Treatment Options for Thyroid Eye Disease

Educational Objectives

The goal of this program is to improve the management of thyroid eye disease. After hearing and assimilating this program, the clinician will be better able to:

1. Cite factors that affect the clinical course of thyroid eye disease.
2. Develop treatment strategies for thyroid eye disease based on duration of the active phase and rate of disease progression.

Summary

Natural history: completely self-limited, with the active phase ending at 6 to 12 mo for people who do not smoke and 2 to 3 yr for people who smoke; lifetime risk for relapse is ≈15%, and the second relapse in untreated events usually occurs ≈10 yr later; predictors of outcomes are relatively poor, and the disease has discrete age-related phenotypes; because the active phase is short, treatment late in the course is unlikely to have a strong effect on the natural history

Phenotypes: majority (≈80%) of cases are mild and do not require treatment; progression can occur slowly over a 6-to-9-mo period or quickly over a 4-wk period; spontaneous improvement is common; patients with mild disease tend to be younger, female sex, and have slow disease progression; aggressive treatment is warranted for patients >40 yr of age, male sex, smokers, and those who have sleep apnea; other conditions associated with more severe eye disease include diabetes mellitus, dermopathy, rapid progression of thyroid eye disease, and early impairment in motility

Patient evaluation: estimate the amount of time remaining in a patient’s active phase (eg, treatment is less likely to have an effect for patients who present at 10 mo vs those who present at 1 mo); consider clinical phenotype, age, and potential side effects of treatment

Disease modulation vs modification: corticosteroids are the prototypical disease-modulating treatment; by contrast, disease-modifying treatment prevents disease progression; these treatments should be considered in terms of whether they can reduce the need for surgery; disease modulators suppress the disease (returns after the drug is discontinued) and do not change the long-term outcomes; disease-modifying treatment influences the disease course such that the irreversible sequalae are fewer

Clinical Activity Score (CAS): measure of the predicted response to steroid treatment; measures of inflammation include pain in the eye socket, pain with eye movement, lid edema, redness of the eyelids, conjunctival hyperemia, chemosis, swollen caruncle, and progression; not a direct measure of disease activity

Gorman score for diplopia: categorizes patients as having no, intermittent, with-gaze-only, or constant diplopia; however, increasingly symmetric involvement of the rectus muscles could reduce diplopia, even though the disease is worsening; head position can also improve diplopia from constant to with-gaze-only, but disease activity is not improving

Treatment

Teprotumumab (TEP): Douglas et al (2020) found greater improvements in CAS and proptosis with TEP compared with placebo; most patients in the TEP group had improvement in proptosis (vs≈50% in the placebo group); ≈40% of patients had regression of proptosis response ≤1 yr after TEP; rate of diplopia recurrence was ≈30% at 1 yr; number of surgeries required was similar between groups; adverse events include diabetes (new-onset or worsened), muscle spasms, and hearing loss

TEP vs other treatment options for short-duration disease (3-6 mo): efficacy — selenium may improve lid retraction in mild disease; reduction in CAS of ≈3 points was observed with TEP, which is similar to that with intravenous (IV) methylprednisolone (MP) and rituximab (eg, Riabni, Rituxan, Truxima), respectively; reduction in proptosis was 1 to 1.5 mm greater with TEP compared with IV MP; improvement in diplopia (based on improvement in Gorman score of >1 grade) was 70% with MP and TEP, respectively, and 50% with rituximab; improvement in quality of life is similar; reactivation rate was 30% with IV MP, 30% to 50% with TEP, and 0% with rituximab; rituximab and radiotherapy are disease-modifying treatments, whereas MP and TEP are disease modulators; safety — death from progressive multifocal leukoencephalopathy occurs in 1 in 25,000 people who take rituximab; aseptic necrosis is the primary safety concern with IV MP; cost — TEP costs ≈$500,000 per treatment, whereas other options are considerably less expensive

Approach for treatment decisions: treat based on risk assessment; disease modulation is effective for patients close to the end of the disease course, whereas disease modification is more likely to be necessary (if needed at all) for a patient at the beginning of the disease course

Low-risk disease: patients are often younger and slower to progress, and a nonsteroidal anti-inflammatory drug (eg, diclofenac) with cold compresses, eye lubrication, and eyelid elevation may be adequate to reduce discomfort; encourage smoking cessation and treatment for sleep apnea (if applicable); high thyroid-stimulating hormone drives the disease in ≥10% of patients; therefore, modulating levels with selenium supplementation may be helpful

Moderate-risk disease: patients have rapid progression, early diplopia, and congestion; treatment with steroids along with radiotherapy for disease modification are recommended; both treatments need 3 mo to take effect; TEP may be considered

High-risk disease: patients have compressive optic neuropathy; a steroid trial is given; if measurable improvement in the compressive optic neuropathy is seen after 2 wk, combination of steroids and radiotherapy is given; if no improvement is seen after steroid trial, optic nerve decompression is recommended; radiotherapy is given if the patient is at the beginning of the disease course

Readings

Eckstein A, Quadbeck B, Mueller G, et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol. 2003 Jun;87(6):773-6. doi: 10.1136/bjo.87.6.773. PMID: 12770979; PMCID: PMC1771717; Hall AJH, Topliss DJ. Medical and surgical treatment of thyroid eye disease. Intern Med J. 2022;52(1):14-20. doi:10.1111/imj.15067; Shah SS, Patel BC. Thyroid eye disease. StatPearls Publishing. 2023 May 22. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582134/; Verity DH, Rose GE. Acute thyroid eye disease (TED): principles of medical and surgical management. Eye (Lond). 2013 Mar;27(3):308-19. doi: 10.1038/eye.2012.284. Epub 2013 Feb 15. PMID: 23412559; PMCID: PMC3597885.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Kazim's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Kazim was recorded at the 22nd Annual Downeast Ophthalmology Symposium, held September 29 to October 1, 2023, in Bar Harbor, ME, and presented by the Maine Society of Eye Physicians and Surgeons. For information on future CME activities from this presenter, please visit www.maineeyemds.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

OP620801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.