What is the cause of anisocoria (unequal pupil size)?

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From the Guidelines

Anisocoria requires immediate medical attention if it is accompanied by symptoms like eye pain, vision changes, drooping eyelid, or headache, as it could indicate a serious condition like stroke, aneurysm, or increased intracranial pressure. The condition is characterized by unequal pupil sizes, which can be normal in about 20% of the population (physiologic anisocoria) with less than 1mm difference that remains consistent in different lighting conditions 1. However, pathologic anisocoria needs to be evaluated thoroughly. Common causes include Horner's syndrome, third nerve palsy, Adie's tonic pupil, medication effects, eye trauma, or inflammation.

Diagnosis and Evaluation

A comprehensive eye examination should be performed, paying particular attention to the sensorimotor examination, evidence of ptosis and anisocoria, and pupillary responses in bright and dim illumination 1. The examination should also include a fundus examination to evaluate for the presence of papilledema or optic atrophy. Evaluation of the third nerve palsy depends on the presumed location of the lesion and is based on other accompanying neurologic findings.

Key Considerations

  • Isolated third nerve palsy is what most clinicians encounter, with important characteristics including whether the pupil is involved and the extent of the motility disorder and ptosis 1.
  • A classic pupil-sparing third nerve palsy has normal pupillary function, complete ptosis, and complete motility dysfunction, almost always secondary to microvascular disease.
  • Pupil-involving third nerve palsy is more concerning and requires urgent evaluation to rule out a compressive lesion, especially an aneurysm involving the posterior communicating artery 1.

Recommendations

  • For any new onset of anisocoria, especially with accompanying symptoms, immediate medical evaluation is necessary to determine the underlying cause and appropriate treatment.
  • Treatment depends entirely on the underlying cause, ranging from no treatment for physiologic anisocoria to medications or surgery for specific conditions.
  • Neuroimaging, including MRI with gadolinium and magnetic resonance angiography (MRA) or computed tomography angiography (CTA), is recommended for pupil-involving third nerve palsy or when a compressive lesion is suspected 1.

From the Research

Definition and Causes of Anisocoria

  • Anisocoria, or a difference in pupil size, is a common condition with a wide range of causes, from benign to life-threatening conditions 2.
  • The causes of anisocoria can be physiological, such as physiological anisocoria, or pathological, such as Horner syndrome, Adie pupil, pharmacological anisocoria, or third nerve palsy 2, 3.
  • Anisocoria can also be caused by traumatic, pharmacologic, inflammatory, or ischemic effects on the eye 3.

Diagnosis and Evaluation of Anisocoria

  • The clinical evaluation of anisocoria involves a thorough understanding of normal ocular neuroanatomy and common causes of pathologic anisocoria 3.
  • Pharmacological aids, such as cocaine 10% eye drops, hydroxyamphetamine eye drops, pilocarpine 0.1% eye drops, pilocarpine 1% eye drops, and apraclonidine, can be used to differentiate the different causes of anisocoria 2.
  • A full ophthalmological examination, as well as tests such as the apraclonidine, cocaine, pilocarpine 0.125%, and pilocarpine 2% tests, may be necessary to determine the cause of anisocoria 4.

Epidemiology and Prognosis of Anisocoria

  • Anisocoria is a clinical sign that does not usually signify a serious disease, but it can be a symptom of underlying conditions such as migraines or psychotropic drug use 4.
  • In some cases, the cause of anisocoria may not be determined, even with a full clinical history and examination 4.
  • Anisocoria can be a manifestation of compressive third cranial nerve palsy, which can be caused by conditions such as arachnoid cysts 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacological testing of anisocoria.

Expert opinion on pharmacotherapy, 2005

Research

Approach to anisocoria in the emergency department.

The American journal of emergency medicine, 2023

Research

[Everyday anisocoria: anisocoria epidemiology in a secondary care setting].

Archivos de la Sociedad Espanola de Oftalmologia, 2012

Research

Arachnoid cyst causing third cranial nerve palsy manifesting as isolated internal ophthalmoplegia and iris cholinergic supersensitivity.

Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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