Ophthalmologists need to play early role in diagnosing thyroid eye disease
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We last featured thyroid eye disease in our June 10, 2021, issue of Healio | OSN. Interested readers might enjoy reviewing that cover story and my perspective.
We have learned much about thyroid eye disease (TED) in the last 2 years. In this commentary, I will focus my comments on diagnosis and medical therapy, especially with Tepezza (teprotumumab-trbw, Horizon Therapeutics/now Amgen).
Thyroid eye disease was first described by Robert Graves, an Irish physician who recognized the association of hyperthyroidism and exophthalmos in 1835, so it is special that an Irish company, Horizon Therapeutics, revolutionized TED treatment 185 years later.
In 1981, after extensive residency and fellowship training, Terry J. Smith, MD, an endocrinologist and currently Frederick G.L. Huetwell Professor Emeritus in Ophthalmology and Visual Sciences at the University of Michigan, began his studies of TED. He discovered that insulin-like growth factor 1 receptor (IGF-1R) was critical to the autoimmune process that led to inflammatory cell infiltration into the orbit, resulting in fibroblast proliferation and enlargement of the ocular muscles and periocular fat. He discovered that the biologic teprotumumab, a human monoclonal antibody, could block this inflammatory process. His work was taken through clinical trials by Horizon, and FDA approval was achieved for the treatment of TED with teprotumumab, an IGF-1R blocking antibody, in January 2020.
The FDA considered teprotumumab an orphan drug and categorized it as a breakthrough therapy, giving it fast track designation and priority review. Upon approval, it was named Tepezza, and a new era of TED therapy was born. The impact of Tepezza on the quality of life of TED patients is another modern-day miracle of the innovation cycle.
Since its approval, it was confirmed that Tepezza can result in sensorineural hearing loss, autophony and/or tinnitus, and every patient is now warned and followed closely for this potential side effect.
Since the product launch in 2020, more than 15,000 patients in the U.S. have been treated with Tepezza. The treatment regimen requires eight intravenous injections over 24 weeks. The cost is about $400,000 for the 24-week course of therapy. Insurance coverage is widely available but requires preauthorization, which can take several months. There are company-supported programs in place to make the treatment available to those without insurance or sufficient financial means.
Most TED patients are treated in tertiary referral centers using a multidisciplinary approach. Critical partners include ophthalmology, endocrinology, otolaryngology and radiology. For most eye care professionals, the vital role is to identify TED early and refer patients to a nearby tertiary medical center.
The patient with a history of hyper- or hypothyroid disease and obvious proptosis is easy to diagnose, and most of these patients are already being cared for in specialty centers. The goal today is to recognize the TED patient at an early stage and initiate therapy promptly. Key early findings are like those of ocular surface disease with burning, itching, a gritty sensation, puffy lids and conjunctival erythema similar to dry eye disease (DED) and allergic or nonspecific conjunctivitis. Nearly 40% of patients seen by a comprehensive ophthalmologist or optometrist have some ocular surface disease symptoms or signs, and these are also the earliest findings in TED. TED patients will be younger than the usual DED patient, usually between 30 to 50 years old. A valuable symptom is morning diplopia and blurred vision, which clears in 30 minutes or so. Motility may be restricted when testing vision, especially when looking up. We are all learning to ask patients to look down during slit lamp examination to evaluate the upper lid margin for collarettes suggesting Demodex infestation. In the TED patient, downgaze may make subtle eyelid retraction more evident. Some patients will have ocular hypertension, and IOP usually increases on upgaze. Exophthalmos measured by Hertel exophthalmometry and lid retraction with exposure remain the classical findings. The most severe cases represent a medical emergency as optic nerve compression can lead to permanent visual loss.
The comprehensive ophthalmologist will often need to participate in managing associated DED, ocular hypertension and diplopia. All patients need to be advised that smoking is a significant risk factor, and referral to a smoking cessation center may be needed. When TED is diagnosed, a baseline visual field and OCT of the optic nerve are indicated and repeated at least annually, much like in the glaucoma patient. Most eye care professionals refer these patients to a tertiary center where blood testing for thyroid dysfunction and an MRI or CT of the orbit are performed. Tepezza can cause or exacerbate hyperglycemia so fasting blood sugar and HbA1c are monitored.
Today there is significant direct-to-consumer advertising about TED, and we can expect more patients in our offices wishing to be screened for this disease. Our goal is to make the diagnosis of TED in patients at an early stage, allowing effective treatment before vision-threatening or psychological side effects occur.
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