What is the differential diagnosis for a patient presenting with right eye ptosis?

Differential Diagnosis of Right Eye Ptosis

The differential diagnosis for unilateral ptosis must be systematically approached by first ruling out life-threatening neurogenic causes (third nerve palsy with aneurysm, Horner syndrome from carotid dissection), then evaluating for myasthenia gravis, followed by consideration of mechanical, aponeurotic, and myogenic etiologies. 1, 2

Immediate Life-Threatening Causes to Rule Out

Third Nerve Palsy with Pupillary Involvement

• Dilated pupil with ptosis represents a neurosurgical emergency requiring urgent neuroimaging (MRI with gadolinium and MR angiography or CT angiography) to exclude posterior communicating artery aneurysm 1, 2, 3
• Complete ptosis with ophthalmoplegia (inability to move eye up, down, or medially) and mydriasis is the classic presentation 3, 4

Horner Syndrome

• Mild ptosis (1-2 mm) with miosis (small pupil) and anhidrosis suggests disruption of the oculosympathetic pathway 1, 2
• Internal carotid artery dissection must be excluded until proven otherwise in acute-onset Horner syndrome 4

Neuromuscular Junction Disease

Myasthenia Gravis

• Variable and fatigable ptosis that worsens with prolonged upward gaze or at end of day is pathognomonic 1, 2, 3
• Ice pack test: Apply ice over closed eye for 2-5 minutes; reduction of ptosis by ≥2 mm is highly specific 1, 3
• May present with fluctuating diplopia, Cogan lid-twitch sign, or slow saccades 3
• Can be unilateral initially before becoming bilateral 4, 5

Neurogenic Causes (Pupil-Sparing)

Microvascular Third Nerve Palsy

• Complete ptosis with complete ophthalmoplegia but normal pupil indicates pupil-sparing third nerve palsy 1
• Almost always secondary to diabetes, hypertension, or hyperlipidemia in this presentation 1
• However, do not assume benign microvascular disease without thorough evaluation if ophthalmoplegia is complete—compressive lesions can present this way 3

Nuclear or Fascicular Lesions

• Brainstem pathology (infarction, demyelination, tumor) affecting third nerve nucleus or fascicle 2, 5
• Look for associated neurological symptoms: ataxia, tremor, hemiplegia, contralateral superior rectus weakness 1, 2

Mechanical Causes

Giant Papillary Conjunctivitis

• Papillary hypertrophy of superior tarsal conjunctiva with mucoid discharge 6
• In severe cases: lid swelling and ptosis 6
• Associated with contact lens wear, exposed sutures, or ocular prosthesis 6

Floppy Eyelid Syndrome

• Upper eyelid easily everted with horizontal lid laxity 6, 2
• Diffuse papillary reaction of superior tarsal conjunctiva 6
• Associated with obesity, sleep apnea, and thyroid disease 6

Giant Fornix Syndrome

• Enlarged superior fornix with coagulum of mucopurulent material causing ptosis 6
• Typically in elderly women (eighth to tenth decade) 6

Orbital Mass or Inflammatory Disease

• Unilateral ptosis with proptosis suggests orbital mass, thyroid eye disease, IgG4-related disease, or idiopathic orbital inflammatory syndrome 6, 2
• Requires MRI orbits without and with contrast for characterization 6

Aponeurotic Ptosis

Levator Aponeurosis Dehiscence or Disinsertion

• Most common cause of acquired ptosis in adults 7, 8
• Good levator function (>10 mm) with high or absent eyelid crease 7
• Associated with aging, chronic eye rubbing, contact lens wear, or prior ocular surgery 7, 8

Myogenic Causes

Chronic Progressive External Ophthalmoplegia (CPEO)

• Bilateral symmetric ptosis and ophthalmoplegia without diplopia (due to symmetry) 5
• Superior rectus muscle preferentially involved with fat replacement on imaging 5
• Hereditary mitochondrial or nuclear myopathy 5

Oculopharyngeal Muscular Dystrophy (OPMD)

• Progressive ptosis with dysphagia, typically onset after age 40 5
• Superior rectus involvement pattern similar to CPEO 5

Critical Examination Components

Pupillary Assessment

• Examine pupils in both bright and dim lighting for anisocoria 1, 2
• Dilated pupil = third nerve palsy emergency 1, 2
• Constricted pupil = Horner syndrome 1, 2

Extraocular Motility

• Complete sensorimotor examination to detect ophthalmoplegia and strabismus 1, 2
• Variable strabismus suggests myasthenia 3

Levator Function

• Measure excursion of upper lid from downgaze to upgaze (normal >15 mm) 7
• Good function (>10 mm) suggests aponeurotic cause 7
• Poor function (<5 mm) suggests neurogenic or myogenic cause 7

Fundus Examination

• Evaluate for papilledema or optic atrophy to rule out life-threatening intracranial pathology 1, 2

Imaging and Laboratory Workup Algorithm

When to Image Urgently

• Ptosis with dilated pupil: immediate MRI/MRA or CTA 1, 2, 3
• Ptosis with ophthalmoplegia, proptosis, or other neurological deficits: MRI head and orbits with contrast 1, 2

When Laboratory Studies Are Indicated

• If neuroimaging normal: serological tests for syphilis and Lyme disease 1, 3
• Consider lumbar puncture with glucose, protein, cell count, cytology, and culture 1, 3
• For suspected myasthenia: acetylcholine receptor antibodies (80-88% sensitivity), anti-MuSK antibodies if seronegative, and single-fiber EMG (>90% sensitivity) 3
• Chest CT to screen for thymoma in confirmed myasthenia 3

When Imaging Is Not Initially Required

• Isolated unilateral ptosis without pupillary abnormalities, ophthalmoplegia, or neurological symptoms typically does not warrant urgent neuroimaging 2
• Aponeurotic ptosis with good levator function and normal examination can be managed clinically 7

Common Pitfalls to Avoid

• Failing to recognize pupil-involving third nerve palsy as a neurosurgical emergency can result in catastrophic outcomes from ruptured aneurysm 2, 3
• Assuming all pupil-sparing third nerve palsies are benign microvascular without proper evaluation can miss compressive lesions 3
• Missing myasthenia gravis due to variable presentation—consider ice test and single-fiber EMG even with negative antibodies 2, 3
• Overlooking Horner syndrome from carotid dissection by not examining for miosis and anhidrosis 4