What is anisocoria?

Anisocoria: Definition, Diagnosis, and Management

Anisocoria is a condition characterized by unequal pupil sizes between the two eyes, which may be physiological (normal variant), pathological, or pharmacological in origin. 1, 2

Types and Causes

Physiological Anisocoria

• Normal variant occurring in up to 20% of the population
• Typically less than 0.5-1.0 mm difference between pupils
• Remains relatively constant in both bright and dim lighting conditions
• Not associated with other ocular or neurological abnormalities

Pathological Anisocoria

Based on whether the abnormal pupil is larger or smaller:

Large Pupil (Anisocoria more obvious in bright light)

• Third Nerve Palsy: Often accompanied by ptosis and limitation in eye movements
• Adie's Tonic Pupil: Poorly reactive to light but constricts slowly with near effort
• Pharmacological Dilation: From medications or eye drops (atropine, tropicamide)

Small Pupil (Anisocoria more obvious in dim light)

• Horner's Syndrome: Characterized by miosis, mild ptosis, and facial anhidrosis on the affected side
• Argyll Robertson Pupil: Small, irregular pupils that react poorly to light but normally to accommodation
• Pharmacological Constriction: From medications or eye drops (pilocarpine)

Diagnostic Approach

Initial Assessment

1. Determine if anisocoria is greater in bright or dim light:

   • Greater in bright light: Abnormal pupil is the larger one
   • Greater in dim light: Abnormal pupil is the smaller one

2. Assess pupillary reactivity to light in both eyes

3. Check for associated findings:

   • Ptosis
   • Limitation in eye movements
   • Facial asymmetry
   • Visual acuity changes

Specialized Testing

• Pilocarpine Test:
  • 0.1% pilocarpine: Hypersensitive constriction in Adie's pupil
  • 1% pilocarpine: No response in pharmacological mydriasis, normal response in third nerve palsy
• Cocaine Test: No dilation in Horner's syndrome when 10% cocaine is applied
• Hydroxyamphetamine Test: Helps localize the lesion in Horner's syndrome
• Apraclonidine Test: Alternative test for Horner's syndrome

Red Flags Requiring Urgent Evaluation

• Anisocoria with sudden onset headache
• Anisocoria with ptosis and limitation of eye movements (possible aneurysm)
• Anisocoria with altered level of consciousness
• Anisocoria with focal neurological deficits
• Relative afferent pupillary defect (RAPD)

Management

Management depends on the underlying cause:

• Physiological Anisocoria: Reassurance, no treatment needed
• Third Nerve Palsy: Urgent neuroimaging (MRI with gadolinium and angiography) to rule out aneurysm 1
• Horner's Syndrome: Evaluation for underlying cause (neck or chest pathology)
• Adie's Pupil: Usually benign, may require dilute pilocarpine for cosmesis
• Pharmacological Anisocoria: Identify and remove offending agent (e.g., ipratropium bromide nebulizer leakage) 3

Documentation and Follow-up

• Photograph pupils for future comparison
• Patients with physiological anisocoria do not require regular follow-up
• Follow-up for pathological causes depends on the specific etiology

Common Pitfalls

• Failing to distinguish between physiological and pathological anisocoria
• Not checking pupil size in both bright and dim lighting conditions
• Missing associated neurological signs
• Overlooking pharmacological causes (especially nebulized medications like ipratropium bromide)
• Using inconsistent definitions of anisocoria (cut points range from >0.3 mm to >2.0 mm difference) 4

Remember that anisocoria can be a sign of serious underlying conditions, so thorough evaluation is essential when the cause is not clearly physiological.