Refers to unequal pupil sizes, and is a common condition.

Also known as unilateral mydriasis.

Causes range from life threatening to completely benign.

The presence of unequal pupil size may be a sign of a serious underlying neurologic condition, and requires careful attention.

When associated with neurologic symptoms such as ptosis or diplopia it may be an indication of dysfunction of the third cranial nerve which is vulnerable to compression from aneurysms and other lesions.

If anisocoria is greater in dim lighting conditions, the abnormal pupil is the smaller pupil since it is unable to fully dilate, and implyies  a problem with the sympathetic pathway which innovates the iris dilator muscle.

If anisocoria courier is greater in bright light conditions, the abnormal pupil is the larger pupil.

The differential diagnosis of a large pupil that is poorly reactive to light includes: a palsy of the third cranial nerve, pharmacologic mydriasis, and a tonic pupil.

A tonic pupil refers to a pupil with parasympathetic denervation and a results in a pupil that is poorly reactive to light but strongly reactive to a near target: see  with infection as with herpes zoster, orbital surgery, or systemic autonomic neuropathies, but also seen idiopathically as Adie tonic pupil.

Can be associated with severe and life-threatening neurologic conditions such as a cerebral herniation, intracranial mass or acute intracranial hemorrhage, Horner syndrome and other space occupying lesions that compress the cranial nerves.

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.

Anisocoria is common, with an estimated prevalence of 20% of the normal population.

Several causes of anisocoria are life threatening, including Horner syndrome due to carotid dissection or third nerve palsy due to aneurysmal expansion or rupture.

Other causes of anisocoria are benign.

The pupil size difference itself seldom produces symptoms.

Physical examination of pupil size in light, pupil size in the dark, pupil reactivity to light and dark help to localize the problem.

Pupil reactivity is graded subjectively on a scale of 0 to 4, to allow quantification of asymmetry.

Associated features are often key to the diagnosis.

Diplopia and ptosis may indicate the presence of a third nerve palsy.

The presence of pain may be associated with an expanding or ruptured intracranial aneurysm causing a compressive third nerve palsy or carotid dissections but is also typical of microvascular ocular motor neuropathies.

Proptosis may suggest the presence of a space-occupying lesion within the orbit.

Mechanical damage to the iris from trauma, surgical intervention, or inflammation or the effects of uveitis may produce anisocoria.

Transient anisocoria reflects benign causes such as migraine headache, and can represent transient parasympathetic or sympathetic dysfunction from other causes.

Has been reported to occur with the use of pharmacological agents such as propofol during general anesthesia.


The causes of anisocoria are diverse and varied; refer to the following flowchart to deduce the specific cause.[3] See the diagram below. Flowchart to assist in the diagnosis of anisocoria (modified with permission from Thompson and Pilley) For specific discussions of several of these topics, see the articles Oculomotor Nerve Palsy and Horner Syndrome.

Horner syndrome

Two conditions produce normally reactive pupils with anisocoria greater in darkness: Horner syndrome and physiologic anisocoria. In the English-language literature, Horner syndrome refers to sympathetic paresis that affects the eye. Features include ptosis, miosis, and anhidrosis; however, the exact presentation varies with the site of the lesion. The causes vary from life-threatening to benign conditions.

The sympathetic pathway begins in the hypothalamus, travels down the brain stem (where it is most often disrupted in the lateral medulla), through the cervical spinal cord to the level of the ciliospinal center of Budge-Waller at C8-T1, then over the lung apex, ultimately ascending with the carotid artery into the cavernous sinus to the pupil dilators and the Muller muscle of the lid. The sudomotor sweat fibers supplying the face exit onto the external carotid and its branches. The sympathetic nerve pathway has 3 divisions: first order (hypothalamus to C8-T1), second order (C8-T1 to superior cervical ganglia), and third order (superior cervical ganglia to the pupil dilators and lid).

Ptosis typically measures 1-2 mm; miosis often measures less than 2 mm and is greatest in the dark. The sympathetic fibers serve to dilate the pupil under conditions of dark or in response to psychosensory stimulation (ie, startle or pain).

Dilation lag refers to the slowed dilation of the affected pupil in response to dark. It can be assessed by viewing the pupils through several cycles of light and dark stimulation.

The anisocoria itself is asymptomatic, and the minimal ptosis often goes unnoticed. The associated features often prompt medical attention, or the condition may be discovered incidentally by an observer.

Pharmacologic testing of Horner syndrome is helpful. Application of a 4-10% cocaine ophthalmic solution can determine whether Horner syndrome is present. However, it will not specify the site or cause. Cocaine prevents reuptake of norepinephrine and dilates a normal pupil but not a sympathectomized pupil. After instilling 1-2 drops of 4-10% solution (painful for several minutes), postdrop anisocoria of greater than 0.8 mm correlates with greater than 1000:1 odds that the patient has Horner syndrome. The drops require approximately 30-45 min for greatest effect, and more than 2 drops may be toxic to the cornea. The test also results in positive urine drug screens for cocaine for several days.

The cocaine drop test helps answer the question “Is this a Horner syndrome?”, but it does not help further localization.

Testing with cocaine can give equivocal results, and it can be difficult to obtain and safely store as a controlled substance. Apraclonidine 1% or 0.5% has been proposed as a substitute.[4, 5] In patients with Horner syndrome, reversal of anisocoria usually occurs after bilateral instillation of apraclonidine. However, false-negative results have been reported in this setting.[6]

Hydroxyamphetamine (Paredrine) stimulates norepinephrine release from an intact third-order sympathetic neuron. • If the third-order neuron is intact and functional, hydroxyamphetamine will dilate the pupil. Conversely, if the third-order neuron is dysfunctional, the medication will not produce this effect.

• Because hydroxyamphetamine dilates the pupil if the first- or second-order ocular sympathetic neurons are dysfunctional, it is not a useful screening drug to detect Horner syndrome (see cocaine test already discussed).

• Accordingly, hydroxyamphetamine helps answer the question “Is the 3rd order sympathetic neuron intact?”

• The test is interpreted by calculating the difference between the degree of anisocoria before and after medication. If, after hydroxyamphetamine instillation, the anisocoria increases by 1.2 mm or more compared to before medication, the lesion is postganglionic with greater than 90% probability.

• Hydroxyamphetamine may be obtained from several pharmacies including Leiter’s (San Jose, CA; phone 800-292-6773) and Thayer’s (Orlando, FL; phone 800-848-4809).

Although the causes of Horner syndrome are variable, several conditions are relatively common. • First-order Horner syndrome often is caused by stroke, most commonly Wallenberg lateral medullary syndrome.

• Cervical spine disease may cause either a first- or second-order Horner syndrome depending on the pathophysiology (eg, disk disease or intrinsic cord disease such as syrinx, tumor, or inflammation).

• Lung apex lesions (eg, tumor) may produce a second-order Horner syndrome.

• Carotid artery dissection often produces pain and is accompanied by Horner syndrome in many patients. See the images below.Horner syndrome secondary to carotid dissection. Note that degree of anisocoria is relatively mild in room light. Also, see the image below of the same patient. Horner syndrome due to carotid dissection. Note the increase in degree of anisocoria under dark conditions.

• Cavernous sinus disease may produce a third-order Horner syndrome, often accompanied by other symptoms such as diplopia.

Oculomotor nerve palsy

Third nerve (oculomotor nerve) palsy affecting parasympathetic innervation to the pupil is often associated with compressive pathophysiology (unlike diabetic or ischemic third nerve palsy, which typically spares the pupil).

The pupil in third nerve palsy is poorly reactive and mydriatic compared with the contralateral pupil, as shown below; accordingly, anisocoria is maximal in light. Typical pupil in third nerve palsy, with mydriasis. Note the inability to adduct the right eye. This patient has a skull-based meningioma that is compressing the right third nerve. At rest, complete ptosis is present in the right eye; however, lid elevation with attempted adduction of the right eye is noted, which is consistent with aberrant regeneration. An isolated dilated pupil without ocular dysmotility or ptosis rarely represents a third nerve palsy. It is more likely related to a tonic or a pharmacologically affected pupil.

Pharmacologic pupil

The pharmacologically dilated pupil is larger than in most other causes of anisocoria (often measuring 8-9 mm).

The pupil fails to respond to light stimuli, near stimuli, or 1% pilocarpine solution; mechanical iris disruption can also account for such findings and can be distinguished with slit lamp examination.

The remainder of the examination findings (ie, motility, eyelids, fundus) should be normal, except near acuity (which is normalized with the use of plus lens reading glasses).

Instillation of atropine-like drugs may be either accidental or intentional, and potential sources of such exposure should be sought (eg, old eye drops in the house, exposure to medications such as inhalers[7] , exposure to toxic plants such as Datura [Angel’s Trumpet][8] ).


Mechanical damage to the iris muscle itself resulting from trauma, surgical intervention (eg, cataract extraction), or inflammation (or the effects or prior inflammation) within the eye (uveitis) may produce anisocoria.

Slit-lamp examination, often a helpful diagnostic tool, demonstrates iris thinning or defects, or evidence of previous or current inflammation.

Tonic pupil

Tonic pupils respond poorly to light but briskly to a near target. This condition constitutes one of the near-light dissociation syndromes. Other near-light dissociation syndromes include the following:

Autonomic neuropathies (eg, DM)

Severe afferent system damage

Aberrant regeneration CN3

Parinaud dorsal midbrain syndrome

Argyll Robertson pupils

The classic tonic pupil is the Adie tonic pupil. Adie tonic pupil responds tonically to near stimulation (the pupil takes longer to redilate after near fixation).

Slit-lamp examination is helpful, often demonstrating iris sector palsy (only a portion of the iris reacts to light), vermiform iris movements (radially oriented iris movements), and providing excellent magnification to observe near-light dissociation. The pupil may be supersensitive to weak (1/8-1/16%) pilocarpine solution, which will not constrict a normal pupil.

Transient anisocoria: This has been documented as an intermittent feature in several conditions. Most often, it reflects benign causes such as migraine headache, especially if no other associated features are present, but it can represent transient parasympathetic or sympathetic dysfunction from other causes.

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