Nov 22, 2007


Background: Anisocoria, or unequal pupil sizes, is a common condition. The varied causes have implications ranging from life threatening to completely benign.

Pathophysiology: Various pathophysiological processes can cause anisocoria. However, pupil size depends upon the effects of the autonomic nervous system and the iris muscle.

The parasympathetic system constricts the iris, while sympathetic channels dilate the iris. The sympathetic system begins in the hypothalamus, descends through the brain stem (including the lateral medulla) and into the cervical cord to synapse in the ciliospinal center of Budge-Waller at the C8-T1 level. The second-order neuron then exits the C8-T1 nerve root, travels over the lung apex, and ascends to the superior cervical ganglia with the carotid artery. The third-order neuron leaves the superior cervical ganglia to ascend with the internal carotid artery through the cavernous sinus, where fibers destined for the pupil dilator and the Mueller muscle of the eyelid travel with the trigeminal nerve. Fibers destined to modulate sweating of the face travel with the external carotid artery. The parasympathetic fibers begin in the Edinger-Westphal subnucleus of cranial nerve III in the midbrain. Parasympathetic fibers destined for the iris sphincter travel with the oculomotor (cranial III) nerve.


  • In the US: Anisocoria is common, although no overall prevalence statistics are available. The incidence and prevalence data for anisocoria depend on the specific pathophysiology.

Mortality/Morbidity: Mortality and morbidity rates associated with anisocoria depend entirely upon the specific pathophysiology.

  • Several causes of anisocoria are life threatening, including Horner syndrome with carotid dissection or third nerve palsy due to aneurysmal expansion or rupture.
  • Other causes of anisocoria are completely benign (eg, simple or physiologic anisocoria), although the evaluation of these disorders may produce morbidity inadvertently.
Medical Care: Depends upon the underlying pathophysiology

Surgical Care: Depends upon the specific etiology

Consultations: Depends upon the underlying cause. Compressive third nerve palsies may require neurosurgical intervention, while ophthalmologists may be helpful in other causes of anisocoria.

Activity: Depends upon the specific etiology

Drugs used in the diagnosis of anisocoria include cocaine, hydroxyamphetamine, and pilocarpine (0.1-1%).
Drug Category: Topical anesthetic agents -- This agent is used for diagnostic testing to detect Horner syndrome.
Drug Name
Cocaine 4-10% (ophthalmic solution) -- Prevents norepinephrine reuptake and accordingly dilates eye with intact sympathetic nervous system supply. Decreases membrane permeability to sodium ions, which, in turn, inhibits depolarization and blocks conduction of nerve impulses.
Adult Dose1-2 gtt 4-10% OU
Pediatric Dose1 gtt 4% OU
ContraindicationsDocumented hypersensitivity
InteractionsIncreases toxicity of MAOIs
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in hypertension, severe cardiovascular disease, thyrotoxicosis; avoid use in traumatized mucosa and sepsis at region of intended application; do not inject; corneal toxicity may result from overuse; urine drug screen will be positive for cocaine at least 24 h after use
<Drug Category: Cholinergic agents -- This agent is used for diagnostic testing related to tonic pupil (0.1% concentration) or pharmacologic dilation-induced anisocoria (1% concentration).
Drug Name
Pilocarpine 0.1 % (Isopto) -- Does not normally constrict pupil; however, with tonic pupil, produces miosis due to cholinergic supersensitivity. Constricts normal pupil or mydriatic pupil due to oculomotor palsy; however, after pharmacologic dilation (eg, atropinelike agents), pilocarpine has no miotic effects.
Adult Dose1-2 gtt OU
Pediatric Dose1 gtt OU
ContraindicationsDocumented hypersensitivity; acute inflammatory disease of anterior chamber; acute iritis; pupillary block glaucoma
InteractionsMay be ineffective when used concomitantly with NSAIDs
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in acute cardiac failure, peptic ulcer, hyperthyroidism, GI spasm, bronchial asthma, Parkinson disease, recent MI, urinary tract obstruction, and hypertension or hypotension; miosis may cause difficulty with dark adaptation and night driving
<Drug Category: Sympathomimetic agents -- Hydroxyamphetamine is useful diagnostically to test integrity of the third-order sympathetic neuron.
Drug Name
Hydroxyamphetamine (Paredrine) -- Dilates pupil if third-order sympathetic neuron intact, and fails to dilate pupil if third-order neuron impaired.
Adult Dose1-2 gtt OU
Pediatric Dose1 gtt OU
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; anatomically narrow (occludable) angle without glaucoma
InteractionsBeta-blockers may cause systemic adverse effects; exaggerated adrenergic effects may result as long as 21 d after MAOIs (supervise and adjust dosage carefully)
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsCaution in hypertension, diabetes, hyperthyroidism, cardiovascular abnormalities, arteriosclerosis; rebound congestion may occur with frequent or extended use; rebound miosis may occur in older persons 1 day after phenylephrine treatment; reinstillation may produce reduction in mydriasis