What are the potential causes and management approaches for a patient presenting with unilateral ptosis without ophthalmoplegia?

Causes of Unilateral Ptosis Without Ophthalmoplegia

Unilateral ptosis without ophthalmoplegia most commonly results from aponeurotic (involutional), myogenic, mechanical, or Horner syndrome etiologies, with the diagnostic approach prioritizing identification of pupillary abnormalities and variable/fatigable characteristics to rule out life-threatening causes before considering benign etiologies.

Immediate Assessment: Rule Out Emergent Causes

Pupillary Examination (Critical First Step)

• Evaluate for anisocoria in both bright and dim illumination to identify Horner syndrome, which presents with mild ptosis, miosis, and anhidrosis from disruption of the oculosympathetic pathway 1
• Check for normal pupillary responses to exclude third nerve palsy with pupillary involvement, though this would typically present with ophthalmoplegia 2, 1
• Perform fundus examination to rule out papilledema or optic atrophy that could indicate life-threatening intracranial pathology 2, 1

Variability and Fatigability Testing

• Apply ice test: place ice pack over closed eyes for 2 minutes; reduction of ptosis by approximately 2 mm is highly specific for myasthenia gravis 1
• Assess whether ptosis worsens with prolonged upward gaze or throughout the day, suggesting myasthenia gravis 2, 1
• Even with isolated ptosis, myasthenia can present variably and may be seronegative, requiring ice test and potentially single-fiber EMG 2, 1

Primary Etiologies of Isolated Unilateral Ptosis

Aponeurotic (Involutional) Ptosis

• Most common cause in adults, resulting from dehiscence or disinsertion of the levator aponeurosis 3
• Typically presents with good levator function (>10 mm) despite significant ptosis 3
• Associated with aging, chronic eye rubbing, contact lens wear, or previous ocular surgery 3

Mechanical Ptosis

• Perform detailed slit-lamp examination for suspected mechanical causes including eyelid masses, chalazion, dermatochalasis, or scarring 2
• Evaluate for floppy eyelid syndrome, which presents with upper eyelid edema and an upper eyelid that is easily everted 2
• Consider orbital masses if accompanied by proptosis, requiring MRI orbits without and with contrast 2, 4

Horner Syndrome

• Presents with mild ptosis (1-2 mm), miosis, and anhidrosis on the affected side 1
• Results from disruption of the oculosympathetic pathway at preganglionic, postganglionic, or central locations 1
• Requires investigation for underlying causes including carotid dissection, apical lung tumor, or brainstem lesions 1

Myogenic Causes

• Myasthenia gravis can present with isolated variable ptosis before developing ophthalmoplegia 2, 1
• Congenital ptosis from levator muscle dysgenesis typically presents at birth but may be unilateral 3, 5
• Chronic progressive external ophthalmoplegia rarely presents without ptosis, making isolated ptosis an atypical presentation 6

Neuroimaging Indications

When Advanced Imaging Is NOT Required

• Unilateral ptosis alone without other neurological symptoms typically does not warrant advanced neuroimaging as first-line investigation 2
• Isolated aponeurotic or mechanical ptosis with clear etiology on examination 2

When MRI Is Indicated

• Ptosis accompanied by proptosis or suspected orbital mass: MRI orbits without and with contrast 2, 4
• Associated neurological symptoms (ataxia, tremor, hemiplegia, other cranial nerve deficits): MRI head and orbits with contrast 2, 1
• Horner syndrome requiring evaluation of the oculosympathetic pathway 1

Laboratory and Additional Testing

For Myasthenia Gravis Suspicion

• Ice test as initial diagnostic maneuver (highly specific if positive) 1
• Acetylcholine receptor antibodies, though may be negative in seronegative myasthenia 2, 1
• Single-fiber electromyography if antibodies negative but clinical suspicion remains high 2, 1

For Infectious or Inflammatory Causes

• If neuroimaging is normal and clinical suspicion remains, obtain serological tests for syphilis and Lyme disease 1
• Consider lumbar puncture with glucose, protein, cell count, cytology, and culture for atypical presentations 1

Critical Pitfalls to Avoid

• Missing myasthenia gravis due to variable presentation: Always perform ice test even with isolated ptosis, as seronegative cases exist 2, 1
• Assuming benign etiology without proper pupillary examination: Horner syndrome requires investigation for serious underlying causes including carotid dissection 1
• Starting corticosteroids without adequate workup: This can mask diagnoses and worsen outcomes in inflammatory conditions 4
• Overlooking contralateral lid retraction: Approximately 10-20% of patients with unilateral ptosis have induced retraction on the contralateral lid (Hering's law), which may unmask after surgical correction 7

Rare Presentations to Consider

• Guillain-Barré syndrome can rarely present with isolated unilateral ptosis without ophthalmoplegia, though this would typically progress to involve other cranial nerves 8
• Isolated cranial nerve III palsy affecting only the levator palpebrae without pupillary involvement or ophthalmoplegia is extremely rare but possible 9