What is the workup for unilateral ptosis?

Diagnostic Workup for Unilateral Ptosis

The diagnostic workup for unilateral ptosis requires a systematic approach focused on identifying the underlying cause, with particular attention to pupillary involvement and associated neurological symptoms to rule out potentially life-threatening conditions.

Initial Assessment

• A detailed medical and ocular history should focus on onset (sudden vs. gradual), duration, variability throughout the day, and associated symptoms such as diplopia, ophthalmoplegia, or other neurological deficits 1, 2
• Comprehensive eye examination should include:
  • Measurement of palpebral fissure height, marginal reflex distance, upper eyelid crease, and levator function 3
  • Assessment for ptosis severity (minimal: 1-2mm, moderate: 3-4mm, severe: >4mm) 4
  • Evaluation for anisocoria and pupillary responses in both bright and dim illumination 1
  • Complete sensorimotor examination to detect strabismus 1
  • Fundus examination to check for papilledema or optic atrophy 1

Diagnostic Algorithm Based on Clinical Findings

For Isolated Ptosis Without Other Neurological Symptoms

• Unilateral ptosis alone typically does not warrant advanced neuroimaging as first-line investigation 2
• Consider aponeurotic, mechanical, or myogenic causes 4, 3
• For variable ptosis that worsens with fatigue:
  • Perform ice test (application of ice pack over closed eyes for 2 minutes) - improvement suggests myasthenia gravis 1
  • Consider rest test as an alternative diagnostic approach 1

For Ptosis with Pupillary Involvement (Third Nerve Palsy)

• Pupil-involving third nerve palsy requires urgent evaluation for compressive lesions, especially posterior communicating artery aneurysm 1
• Immediate neuroimaging is recommended:
  • MRI with gadolinium and magnetic resonance angiography (MRA) or computed tomography angiography (CTA) 1
  • If high suspicion for aneurysm despite normal initial imaging, consider catheter angiogram 1

For Ptosis with Associated Findings

• If accompanied by proptosis or suspected orbital mass: MRI orbits without and with contrast 2
• If accompanied by contralateral superior rectus weakness: Consider nuclear third nerve lesion 1
• If accompanied by sixth nerve and fourth nerve paralysis: Consider cavernous sinus pathology 1
• If variable ptosis with variable strabismus that changes with fatigue:
  • Test for myasthenia gravis with:
    • Acetylcholine receptor antibody (AChR-Ab) testing (note: ~50% of ocular myasthenia cases are seronegative) 1
    • Consider muscle-specific kinase (anti-MuSK) and lipoprotein-related protein 4 (LRP4) antibody testing in seronegative cases 1
    • Single-fiber electromyography (>90% sensitive for ocular myasthenia) 1

Special Considerations

• In children with unilateral ptosis, evaluation should focus on:

  • Ruling out pseudoptosis 5
  • Assessing for amblyopia risk 5, 6
  • Evaluating for Horner syndrome (miosis, anhidrosis) or third nerve palsy 5

• For ptosis with associated neurological symptoms (ataxia, tremor, hemiplegia):

  • Consider brainstem pathology affecting the third nerve nucleus or fascicle 1
  • MRI head and orbits without and with contrast is recommended 2

• For ptosis with slow progression and no pupillary involvement:

  • Consider chronic progressive external ophthalmoplegia or myasthenia gravis 1, 3
  • Evaluate for systemic myopathies if other muscle weakness is present 4, 3

Pitfalls to Avoid

• Failing to recognize pupil-involving third nerve palsy as a potential neurosurgical emergency 1
• Assuming microvascular etiology in pupil-sparing third nerve palsy with partial extraocular muscle involvement or incomplete ptosis - these cases still require neuroimaging 1
• Missing myasthenia gravis due to variable presentation and potential seronegativity - consider ice test and single-fiber EMG even with negative antibody testing 1
• Overlooking iatrogenic causes such as prior Botulinum toxin injection in the differential diagnosis 7