What You Need to Know to Manage TED
AT A GLANCE
- Thyroid eye disease (TED) is an autoimmune condition that affects the soft tissues around the eye.
- Clinical findings can be similar for dry eye disease and TED, but the key to treating the latter is addressing its root cause.
- Optometrists are often the first health care providers to diagnose TED, so it is important for them to be familiar with the condition and its management.
Dry eye disease (DED) is chronic, progressive, and multifactorial, and it affects more than 16 million people in the United States alone.1 DED is typically broken into two categories based on its root cause: aqueous deficiency or meibomian gland dysfunction. Management is guided by patients’ signs and symptoms.
Important to the differential diagnosis is a familiarity with thyroid eye disease (TED). Patients with TED often present to the optometrist’s office with clinical findings similar to DED, but conventional DED therapies are ineffective. Your ability to recognize TED can help you to provide appropriate care.
GRAVES DISEASE
TED differs from Graves disease. The latter is an autoimmune condition that produces hyperthyroidism and has an incidence rate of 0.02% to 0.05%. Approximately 40% of patients with Graves disease experience progression to TED, and the severity of their symptoms ranges from mild to moderate.
TED is an autoimmune condition that affects the soft tissues around the eye, and its incidence rate is 0.016% for women and 0.003% for men.2 The terms Graves orbitopathy and Graves eye disease are synonymous with TED. It is important to note that the condition can affect individuals with just hyperthyroidism and/or Hashimoto disease.
DIAGNOSIS
Presentation
When patients with TED first present to your office, they may exhibit the generalized dry eye symptoms of red, watery, burning eyes that are unresponsive to conventional DED management. During your subsequent investigation, attempt to correlate patients’ systemic medical health with their ocular presentation. Look for signs of eyelid retraction, lagophthalmos, proptosis, transient diplopia/extraocular dysmotility, possible corneal exposure, and optic nerve involvement.3
There are two distinct phases of TED, the acute or active phase and the chronic or inactive phase. The acute phase occurs suddenly and can last up to 3 years. In the chronic phase, symptoms may improve, but the appearance of proptosis can remain.4
Grading System
Grading TED involves using a clinical activity score. The Table provides a means of identifying patients with TED who may benefit from immunosuppressive therapy. The process is similar to grading DED severity using the score on a Standard Patient Evaluation of Eye Dryness questionnaire. The NOSPECS classification provides a severity score but does not determine clinical activity or provide a guide for management.5 Diagnosing TED should include ordering a general physical and blood work (labs to include T3, T4, and thyroid-stimulating hormone receptor), and possibly an orbital CT.
UNDERLYING PATHOPHYSIOLOGY
In TED, orbital fibroblasts are activated, leading to the expansion of soft tissues (fat and muscle) around the eye. This can cause proptosis, diplopia, pain, redness, tearing, and decreased vision. Overexpression of an insulin-like growth factor 1 receptor (IGF-1R) and interaction with TSHR occur, and a complex forms on the orbital fibroblasts.
Autoantibodies to IGF-1R then bind to the complex, leading to the activation of the fibroblasts and the release of the proinflammatory cytokines (interleukin and tumor necrosis factor). The latter can result in tissue expansion and edema.6
MANAGEMENT
Managing TED can include treating the patient’s secondary DED symptoms, but the key is to address the root cause of orbital soft tissue inflammation. Teprotumumab-trbw (Tepezza, Horizon Therapeutics) is a monoclonal immunoglobulin that binds and blocks the signal transduction of the IGF-1R/TSH-R complex on the orbital fibroblasts to reduce orbital inflammation.7 Intravenous infusions are administered by medical professionals over the course of 5 months (one dose delivered every 3 weeks for a total of eight infusions). Each administration is typically 60 to 90 minutes in duration and performed at an infusion clinic.
Because teprotumumab-trbw can mimic insulin receptors (90% of human insulin receptors are half insulin and half IGF-1 receptors), the side effects of treatment can include hyperglycemia. Fasting blood glucose and A1-C tests are recommended before treatment begin, and the patient’s blood sugar level should be measured at each infusion with a finger stick test.8 Other side effects to monitor for include an exacerbation of preexisting inflammatory bowel disease, muscle spasms, nausea, alopecia, diarrhea, fatigue, hearing impairment, dysgeusia, headache, and dry skin.9
Managing TED involves multiple disciplines. Work closely with your local ophthalmologist, primary care physician, endocrinologist, oculoplastic surgeon, and/or rheumatologist when treating patients with teprotumumab-trbw. I typically see patients halfway through the series (at 2–3 months) to monitor them for improvement and side effects.
Be sure to educate patients with TED on the disease itself and remind them to avoid smoking and practice a healthy lifestyle. The addition of selenium and vitamin D supplements and Brazil nuts to a patient’s diet can help to control thyroid dysfunction.10
CASE REPORT
A 71-year-old White female with Graves disease presented to the clinic for a dry eye examination. She had previously undergone orbital decompression surgery in 2013, but was referred to the clinic for burning, tearing, orbital pain, and double vision (Figure). Her diplopia was being managed with prism in her eyeglasses. The patient had optic atrophy in the right eye and she reported using only artificial tears daily and gels or ointments at night.
The patient’s clinical activity score was a 3 based on scoring 1 point each for gaze-evoked orbital pain, eyelid swelling, and eyelid erythema. Dry eye testing revealed normal osmolarity (287/294), elevated levels of MMP-9, normal Schirmer (18 mm/20 mm), and normal meibography.
We started the patient on teprotumumab-trbw treatment, and a few weeks after the first two doses, she reported improvement in pain, double vision, and lid edema.
THE FIRST TO KNOW
Optometrists are often the first providers involved in diagnosing TED. If a patient with DED is not responding to conventional therapy, look for the signs and symptoms of TED. Work closely with your physician colleagues to order imaging and blood tests and consider offering teprotumumab-trbw to address the root cause of orbital inflammation.
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