Anisocoria is an inequality in the diameter of the two pupils, greater than 0,3 millimeters: the two pupils are then of different size. Anisocoria can be linked either to unilateral mydriasis, that is to say the increase in the size of one of the two pupils, or, conversely, to miosis making a pupil smaller than the other.

The causes of anisocoria are very variable, ranging from mild aetiologies to potentially very serious pathologies, such as neurological damage. Various methods allow an accurate diagnosis, which must be established urgently to prevent potentially serious consequences, such as those of a stroke, of which anisocoria is also a symptom.

What is anisocoria

A person has anisocoria when his two pupils are of different size: either due to unilateral mydriasis, therefore the increase in the size of one of his two pupils, or due to unilateral miosis , that is, of its narrowing. Anisocoria characterizes a difference in pupillary diameters greater 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 bulb of the eye, is made up of cells that give it its color (called melanocytes) and muscle fibers: its main function is to regulate the amount of light that enters the bulb of the eye. eye through the pupil.

In fact, the pupil (which means, “little person”, because this is where you see yourself when you look a person in the eye), which is therefore the central opening of the iris, appears black because when you look Through the lens, it is the posterior part of the eye that appears (choroid and retina), which is highly pigmented.

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

• when intense light stimulates the eye, it is the parasympathetic fibers of the vegetative nervous system that come into play. Thus, the parasympathetic fibers of the oculomotor nerve stimulate the contraction of the circular or annular fibers of the iris (or sphincter muscles of the pupil) inducing a contraction of the pupil, that is to say the reduction of the pupillary diameter.
• conversely, if the light is weak, this time it is the sympathetic neurons of the vegetative nervous system which are activated. They stimulate the radiary fibers or dilator muscles of the pupil, inducing dilation of the diameter of the pupil.

Any anisocoria requires an ophthalmological assessment and, often, neurological or neuroradiological. The anisocoria can therefore be linked to a miosis of one of the two pupils, caused by the activation of the parasympathetic system which generates that of the sphincter of the iris, or to a mydriasis of one of the pupils, triggered by the sympathetic system activating the dilator muscle of the iris.

There is a physiological anisocoria, which affects about 20% of the population.

How to recognize anisocoria?

Anisocoria is visually recognizable by the fact that the two pupils are not the same size. Most ophthalmologists see several patients with anisocoria during a typical day of consultation. Most of these people don’t know about it, but some come specifically to have it assessed.

Tests using lighting will make it possible to diagnose which is the pathological pupil: thus, an anisocoria increased in strong light will indicate that the pathological pupil is the largest (poor contraction of the pathological pupil), and conversely an anisocoria increased in low light will indicate that the pathological pupil is the smallest (poor relaxation of the pathological pupil).

Risk factors

In terms of iatrogenic factors (linked to drugs), healthcare staff, such as nurses working in hospitals, may be at risk of developing pharmacological-type anisocoria, which turns out to be benign, following exposure to certain drugs. products, such as scopolamine patches: these can cause anisocoria that will shrink on its own within days.

Moreover, among the mechanical factors, there is, in children, a risk of anisocoria caused by difficult childbirth, in particular when forceps are used.

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

Physiological anisocoria

This phenomenon of physiological anisocoria, which is present without there being any associated disease, affects between 15 and 30% of the population. It has been present for a long time, and the size difference between the two pupils is less than 1 millimeter.

Ocular etiologies only

Purely ocular causes of anisocoria are easily diagnosed during standard eye examination:

• contusion;
• uvéite;
• acute glaucoma.

Mechanical anisocoria

There are mechanical causes of anisocoria, which can then be linked to a history of trauma (including surgery), to intra-ocular inflammation that can lead to adhesions between the iris and the lens, or even to congenital anomalies. .

Adie’s tonic pupil

Adie’s pupil or Adie’s syndrome is a rare disease, which usually affects only one eye: this eye has a large pupil, strongly dilated, weakly reactive or non-reactive in the event of light stimulation. It is seen more often in young women, and its origin is most often unknown. Bégnine, it may or may not present visual symptoms, such as sometimes discomfort when reading.

Pharmacologically dilated pupils

Pupils dilated due to a pharmacological substance exist in two situations: accidental exposure to an agent that affects pupil-motor function, or intentional exposure.

Some of the agents known to dilate the pupil are:

• scopolamine patches;
• inhaled ipratopium (an asthma medication);
• nasal vasoconstrictors;
• glycopyrrolate (a medicine that slows down the activity of the stomach and intestines);
• and herbs, such as Jimson grass, Angel’s Trumpet or nightshade.

Narrowed pupils are seen during the exposure with:

• the pilocarpine;
• prostaglandins;
• opioids;
• clonidine (an antihypertensive drug);
• organophosphate insecticides.

Failure of pilocarpine to contract the pupil is a sign of iatrogenic dilation of the pupil.

Horner Syndrome

Claude-Bernard Horner syndrome is a disease that combines ptosis (fall of the upper eyelid), miosis and a feeling of enophthalmos (abnormal depression of the eye in the orbit). Its diagnosis is essential, because it can be associated with a lesion on the ocular sympathetic pathway, and could then be a sign, among other things, of:

• lung or mediastinal tumors;
• neuroblastoma (more common in children);
• dissections of the carotid arteries;
• thyroid damage;
• trigemino-dysautomatic headaches and autoimmune ganglionopathies (see below).

Nervous paralysis

Oculomotor nerve palsy may also be involved in anisocoria.

Neurovascular pathologies 

• Stroke: this is a cause that must be identified very quickly in order to be able to react within six hours of the stroke;
• Artery aneurysm (or bulge).

Pourfour du Petit syndrome

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

Trigemino-dysautomic headache

These headaches are characterized by pain in the head and most of the time discharge from the nasal mucosa and the shedding of tears. They are associated with miosis of the pupil in 16 to 84% of cases. They can be characterized by imaging. Consultation with a neurologist or neuro-ophthalmologist is recommended to guide treatment and confirm the diagnosis in certain atypical cases.

Autoimmune ganglionopathy of the autonomic system

This rare disease presents with autoantibodies targeting the ganglia of the autonomic nervous system. Both systems, sympathetic and parasympathetic, can be affected; With regard to pupil anomalies, it is the parasympathetic ganglia that are most frequently affected. Thus, 40% of patients present with pupil abnormalities, including anisocoria. This pathology exists at any age, and can present with symptoms such as those of encephalitis. It can be cured spontaneously, but neuronal damage may remain, hence the frequent indication for immunotherapy.

There is no real risk of complication in itself of anisocoria, the risks of complication are those of the pathologies associated with it. If anisocoria is sometimes of benign cause, it can also be a symptom of diseases which can be very serious, especially when they are neurological. These are therefore emergencies, which must be diagnosed as quickly as possible, via various tests:

• Imaging tests such as MRI of the brain may need to be used very quickly, especially if a stroke is suspected, and sometimes angiography of the head and neck (which shows signs of blood vessels).

All these tests must make it possible to orient the diagnosis as quickly as possible to avoid significant complications, such as those following a stroke, since if it is taken care of within six hours, the consequences will be much less important. And in addition, to sometimes avoid unnecessary imaging exams, tests using eye drops are effective:

• thus, pharmacological anisocoria, due to a drug, can be distinguished from pupillary dilation of neurological origin by using the eye drops test with 1% pilocarpine: if the dilated pupil does not shrink after thirty minutes, it is is evidence of pharmacological blockade of the iris muscle.
• Tests using eye drops can also guide the diagnosis of Horner’s syndrome: in case of doubt, a drop of 5 or 10% cocaine eye drops should be instilled in each eye, and the changes in pupillary diameters should be observed: cocaine causes mydriasis of the normal pupil, while it has little or no effect in Horner syndrome. Apraclodine eye drops are also useful in confirming Horner’s syndrome, it is now preferable to the cocaine test. Finally, imaging now makes it possible to visualize the entire sympathetic pathway in order to diagnose Horner’s syndrome: it is today an essential test.

Assessment of unilateral mydriasis or miosis can be a diagnostic challenge and is considered a neurological emergency. Through the patient’s history, his physical auscultation and various investigations, the diagnoses can be established and direct towards the appropriate treatment.

In the era of modern medicine, in case of stroke, tissue plasminogen activator is a treatment that has allowed great advances in treatment. Administration should be early – within 3 to 4,5 hours of onset of symptoms. The importance of the diagnosis must be emphasized here: because the administration of this tissue plasminogen activator will have, in ineligible patients, consequences which may be catastrophic, such as an increased risk of bleeding.

In fact, the treatments will be very specific to each type of pathology presenting a symptom of anisocoria. In all cases, a doctor must be consulted in the event of anisocoria, then specialists, such as neurologists and neuro-ophthalmologists, or ophthalmologists, who can institute specific care for each disease. It should be kept in mind that this is a symptom that must be treated urgently, because while it can characterize benign diseases, it can also be linked to life-threatening emergencies.