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Anisocoria Diagnosis, Treatment, Complication

Anisocoria Diagnosis/Anisocoria or unequal pupil size, may be an early sign of an impending neurologic emergency in any patient and often suggestive of a life threatening condition affecting cranial nerve function, such as tumour compression, intracranial hypertension with impending uncal herniation, expanding intracranial aneurysm, or haemorrhage. Benign mydriasis can be due to prior trauma, medication effects, and congenital abnormalities. Determining the cause of anisocoria can be challenging in critical care settings because patients often are sedated, paralysed, intubated, or have a baseline altered mental status that makes full neurologic examination difficult.

Anisocoria, or a difference in pupil size, is a common condition. Its aetiology ranges from benign to life-threatening conditions. The clinical evaluation of anisocoria is discussed, emphasising the pharmacological aids (e.g., cocaine 10% eye drops, hydroxyamphetamine eye drops, pilocarpine 0.1% eye drops, pilocarpine 1% eye drops, apraclonidine) used in differentiating the different causes of anisocoria (e.g., physiological anisocoria, Horner syndrome, Adie pupil, pharmacological anisocoria, third nerve palsy).

Anisocoria Diagnosis

Causes of Anisocoria

Anisocoria is a common condition, defined by a difference of 0.4 mm or more between the sizes of the pupils of the eyes.^[rx]Anisocoria has various causes

Physiological anisocoria – About 20% of normal people have a slight difference in pupil size which is known as physiological anisocoria. In this condition, the difference between pupils is usually less than 1 mm.^[rx]
Horner’s syndrome
Mechanical anisocoria – Occasionally previous trauma, eye surgery, or inflammation (uveitis, angle closure glaucoma) can lead to adhesions between the iris and the lens.
Adie tonic pupil – Tonic pupil is usually an isolated benign entity, presenting in young women. It may be associated with loss of deep tendon reflex (Adie’s syndrome). Tonic pupil is characterized by delayed dilation of iris especially after near stimulus, segmental iris constriction, and sensitivity of pupil to a weak solution of pilocarpine.
Oculomotor nerve palsy – Ischemia, intracranial aneurysm, demyelinating diseases (e.g., multiple sclerosis), head trauma, and brain tumors are the most common causes of oculomotor nerve palsy in adults. In ischemic lesions of the oculomotor nerve, pupillary function is usually spared whereas in compressive lesions the pupil is involved.
Neurological disorders – A number of conditions that damage nerves in the brain or spinal cord can cause anisocoria. One of the most significant of these is Horner’s syndrome [see below]. People with nervous system disorders that cause anisocoria often also have a drooping eyelid, double vision and/or strabismus. Brain disorders associated with anisocoria include strokes, hemorrhage (spontaneous or due to head injury) and, less commonly, certain tumors or infections.
Pharmacological agents – with anticholinergic or sympathomimetic properties will cause anisocoria, particularly if instilled in one eye. Some examples of pharmacological agents which may affect the pupils include pilocarpine, cocaine, tropicamide, MDMA, dextromethorphan, and ergolines. Alkaloids present in plants of the genera Brugmansia and Datura, such as scopolamine, may also induce anisocoria.^[rx]
Migraines^[rx]
Eye trauma – For example, read about David Bowie’s eyes below.
Certain eye medications – For example, pilocarpine eye drops used to treat glaucoma may cause the pupil of the treated eye to be smaller than the other pupil.
Inflammation of the iris – Iritis (anterior uveitis) can cause anisocoria that usually is accompanied by eye pain.
Glaucoma
Injury to the eye
Corneal ulcer
Uveitis Eye disease
Posterior synechia
Iris atrophy
Iris hypoplasia
Congenital defect within the iris
Eye degeneration
Cancer within the affected eye
Horner’s syndrome
Brain disease
Fibrocartilaginous embolism
Head trauma
Hydrocephalus
Infectious and inflammatory disease, such as meningitis and encephalitis Infection in the middle ear
Hepatic encephalopathy
Dysautonomia
Thiamine deficiency
Chemical or toxin poisoning, such as from atropine, phenobarbital, or organophosphates

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Anisocoria Diagnosis

Symptoms of Anisocoria

A droopy upper eyelid.
Eye pain.
A severe headache.
Vision problems, such as double vision.
Loss of vision.
Different sized pupils, one being either bigger or smaller than the other
White part of eye, or sclera, is reddened, bluish, or cloudy
Eye discharge
Droopy eyelid
Cloudy cornea
Growths near the eye
Excessive rubbing of eye or face
Squinting
Lessened activity
Corneal injury such as an ulcer
Retinal disease
Scar tissue formation between the iris and the lens (called posterior synechia), a condition that may develop subsequent to uveitis
Iris atrophy, or a decrease in the amount of tissue within the iris, usually a degenerative change associated with aging
Congenital defect of the iris, in which the iris tissue does not develop properly
Spastic pupil syndrome – a syndrome that may be associated with Feline Leukemia virus infection

Diagnosis of Anisocoria

Test for pupillary dilatation lag to show impaired pupillary dilation in paresis of the iris dilator¹

In ambient light, estimate the difference in size between pupils (anisocoria).
Illuminate the eyes tangentially from below with a light source (e.g., flashlight) and switch off the room light.
Observe the dilatation dynamics of both pupils carefully for 20 seconds. Photos may be taken at 5, 10, 15 and 20 seconds.
In a patient with Horner syndrome, the normal pupil will dilate rapidly immediately after the room light is switched off; dilatation of the Horner pupil will be delayed because of sympathetic denervation.
After the first few seconds of darkness, the Horner pupil will dilate slowly from the decreasing parasympathetic tone and will reach its maximal dilatation after 15–20 seconds.
Anisocoria will be greater after 5 seconds in darkness than after 15–20 seconds.
The presence of anisocoria with dilatation lag is highly suggestive, but not pathognomonic, of Horner syndrome.
Blood studies such as CBC and blood differential
Cerebrospinal fluid studies (lumbar puncture)
CT scan of the head
Computed tomography (CT) angiography
Magnetic resonance (MR) angiography
Doppler ultrasonography
Digital subtraction angiography
Transoral carotid ultrasonography

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Treatment of Anisocoria

Treatment for the eye condition uveitis involves the administration of

Corticosteroids,
Prednisolone,
Non-steroidal anti-inflammatories
Antimicrobials or mydriatic-cycloplegic drugs – such as atropine or tropicamide which help to relax the iris muscles.
Glaucoma – treatment can include topical creams or drops to lower eye pressure and inflammation, along with beta-blocking drugs, diuretics, cholinesterase inhibiting drugs, corticosteroids, and mitotic medications.
Infectious conditions – such as meningitis and encephalitis, are often treated with fluid, electrolyte and oxygen therapies.
Medication – can be prescribed that is appropriate to the cause of the meningitis and encephalitis, and can include corticosteroids, antibiotics, antifungals, pain medications, and anticonvulsant drugs.
Artificial tear drops – Lubricants (also called artificial tears) are synthetic (manmade), water-based solutions that are used to lubricate the eye and thicken tears. Artificial tears are formulated as solutions or suspensions, varying in viscosity. Many people develop sensitivity to the preservatives in these solutions, causing increasing redness, burning, or itching. Most of these products are also available in a preservative-free (PF) form. Artificial tears usually are used two to five times a day as needed for relief of symptoms.
Artificial tear ointments or emollients – Ointments also are useful lubricants. These products are not water-based and contain lubricating ingredients similar to petroleum jelly. Examples of ointments include Lacri-Lube, Moisture Eyes PM, and Refresh PM. Their advantage over a water-based solution is that they remain in the eye longer. These ointments cause visual blurring immediately after their use. Therefore, they are often used only prior to sleep.
Eye washes – Eye washes (also known as ocular irrigants) are used to cleanse and/or rinse debris from the eye. These products are balanced to the proper acidity and electrolyte concentration so as to be non-irritating to the eye. Washes are available as liquids or drops. These products may contain boric acid with sodium borate, sodium phosphate, or sodium hydroxide to maintain the proper acidity. Examples of washes include AK Rinse, Dacriose, and Eye-Stream.
Hyperosmotics – Hyperosmotics are used to treat corneal swelling. Hyperosmotics draw water out of the cornea and thus reduce corneal swelling. Most OTC hyperosmotics contain sodium chloride in various concentrations as either a solution or an ointment. The 2% solution tends to cause less stinging and burning than the 5% solution but is much less effective in treating corneal swelling. An example of a hyperosmotic for corneal swelling is Adsorbonac.
Scrubs – Eyelid scrubs are useful for removing oils, debris, or loose skin that can be associated with eyelid inflammation. Soap agents provide the foaming action. An example of this type of product is Eye-Scrub.
Decongestants – Decongestants are used to shrink swollen blood vessels in the congested (red) eye, for example, in conjunctivitis. Phenylephrine is the most common decongestant for this purpose. Patients at risk for angle-closure glaucoma should cautiously use phenylephrine because it can cause an attack of the disease. Rebound congestion, in which blood vessels become dilated even with continued use of decongestants, is a common side effect of phenylephrine. Therefore, if no improvement in redness or symptoms occurs within 72 hours of use, phenylephrine should be discontinued. A frequent side effect of phenylephrine is dilation of the pupils. If phenylephrine is absorbed from the eye into the body, an increase in blood pressure may occur, although this is rare. Nevertheless, patients with high blood pressure should be cautious in using phenylephrine. Additionally, if phenylephrine is absorbed, side effects may occur due to interactions with atropine, tricyclic antidepressants , and monoamine oxidase inhibitors such as phenelzine sulfate or tranylcypromine sulfate, reserpine, guanethidine, or methyldopa.
Antihistamines – Ocular antihistamines are available OTC. These antihistamines are combined with ocular decongestants for the treatment of congestion (conjunctivitis), particularly when caused by allergy. Pheniramine maleate and antazoline both block histamine receptors in the eye, and thus provide relief from the symptoms of itchy, watery eyes. Antazoline may increase pressure slightly in the eye (of concern to patients with glaucoma) whereas pheniramine maleate has little effect on pressure. Common side effects of antihistamines include burning, stinging, and discomfort in the eye. Important side effects that may be associated with oral antihistamines have not been reported with ocular antihistamines. Antihistamines should not be used in patients at risk for developing angle-closure glaucoma. Examples of products that combine an antihistamine and decongestant are Naphcon A and Ocuhist.
Newer allergy eye-drop preparations – Recently, new classes of eye drops for the treatment of itching due to allergy have become available over the counter. Zaditor, a nonsteroidal anti-inflammatory drop, is an example of these.