What are the causes of anisocoria?

Causes of Anisocoria

Anisocoria (pupil size difference) can be caused by various conditions ranging from benign to life-threatening, with the most concerning causes being third nerve palsy from posterior communicating artery aneurysm, cavernous sinus pathology, or intracranial bleeding. 1

Physiological Anisocoria

• Physiological anisocoria is a common benign condition where there is a small difference (usually <1 mm) in pupil size that remains relatively constant in different lighting conditions 1

Pathological Causes

Third Nerve Palsy

• Pupil-involving third nerve palsy is concerning for compressive lesions, especially aneurysms of the posterior communicating artery 1
• Other causes include tumors (meningioma, schwannoma, metastatic lesions), trauma, and subarachnoid hemorrhage 1
• Associated findings may include ptosis and extraocular muscle weakness (especially medial rectus, superior rectus, inferior rectus, and inferior oblique) 1
• Localization is critical:
  • Nuclear lesions may have associated red nucleus involvement (ipsilateral tremor) or cerebral peduncle involvement (ipsilateral hemiparesis) 1
  • Subarachnoid space lesions often affect the pupil due to peripheral location of pupillary fibers 1
  • Cavernous sinus lesions may present with multiple cranial nerve palsies (III, IV, VI, V1) 1

Horner Syndrome

• Characterized by miosis (pupillary constriction), mild ptosis, and sometimes anhidrosis 1
• Results from interruption of sympathetic innervation to the eye 2
• Can be caused by lesions along the sympathetic pathway:
  • Central (brainstem lesions)
  • Preganglionic (lung apex tumors, neck trauma)
  • Postganglionic (carotid dissection, cavernous sinus pathology) 2

Adie's Tonic Pupil

• Presents with a dilated pupil that constricts slowly to light but shows enhanced constriction to near effort 2
• Results from damage to the ciliary ganglion or postganglionic parasympathetic fibers 2
• Often idiopathic but may be associated with viral infections or trauma 2

Pharmacological Causes

• Topical or systemic medications with anticholinergic properties can cause mydriasis:
  • Nebulized ipratropium bromide leaking from face masks during respiratory treatments 3
  • Scopolamine from transdermal patches or accidental exposure 4
  • Plant toxins (Datura, Brugmansia) containing tropane alkaloids like atropine 5
• Topical sympathomimetics (e.g., phenylephrine) can also cause mydriasis 2

Diagnostic Approach

Clinical Assessment

• Determine which pupil is abnormal by checking pupillary responses in both bright and dim illumination 1
• The abnormal pupil is typically the one that changes less between lighting conditions 1
• Assess for associated findings such as ptosis, extraocular movement limitations, or other neurological signs 1

Pharmacological Testing

• Cocaine 10% test: No dilation in Horner syndrome (confirms diagnosis) 2
• Hydroxyamphetamine test: Differentiates preganglionic from postganglionic Horner syndrome 2
• Pilocarpine 0.1% test:
  • Constriction in Adie's pupil (denervation hypersensitivity)
  • No response in pharmacological mydriasis 2, 4
• Pilocarpine 1% test:
  • No constriction in pharmacological mydriasis
  • Constriction in third nerve palsy 2, 6

Red Flags Requiring Urgent Evaluation

• New-onset pupil-involving third nerve palsy (urgent neuroimaging including MRA or CTA to rule out aneurysm) 1
• Anisocoria with headache, altered mental status, or other neurological deficits (possible intracranial hemorrhage) 1
• Anisocoria with signs of increased intracranial pressure (papilledema, decreased level of consciousness) 1

Clinical Pearls

• Always check if anisocoria is greater in bright or dim light to determine if the larger or smaller pupil is abnormal 1
• Pupil-involving third nerve palsy requires urgent neuroimaging, even if the pupil appears normal at initial presentation 1
• Consider recent medication exposure, including nebulizer treatments and transdermal patches, before extensive neurological workup 3, 4
• Pharmacological anisocoria typically resolves within 24 hours to several days 3, 4