Anisocoria Latest Facts: Causes, Risk Factors, Diagnosis and Treatments

Anisocoria is an eye condition where the diameter of the pupil in one eye is different from the one in the other eye. Anisocoria may be related to unilateral mydriasis, i.e., enlargement of one of the two pupils, or, conversely, to myosis, in which one pupil becomes smaller than the other.

Anisocoria. Image Courtesy of Tair1978

The causes of anisocoria vary widely, ranging from benign etiologies to potentially very serious pathologies, such as neurological damage. Several methods are available for accurate diagnosis, which must be done urgently to prevent potentially serious consequences, such as stroke, of which anisocoria is also a symptom.

What is anisocoria?

A person suffers from anisocoria when both pupils are different in size: either by unilateral mydriasis, which is the dilation of one of the pupils, or by unilateral myosis, which is their constriction. Anisocoria characterizes a difference in pupil diameter of more than 0.3 millimeters.

The pupil is the opening in the center of the iris through which light enters the posterior cavity of the eyeball. The iris, the colored part of the eyeball, consists of color-producing cells (called melanocytes) and muscle fibers: Its main function is to regulate the amount of light entering the eyeball through the pupil.

In fact, the pupil (which means “little person” because that is where you see yourself when you look into a person’s eyes), which is the central opening of the iris, appears black because when you look through the lens, the back of the eye (choroid and retina), which is highly pigmented, appears.

Reflexes regulate the cells of the pupil, depending on the intensity of light:

When intense light stimulates the eye, the parasympathetic fibers of the autonomic nervous system come into play. Thus, the parasympathetic fibers of the oculomotor nerve stimulate contraction of the circular or annular fibers of the iris (or the sphincters of the pupil), which cause constriction of the pupil, i.e., a decrease in pupil diameter.

On the other hand, if the light is weak, this time the sympathetic neurons of the autonomic nervous system are activated. They stimulate dilation of the radial fibers or pupillary muscles, causing dilation of the pupil diameter.

Any anisocoria requires ophthalmologic evaluation and often neurologic and neuroradiologic evaluation. Therefore, anisocoria may be related to myosis of either pupil caused by activation of the parasympathetic nervous system, which activates the iris sphincter, or to mydriasis of either pupil caused by the sympathetic nervous system, which activates the iris dilator muscle.

How do you diagnose anisocoria?

Anisocoria can be diagnosed visually by the fact that the two pupils are not the same size. Most ophthalmologists see several patients with anisocoria on a typical day. Most of these people are not aware of it, but some come in specifically for evaluation.

Tests that use light help diagnose which pupil is the pathological pupil: for example, a large anisocoria with a lot of light indicates that the sick pupil is the largest (poor pupillary contraction), and conversely, a large anisocoria with little light indicates that the sick pupil is the smallest (poor pupillary relaxation).

Risk factors

Regarding iatrogenic (drug) factors, health care workers, such as nurses working in hospitals, are at risk of developing anisocoria of a pharmacologic nature after exposure to certain products, such as scopolamine patches, which turn out to benign: These can produce anisocoria that resolves on its own within a few days.

In addition, among the mechanical factors, there is a risk of anisocoria in children due to difficulties during delivery, especially when forceps are used.

Causes of anisocoria

The etiologies of anisocoria are very diverse: it is a symptom of pathologies that can range from benign to neurological or even vital emergencies.

Physiological anisocoria

This phenomenon of physiological anisocoria, which occurs without an accompanying disease, affects between 15 and 30% of the population. It has been present for a long time, and the difference in size between the two pupils is usually less than 1 millimeter.

Ocular etiologies only

Purely ocular causes of anisocoria can be easily diagnosed in the standard ophthalmic examination:

Injury
Uveitis
Acute glaucoma

Mechanical anisocoria

There are mechanical causes of anisocoria that may be related to a history of trauma (including surgery), intraocular inflammation that can lead to adhesions between the iris and lens, or congenital anomalies.

Adie’s tonic pupil

Adie’s pupil or Adie’s syndrome is a rare condition that usually affects only one eye: that eye has a large, severely dilated pupil that responds weakly or not at all to light stimulation. It is more common in young women and its origin is often unknown. Initially, visual symptoms may or may not occur, such as sometimes discomfort when reading.

Pharmacologically dilated pupils

Dilated pupils as a result of a pharmacologic agent occur in two situations: accidental exposure to an agent that affects the pupillary motor function or intentional exposure.

Known agents that dilate the pupil include:

Scopolamine patches
Inhaled ipratropium (an asthma medication)
Nasal vasoconstrictors
Glycopyrrolate (a drug that slows down the activity of the stomach and intestines)
and herbs, such as datura or angel’s trumpet.

Constricted pupils are also seen with exposure to:

Pilocarpine
Prostaglandins
Opiates
Clonidine (an antihypertensive)
Organophosphate insecticides.

The absence of contraction in the pupil with pilocarpine is a sign of an iatrogenic cause.

Horner syndrome

Claude Bernard Horner syndrome is a condition that combines ptosis (drooping of the upper eyelid), myosis, and an abnormal depression of the eye in the orbit. Diagnosis is important because it may be associated with injury to the ocular sympathetic pathway and may be a sign of, among other things:

Tumors in the lungs or mediastinum
Neuroblastoma (more common in children)
Carotid artery dissections
Thyroid lesions
Trigeminal autonomic cephalalgias
Autoimmune ganglionopathy
Nerve palsy: oculomotor nerve palsy may also be involved in anisocoria.

Neurovascular diseases

Stroke: This is a cause that must be recognized very quickly so that a response can be given within six hours of the stroke. Aneurysm of the artery (or clot).

Pourfour du Petit Syndrome

Pourfour du Petit syndrome, a syndrome of excitation of the sympathetic system, shows mainly mydriasis and retraction of the eyelid: it is a rare syndrome, very often due to a malignant tumor.

Trigeminal autonomic cephalalgias

These headaches are characterized by headache and runny nose and tears. They are associated with pupillary myosis in 16-84% of cases. They can be characterized by pictures. Consultation with a neurologist or neuro-ophthalmologist is recommended to guide treatment and confirm the diagnosis in certain atypical cases.

Autoimmune ganglionopathy

In this rare disease, antibodies target the nodes of the autonomic nervous system. Both the sympathetic and parasympathetic nervous systems may be affected. In terms of pupillary abnormalities, the parasympathetic nodes are most commonly affected. Thus, 40% of patients have pupillary abnormalities, including anisocoria. This pathology exists at any age and may present with symptoms such as encephalitis. It can be cured spontaneously, but neuronal damage may remain, hence the frequent indication for immunotherapy.

Risks of complications in anisocoria

There is no real risk of complications from anisocoria per se; the risks of complications are those of the pathologies associated with it. Although anisocoria is sometimes benign, it can also be a symptom of diseases that can be very serious, especially if they are neurological. These are emergencies that should be diagnosed as soon as possible through various tests.

Imaging tests, such as an MRI of the brain, may be needed very quickly, especially if a stroke is suspected, and sometimes an angiogram of the head and neck (which can visualize the blood vessels).

All of these tests should allow the diagnosis to be made as quickly as possible to avoid the serious complications that occur after a stroke because if it is treated within six hours, the after-effects are much less severe. In addition, to avoid sometimes unnecessary imaging studies, eye drop tests have proven effective.

For example, pharmacologic anisocoria caused by a drug can be distinguished from pupillary dilation of neurologic origin by testing an eye drop containing 1% pilocarpine: If the dilated pupil does not contract after thirty minutes, this is evidence of pharmacologic blockade of the iris muscle.

Eye drop tests can also help diagnose Horner’s syndrome: if in doubt, instill a drop of 5% or 10% cocaine in each eye and observe the evolution of pupil diameters: cocaine causes mydriasis of the normal pupil, whereas it has little or no effect in Horner’s syndrome. Apraclonidine eye drops are also useful to confirm Horner’s syndrome and are now preferred over cocaine testing. Still, because imaging now allows visualization of the entire sympathetic pathway for diagnosis of Horner syndrome: it is now an essential test.

Treatment and prevention of anisocoria

The evaluation of unilateral mydriasis or myosis can be a diagnostic challenge and is considered a neurologic emergency. Through history, physical auscultation, and various examinations, diagnoses can be made and appropriate treatment initiated.

In the era of modern medicine, the treatment of stroke with tissue plasminogen activator has led to great progress. It should be administered early, within 3 to 4 1/2 hours after the onset of symptoms. The importance of diagnosis should be emphasized here, because the administration of tissue plasminogen activator to unfit patients has potentially disastrous consequences, such as the increased risk of bleeding.

Indeed, treatments will be very specific for each type of pathology presenting an anisocoria symptom. In any case, it is necessary to consult a doctor in case of anisocoria, and then specialists, such as neurologists and neuro-ophthalmologists or ophthalmologists, who are able to provide specific care for each disease. It should be noted that this is a symptom that requires urgent treatment, because although it may be a symptom of benign diseases, it may also be associated with vital emergencies.