Management of Thyroid Eye Disease

Publication Date: December 13, 2022
Last Updated: January 27, 2024

Diagnosis and assessment

Key Point 3.1

Early diagnosis of TED and simple measures to prevent TED development or progression should be pursued.
6731

Key Point 3.2

Endocrinologists managing patients with Graves’ disease should identify referral pathways that ensure patient access to TED specialty care.
6731

Key Point 3.3

Ophthalmologists are key to the management of TED and should always be involved in the care of patients with moderate-to-severe and sight-threatening TED.
6731

Key Point 4.1.1

Endocrinologists should be familiar with basic elements of a TED examination enabling assessment of both activity and severity.
6731

Key Point 4.1.2

Assessment of patients with TED should include activity, severity (with particular attention to impaired ocular motility and visual loss), trend across time, and impact on daily living.
6731

Key Point 4.2.1

The physical and psychosocial impact of TED should be assessed for each patient, as it informs treatment decisions. When formal quantification of quality of life (QOL) is deemed appropriate, Graves’ orbitopathy-quality of life (GO-QOL) is the preferred instrument.
6731

Key Point 4.4.1

Orbital imaging using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) is preferred for atypical or severe cases of TED to help determine activity and to exclude other etiologies that could be confused with TED.
6731

Key Point 4.4.2

Noncontrast CT is the preferred modality in patients with TED who are being considered for surgery.
6731

Activity and severity definitions for patients with thyroid eye disease

Having trouble viewing table?
  • Activity
    • Clinical activity score
      • The 7-item CAS is shown hereunder. Each item scores 1 point if presenta
        • Spontaneous retrobulbar pain
        • Pain on attempted up or lateral gaze
        • Redness of the eyelids
        • Redness of the conjunctiva
        • Swelling of the eyelids
        • Inflammation of the caruncle and/or plica
        • Conjunctival edema, also known as chemosis
    • Active TED
      • A CAS ≥ 3/7 usually implies active TED. A history or documentation of progression of TED based on subjective or objective worsening of vision, soft tissue inflammation, motility, or proptosis is suggestive of active TED independently of the CAS
  • Severity
    • Sight-threatening TED
      • Patients with DON and/or corneal breakdown and/or globe subluxation (Fig. 2F)
    • Moderate-to-severe TED
      • Patients without sight-threatening disease whose eye disease has sufficient impact on daily life to justify the risks of medical or surgical intervention. Patients with moderate-to-severe TED usually have any one or more of the following: lid retraction ≥2 mm, moderate or severe soft tissue involvement, proptosis ≥3 mm above normal for race and sex, or diplopia (Gorman score 2–3).
  • Mild TED
    • Patients whose features of TED have only a minor impact on daily life insufficient to justify immunosuppressive or surgical treatment. They usually have only one or more of the following: minor lid retraction (<2 mm), mild soft tissue involvement, proptosis <3 mm above normal for race and sex, transient or no diplopia, and corneal exposure responsive to lubricants.

aA 10-item CAS is also sometimes used and includes additional points for increase of at least 2 mm in proptosis, decrease of at least 8° in any duction, and decrease of visual acuity by two lines. A limitation of the 10-item CAS is that it requires an earlier assessment of the mentioned measures, which is usually unavailable on first consultation. See Bartalena et al.


Characteristics of high-risk thyroid eye disease patients

Having trouble viewing table?
  • Background
    • Male sex
    • Age >50 years
    • Tobacco smoker
  • History
    • Unstable thyroid function
    • Diabetes mellitus
    • Radioiodine in the past 6 months
    • Progressive symptoms and/or signs of TED
    • Orbital aching
    • Diplopia
  • Examination
    • Marked soft tissue inflammatory features
    • Lagophthalmos (Fig. 2A)
    • Impaired ocular motility, particularly elevation

The features outlined are associated with an increased probability of developing sight-threatening TED


Formal ophthalmic examination for thyroid eye disease based on vision, inflammation, strabismus, appearance

Having trouble viewing table?

Primary indications for imaging in suspected or confirmed thyroid eye disease

Having trouble viewing table?
  • Exclusion of other diseases in atypical TED
    • Euthyroid, without history of thyroid dysfunction
    • Clinically unilateral or markedly asymmetric
    • Absent upper lid retraction
    • Upper lid ptosis
    • Atypical strabismus
    • Severe orbital pain
  • Assessment in confirmed TED
    • Sight-threatening TED
    • Planning of orbital and in some cases strabismus surgery

Initial care and referral for specialty care

Key Point 5.1.1

Local ocular measures and lifestyle intervention should be offered to all patients with TED. Lubricants and nocturnal eye masks may be used to prevent or treat corneal exposure. Ocular occlusion and prisms may be offered to relieve diplopia. The importance of smoking reduction or cessation should be explained, and smokers offered support for this goal.
6731

Key Point 5.3.1

Input from both endocrinologists and ophthalmologists with TED expertise is recommended for optimal management in patients with moderate-to-severe and sight-threatening TED.
6731

Key Point 5.4.1

An ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate-to-severe TED, and when surgical intervention needs to be considered. Urgent referral is required when sight-threatening TED is suspected or confirmed.
6731

Key Point 6.1.1

A single course of selenium selenite 100 μg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency.
6731

Key Point 6.2.1

The clinician should regularly assess the psychosocial impact of concerns about appearance.
6731

TED Management Algorithm

Link to External Image

Therapy of moderate–severe TED

Key Point 7.1.1

Infusion therapies for TED should be administered in a facility with appropriate monitoring under the supervision of experienced staff. Awareness and surveillance for adverse side effects are recommended throughout the treatment period.
6731

Key Point 7.1.2

Clinicians should balance the demonstrated efficacy of recently introduced therapies against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness.
6731

Key Point 7.1.1.1

Intravenous glucocorticoid (IVGC) therapy is a preferred treatment for active moderate-to-severe TED when disease activity is the prominent feature in the absence of either significant proptosis (see Section 2.1 for definition) or diplopia.
6731

Key Point 7.1.1.2

Standard dosing with IVGC consists of intravenous methylprednisolone (IVMP) at cumulative doses of 4.5 g over ~3 months (0.5 g weekly × 6 weeks followed by 0.25 g weekly for an additional 6 weeks).
6731

Key Point 7.1.1.3

Poor response to IVMP at 6 weeks should prompt consideration for treatment withdrawal and evaluation of other therapies. Clinicians should be alert for worsening diplopia or onset of dysthyroid optic neuropathy (DON) that have occurred even while on IVMP therapy.
6731

Key Point 7.1.1.4

A cumulative dose of IVMP >8.0 g should be avoided.
6731

Key Point 7.1.2.1

Rituximab (RTX) and tocilizumab (TCZ) may be considered for TED inactivation in glucocorticoid (GC)-resistant patients with active moderate-to-severe TED. Teprotumumab (TEP) has not been evaluated in this setting.
6731

Key Point 7.1.3.1

TEP is a preferred therapy, if available, in patients with active moderate-to-severe TED with significant proptosis (see Section 2.1 for definition) and/or diplopia.
6731

Key Point 7.1.4.1

Evidence from randomized controlled trials (RCTs) is limited and divergent but suggests efficacy of RTX for inactivation of TED and prevention of relapses at >1 year, particularly in patients with TED of <9 months’ duration.
6731

Key Point 7.1.4.2

RTX therapy is acceptable in patients with active moderate-to-severe TED and prominent soft tissue involvement.
6731

Key Point 7.1.6.1

TCZ is an acceptable treatment for TED inactivation in GC-resistant patients with active moderate-to-severe disease.
6731

Key Point 7.2.1

Radiotherapy (RT) is a preferred treatment in patients with active moderate-to-severe TED whose principal feature is progressive diplopia.
6731

Key Point 7.2.2

RT should be used cautiously in diabetic patients to avoid possible retinopathy. It is relatively contraindicated for those younger than 35 years of age to avoid a theoretical lifetime risk of tumors developing in the radiation field.
6731

Key Point 7.3.1.1

Surgery for moderate-to-severe TED should be performed by an orbital surgeon experienced with these procedures and their complications.
6731

Key Point 7.3.1.2

Rehabilitative surgery for moderate-to-severe TED should only be performed when the disease is inactive and euthyroidism has been achieved and maintained.
6731

Key Point 7.3.2.1

The specific surgical approach should be tailored to the indication (DON, proptosis), type of orbitopathy (muscle or fat predominant congestive disease), and desired reduction in proptosis.
6731

Key Point 7.3.3.2

In patients with diplopia and inactive TED, binocular single vision in the primary position of gaze may be restored with strabismus surgery or permanent prisms ground into the spectacle lenses.
6731

Key Point 7.3.4.1

Eyelid retraction and fat prolapse are surgically corrected when TED is inactive and euthyroidism is achieved, and after surgical decompression and strabismus surgery as indicated.
6731

Therapy of sight-threatening TED

Key Point 8.1.1

Patients with DON require urgent treatment with IVGC therapy, with close monitoring of response and early (after 2 weeks) consideration for decompression surgery if baseline visual function is not restored and maintained with medical therapy.
6731

Key Point 8.2.1

RT may be considered for preventing or as an adjunct to treating DON.
6731

Key Point 8.3.1

In patients with compressive DON, orbital decompression of the deep medial wall and orbital floor should be considered to restore vision by reducing apical compression on the optic nerve.
6731

Recommendation Grading

Abbreviations

  • CT: Computed Tomography
  • DON: Dysthyroid Optic Neuropathy
  • IVGC: Intravenous Glucocorticoid
  • IVMP: Intravenous Methylprednisolone
  • QOL: Quality Of Life
  • RT: Radiotherapy
  • RTX: Rituximab
  • TCZ: Tocilizumab
  • TED: Thyroid Eye Disease
  • TEP: Teprotumumab

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Management of Thyroid Eye Disease

Authoring Organizations

Publication Month/Year

December 13, 2022

Last Updated Month/Year

January 30, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this Consensus Statement.

Target Patient Population

Nonpregnant adults (age ≥ 18 years) with TED

Target Provider Population

Endocrinologists, ophthalmologists, and other clinicians caring for adult patients with thyroid eye disease

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, optometrist, physician, physician assistant

Scope

Diagnosis, Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D013959 - Thyroid Diseases, D006111 - Graves Disease, D049970 - Graves Ophthalmopathy

Keywords

Graves' disease, hyperthyroidism, thyroid eye disease, TED

Source Citation

Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, Mombaerts I, Salvi M, Stan MN. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022 Dec 8;11(6):e220189. doi: 10.1530/ETJ-22-0189. PMID: 36479875; PMCID: PMC9727317.