When there are several ocular manifestations associated with thyroid eye disease (TED), how does one know the right time to treat?

TED is a progressive, complex autoimmune disease that affects multiple components of the orbit, such as the extraocular muscles and orbital adipose tissue, where there is a poor response to traditional treatments.¹ (See “Understanding the TED Diagnosis,” Optometric Management May 2022, bit.ly/OMTEDMay22 ). Because of the disease’s multiple clinical presentations, such as ocular surface disease, diplopia, etc., treatment of TED may get delayed in favor of treating these individual conditions first. With such delays, TED may progress, which can reduce the effectiveness of therapies. Understanding the pathogenesis and overall disease process, described below, and the introduction of a new therapy have improved the approach for treating TED.

According to Rundle’s curve, which illustrates the natural course of the disease, two different phases of TED play a large role in treatment (see Figure 1).² The active phase is where most clinical manifestations arise, due to inflammation and can last one to-three years.³ Initiating therapy earlier is critical to help lessen the severity of signs and symptoms. During the inactive phase, patients are at a higher risk of developing fibrosis. Though the active phase can be a self-limiting process, treating patients in this phase can help prevent worse outcomes.²

Note that smoking, the greatest risk factor for TED,⁴ increases the active phase, possibly by an extra one to two years on Rundle’s curve.

Treating TED can require multiple professions: eye care, primary care, endocrinology, or internal medicine providers.²

CONSERVATIVE AND MEDICAL TREATMENT

Treatment of TED has focused primarily on its inflammation and symptoms, but never on the pathogenesis. To help mitigate the most common sign of TED, botulinum toxin injection can be used to relax the eyelid muscles.⁵ Treatments, such as frequent topical lubrication, contact lenses, cyclosporine, corticosteroids, amniotic membranes, and autologous serum can be used in severe cases of ocular surface disease.

Monocular occlusion, Fresnel prism, and ground in prism can be prescribed to help with diplopia.¹ Vitamin D and selenium supplementation are thought to aid in reducing TED progression.^3,5,6 In patients who have moderate-to-severe TED, short-term treatment using oral and intravenous corticosteroids have been beneficial in reducing inflammation.^1,2 There is conflicting evidence on the impact of steroid-sparing biologic agents, such as rituximab or immunosuppressants.^1,2

SURGICAL REHABILITATION AND NEWER TECHNOLOGIES

In advanced cases where there is compressive optic neuropathy, intravenous corticosteroids are first initiated, followed by orbital decompression. Surgical intervention is suggested in patients who have moderate-to-severe inactive disease. It is recommended that orbital decompression be the first surgical treatment followed by extraocular muscle surgery, and then eyelid procedures if indicated.⁵

In January 2020, the FDA approved the infusion Tepezza (teprotumumab, Horizon Therapeutics) for the treatment of TED.⁷ This antigen-specific therapy has been found to halt disease progression, reduce in-flammation, improve proptosis, reduce diplopia, and increase quality of life in patients who have moderate-to-severe, active TED.⁸

There are no contraindications with teprotumumab.⁹ However, there are a few adverse effects, so caution should be taken in those who have had previous infusion reactions, preexisting inflammatory bowel disease, pregnancy, heart disease, emphysema or diabetes.^2,7 Side effects can include muscle spasm, alopecia, diarrhea, fatigue, nausea, dry skin, headache, hearing impairment, dysgeusia, hyperglycemia, and menstrual disorders.^9,10 The earlier this treatment can be initiated, the more successful the outcome. This new treatment can be considered as a first line therapy, especially in the active phase.³

The next installment of “Thyroid Eye Disease,” scheduled for October OM, will discuss pearls for practice management and patient education. OM

REFERENCES

1. Weiler, DL. Thyroid eye disease: a review. Clin Exp Optom. 2017: 20-25.doi:10.1111/cxo.12472.
2. Patel A, Yang H, Douglas RS. Douglas. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019 Dec;208:281-288. doi: 10.1016/j.ajo.2019.07.021.
3. Wang W, Patel A, Douglas RS. Thyroid Eye Disease: How A Novel Therapy May Change the Treatment Paradigm. Ther Clin Risk Manag. 2019; 15: 1305–1318. Published online 2019 Nov 11. doi: 10.2147/TCRM.S193018.
4. Cawood TJ, Moriarty P, O’Farrelly C, O’Shea D. Smoking and Thyroid-Associated Ophthalmology: A Novel Explanation of the Biological Link. J Clin Endocrinol Metab. 2007; 01:59-64. doi.org/10.1210/jc.2006-1824.
5. Marcocci C, Marino M. Treatment of mild, moderate-to-severe and very severe Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metabol. 2012; 26: 325–337.
6. Sadaka A, Nguyen K, Amina M, Rosbel R, Berry S, Lee A. Vitamin D and Selenium in a Thyroid Eye Disease Population in Texas. Neuro-ophthalmology (Aeolus Press) 2019 43 (5) 291-294. 25. doi:10.1080/01658107.2019.1566382.
7. FDA Approves first treatment for thyroid eye disease. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-thyroid-eye-disease . Published January 21, 2020. Accessed May 24, 2022.
8. Teo MH, Smith TJ, Joseph SS. Efficacy and Safety of Teprotumumab in Thyroid Eye Disease. Ther Clin Risk Manag. 2021; 17: 1219–1230. Published online 2019 Nov 11. doi: 10.2147/TCRM.S193018.
9. FDA.Tepezza Prescribing Information. www.accessdata.fda.gov/drugsatfda_docs/label/2020/761143s000lbl.pdf . Published January 20, 2020. Accessed May 1,2022.
10. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017 376(18):1748-1761. doi: 10.1056/NEJMoa1614949.

Dr. Huegel graduated from the Southern College of Optometry, and is currently completing her residency in ocular disease and anterior segment at Associated Eye Care in Stillwater, Minn.