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

From the Guidelines

Anisocoria is most commonly caused by third nerve palsy, which can be due to microvascular disease, compressive lesions, or other conditions, and requires urgent evaluation to rule out life-threatening causes such as aneurysms. When evaluating anisocoria, it is essential to determine which pupil is abnormal by checking both in light and dark conditions, as the abnormal pupil will show less change 1. The causes of anisocoria can range from benign, such as physiologic anisocoria, to concerning conditions like Horner's syndrome, Adie's tonic pupil, medication effects, trauma, or intracranial pathology.

Key Considerations

• A comprehensive eye examination with attention to sensorimotor exam, evidence of ptosis and anisocoria, and pupillary responses in bright and dim illumination is crucial 1.
• Evaluation of the third nerve palsy depends on the presumed location of the lesion and is based on other accompanying neurologic findings, with pupil-involving third nerve palsy being more concerning and requiring urgent neuroimaging to rule out compressive lesions or aneurysms 1.
• Neuroimaging, including MRI with gadolinium and magnetic resonance angiography (MRA) or computed tomography angiography (CTA), is recommended for evaluating third nerve palsy, especially if the pupil is involved 1.

Diagnostic Approach

• A detailed medical and ocular history should include specific questions about patient symptoms, speed of onset of the strabismus, and possible associated unilateral or bilateral ptosis or other neurologic symptoms 1.
• Active force generation testing in the office may help identify muscles with residual function vs. completely paretic muscles 1.
• If neuroimaging is normal, the next step would be serologic testing for infectious diseases, with consideration given to lumbar puncture that would include glucose, protein, cell count, and cytology and culture 1.

From the Research

Causes of Anisocoria

• Anisocoria can be caused by various factors, including traumatic, pharmacologic, inflammatory, or ischemic effects on the eye 2
• It can also result from physiological variants, which are usually benign 2, 3
• Pharmacologic anisocoria can occur due to the use of certain medications, such as ipratropium bromide, which can cause mydriasis if it comes into contact with the eye 4, 5
• Other substances, like those found in the Angel's trumpet plant, can also cause anisocoria due to contamination of the eye 6
• In some cases, anisocoria can be a sign of a life-threatening disease, making it essential to understand its pathophysiology and diagnosis 3

Pharmacologic Causes

• Nebulized ipratropium bromide can cause anisocoria if the aerosol leaks into the eye during treatment 4, 5
• The use of a pilocarpine test can help differentiate pharmacologic anisocoria from other causes, such as third nerve palsy and Adie's pupil 4
• Discontinuation of the offending medication can lead to complete resolution of anisocoria, as seen in cases where ipratropium bromide was discontinued 5

Non-Pharmacologic Causes

• Traumatic effects on the eye can cause anisocoria, although the provided studies do not elaborate on this topic in detail 2
• Inflammatory or ischemic effects on the eye can also lead to anisocoria, but the studies do not provide further information on these causes 2
• Contact with certain plants, like the Angel's trumpet plant, can cause anisocoria due to the presence of active components like hycosamine, atropine, and scopolamine 6