Anisocoria: Definition, Pathophysiology, Symptoms, Causes and Treatment

This term is used to describe when a person has uneven pupils.

A pupil may be larger than normal (dilated), or a pupil may be smaller than normal (constricted), resulting in pupils of different sizes.


Isolated anisocoria is usually asymptomatic and is discovered incidentally. Anisocoria may occasionally be associated with visual symptoms (eg, unilateral photosensitivity with mydriasis, decreased accommodation with Horner syndrome) or associated features that lead to evaluation, for example:

Start of anisocoria

Old photographs of patients often help date anisocoria that is not accompanied by other symptoms.

A careful history can establish the etiology of anisocoria in some cases. Contact with a wide variety of agents, such as eye drops, scopolamine patches, asthma inhalers, or pet flea collars with anticholinesterase can cause anisocoria.

Intraocular surgery can sometimes alter the size or reaction of the pupil.

Causes of anisocoria headache include Horner syndrome and trigeminal autonomic headaches, including headache.


The size of the pupil depends on the effects of the autonomic nervous system and the iris muscle, and numerous pathophysiological processes can cause anisocoria.

From the standpoint of the autonomic nerve, the parasympathetic system restricts the iris, while anatomically distinct sympathetic channels dilate the iris.

The sympathetic system begins in the hypothalamus, descends through the brainstem (including the lateral cord) and into the cervical cord to synapse at the Budge-Waller ciliospinal center at the C8-T1 level.

The second-order neuron then exits the C8-T1 nerve root, travels over the pulmonary apex, and ascends to the superior cervical ganglia with the carotid artery.

The third-order neuron leaves the upper cervical ganglia to ascend as a plexus around 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 via the superior orbital fissure towards its orbital targets.

Physical exam and symptoms

Key aspects of the physical exam (for example, pupil size in light, pupil size in dark, pupil reactivity to light and dark) help locate the problem.

Additional historical features such as pain, diplopia, ptosis, numbness, ataxia, dysarthria, or weakness help generate a differential diagnosis.

Pupil size (in mm) should be assessed in both light and dark, with the patient looking at the distance.

Illumination of the pupil by obliquely illuminating a light from below the patient’s face and a handheld pupil meter (found on most near vision cards) helps to make an accurate assessment.

Pupil documentation should include the millimeter size of the pupils in light, the size in dark, the light and dark reactivity of the pupils, the shape and color of the iris, and comment on the presence or absence of a relative afferent pupillary defect. (RAPD).

The use of magnifying lenses (eg, 20 diopter indirect ophthalmoscopic lenses), slit lamp, autorefractor, or pupillometer greatly helps in examining the pupil.

Pupil reactivity

Pupil reactivity is subjectively graded on a scale from 0 (no reaction) to 4 (very fast reaction), primarily to allow quantification of left and right asymmetry.

Similar to muscle stretch reflexes, symmetry is often more important than absolute number degree.

When evaluating the pupil’s reaction to light, be careful to shine the light along the visual axis (this can be problematic if there is significant ocular misalignment).

Parasympathetic fibers begin in the Edinger-Westphal subnucleus of cranial nerve III in the midbrain.

Parasympathetic fibers travel with the oculomotor (cranial III) nerve, traverse the cavernous sinus, and enter the orbit through the superior orbital fissure for synapse in the ciliary ganglia. The short ciliary nerves then innervate the iris sphincter and the muscles of accommodation.

Causes of anisocoria

Many cases of mild anisocoria are normal and have no underlying pathology or history of trauma. Generally, these cases of anisocoria where one pupil is larger than the other by less than 1.0 mm with no apparent cause are called simple anisocoria, benign anisocoria, or physiological anisocoria.

In a study on the prevalence of anisocoria, researchers photographed the students of 128 normal subjects in dim light for five consecutive days. Photographs were taken in the morning and in the afternoon each day.

Fifty-two of the subjects (41 percent) had an anisocoria of 0.4 mm or more at one time or another during these five days. In any photo shoot, a fairly constant number of subjects (19 percent) showed this amount of mild anisocoria.

The prevalence of anisocoria did not vary with the time of day or from day to day; it was also not influenced by the subject’s sex, age, or eye color.

Other research also suggests that approximately 20 percent of the general population has mild benign anisocoria.

A significant anisocoria, however, can have several causes and some can be medical problems. Causes of significant anisocoria (one pupil larger than the other by more than 1.0 mm) include:

Eye trauma:

Bumps, bruises.

Certain eye medications:

For example, pilocarpine eye drops used to treat glaucoma can make the pupil of the treated eye smaller than the other pupil.

Inflammation of the iris:

Iritis (anterior uveitis) can cause anisocoria which is usually accompanied by eye pain.

Adie’s tonic pupil:

This benign condition (also called Adie’s pupil, tonic pupil, or Adie’s syndrome) usually causes one pupil to be noticeably larger than the other. The affected pupil also does not react to light. In most cases, the cause of Adie’s pupil is unknown.

But it can be associated with eye trauma (including trauma caused by complicated cataract surgery), lack of blood flow (ischemia), or infection.

Neurological disorders:

A number of conditions that damage the nerves in the brain or spinal cord can cause anisocoria. One of the most significant of these is Horner syndrome.

People with nervous system disorders that cause anisocoria often also have droopy eyelids, double vision, and / or squint.

Brain disorders associated with anisocoria include strokes, bleeding (spontaneous or from head injury), and, less commonly, certain tumors or infections.

Horner Syndrome:

The three classic symptoms of Horner syndrome (sometimes called Horner syndrome or Horner syndrome) are:

  1. Ptosis (droopy eyelid).
  2. Miosis (constriction of a pupil, causing anisocoria).
  3. Facial anhidrosis (loss of sweat around the affected eye).

Horner syndrome can also be differentiated from simple (benign) anisocoria by how quickly the pupil dilates in dim light conditions.

Normal pupils (including those that are slightly uneven in size) dilate within five seconds of dimming the lights in the room.

It usually takes 10-20 seconds for a student with Horner syndrome to dilate in dim light conditions or in a dark room.

Horner syndrome is usually caused by an underlying medical problem, such as a stroke, tumor, or spinal cord injury. But in some cases, no cause can be found.

There is no specific treatment for Horner syndrome, but if it is associated with an identified medical problem, treating that condition may resolve Horner’s symptoms, including anisocoria.

David bowie eyes:

One of the most distinctive physical characteristics of the late singer, songwriter, and producer David Bowie were his eyes.

Many people believe that he had two different colored eyes, a condition called heterochromia. But the real reason David Bowie’s eyes are so striking is the anisocoria.

Bowie was born with blue eyes. But a fight with a friend when they were teenagers left one of their eyes permanently dilated, giving that eye a much darker look.

What to do if you have anisocoria

If you or someone else notice that you have one pupil larger than the other, see your eye doctor right away, especially if you have any of the following:

  • Droopy eyelid (ptosis).
  • Double vision.
  • Loss of vision
  • Headache or neck pain.
  • Eye pain.
  • Recent head or eye injury.

If the difference in pupil size is smaller and your pupils react normally to tests performed by your ophthalmologist, there may be nothing to worry about.

But you should have an eye care professional evaluate your uneven students before assuming all is well.


Physiologic anisocoria does not affect vision or eye health, so treatment will not be necessary. If anisocoria is related to another eye disorder, treatment will depend on the cause.

If you have benign anisocoria and one pupil is larger than the other, ask your ophthalmologist about photochromic lenses.

These eyeglass lenses will automatically darken in sunlight to reduce any light sensitivity (photophobia) you may be experiencing.

Photochromic lenses will also protect your eyes from harmful UV rays and high energy blue light, especially the eye with the larger pupil if it does not react normally to light.