What is the differential diagnosis and management for new onset diplopia (double vision)?

Differential Diagnosis for New-Onset Diplopia

New-onset diplopia requires immediate anatomical localization to distinguish monocular from binocular causes, with binocular diplopia representing the majority of neurologically significant cases that demand systematic evaluation of cranial nerves III/IV/VI, extraocular muscles, neuromuscular junction, and central pathways. 1

Initial Classification

The first critical step is determining whether diplopia persists with one eye covered:

• Monocular diplopia (persists with one eye covered): Indicates ocular media pathology including refractive error, cataracts, corneal irregularities, or retinal disease 2, 3
• Binocular diplopia (resolves with either eye covered): Indicates misalignment of the visual axes requiring neurologic evaluation 1, 2

Cranial Nerve Palsies (Most Common Neurologic Causes)

Sixth Nerve (Abducens) Palsy

• Most common cranial neuropathy causing horizontal diplopia worse at distance and in lateral gaze toward the affected side 1
• Vasculopathic causes (diabetes, hypertension) account for the majority in adults, typically resolving within 6 months 1
• Red flags requiring urgent imaging: young age without vascular risk factors, progressive symptoms, or additional neurologic signs 1

Third Nerve (Oculomotor) Palsy

• Presents with combined horizontal and vertical diplopia, ptosis, and accommodative difficulty 1
• Critical distinction: pupil-involving versus pupil-sparing 1
• Pupil-involving third nerve palsy is a medical emergency requiring urgent evaluation for aneurysm or compressive lesion 1
• Pupil-sparing cases in patients with vasculopathic risk factors may be observed initially 1

Fourth Nerve (Trochlear) Palsy

• Characterized by vertical diplopia worse in downgaze and reading, with annual incidence of 6.3 per 100,000 1
• Most commonly caused by trauma, more common in males 1
• Parks-Bielschowsky three-step test confirms diagnosis: hypertropia greatest in lateral gaze to opposite side and head tilt to same side 4

Supranuclear and Brainstem Pathology

Internuclear Ophthalmoplegia

• Lesion of medial longitudinal fasciculus in brainstem 1
• Primary considerations: demyelinating plaque in younger patients, stroke in older patients with acute onset 1
• Requires urgent vascular imaging (CTA, MRA, or DSA) if acute onset with posterior circulation symptoms 1

Orbital and Restrictive Causes

Thyroid Eye Disease

• Most common cause of restrictive strabismus in adults, with inferior and medial rectus muscles most frequently affected 1
• May present as new-onset diplopia even without obvious proptosis 4

Orbital Trauma

• Multiple mechanisms: muscle avulsion, entrapment, hemorrhage, edema, fracture, and cranial neuropathies 1
• Diplopia occurring in 58-68% of orbital blowout fractures 1
• Diplopia persisting beyond 6 months is unlikely to resolve spontaneously 1

Neuromuscular Junction Disorders

Myasthenia Gravis

• Characterized by variable, fatigable diplopia and ptosis 1
• 66-85% respond to corticosteroids 1
• Acetylcholine receptor antibody testing is diagnostic 1
• Fatigable upgaze and ice pack test aid bedside diagnosis 3

Post-Surgical Causes

Fixation Switch Diplopia

• Decompensated childhood strabismus triggered by changes in ocular dominance 4, 1
• Common triggers include:
  • Monovision correction for presbyopia (38% of cases) 4
  • Myopia development in previously preferred eye (25% of cases) 4
  • Incorrect refractive correction (38% of cases) 4
  • Cataract surgery in nondominant eye resulting in better visual acuity 4
  • Asymmetric vision loss from macular degeneration or diabetic retinopathy 4

Anesthetic Myotoxicity

• 0.18% incidence of secondary strabismus after cataract surgery, 0.23% with retrobulbar block 4
• Risk factors: injection by non-ophthalmologist, left eye injection, absence of hyaluronidase 4
• Superior and inferior rectus muscles most commonly affected 4

Other Surgical Complications

• Glaucoma filtering surgery: 1% transient strabismus after trabeculectomy, 3% after plate reservoir surgery 4
• Scleral buckling: multifactorial causes including muscle trauma, scarring, aniseikonia 4
• Pterygium surgery: medial rectus injury or restrictive scarring 4
• Blepharoplasty: trochlear damage (upper lid) or inferior rectus damage (lower lid) 4

Critical Red Flags Requiring Urgent Evaluation

The following presentations demand immediate neuroimaging and/or subspecialty consultation: 1

• Pupil-involving third nerve palsy (aneurysm until proven otherwise)
• Multiple cranial nerve palsies
• Acute onset with posterior circulation symptoms (vertigo, ataxia, dysarthria)
• Papilledema or elevated intraocular pressure
• Giant cell arteritis symptoms in elderly patients (headache, jaw claudication, scalp tenderness)
• Progressive symptoms or failure to resolve
• Young patients without vasculopathic risk factors

Diagnostic Approach Algorithm

For all new-onset diplopia: 1, 2, 3

1. Confirm monocular versus binocular by covering each eye
2. If binocular, perform red glass test to characterize horizontal versus vertical separation
3. Assess extraocular movements in nine positions of gaze
4. Examine pupils for anisocoria or reactivity abnormalities
5. Evaluate for proptosis and resistance to retropulsion (orbital disease)
6. Test for fatigability (myasthenia gravis)
7. Obtain detailed history of trauma, surgery, systemic disease, medications

Neuroimaging indications (MRI brain and orbits with contrast): 1

• Young patients without vasculopathic risk factors
• Pupil-involving third nerve palsy
• Multiple cranial neuropathies
• Progressive symptoms or failure to resolve within expected timeframe
• Additional CNS signs or symptoms

Common Pitfalls to Avoid

• Failing to distinguish pupil-involving from pupil-sparing third nerve palsy, which has critical implications for aneurysm risk 1
• Overlooking fixation switch diplopia in patients with recent monovision correction or asymmetric cataract surgery 4
• Assuming all isolated sixth nerve palsies are benign without considering age and risk factors 1
• Missing myasthenia gravis by not testing for fatigability or performing ice pack test 3
• Neglecting to screen for thyroid eye disease in patients with restrictive strabismus 1
• Failing to obtain urgent imaging for posterior circulation symptoms or multiple cranial neuropathies 1