What are the causes of exophthalmos (proptosis)?

Causes of Exophthalmos (Proptosis)

Thyroid eye disease (TED) is the most common cause of exophthalmos, but there are numerous other etiologies including orbital tumors, inflammatory conditions, vascular abnormalities, and infections that must be considered in the differential diagnosis. 1

Major Causes of Exophthalmos

Endocrine Disorders

• Thyroid Eye Disease (Graves' Ophthalmopathy)
  • Most common cause of bilateral exophthalmos 1
  • Characterized by tendon-sparing enlargement of extraocular muscles 1, 2
  • Can occur in hyperthyroid, hypothyroid (including Hashimoto's thyroiditis), or euthyroid states 3, 4
  • Often presents with lid retraction, restrictive strabismus, and orbital congestion 1

Neoplastic Conditions

• Orbital Tumors
  • Primary orbital tumors (e.g., cavernous hemangioma) 5
  • Lacrimal gland tumors
  • Optic nerve tumors (e.g., meningioma, glioma)
  • Metastatic tumors to the orbit
  • Lymphoma 1

Inflammatory Conditions

• Idiopathic Orbital Inflammatory Syndrome (IOIS)
• IgG4-Related Disease 1
• Sarcoidosis
• Granulomatosis with polyangiitis

Vascular Abnormalities

• Carotid-Cavernous Fistula (CCF)
  • Can present with proptosis, orbital congestion, and chemosis 1
• Orbital varix
• Arteriovenous malformations

Infectious Causes

• Orbital cellulitis
• Extension from paranasal sinusitis 6
• Orbital abscess
• Fungal infections

Other Causes

• Trauma
  • Orbital fractures with soft tissue herniation
  • Orbital hemorrhage
• Myasthenia Gravis
  • Increased incidence in patients with TED 1
• Pseudoproptosis
  • Asymmetric globe position due to contralateral enophthalmos
  • High myopia with axial elongation
  • Asymmetric facial structure 5

Diagnostic Approach

Clinical Evaluation

• Measure exophthalmos with an exophthalmometer (>21mm or >2mm asymmetry is abnormal) 2, 5
• Assess for eyelid retraction, lid lag, and restrictive strabismus
• Evaluate for signs of optic neuropathy (visual acuity, color vision, visual fields, pupillary exam) 1
• Look for fixation duress (brow elevation and eyelid retraction on attempted upward gaze) 1

Imaging Studies

• CT Scan of Orbits (First-line)

  • Superior for evaluating bony anatomy and orbital volumes
  • Shows characteristic findings in TED: tendon-sparing extraocular muscle enlargement 1, 2
  • Essential when considering orbital decompression surgery 2
  • Helps assess orbital apex crowding 1

• MRI of Orbits

  • Better soft tissue characterization
  • Superior for assessing disease activity in TED
  • Diffusion-weighted imaging helpful when lymphoma is suspected 1
  • Preferred when optic nerve or intracranial pathology is suspected 1

• Vascular Studies

  • CTA, MRA, or DSA when vascular abnormalities (e.g., carotid-cavernous fistula) are suspected 1

Laboratory Studies

• Thyroid function tests (TSH, free T4)
• Thyroid antibodies (anti-TPO, anti-thyroglobulin, TSI)
• Other tests based on clinical suspicion (e.g., ACE for sarcoidosis, IgG4 levels)

Clinical Pearls

• Bilateral exophthalmos is most commonly due to thyroid eye disease, while unilateral exophthalmos raises suspicion for orbital mass lesions 1
• The size of extraocular muscles on imaging does not directly correlate with the degree of muscle dysfunction in TED 1, 2
• Orbital radiographs are insufficient for detecting orbital pathology and have been largely replaced by CT and MRI 1, 2
• Consider myasthenia gravis in patients with TED who have atypical ocular motility findings 1

By systematically evaluating patients with exophthalmos and utilizing appropriate imaging studies, the underlying cause can be identified and appropriate management initiated to prevent vision-threatening complications.