Treatment of Malignant Exophthalmos or Graves' Induced Orbitopathy
Both teprotumumab (Tepezza) and intravenous corticosteroids are effective treatments for Graves' orbitopathy, with teprotumumab showing superior efficacy in reducing proptosis and improving clinical outcomes in active disease.
First-Line Treatment Options
Teprotumumab (Tepezza)
- Teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, reduces proptosis and clinical activity score in many patients with active Thyroid Eye Disease (TED) 1
- Demonstrates significant reduction in extraocular muscle size and orbital fat volume 1
- Improves subjective diplopia scores in both active and chronic TED 1
- Reduces the need for subsequent strabismus surgery 1
- Considered most efficacious in terms of overall response rate and proptosis reduction compared to other treatments 2
Intravenous Corticosteroids
- High-dose pulse steroid infusion (IV methylprednisolone) is effective for severe proptosis or compressive optic neuropathy 1
- More effective and better tolerated than oral glucocorticoids 3
- Optimal regimen is a cumulative dose of 4.5g of IV methylprednisolone in 12 weekly infusions 4
- Higher cumulative doses (not exceeding 8g) can be used as monotherapy in more severe cases 4
- Rapidly reduces clinical activity score within the first week of therapy 5
Treatment Considerations
Disease Severity Assessment
- Treatment selection should be based on clinical activity and severity of Graves' orbitopathy 4
- For mild and active GO: control of risk factors, local treatments, and selenium supplementation (in selenium-deficient areas) 4
- For moderate-to-severe and active GO: IV glucocorticoids or teprotumumab 4
- For sight-threatening GO: high-dose IV methylprednisolone and urgent orbital decompression if unresponsive 4
Teprotumumab Limitations
- Not universally available 1
- Associated with adverse reactions including hyperglycemia, muscle spasms, nausea, alopecia, diarrhea, tinnitus, hearing impairment, dysgeusia, headache, weight loss, nail disorders, and menstrual disorders 1
- Relatively contraindicated in patients with inflammatory bowel disease 1
- Absolutely contraindicated in pregnancy 1
- Should be used with caution in patients with pre-existing hearing loss 1
IV Corticosteroid Considerations
- Produces favorable effects in most patients (87.8% response rate) 3
- Better tolerated than oral corticosteroids with fewer side effects (56.1% vs 85.4%) 3
- Can be combined with mycophenolate sodium for enhanced efficacy 4
- Rare but serious adverse events can occur, including hepatitis 3
Other Treatment Options
Second-Line Treatments
- Orbital radiotherapy combined with oral or IV glucocorticoids 1, 4
- Rituximab 4, 2
- Tocilizumab 4
- Oral prednisone/prednisolone combined with either cyclosporine or azathioprine 4
Supportive Measures
- Ocular lubricants to combat exposure related to eyelid retraction and proptosis 1
- Punctal plugs can be useful 1
- Smoking cessation counseling 1
- Selenium supplementation in patients with selenium deficiency 1
Treatment Algorithm
For active moderate-to-severe Graves' orbitopathy:
For sight-threatening Graves' orbitopathy:
For mild active Graves' orbitopathy:
- Control of risk factors, local treatments, selenium supplementation 4
Important Considerations
- Antithyroid drugs alone do not effectively treat the orbitopathy as exophthalmos is due to antibodies, not high T3/T4 levels 4
- Thyroidectomy alone does not resolve established orbitopathy 4
- Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations 4
- Early referral to specialized centers is fundamental for most patients with GO 4