Abnormal Pupils — Argyll Robertson, Marcus Gunn, Adie, Horner and Hutchinson Pupils

Pupil size is a balance between two muscles. The sphincter pupillae (parasympathetic, via the oculomotor nerve and ciliary ganglion) constricts the pupil; the dilator pupillae (sympathetic, three-neuron chain) dilates it. A lesion that weakens constriction leaves a large pupil; a lesion that weakens dilation leaves a small one.

The light reflex runs through four neurons: retina → optic nerve and tract → pretectal nucleus → both Edinger-Westphal nuclei → oculomotor nerve → ciliary ganglion → sphincter pupillae. Because each pretectal nucleus projects to both Edinger-Westphal nuclei, light in one eye constricts both pupils — the direct and consensual reflexes. The near response (accommodation, convergence, miosis) uses a separate, more ventral route to the same nuclei, which is why some lesions spare it.

Physiological anisocoria is common — about 10% to 20% of people — and the difference stays about the same in light and dark. For pathological anisocoria, measure both pupils in bright light and again in dim light.

Argyll Robertson pupils are small, irregular, usually bilateral pupils that do not constrict to light but constrict promptly to a near target — light-near dissociation. Described by Douglas Argyll Robertson in the 1860s, the sign is highly specific for late (neuro)syphilis; about half of patients with tabes dorsalis have pupil irregularities and many of these are Argyll Robertson pupils.

The lesion is thought to lie in the rostral midbrain near the Sylvian aqueduct, damaging light-reflex fibres on the dorsal side of the Edinger-Westphal nucleus while sparing the more ventral near-response fibres. A patient with Argyll Robertson pupils needs CSF examination for neurosyphilis — see Syphilis — Stages and Serology.

The Adie (tonic) pupil results from damage to the ciliary ganglion or the postganglionic parasympathetic fibres. It is a large pupil with a poor or absent light reaction and a slow, sustained (tonic) constriction to near with slow redilation — another cause of light-near dissociation. Holmes-Adie syndrome adds reduced or absent tendon reflexes, most often the ankle jerk.

• Typically young adults (25 to 45 years), women more than men (about 2.6 to 1). Usually idiopathic; may be unilateral or bilateral.
• Accommodating fibres outnumber pupillary fibres about 30 to 1; after injury, regenerating accommodation fibres reach the iris sphincter — aberrant regeneration explains the tonic near response.
• Dilute pilocarpine (0.1% to 0.125%) constricts the Adie pupil but not a normal pupil — cholinergic denervation supersensitivity, present in about 80% of tonic pupils.
• Over years the pupil may become smaller — the 'little old Adie' pupil.
• Ross syndrome = tonic pupil + hyporeflexia + segmental anhidrosis.
• Usually needs no treatment; reading glasses help the accommodative weakness.

A Marcus Gunn pupil, or relative afferent pupillary defect (RAPD), signals asymmetric damage to the afferent pathway — the retina or, most often, the optic nerve. It is detected with the swinging flashlight test: light on the normal eye constricts both pupils; when the light swings to the affected eye, both pupils dilate (paradoxical dilation) because that eye sends a weaker signal.

• Optic nerve causes: optic neuritis, ischaemic optic neuropathy, traumatic optic neuropathy, compressive lesions, asymmetric glaucoma (about 26% or more of retinal ganglion cells must be lost).
• Retinal causes: large retinal detachment, central retinal artery or vein occlusion.
• If one pupil is fixed by an efferent lesion, an RAPD can still be detected by watching the other pupil — the reverse method.
• Media opacity is a trap: a dense cataract may produce a small RAPD in the opposite eye because of light scatter, and anisocoria over 2 mm can create an apparent RAPD in the eye with the smaller pupil.

Horner syndrome is interruption of the oculosympathetic chain and gives the triad of partial ptosis, miosis and facial anhidrosis. The small pupil reacts normally to light and near, but shows dilation lag, and the anisocoria is greater in the dark. Congenital Horner can cause iris heterochromia.

In transtentorial (uncal) herniation, the medial temporal lobe (uncus) is pushed over the tentorial edge and compresses the oculomotor nerve. The result is an ipsilateral dilated, poorly reactive pupil — the Hutchinson pupil, first described by Jonathan Hutchinson — with falling consciousness and contralateral hemiparesis. A brief early constriction may rarely precede the dilation. Notching of the opposite cerebral peduncle against the tentorium can produce ipsilateral hemiparesis — the Kernohan-Woltman false-localising sign.

Why the pupil goes first: the pupillomotor parasympathetic fibres run superficially on the oculomotor nerve. Compression (aneurysm, uncal herniation, tumour) hits them early → pupil-involving third nerve palsy. Microvascular ischaemia (diabetes, hypertension) damages the core of the nerve via the vasa nervorum → pupil-sparing palsy. In one dataset pupil involvement occurred in about 63% of compressive palsies but only 17% of microvascular ones.

Pilocarpine acts directly on the sphincter. Dilute pilocarpine (about 0.1%) constricts only a denervated (Adie) pupil. 1% to 2% pilocarpine constricts a normal pupil and a third nerve palsy pupil; if even this strength fails, the pupil has been pharmacologically dilated (for example by anticholinergic drops). Common causes of small pupils include opiates, clonidine, organophosphates, pilocarpine and prostaglandin drops.

Related: Cranial Nerves for the course of the oculomotor nerve, Primary Glaucoma for optic nerve damage that can produce an RAPD, and Stroke Management for acute neurological pupil signs.