT), or rehabilitative surgery, he told MedPage Today. Steroids can reduce TED symptoms, but are not disease-modifying. Surgical rehabilitation can include orbital decompression, extraocular muscle surgery, and eyelid repositioning, as well as soft-tissue volume and redraping.

When assessing disease severity, a clinician takes into account the amount of eye protrusion, double vision, and soft-tissue changes, as well as impact on quality of life, explained Rachel Arakawa, MD, of Mount Sinai Health System in New York City.

Another factor that can drive the treatment decision is whether the TED is in its active or inactive phase.

The active phase of eye disease occurs initially and can present with dry eye, swelling, and eye pain that can last for 6 months to over 2 years, Arakawa told MedPage Today. "It is followed by the inactive phase where scar-like tissue can cause chronic disfigurement and vision changes."

She noted that some patients with inactive disease may require surgical correction of eye protrusion, cross eyes, eyelid abnormalities, and cosmetic concerns, adding that "in rare circumstances, surgery may be needed to take pressure off the optic nerve in order to preserve vision."

For active disease, severity is key. For more mild disease, treatments typically consist of thyroid-normalizing medications, lubricating eye drops, and selenium supplements, an antioxidant shown to decrease eye inflammation, Arakawa noted.

For moderate-to-severe active disease, intensive treatments such as steroids or RT are on the table. "These are sometimes effective, but can be associated with severe side effects and can leave patients with unsatisfactory results. Importantly, steroids fail to reliably improve diplopia and proptosis [bulging of the eyes]," Smith cautioned.

Michael K. Yoon, MD, of the Center for Thyroid Eye Disease and Orbital Surgery at Mass Eye and Ear in Boston, pointed out that orbital RT is not done very often in the U.S., but the modality can help improve some symptoms of TED, particularly double vision. He told MedPage Today that RT is "a painless treatment [that] is typically given as 10 sessions over 2 weeks." Candidates for orbital RT are those in the early, active phase of the disease with moderate-to-severe, or rapidly progressive, disease.

The newest treatment for TED, teprotumumab (Tepezza), gained FDA approval in January 2020, and is the first agency-approved, non-surgical treatment for TED. It is a fully human monoclonal antibody inhibitor of insulin-like growth factor-1 receptor that is administered in eight doses, given as 30- to 90-minute infusions, once every 3 weeks.

The drug specifically targets the underlying disease mechanism of TED, reducing inflammation and tissue remodeling around the eye, and improves symptoms of proptosis, diplopia, and eye pain, Smith said. He also noted that teprotumumab "is approved to broadly treat TED, which includes patients in both the acute (active) and chronic (inactive) phases of the disease."

The FDA approval was based on positive findings from the phase II and phase III OPTIC trials, which demonstrated an average 2.82 mm reduction in proptosis after 24 weeks of infusions. However, the trials only tested treatment in patients with active TED.

Yoon pointed out that participants in the clinical trials had received their diagnosis less than 9 months earlier, so "patients with a relatively recent diagnosis of TED, the presence of proptosis, and inflamed eyes are most likely to see a benefit." But he noted that "there is increasing evidence that patients with severe TED and vision loss likely will benefit from teprotumumab as well."

Smith added that a growing number of case reports are demonstrating improvements in TED -- including in proptosis and diplopia -- with teprotumumab in the chronic phase, which is the basis of a phase IV trial that is currently underway.

"Not all medications ... work on all patients or to the same degree," Yoon said. "However, most specialists treating TED have found that the amount of improvement seen with teprotumumab is better than the other existing treatments."

Arakawa cautioned that there are no head-to-head trials of teprotumumab against other treatment options, like IV steroids, so "it's hard to know if teprotumumab is superior to other treatments. More research is needed to determine long-term responses, as well as who would most likely benefit from the drug."

Yoon agreed, adding that "proper patient selection remains the most critical indicator of possible success."

Of course, the agent has the potential for adverse events. Yoon advised that patients with TED and pre-existing diabetes should monitor their blood sugar because teprotumumab can lead to hyperglycemia. Another possible toxicity with teprotumumab is hearing loss, which in rare cases can be severe and permanent, he said, adding that pre-treatment hearing tests are recommended.

Arakawa explained that "there are no standard guidelines for when to use teprotumumab." She recommended that an endocrinologist and ophthalmologist work together to individualize treatment, including taking into account hurdles such as drug availability and cost.

Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Smith reported a relationship with Horizon Therapeutics.

Yoon reported relationships with Sling and Viridian Therapeutics.

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