How do you determine which pupil is abnormal in anisocoria?

Assess the anisocoria in both dim and bright light. If the size difference is greater in dim light, the smaller (miotic) pupil is abnormal because it fails to dilate with darkness, indicating a sympathetic pathway defect (Horner syndrome). If the difference is greater in bright light, the larger (mydriatic) pupil is abnormal because it fails to constrict with light, indicating a parasympathetic or efferent defect (CN III palsy, Adie's pupil, or pharmacological mydriasis).

What are the classic signs of Horner syndrome?

The classic triad of Horner syndrome is ipsilateral miosis (small pupil), ptosis (drooping upper lid), and anhidrosis (decreased sweating on the ipsilateral face). The miosis is worse in dim light because the sympathetic pathway normally drives pupil dilation. Horner syndrome results from disruption of the three-neuron sympathetic arc at any of its levels: central (first-order), preganglionic (second-order), or postganglionic (third-order).

Why is a pupil-involving CN III palsy an emergency?

The parasympathetic fibers that constrict the pupil travel on the outside of the CN III nerve bundle, making them vulnerable to external compression before the internal ischemia-sensitive motor fibers are affected. A posterior communicating artery aneurysm compresses CN III from outside, affecting the pupillary fibers early. This is a neurosurgical emergency because aneurysm rupture causes subarachnoid hemorrhage with high mortality. Pupil-involving CN III palsy requires immediate neuroimaging to rule out aneurysm.

Anisocoria and Pupil Abnormalities: CPO Exam Guide

What Is Anisocoria?

Anisocoria is an unequal pupil size between the two eyes. Approximately 20% of the normal population has physiological anisocoria of up to 1 mm that is equal in both dark and light conditions. Any anisocoria greater than 1 mm, or that changes with lighting conditions, warrants clinical investigation.

Assessing Anisocoria

The key to evaluating anisocoria is determining which eye is abnormal and under what lighting conditions the difference is greatest:

Anisocoria greater in dim light: the smaller (miotic) pupil is abnormal. It fails to dilate properly. This points to a defect in the sympathetic pathway (Horner syndrome).
Anisocoria greater in bright light: the larger (mydriatic) pupil is abnormal. It fails to constrict properly. This points to a defect in the parasympathetic (efferent) pathway (CN III palsy, Adie's pupil, pharmacological dilation).

The rule for anisocoria assessment: the abnormal pupil is the one that does not behave appropriately for the lighting conditions. In dim light, both pupils should dilate; in bright light, both should constrict. The one that fails to follow this rule is the pathological one.

Horner Syndrome

Horner syndrome results from disruption of the sympathetic innervation to the eye. The classic triad is:

Miosis: small pupil (sympathetics normally dilate the pupil)
Ptosis: drooping of the upper eyelid (Muller's muscle sympathetically innervated)
Anhidrosis: decreased sweating on the ipsilateral face (if lesion is at first-order or second-order neuron)

Horner syndrome is classified by the level of the lesion in the three-neuron sympathetic arc:

First-order neuron: hypothalamus to ciliospinal center (C8-T2); causes include stroke, syrinx, Pancoast tumor
Second-order neuron: ciliospinal center to superior cervical ganglion; causes include Pancoast tumor, neck dissection, carotid artery dissection
Third-order neuron: superior cervical ganglion to the eye; carotid artery dissection, cluster headache

A new-onset Horner syndrome in a patient with ipsilateral neck pain should raise urgent concern for carotid artery dissection, a serious vascular emergency. Prompt referral for imaging is essential.

CN III (Oculomotor) Palsy

A CN III palsy causes a fixed, dilated (mydriatic) pupil because CN III carries the parasympathetic fibers that constrict the pupil. In addition to the dilated pupil, expect:

Ptosis (levator palpebrae is CN III innervated)
"Down and out" eye position (unopposed action of CN IV and VI)
Ophthalmoplegia (inability to move the eye in most directions)

The pupillary involvement distinguishes a surgical CN III palsy (compressive, like a posterior communicating artery aneurysm — pupil involved) from a medical CN III palsy (ischemic — pupil often spared).

Assuming a CN III palsy with a dilated, fixed pupil is not an emergency. A pupil-involving CN III palsy raises urgent concern for a posterior communicating artery aneurysm, which can rupture causing subarachnoid hemorrhage. This is a neurosurgical emergency requiring immediate imaging.

Adie's Tonic Pupil

Adie's tonic pupil is a benign parasympathetic denervation of the ciliary ganglion, typically unilateral and more common in young women. Findings include:

Large (mydriatic) pupil in bright light, often asymmetric
Very slow, tonic constriction to prolonged near stimulation
Light-near dissociation (better near response than light response)
Supersensitivity to dilute pilocarpine (0.1%) which constricts Adie's pupil but not a normal pupil

Key Takeaways

Anisocoria greater in dim light: sympathetic defect (Horner syndrome)
Anisocoria greater in bright light: parasympathetic/efferent defect (CN III, Adie's)
Horner: miosis + ptosis + anhidrosis; sympathetic pathway lesion
CN III palsy: dilated fixed pupil + down-and-out eye + ptosis; rule out aneurysm urgently
Adie's: dilated pupil with tonic near response; benign; responds to dilute pilocarpine