What are the causes of bilateral exophthalmos?

Causes of Bilateral Exophthalmos

Thyroid eye disease (Graves' orbitopathy) is the most common cause of bilateral exophthalmos, accounting for approximately 80% of bilateral cases, while other causes include orbital inflammatory conditions, infiltrative diseases, vascular abnormalities, and neoplasms. 1, 2

Primary Causes

1. Endocrine Disorders

• Thyroid Eye Disease (Graves' Orbitopathy)

  • Most common cause of bilateral exophthalmos 2
  • Characterized by enlargement of extraocular muscles, increased orbital fat volume, and venous stasis 1
  • Typical findings include soft tissue congestion, eyelid retraction, restrictive extraocular myopathy, and potential optic neuropathy 1
  • Incidence: 16 per 100,000 per year in women and 2.9 per 100,000 per year in men 1
  • Risk factors: Female gender (8:1 female-to-male ratio), smoking, age 40-50 years, radioactive iodine treatment 1

• Hashimoto's Thyroiditis

  • Less common cause of orbitopathy (approximately 5% of thyroid-associated orbitopathy cases) 3
  • May present with similar orbital changes as Graves' disease but typically less severe

2. Inflammatory Conditions

• Orbital Inflammatory Syndrome (Idiopathic Orbital Inflammation)

  • Can present with bilateral orbital inflammation
  • Characterized by pain, redness, and swelling

• Granulomatous Diseases

  • Sarcoidosis
  • Granulomatosis with polyangiitis (formerly Wegener's)
  • IgG4-related disease

3. Infiltrative Disorders

• Amyloidosis
• Histiocytosis
• Lymphoproliferative disorders
  • Orbital lymphoma
  • Leukemic infiltration

4. Vascular Abnormalities

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

5. Neoplastic Conditions

• Metastatic disease to both orbits
• Lymphoma
• Lacrimal gland tumors (bilateral)

6. Structural Abnormalities

• High axial myopia with strabismus fixus (Heavy Eye Syndrome)
  • Can present with exophthalmos and requires MRI or CT for confirmation 1
  • Associated with exposure keratopathy requiring monitoring and treatment 1

Clinical Evaluation

Diagnostic Approach

1. History and Examination

   • Duration and progression of exophthalmos
   • Associated symptoms (diplopia, pain, vision changes)
   • Systemic symptoms (weight changes, palpitations, fatigue)
   • Measurement of proptosis using exophthalmometry

2. Laboratory Testing

   • Thyroid function tests (TSH, free T4, free T3)
   • Thyroid antibodies (TSI, TRAb, anti-TPO, anti-thyroglobulin)
   • Complete blood count
   • Inflammatory markers (ESR, CRP)

3. Imaging

   • CT scan - First-line imaging for suspected Graves' disease 4
   • MRI - Better for soft tissue evaluation and optic nerve assessment
   • Both can identify:
     • Extraocular muscle enlargement
     • Increased orbital fat
     • Lacrimal gland enlargement
     • Orbital masses
     • Bone abnormalities

Management Considerations

Acute Management

• Protect corneal integrity with lubricants, moisture chambers, or temporary tarsorrhaphy for severe exposure 5
• Monitor for signs of optic neuropathy (vision loss, color vision changes, RAPD)
• Refer to orbital specialist for vision-threatening disease 1

Definitive Treatment

• For Thyroid Eye Disease:

  • Medical management during active inflammatory phase
  • Orbital decompression for severe exophthalmos or compressive optic neuropathy 5
  • Strabismus surgery for persistent diplopia after disease stabilization 1

• For Other Causes:

  • Treatment directed at underlying condition
  • Surgical intervention for space-occupying lesions

Clinical Pearls and Pitfalls

• Pearl: While unilateral exophthalmos more commonly suggests a space-occupying lesion, bilateral exophthalmos is most often due to thyroid eye disease 2

• Pitfall: Not all patients with thyroid eye disease have abnormal thyroid function tests; some may be euthyroid at presentation

• Pearl: The presence of eyelid retraction strongly suggests thyroid eye disease as the cause of exophthalmos

• Pitfall: Failing to distinguish pseudoenophthalmos (as seen in Horner syndrome) from true exophthalmos can lead to unnecessary workup 6

• Pearl: In thyroid eye disease, the inferior rectus muscle is most commonly affected, followed by the medial rectus muscle 1