Diagnosing and Managing Thyroid Eye Disease

CHICAGO — Endocrinologists should consider ways to refine their in-clinic eye exams for patients with thyroid eye disease, including testing for color vision, visual acuity, pupillary reaction, and resistance to retropulsion and Hertel exophthalmometry, according to a presentation at the American Thyroid Association (ATA) 2024 Meeting.

The lack of a Hertel exophthalmometer may be the biggest obstacle to optimal endocrine-based eye care, said endocrinologist Chrysoula Dosiou, MD, of Stanford University, Stanford, California.

Many of her colleagues “say they don’t know how to use a Hertel,” said Dosiou. “I highly encourage endocrinologists to get one. It’s not an expensive instrument, and you’ll be surprised how often you use it, including with pediatric patients.”

Referral to an ophthalmologist would be needed for additional testing — such as intraocular pressure measurements, a slit lamp exam, and an optic nerve exam — to definitively diagnose thyroid eye disease, said ophthalmologist Suzanne Freitag, MD, of Harvard University, Boston, who presented the session jointly with Dosiou.

Of these, the optic nerve exam is most important for assessing disease severity, Freitag said. “Compressive optic neuropathy is the most dreaded finding in thyroid eye disease patients,” she said. “It occurs in about 5% of thyroid eye disease patients and, if untreated, can lead to permanent vision loss.”

For optimal diagnosis and management of thyroid eye disease, endocrinologists and ophthalmologists need to work together, Dosiou and Freitag emphasized.

The endocrinologist’s role is to manage thyroid dysfunction; treat modifiable risk factors such as smoking, vitamin D deficiency, and hypercholesterolemia; perform baseline eye exam and Hertel measurements; and educate patients regarding thyroid eye disease symptoms, said Dosiou.

They also need to know when to refer the patient to ophthalmology and how urgently, she added.

When to Refer to Ophthalmology

The presenters shared the criteria for nonurgent referral to ophthalmology from the most recent Thyroid Eye Disease Consensus Statement by the ATA and European Thyroid Association.

These include:

• Active thyroid eye disease before radioiodine therapy
• Persistent, nonprogressive thyroid eye disease
• High-risk profile (age > 50 years, male sex, persistent thyroid dysfunction, smoker, and diagnosis of diabetes)
• Residual defect in ocular appearance or function, for possible rehabilitative surgery

Freitag suggests ophthalmology referral for all patients with orbital involvement.

“Look for a good comprehensive ophthalmologist who will take patients with mild disease to treat their dry eye and other symptoms,” she said. “You should also have an ophthalmologist to refer to when you have a patient with thyroid eye disease that needs urgent treatment.”

“Endocrinologists often expect inflammation but should know that the optic disc is usually not swollen in compressive optic neuropathy,” she added.

Dosiou said she doesn’t hesitate to refer patients to trusted ophthalmologists. “Pretty much every patient gets a referral who has anything except very mild or very stable TED [thyroid eye disease],” she said. “I refer everyone else, and my main decision is whether or not it’s going to be an urgent referral or a routine referral.”

Once a patient has been referred, the ophthalmologist can help with doing an accurate initial diagnosis at presentation; performing a comprehensive initial ophthalmic exam; and ruling out and treating ocular comorbidities, including sight-threatening disease.

Choices in Imaging

When asked when she orders imaging for patients with thyroid eye disease, Freitag said she orders imaging whenever there is a suggestion of orbital involvement. “If someone just has dry eyes or scratchiness, I will not image them. But if someone has double vision, restricted motility, or proptosis, I do a CT without contrast,” she said. “The acquisition time of the imaging is a minute or two, so patients are right back in clinic very quickly with the information I need.”

MRI remains the imaging tool of choice in other regions of the world, said Freitag. “When I’ve used MRI, I thought it was important to give contrast because we want to see how much inflammation is going on,” she said. “But what I learned at the recent American Academy of Ophthalmology meeting is that we don’t need to order contrast for this indication, which makes scheduling easier and saves the patient time in the scanner, the needlestick, and exposure to the contrast agent.”

Managing and Selecting Treatment

Both the endocrinologist and ophthalmologist should weigh in on treatment options, said Freitag and Dosiou.

The endocrinologist will look at treatment in the context of patient comorbidities and treat any endocrine complications of therapy. In addition, they will monitor the patient for stability and know when to refer to ophthalmology for rehabilitative surgery.

The ophthalmologist will provide localized therapies and use rehabilitative surgery to treat inactive moderate-severe disease.

Dosiou and Freitag discussed selection criteria for two of the biologic therapies available to treat thyroid eye disease: The monoclonal antibody teprotumumab, which inhibits the insulin-like growth factor 1 receptor, and the monoclonal antibody tocilizumab, which blocks the activity of interleukin-6.

For teprotumumab, they noted that contraindications include active inflammatory bowel disease, uncontrolled diabetes (A1c > 9), pregnancy/lactation or actively trying to conceive, and age

Teprotumumab can be used with caution in older adults and those with underlying hearing impairments, they said.

Patients should be screened and monitored while on teprotumumab, including, where applicable, pregnancy tests at baseline and before each infusion; audiograms at baseline, treatment midpoint, and 6 months post-treatment; fasting blood glucose at baseline and before each infusion; and A1c at baseline, treatment midpoint, and 6 months post-treatment.

For tocilizumab, contraindications include active infection, immunosuppression, active or latent tuberculosis, hepatic impairment, and prior diverticulitis.

Freitag noted that tocilizumab may be less expensive than teprotumumab and less susceptible to shortages.

Additionally, rituximab, IV steroids, and orbital radiation continue to be viable treatment modalities in many cases, Dosiou said.

Dosiou and Freitag disclosed no relevant financial relationships.