Pupillary response

David Goldemund M.D.
Updated on 14/10/2024, published on 11/10/2024

examination of the pupils helps localize lesions in the visual pathways and autonomic nervous system
aids in monitoring neurological status (changes in pupil size, shape, and reactivity can indicate brainstem lesion, increased intracranial pressure, or impending herniation) → Pupillary response in unconscious patients
pupillary responses provide insight into sympathetic and parasympathetic integrity

iris sphincter muscle (sphincter pupillae) is composed of smooth muscle fibers arranged in a circular pattern around the pupillary margin of the iris
- it contracts to decrease the pupil’s diameter in bright light or during near vision (accommodation)
- it is under parasympathetic control
iris dilator muscle (dilator pupillae) is radial in orientation
- it dilates the pupil (mydriasis) in response to low light conditions, stress, or as the “fight-or-flight” response
- it is under sympathetic control

Parasympathetic pathway (pupillary constriction – miosis)

Edinger-Westphal nucleus (midbrain) → preganglionic fibers travel with the oculomotor nerve (CN III) → ciliary ganglion → postganglionic fibers innervate the sphincter pupillae muscle (via short ciliary nerves)
constricts the pupil in response to light and during accommodation
neurotransmitter: acetylcholine
receptors: muscarinic cholinergic receptors (primarily M3 subtype)

Sympathetic pathway (pupillary dilation – mydriasis)

hypothalamus → ciliospinal center of Budge (spinal cord levels C8–T2) → preganglionic fibers exit the spinal cord and ascend to the superior cervical ganglion → postganglionic fibers travel along the internal carotid artery, through the cavernous sinus, and reach the dilator pupillae muscle (via the long ciliary nerves)
dilates the pupil in response to darkness (to increase light entry), stress, or fear
neurotransmitter: norepinephrine
receptors: alpha-1 adrenergic receptors

Sudomotor sympathetic pathway

postganglionic sudomotor fibers are part of the periarterial carotid plexus
- sudomotor fibers for the medial forehead run along the ICA through the carotid canal
- sudomotor fibers for the maxillary and mandibular regions run along the ECA
preganglionic lesions affect the entire ipsilateral side of the face; manifestation of postganglionic lesions depends on whether the plexus around the ICA or ECA is involved.

Light reflex

photoreceptors in the retina → optic nerve (CN II) → pretectal nuclei in the midbrain → bilateral Edinger-Westphal nuclei → sphincter pupillae
as a result, both pupils constrict when light is shone in one eye (direct and consensual responses)

Near reflex

pathway involves input from the visual cortex to the Edinger-Westphal nucleus and the oculomotor nucleus (CN III)
adjusts the optical system for near vision
- pupil constriction improves the depth of focus
- ciliary muscles adjust the lens curvature (accommodation)
- medial rectus muscles turn the eyes inward (convergence)

pupil size and shape
- normal pupils are round, regular, and equal in size (isocoric)
  - in adults, the typical pupil size ranges from 2 to 4 mm in diameter in bright light and 4 to 8 mm in the dark
- anisocoria (difference in pupil sizes) can be physiologic or pathologic
light reflex
- the pupil constricts to direct illumination (direct response) and the illumination of the fellow eye (consensual response)
- both pupils dilate in the dark
swinging flashlight test →Relative Afferent Pupillary Defect (RAPD) or Marcus Gunn pupil
near/accommodation reflex
- test requires voluntary effort
- pupillary constriction and eye convergence occur when the patient focuses on a near object (along with accommodation)

features:
- mydriasis, unreactive to light
- ptosis (due to levator palpebrae superioris paralysis)
- ophthalmoplegia – eye positioned “down and out” due to unopposed lateral rectus and superior oblique muscles
causes: lesions affecting the oculomotor nerve, such as aneurysms (posterior communicating artery), tumors, or increased intracranial pressure

features:
- miosis (due to unopposed parasympathetic activity)
- semiptosis – paralysis of the superior tarsal muscle (Müller’s muscle)
- enophthalmos
- anhidrosis on the affected side
  - sudomotor fibers for the maxillary and mandibular regions run along the ECA
  - sudomotor fibers for the medial forehead run along the ICA through the carotid canal
disruption of the sympathetic pathway at any point from the hypothalamus to the eye
- first-order neuron lesion (hypothalamus) – stroke, tumor
- second-order neuron lesion (preganglionic) – Pancoast tumor, cervical trauma or surgery, aortic aneurysm
- third-order neuron lesion (postganglionic) – carotid dissection, cluster headaches, cavernous sinus pathology

Adie tonic pupil, also known as Holmes-Adie syndrome, is a neurological disorder characterized by:
- anisocoria with a dilated tonic pupil
  - most cases are unilateral (80%) but can become bilateral
  - anisocoria is greater in the light compared to in the dark (due to dysfunction of the parasympathetically innervated iris sphincter muscle ⇒ the large pupil is abnormal)
  - the pupils constrict more to accommodation than to light
  - a slit lamp examination often shows sectoral palsy of the iris sphincter, with vermiform movements of the pupillary margin
  - low-dose pilocarpine constricts the tonic pupil more than the normal pupil (due to hypersensitivity of denervated fibers), followed by a slow and sustained relaxation
- loss of deep tendon reflexes (most commonly the Achilles reflex)
more common in young women
symptoms: photophobia and difficulty adapting to the dark
etiology: damage to postganglionic parasympathetic fibers in the ciliary ganglion, often idiopathic, viral, posttraumatic, etc.
pathophysiology:
- damage to the ciliary ganglion causes denervation hypersensitivity with postsynaptic receptor upregulation
- reinnervation process is often aberrant, and fibers intended for the ciliary body may end up in the pupil (aberrant regeneration)
- as a result, near accommodation produces more miosis compared to the response to light; the reaction is tonic

affected pupil constricts less (appears to dilate) when the light is swung from the normal eye to the affected eye
caused by optic nerve damage (e.g., optic neuritis) or severe retinal disease

small, irregular pupils
light-near dissociation – pupils constrict poorly to light but normally constrict during accommodation
classically associated with neurosyphilis (DDx – dorsal midbrain lesion, diabetic neuropathy)