What is the clinical management and treatment of thyroid eye disease?

Treatment of Thyroid Eye Disease: Clinical Management

Thyroid eye disease requires systematic assessment of disease activity and severity to guide treatment, with systemic corticosteroids as first-line therapy for moderate-to-severe active disease, teprotumumab for active disease with proptosis reduction, and surgical interventions reserved for inactive disease or vision-threatening complications. 1, 2, 3

Disease Assessment and Classification

Activity and Severity Grading

• Use the Clinical Activity Score (CAS) to determine disease activity, with scores ≥3 indicating active inflammation and scores ≥5 with documented symptoms demonstrating active moderate-to-severe disease requiring medical intervention 1
• Apply the NOSPECS classification system to grade severity: N (no signs), O (only signs), S (soft tissue involvement), P (proptosis), E (extraocular muscle involvement), C (corneal involvement), S (sight loss) 2
• Very severe disease is defined by compressive optic neuropathy or severe exposure keratopathy threatening vision, requiring urgent orbital decompression 1

Baseline Evaluation Requirements

• Measure proptosis by exophthalmometry to establish baseline 1
• Screen for optic neuropathy with visual acuity, color vision, visual fields, pupillary examination, and fundus examination 1
• Assess diplopia using standardized grading 1
• Document extraocular muscle restriction, particularly inferior rectus (most commonly affected) and medial rectus 1
• Consider orbital imaging to evaluate extraocular muscle size and orbital fat volume 1

Risk Factor Modification

Essential Interventions

• Smoking cessation is mandatory, as smoking significantly increases both risk and severity of thyroid eye disease 1, 3
• Achieve and maintain euthyroid status through coordination with endocrinology 2, 3
• Evaluate and correct vitamin D deficiency, as low serum vitamin D is associated with increased disease risk 1

Treatment Algorithm by Disease Activity and Severity

Mild Disease (CAS <3, No Vision Threat)

• Observation with symptomatic management is appropriate 2
• Consider oral selenium supplementation 2
• Provide artificial tears for ocular surface protection 2
• Monitor thyroid function and disease progression 2

Moderate-to-Severe Active Disease (CAS ≥3-5)

First-Line Therapy

• High-dose intravenous methylprednisolone is the first-line treatment for moderate-to-severe active disease 2, 3
• Systemic corticosteroids remain the most commonly used and established treatment 4, 3

Steroid-Sparing and Combination Agents

• Add mycophenolate sodium to prevent deterioration after steroid cessation, as antiproliferative agents provide substantial benefit in maintaining disease control 5
• Methotrexate is useful as steroid-sparing medication and in steroid-resistant or intolerant patients 6
• Cyclosporine, azathioprine, or mycophenolate in combination with steroids may achieve stable long-term results 4, 6

Biologic Therapies

• Teprotumumab (anti-IGF-1R) substantially reduces proptosis and CAS in patients with active disease and should be considered for patients with CAS ≥5 and documented symptoms 1, 5
• Rituximab (anti-CD20) reduces inflammation and may be effective in active disease 5, 6
• Tocilizumab (anti-IL-6) appears very effective as second-line therapy after steroid failure, potentially benefiting both inflammation and proptosis 5, 6
• Infliximab might be useful in severe disease with optic nerve compression resistant to steroids and decompression 6

Vision-Threatening Disease (Optic Neuropathy or Severe Exposure)

Urgent Management

• High-dose intravenous methylprednisolone with early tarsorrhaphy and urgent orbital decompression for active vision-threatening disease 2, 3
• Infliximab may be considered for optic nerve compression resistant to steroids and decompression 6
• Multimodality approach often required, combining medical and surgical interventions 3

Orbital Radiotherapy

• Consider orbital radiotherapy primarily for extraocular muscle dysfunction in active disease 4, 3
• Benefits appear limited to improvement of extraocular muscle dysfunction rather than proptosis or soft tissue changes 4
• Often used in combination with corticosteroids rather than as monotherapy 3

Surgical Management for Inactive Disease

Timing and Sequence

• Surgical interventions should be performed only after disease has become inactive (CAS <3 for at least 6 months) 2
• Follow the established surgical sequence: orbital decompression first, then strabismus surgery, then eyelid surgery 2

Specific Procedures

• Orbital decompression for persistent proptosis, exposure keratopathy, or compressive optic neuropathy in inactive disease 2, 3
• Strabismus surgery can restore binocular vision in primary gaze and reading position for the 30-50% of patients with restrictive myopathy 1
• Eyelid surgery for persistent retraction after disease stabilization 2

Special Considerations and Monitoring

Teprotumumab-Specific Precautions

• Assess for pre-existing hearing loss before initiating teprotumumab and counsel patients about hearing risk, as hearing changes may be permanent in rare cases 1
• Establish baseline audiometry and monitor throughout treatment 1
• Document baseline CAS, proptosis, and diplopia to track treatment response 1

Retreatment Considerations

• Prior positive response to teprotumumab suggests high likelihood of benefit with retreatment 1
• Ensure thyroid function tests are controlled before retreating 1
• Re-establish baseline measurements before second course 1

Alternative Options if Inadequate Response

• Consider orbital decompression, high-dose steroids, or radiation treatment if inadequate response to medical therapy 1
• Strabismus surgery may be needed for persistent diplopia despite medical management 1

Multidisciplinary Coordination

Systematic assessment and management by both endocrinologist and ophthalmologist is essential to achieve and maintain euthyroidism and properly sequence treatments according to disease activity and severity 2