What is the differential diagnosis for diplopia (double vision)?

Differential Diagnosis of Diplopia

Diplopia requires immediate anatomical localization to distinguish between monocular (optical/ocular pathology) and binocular (neurologic/muscular) causes, with binocular diplopia representing the majority of neurologically significant cases requiring systematic evaluation of the extraocular muscles, cranial nerves III/IV/VI, neuromuscular junction, and central pathways. 1

Initial Classification: Monocular vs. Binocular

Monocular Diplopia

• Persists when the unaffected eye is closed and typically disappears with pinhole testing 2
• Primary causes include:
  • Refractive errors and optical media abnormalities (cataracts, corneal irregularities) 2, 3
  • Dry eye disease 3
  • Spectacle-induced aberrations 2
  • Rarely: papilledema in idiopathic intracranial hypertension 3
• Key diagnostic feature: Non-organic monocular diplopia shows no change in image position with head tilt 2

Binocular Diplopia

• Disappears when either eye is closed 2
• Results from misalignment of visual axes preventing fusion 2
• Represents the primary concern for neurologic pathology 4

Anatomical Localization for Binocular Diplopia

Cranial Nerve Palsies

Sixth Nerve (Abducens) Palsy - Most common cranial neuropathy

• Horizontal diplopia worse at distance and in lateral gaze toward affected side 1
• Vasculopathic causes (diabetes, hypertension) account for majority in adults, typically resolving within 6 months 1
• Other etiologies: trauma (basilar skull fracture), neoplasm, increased intracranial pressure, demyelination 1
• Bilateral involvement suggests: clival chordoma, increased ICP, or meningeal process 1
• Neuroimaging indicated for: young patients, other cranial neuropathies, elevated IOP, lack of vasculopathic risk factors, or no resolution by 6 months 1

Third Nerve (Oculomotor) Palsy - Second most common cranial neuropathy

• Presents with combined horizontal and vertical diplopia, ptosis, and accommodative difficulty 1
• Critical distinction: pupil-involving vs. pupil-sparing
  • Pupil-involving suggests compressive etiology (aneurysm, tumor) requiring urgent imaging 1
  • Pupil-sparing suggests vasculopathic cause 1
• Eye position: abducted, infraducted, and incyclotorted due to preserved lateral rectus and superior oblique function 1
• Annual incidence: 4 per 100,000 1
• Giant cell arteritis must be excluded in elderly with scalp tenderness or jaw claudication 1

Fourth Nerve (Trochlear/Superior Oblique) Palsy

• Vertical diplopia worse in downgaze and reading 1
• Annual incidence: 6.3 per 100,000, more common in males 1
• Most commonly caused by trauma 1
• Parks-Bielschowsky three-step test: hypertropia greatest in opposite lateral gaze and head tilt to same side 1
• Excyclotorsion commonly present 1
• Neuroimaging rarely indicated for isolated unilateral cases or bilateral traumatic cases, but required if additional CNS signs present 1

Supranuclear and Brainstem Pathology

Internuclear Ophthalmoplegia (INO)

• Lesion of medial longitudinal fasciculus in brainstem 1
• Primary considerations: demyelinating plaque (multiple sclerosis) in younger patients; stroke in older patients with acute onset 1
• Other causes: tumor, hemorrhage, infection 1

Skew Deviation

• Vertical misalignment from vestibular pathway disruption 1
• Rostral pons/midbrain lesions: contralateral hypotropia and head tilt 1
• Vestibular periphery/medulla/caudal pons lesions: ipsilateral hypotropia and head tilt 1
• Requires neurologic/neuro-otologic evaluation 1

Orbital and Extraocular Muscle Pathology

Thyroid Eye Disease (TED)

• Most common cause of restrictive strabismus in adults 1
• Inferior and medial rectus muscles most frequently affected 1
• Diplopia occurs in 58-68% of orbital blowout fractures 1
• Requires multidisciplinary approach with endocrinology and oculoplastics 1

Orbital Trauma

• Diplopia reported in 58-68% of blowout fractures, with 7-24% requiring surgical correction 1
• Multiple mechanisms: muscle avulsion, entrapment, hemorrhage, edema, fracture, cranial neuropathies 1
• Diplopia persisting beyond 6 months unlikely to resolve spontaneously 1
• Forced duction testing essential to distinguish restrictive from paretic causes 1

Orbital Masses and Inflammation

• Neoplasms, granulomatous disease (sarcoid), infectious processes (TB, fungal, Lyme meningitis) 1
• Ocular myositis 2
• Multiple ipsilateral cranial nerve palsies (III, IV, VI) suggest cavernous sinus or orbital apex lesion 1

Neuromuscular Junction Disorders

Myasthenia Gravis

• Variable, fatigable diplopia and ptosis 1
• 66-85% respond to corticosteroids; minimal response to edrophonium in strabismus-associated cases 1
• Acetylcholine receptor antibody testing diagnostic 1
• Efgartigimod alfa-fcab FDA-approved for anti-acetylcholine receptor positive patients 1
• Thymectomy indicated for thymoma; may reduce symptoms in select populations 1
• Strabismus surgery considered only after 2-3 years of disease stabilization 1

Chronic Progressive External Ophthalmoplegia (CPEO)

• Slowly progressive, bilateral ophthalmoplegia with ptosis 2
• Mitochondrial myopathy 2

Vascular Causes

Posterior Circulation Stroke

• Acute diplopia may represent posterior circulation arterial stroke, intracranial hemorrhage, or venous sinus thrombosis 1
• Requires urgent vascular imaging (CTA, MRA, or DSA) 1

Other Causes

Decompensated Childhood Strabismus

• Fixation switch diplopia: new-onset diplopia when fixation switches to previously nondominant eye 1
• Common triggers: monovision correction (38%), myopia development in preferred eye (25%), incorrect refractive correction (38%) 1
• Trial of monovision with contact lenses prudent before refractive surgery 1

Superior Oblique Myokymia and Ocular Neuromyotonia

• Episodic, monocular oscillopsia with vertical/torsional diplopia 2

Critical Red Flags Requiring Urgent Evaluation

• Pupil-involving third nerve palsy (aneurysm until proven otherwise) 1
• Multiple cranial nerve palsies (cavernous sinus/skull base pathology) 1
• Acute onset with posterior circulation symptoms (stroke) 1
• Papilledema or elevated IOP (increased intracranial pressure) 1
• Giant cell arteritis symptoms in elderly (scalp tenderness, jaw claudication) 1
• Progressive symptoms or additional neurologic signs 1

Diagnostic Approach

Immediate assessment should determine:

• Monocular vs. binocular (cover test) 2
• Pattern of misalignment (horizontal, vertical, torsional, combined) 1
• Pupil involvement 1
• Presence of ptosis 1
• Variability/fatigability (myasthenia) 1
• Associated neurologic signs 1
• Proptosis or orbital signs (TED, tumor, trauma) 1

Neuroimaging (MRI brain and orbits with contrast) indicated for:

• Young patients without vasculopathic risk factors 1
• Pupil-involving third nerve palsy 1
• Multiple cranial neuropathies 1
• Progressive symptoms or failure to resolve 1
• Additional CNS signs 1
• Symptomatic diplopia with poor fusional amplitudes (possible schwannoma) 1