Diplopia: Clinical Evaluation

1. First Step - Monocular vs. Binocular

• Monocular diplopia - persists with one eye closed. Almost always an ocular (non-neurological) cause: corneal abnormality, uncorrected refractive error, cataract, lens dislocation, foveal traction, or rarely malingering/psychiatric disease. Test with a pinhole: diplopia from refractive error resolves; diplopia from retinal or lenticular pathology does not.
• Binocular diplopia - resolves when either eye is covered. This means ocular misalignment is present and requires systematic neurological evaluation.

2. Key Historical Features in Binocular Diplopia

• Direction of diplopia: purely horizontal, purely vertical, or torsional
• Gaze position that worsens it: e.g., worse looking left, worse reading/looking down
• Mode of onset: acute vs. gradual
• Intermittency and diurnal variation: worse at end of day = myasthenia gravis
• Head tilt: compensatory head posture suggests CN IV palsy
• Associated symptoms: ptosis, pain, proptosis, headache, jaw claudication, fever, weakness, ataxia
• Medical history: diabetes, hypertension, thyroid disease, cancer, MS

3. Structural Causes (Orbital/Restrictive Diplopia)

4. Neuromuscular Cause: Myasthenia Gravis

• Diplopia fluctuates, worsens with fatigue/at end of day, improves with rest
• Not confined to a single CN distribution
• Pupils always normal
• May have fatigable ptosis (unilateral or bilateral)
• ~50% of patients present with purely ocular symptoms
• Bedside ice test: apply ice to closed eyelid for 5 minutes; improvement of ptosis ~5 mm = positive (cold mitigates acetylcholinesterase inhibition)
• Labs: anti-AChR antibodies (may be negative in purely ocular form); anti-MuSK antibodies
• Beware: Botulism from food or wound poisoning can mimic ocular myasthenia

5. CN Palsy Patterns

Extraocular muscle actions by gaze position

CN III (Oculomotor) Palsy

• Muscles affected: medial rectus, superior rectus, inferior rectus, inferior oblique, levator palpebrae, iris sphincter
• Eye position: down and out (unopposed lateral rectus + superior oblique)
• Signs: ptosis, dilated pupil (parasympathetic fibers run on the outside of the nerve = vulnerable to compression)
• Diplopia: in all directions except lateral gaze to the affected side
• Pupil-involving CN III: urgent neuroimaging + CT/MR angiogram to exclude posterior communicating artery aneurysm
• Pupil-sparing CN III: typically microvascular ischemia (diabetes, hypertension); spontaneous recovery in months
• Aberrant regeneration (lid elevates on downgaze/adduction): indicates compressive or traumatic etiology - NOT seen with microvascular CN III

• Nothnagel's: CN III + cerebellar ataxia (superior cerebellar peduncle)
• Benedikt's: CN III + contralateral tremor/chorea/athetosis (red nucleus)
• Weber's: CN III + contralateral hemiparesis (cerebral peduncle)

CN IV (Trochlear) Palsy

• Muscle affected: superior oblique (depresses and intorts the globe)
• Result: hypertropia + excyclotorsion of the affected eye
• Complaint: vertical diplopia, especially on reading or looking down
• Bielschowsky head tilt test (cardinal feature): diplopia worsens on tilting head toward the side of palsy, improves on tilting away
• Common causes: closed head trauma (nerve crosses at dorsal midbrain, vulnerable to tentorial impact), microvascular ischemia, congenital (review old photos for habitual head tilt)
• No aneurysmal cause expected (unlike CN III)
• Management: base-down prism; if persistent, inferior oblique weakening surgery

CN VI (Abducens) Palsy

• Muscle affected: lateral rectus
• Result: failure of abduction; eye esotropic at rest
• Complaint: horizontal diplopia, worst on gaze to the side of the lesion
• Important distinction: CN VI nucleus lesion vs. fascicle lesion
  • Nuclear lesion = complete ipsilateral gaze palsy (both ipsilateral LR and contralateral MR fail via MLF)
  • Fascicle lesion = isolated lateral rectus weakness only

• Foville's (dorsal pons): lateral gaze palsy + ipsilateral facial palsy + contralateral hemiparesis
• Millard-Gubler (ventral pons): lateral rectus weakness only + ipsilateral facial palsy + contralateral hemiparesis
• Gradenigo's syndrome (petrous apex): mastoiditis + deafness + pain + CN VI palsy

6. Internuclear Ophthalmoplegia (INO)

• Finding: failure of adduction of one eye on horizontal gaze (with preserved adduction on convergence) + nystagmus in the abducting eye
• Cause: most commonly MS (bilateral INO = virtually pathognomonic for MS), also brainstem infarct
• In patients with MS, diplopia may be the presenting (isolated) syndrome

7. Other Important Neurological Causes

8. Bedside Examination Tools

Cover Test

• More sensitive than motility testing for subtle misalignment
• Perform in primary gaze, then with head turned/tilted in each direction fixating a distant target
• Detects comitant deviations (equal in all gaze positions = strabismus) vs. incomitant (CN palsy, restrictive)

Red Glass Test

• Place red glass over one eye (typically right); patient follows a white light in 9 gaze positions
• Reports positions of red (right eye) and white (left eye) images
• Image further from midline in the direction of attempted gaze = from the abnormal eye

Corneal Light Reflex (Hirschberg Test)

• Shine flashlight from directly in front; symmetric corneal reflections = normal
• Displaced reflection = eye misalignment

Ice Test (for Myasthenia)

• Ice pack on closed eyelid for 5 minutes
• Improvement in ptosis (~5 mm) = positive for myasthenia

9. Ancillary Testing

10. Diagnostic Algorithm Summary

Diplopia
   |
   ├─ Monocular (persists with one eye closed)
   │     → Ocular cause (cornea, lens, retina)
   │     → Pinhole test (resolves = refractive; persists = structural)
   │
   └─ Binocular (resolves covering either eye)
         |
         ├─ Signs of orbital disease (proptosis, pain, restricted motility atypical pattern)
         │     → Restrictive: Thyroid, pseudotumor, fracture, tumor, GCA
         │     → MRI orbit
         │
         ├─ Variable, fatigue-related, pupils normal
         │     → Myasthenia gravis
         │     → Ice test, AChR antibodies, EMG
         │
         └─ Follows CN distribution
               |
               ├─ CN III: Down-out eye + ptosis ± dilated pupil
               │     Pupil involved → aneurysm workup (CTA/MRA)
               │     Pupil spared + microvascular risk → ischemic CN III
               │
               ├─ CN IV: Vertical diplopia, worse reading, head tilt
               │     Bielschowsky test; closed head trauma common
               │
               ├─ CN VI: Horizontal diplopia, esotropia, worse ipsilateral gaze
               │     Gaze palsy → nuclear; isolated LR → fascicle
               │
               └─ Supranuclear / other
                     INO (MLF) → MS or stroke
                     Gaze palsy → frontal/pontine
                     Cavernous sinus → multiple CN (III+IV+V1+VI)