Unequal pupils


Unequal pupils (anisocoria) may be caused by disease of the:

  • eye

  • orbit

  • brain

  • neck

  • upper chest

Patients occasionally present because a difference in the sizes of their pupils has been noticed by their family, an examining practitioner or the patient themselves. Alternatively, you might notice anisocoria while examining the patient for another complaint.

As ophthalmologists, we all need to have a practical plan for assessing patients with unequal pupils. On history and examination, we need to decide if the patient can be clinically diagnosed and reassured (e.g. Holmes-Adie tonic pupil) or requires referral or investigation (e.g. Horner syndrome).

Anisocoria can be physiologic or pathologic. Physiologic anisocoria is common: one in five normal subjects has a slight but noticeable difference in the size of their pupils. Physiologic anisocoria can be recognized because the patient is asymptomatic, both pupils constrict briskly to light and dilate briskly to dark, there is no ptosis and ocular movements are normal.

Pathologic anisocoria is due to disease in one of three places:

  • in the iris itself

  • in the neural pathway that causes pupil constriction (the parasympathetic chain)

  • in the neural pathway that causes pupil dilation (the sympathetic chain)

Iris disease

  • overall, the most common cause of pathologic anisocoria seen by ophthalmologists is change in the iris itself, most often due to previous cataract or corneal surgery. Previous blunt trauma can also cause persisting traumatic mydriasis. Infrequently, the patient may have (purposefully or accidentally) instilled a dilating or constricting substance into the eye

Parasympathetic chain disease (brain, third nerve, ciliary ganglion)

  • third nerve disease can very rarely present with just a dilated pupil but almost always ptosis, motility disturbance or both signifies that a partial third nerve palsy is present. More commonly, ciliary ganglion disease of unknown cause results in the Holmes-Adie tonic pupil syndrome, which can be recognized by light-near dissociation, spiraling of the iris on slit-lamp examination and the absence of other neurologic symptoms or signs other than (sometimes) areflexia

Sympathetic chain disease (brain, neck, upper chest)

  • Horner syndrome is caused by a lesion anywhere in the sympathetic chain which descends from the hypothalamus in the center of the brain down through the brainstem and cervical spinal cord, runs across the top of the lung, then ascends with the internal carotid artery upwards through the neck and then forwards through the cavernous sinus to reach the orbit. Common causes for Horner syndrome include a tumor compressing any part of the chain in the head, neck or upper chest; an internal carotid artery (ICA) dissecting aneurysm in the neck; a presumed ischemic insult due to atherosclerosis; or a congenital defect in the sympathetic chain

Examination checklist

Unequal pupils

Have you asked about, and looked for, all the following key features?


  • how was the anisocoria first noticed: on a routine check or was the patient having visual or neurologic symptoms?

  • any ophthalmic symptoms?

    • blurred vision or field loss? (possible orbital apex tumor)

    • transient visual loss? (ICA dissection)

    • diplopia? (possible partial third nerve palsy from aneurysm or tumor)

  • previous ophthalmic history: eye trauma or surgery? (possible traumatic mydriasis)

  • any neurologic symptoms: headache, numbness or weakness?

  • previous medical and surgical history

    • cancer?

    • use of topical agents or inhalants (e.g. antiasthmatic nasal sprays)

    • previous neck trauma, e.g. car accident “whiplash” injury, chiropractic manipulation or roller-coaster ride? (possible Horner syndrome from ICA dissection)

  • if patient over 50: symptoms of giant cell arteritis?

  • system review questions

    • hemifacial, neck or arm pain? (possible Horner syndrome from ICA dissection)

    • any clues to the cause anywhere in the body?


  • visual acuity

  • color vision testing

  • visual field testing to confrontation

  • eye movement testing

  • pupils

    • estimate pupil sizes

    • do both pupils constrict rapidly and fully to light? If not, do they constrict to near?

    • do both pupils dilate rapidly and fully in the dark?

    • relative afferent pupillary defect (RAPD)?

  • eyelids: ptosis? (possible partial third nerve palsy or Horner syndrome)

  • orbits

  • decreased corneal or facial sensation to light touch?

  • if possible Horner syndrome:

    • examine the neck (lumps or lymphadenopathy?)

    • examine the hands (clawing or finger abduction or adduction weakness?)

    • “spoon test” for facial sweating (p. 285)

  • if patient over 50: palpate temporal arteries

  • full neurologic examination: if the patient has neurologic symptoms

Plus: perform perimetry if:

  • field defect to confrontation, or

  • decreased visual acuity, color acuity or RAPD

Management flowchart

Unequal pupils

Approach to anisocoria


  • a difference in the size of the pupils


  • may be caused by dysfunction of sympathetic or parasympathetic pathway


  • never caused by an afferent pathway lesion unless that lesion also affects efferent sympathetic or parasympathetic pathway


  • what is the most important question to answer in a patient with anisocoria?


  • are both pupils normally reactive to light or is one (or both) poorly reactive?


  • if both pupils are reactive, the lesion is probably in the sympathetic pathway because pupillary constriction (parasympathetic pathway) is intact, whereas if one pupil is poorly or non-reactive (and there is no RAPD!), the lesion is probably in the parasympathetic pathway (brainstem, third nerve, ciliary ganglion, short ciliary nerves, iris sphincter)

Anisocoria with normally reactive pupils

Differential diagnosis

  • common

    • physiologic anisocoria

    • Horner syndrome

  • uncommon: intermittent pupillary mydriasis of young (some cases)

Physiologic anisocoria ( Fig. 9.1 )

  • present in 15–20% of normal people

  • present at birth

  • may be very obvious or very subtle

  • may change both size and side by hour

  • no visual effects

  • if the patient is asymptomatic and there is normal motility and no ptosis, no pharmacologic testing or other investigations are required

  • occasionally, however, if by coincidence there is a mild ptosis of another cause, there can be concern that the patient could have Horner syndrome

  • pharmacologic testing to differentiate physiologic anisocoria from Horner syndrome:

    • the transmitter substance at the neuromuscular junction of the sympathetic pathway is norepinephrine

    • 10% cocaine blocks the reuptake of norepinephrine

    • patients with physiologic anisocoria have normal release of norepinephrine at the junction of the sympathetic neuron and the iris dilator

    • a patient with physiologic anisocoria will show dilation of both pupils 45 minutes after two drops of 10% cocaine are instilled in both eyes (compared with Horner syndrome in which there is no dilation) ( Fig. 9.1 )


Physiologic anisocoria in a child. A Before pharmacologic testing with topical 4% cocaine. There is obvious anisocoria with the left pupil smaller than the right. Both pupils reacted normally to light. B Forty-five minutes after topical instillation of 4% cocaine on both sides, both pupils are widely dilated.

Horner syndrome ( Fig. 9.2 and )

  • results from damage to oculosympathetic system

  • damage may affect first-, second- or third-order neuron in pathway


Left Horner syndrome in a young man after a roller-coaster ride. Note anisocoria with left pupil smaller than right. Both pupils were normally reactive to light. Note associated left upper and lower lid ptosis. The patient was subsequently found to have a left internal carotid artery dissection.


  • anisocoria with smaller pupil on side of lesion

  • pupils normally reactive to light (actually, Horner pupil is hyperreactive to light)

  • ipsilateral upper eyelid ptosis (from involvement of Muller’s muscle)

  • upside-down ptosis of ipsilateral lower lid (lower lid slightly higher)

  • apparent enophthalmos (from ptosis of upper and lower lids)

Pharmacologic testing to confirm the diagnosis of Horner syndrome ( Table 9.1 )

Jun 25, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Unequal pupils

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