What are the causes of bilateral exophthalmos?

Causes of Bilateral Exophthalmos

The most common cause of bilateral exophthalmos is thyroid eye disease (Graves' disease), accounting for approximately 80% of bilateral cases. 1

Primary Causes

1. Thyroid-Related Disorders

• Graves' disease/Thyroid Eye Disease (TED)
  • Most frequent cause (80% of bilateral cases) 2
  • Characterized by inflammation and congestion of orbital tissues 1
  • Clinical features include:
    • Soft tissue congestion with preseptal fat pad enlargement
    • Eyelid retraction
    • Restrictive extraocular myopathy (most commonly affecting inferior rectus, followed by medial rectus) 1
    • May occur with hyperthyroidism, normal thyroid function (euthyroid GO), or even hypothyroidism 3
  • Risk factors:
    • More common in women (8:1 female-to-male ratio)
    • Peak onset in fourth to fifth decade of life
    • Smoking significantly increases risk and severity
    • Radioactive iodine treatment
    • High anti-thyroid antibody titers
    • Vitamin D deficiency 1

2. Orbital Inflammatory Conditions

• Orbital inflammatory syndrome/pseudotumor
• Sarcoidosis
  • Can present with granulomatous inflammation
  • Bimodal age presentation (highest incidence between ages 20-39) 1
• Vasculitis
  • Can affect multiple vessels and organs (lungs, lymph nodes, kidneys, skin, nervous system)
  • Examples include granulomatosis with polyangiitis (formerly Wegener's) 1

3. Orbital Neoplasms

• Bilateral orbital lymphoma
  • Can coexist with Graves' disease, complicating diagnosis 4
  • May present as worsening unilateral exophthalmos in a patient with known bilateral TED
• Metastatic tumors
• Leukemic infiltrates

4. Vascular Disorders

• Carotid-cavernous fistulas (can be bilateral)
• Orbital varix
• Arteriovenous malformations

5. Other Systemic Conditions

• Graft-versus-host disease
  • Can involve multiple tissues including the orbit 1
• Stevens-Johnson syndrome/toxic epidermal necrolysis
  • Can cause severe mucocutaneous reactions affecting orbital tissues 1

Less Common Causes

• High axial myopia with strabismus fixus (Heavy Eye Syndrome)
  • Can present with exophthalmos and restrictive myopathy 1
• Histiocytosis
• Mucopolysaccharidoses
• Osteopetrosis
• Neurofibromatosis

Diagnostic Approach

Imaging

• CT scan should be the initial imaging modality for suspected bilateral exophthalmos 5

  • Excellent for evaluating bony structures and orbital walls
  • Can identify extraocular muscle enlargement typical of TED

• MRI provides superior soft tissue contrast

  • Particularly useful for evaluating optic nerve, intracranial extension, and soft tissue masses
  • Contraindicated if metallic foreign body is suspected 1

Clinical Evaluation

• Assess for signs of systemic disease (thyroid dysfunction, vasculitis, sarcoidosis)
• Evaluate for vision-threatening complications:
  • Compressive optic neuropathy
  • Exposure keratopathy
  • Elevated intraocular pressure 1

Important Clinical Considerations

• Unilateral worsening of exophthalmos in a patient with known bilateral TED should raise suspicion for other pathology, particularly lymphoma 4
• Bilateral exophthalmos with normal thyroid function tests does not rule out TED, as ophthalmopathy can precede thyroid dysfunction in up to 20% of cases 4
• Patients with bilateral exophthalmos require careful monitoring for vision-threatening complications, including corneal exposure and optic neuropathy 1, 6
• Smoking cessation is critical in patients with TED as smoking significantly worsens disease progression and reduces treatment effectiveness 1

Remember that while bilateral presentation strongly suggests thyroid eye disease, a thorough evaluation is necessary to rule out other potentially serious causes, especially when clinical features are atypical or response to treatment is poor.