The presentation is dependent on the cause of the anisocoria. It seldom causes any symptoms (the symptoms are usually of the underlying pathology). Many times it is found incidentally and examination of old photographs may assist.

A pupil exam is required to identify the pupil with the problem. First the pupils have to be examined in dark and light rooms. The small pupil is abnormal if the anisocoria is worse in the dark and the larger pupil is abnormal if the anisocoria is worse in the light when compared to dark conditions.

History of any associated conditions and drugs is necessary to find the cause. A full eye exam is required to find the cause and other signs such as ptosis and double vision [6] [7].

• Inflammation

  Most patients with iritis (intraocular inflammation) have marked eye discomfort and ... [accesspediatrics.mhmedical.com]

  Difference in pupil diameters as viewed in dim illumination May be physiologic (normal variant) if diameter difference is 1mm or less and both pupils react briskly and equally to light Pathologic causes are eye inflammation (anterior uveitis) or trauma [kellogg.umich.edu]

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

  Anisocoria can occur as a result of injury (e.g. to the iris sphincter muscle), inflammation (e.g. iridocyclitis), diseases of the iris, paralysis of the third nerve, angle-closure glaucoma, systemic diseases (e.g. diabetes, syphilis) or accidental drug [medical-dictionary.thefreedictionary.com]

• Swelling

  Uncal Hernation – brain swelling after injury or stroke All new pupil abnormalities need to be evaluated by a doctor. [rooteyedictionary.com]

  […] unequal pupil sizes may include: Aneurysm in the brain Bleeding inside the skull caused by head injury Brain tumor or abscess (such as, pontine lesions) Excess pressure in one eye caused by glaucoma Increased intracranial pressure, because of brain swelling [nlm.nih.gov]

  Bleeding, swelling. Diseases of the iris. Circulatory disorders of the brain. Diseases of the nervous system. Infectious diseases – epidemic encephalitis, complications of syphilis, visceral leishmaniasis. Heredity. [medical-enc.com]

  Concussion is dangerous because it can cause bruising of the brain tissue and associated swelling. (Recent research has shown that re-injury to the brain before an earlier concussion can heal is a factor in even more serious damage. [kanataoptometry.ca]

• Asymptomatic

  The girl remained asymptomatic but remarked that she felt like “something was getting in (her) eye” during the nebulizer treatment. [pediatricsconsultant360.com]

  The patient with ATP may be totally asymptomatic, and is often brought to a physician's office by a friend or relative who notices that he or she has one large pupil. [ophthalight.com]

  An asymptomatic 65-year-old patient with no prior ocular surgery but a history of hypertension, hyperlipidemia, and hypothyroidism was noted to have a left miotic pupil during a routine ophthalmic examination. [n.neurology.org]

  […] cough, chest pain, or dyspnea (Horner syndrome); genital lesions, adenopathy, rashes, or fever (syphilis Syphilis Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential symptomatic stages separated by periods of asymptomatic [msdmanuals.com]

  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. [emedicine.medscape.com]

• Surgical Procedure

  Also, there are reports of a variety of unusual causes involving a number of medicines as well as surgical procedures that usually occur on the face. [statpearls.com]

  After the surgical procedures, there were no signs of iatrogenic lesions and we observed a correct hemostasis of the surgical site. [medsci.org]

  Lesions can be found along the oculosympathetic pathway caused by birth trauma, surgical procedures, benign and malignant neoplasia, lymphadenopathy, vascular and cerebral malformations, carotid artery thrombosis, or dissection in pediatric patients [ [hindawi.com]

• Short Stature

  short children 7.2.7 Syndromic growth disorders 7.2.8 Tall stature 7.2.9 Delayed puberty and hypogonadism 7.2.10 Premature sexual maturation 7.3 Congenital adrenal hyperplasia in children 7.4 Late effects of cancer treatment 7.5 Transition in endocrinology [oxfordmedicine.com]

• Neck Pain

  Go to the emergency room right away if your pupils are different sizes and you experience any of the following symptoms at the same time: Eye pain. Blurry, double or loss of vision. Light sensitivity. Neck pain. Nausea and vomiting. [my.clevelandclinic.org]

  But if there are underlying disorders causing your unequal pupils, you may have symptoms related to those: Problems moving your eye around Pain in your eye Ptosis (drooping eyelid) Headache Fever Nausea and vomiting Reduced sweating Neck pain If you have [webmd.com]

  This was a 19-year-old man, with no significant clinical history or known toxic habits, who attended the emergency room due to a 12-h history of cervical neck pain associated with central chest discomfort, and a “crackling” sound on palpation of the neck [archbronconeumol.org]

• Sweating

  The syndrome is characterized by anisocoria (pupil smaller on the affected side), mild ptosis, and anhidrosis (decreased sweating on the affected side of the face) (Figure 18–1). It typically does not cause vision problems. [accesspediatrics.mhmedical.com]

  Abstract Four patients with anhidrosis associated with normal sweat glands at skin biopsy are reported. One patient had a positive family history. All of them had pupillary asymmetry. [ncbi.nlm.nih.gov]

  These nerves also control the muscles that open your eyelids and activate the sweat and tear glands on your face. Horner syndrome occurs when these nerves do not work. [nanosweb.org]

  The pupil on the affected side is small, that side of the face does not sweat, and the upper eyelid is droopy (ptosis). The eye may be sunken into its socket. Horner's syndrome may be a dangerous sign. [webmd.com]

  It is often, though not always, part of a triad of signs, the other two being an ipsilateral droopy eyelid (ptosis), and lack of sweating (anhidrosis). [morancore.utah.edu]

• Decreased Sweating

  The syndrome is characterized by anisocoria (pupil smaller on the affected side), mild ptosis, and anhidrosis (decreased sweating on the affected side of the face) (Figure 18–1). It typically does not cause vision problems. [accesspediatrics.mhmedical.com]

  sweating, a small pupil, or drooping eyelid all on the affected side (Horner syndrome) Diabetic occulomotor nerve palsy Prior eye surgery for cataracts Treatment depends on the cause of the unequal pupil size. [nlm.nih.gov]

  sweating, a small pupil, or drooping eyelid all on the affected side (Horner syndrome) Diabetic oculomotor nerve palsy Prior eye surgery for cataracts Home Care Treatment depends on the cause of the unequal pupil size. [pennstatehershey.adam.com]

  sweating, a small pupil, or drooping eyelid all on the affected side (Horner syndrome) Home Care Treatment depends on the cause of the unequal pupil size. [coordinatedhealth.com]

• Erythema

  Less common signs: Lack of sweating and erythema unilaterally. Urgent to determine location of the lesion with imaging along the sympathetic pathway or referral to an ophthalmologist as the cause can be life threatening. [morancore.utah.edu]

• Anisocoria

  Anisocoria is unequal pupil sizes. Anisocoria itself does not cause symptoms. [merckmanuals.com]

  Degree of anisocoria is about the same in the dark. A Horner's pupil will result in anisocoria that is greater in the dark than in the light (abnormal pupil is the smaller one). [webeye.ophth.uiowa.edu]

  Horner syndrome Two conditions commonly produce normally reactive pupils with anisocoria equal or greater in darkness: Horner syndrome and physiologic anisocoria. [emedicine.medscape.com]

  Measure amount of anisocoria in dim illumination; more than 1.5mm usually pathologic, especially if pupil constricts poorly to light Refer to ophthalmologist if findings suggest pathologic anisocoria Refer urgently if you suspect third nerve palsy (could [kellogg.umich.edu]

• Eye Pain

  An ophthalmologist should be seen to rule out ocular causes of eye pain and pupil asymmetry, especially when vision loss or changes, redness or discharge from the eye(s) is present. [hopkinsmedicine.org]

  The Patient A 61-year-old female complains of sudden onset right eye pain, headache, blurred vision, and vomiting 2 hours prior to coming to the ED. Physical examination reveals a patient who is alert and in pain. Vital signs are normal. [emra.org]

• Blurred Vision

  A 12 year old boy presented with an acute onset of anisocoria and blurred vision. Ocular motility was normal but his right pupil was dilated, round but sluggishly reactive to light. [ncbi.nlm.nih.gov]

  The Patient A 61-year-old female complains of sudden onset right eye pain, headache, blurred vision, and vomiting 2 hours prior to coming to the ED. Physical examination reveals a patient who is alert and in pain. Vital signs are normal. [emra.org]

• Diplopia

  Symptoms and signs include diplopia, ptosis, and paresis of eye adduction and of upward and downward gaze... read more is likely. [msdmanuals.com]

  Call it pathologic if anisocoria greater than 1mm in dim illumination, one pupil constricts poorly to light, or pupil shape irregular If you find ptosis on side of smaller pupil, consider Horner syndrome If you find ptosis, diplopia, or abnormal eye movements [kellogg.umich.edu]

  Ophthalmoparesis and diplopia are considered early findings of MFS, and pupillary abnormalities indicating internal ophthalmoplegia are well described. [hindawi.com]

  As long as there are no other accompanying signs and symptoms (e.g., diplopia, pain, ptosis), this represents a benign, normal anatomic variant. • Horner's Syndrome Horner's syndrome results from disruption of the sympathetic fibers anywhere between the [casemed.case.edu]

  In diplopia it mentions a simple analysis of the disorder and its most frequent neurogenic and myogenic causes. [medvik.cz]

• Photophobia

  The Patient A 65-year-old male with sarcoidosis complains of gradual onset left eye pain and photophobia. These symptoms have occurred previously. Consensual and direct photophobia is present. [emra.org]

  About 80 percent of patients with ATP may have symptoms such as anisocoria, photophobia, and difficulty with dark adaptation. ATP prevalence is about two cases per 1000 population. [ophthalight.com]

  Case summary A 53-year-old woman with congenital deafness visited the clinic complaining of photophobia and heterochromic iris in the left eye. Her best-corrected visual acuity was 1.0 in the right eye and 0.7 in the left eye. [synapse.koreamed.org]

  Photophobia. Double sight surroundings. Causes The most common causes of anisocoria: Eye injury – occurrence of hematomas. Bleeding, swelling. Diseases of the iris. Circulatory disorders of the brain. Diseases of the nervous system. [medical-enc.com]

• Suggestibility

  Some Common Causes of Anisocoria Cause Suggestive Findings Adie tonic pupil (idiopathic impaired constriction) Pupils that respond more to accommodation than to light; delayed dilation after constriction Argyll Robertson pupil (due to syphilis) Pupils [merckmanuals.com]

  […] one pupil constricts poorly to light, or pupil shape irregular If you find ptosis on side of smaller pupil, consider Horner syndrome If you find ptosis, diplopia, or abnormal eye movements or alignment, consider third nerve palsy Irregular pupil shape suggests [kellogg.umich.edu]

  Anisocoria which is worsened (greater asymmetry between the pupils) in the dark suggests the small pupil (which should dilate in dark conditions) is the abnormal pupil and suggests Horner's syndrome or mechanical anisocoria. [wikiplanet.click]

  Mydriasis was temporary in both cases, suggesting that the anisocoria was most likely related to Adie syndrome. [ncbi.nlm.nih.gov]

• Stroke

  […] other diagnoses that can mimic a stroke. [casereports.bmj.com]

  Antiplatelet therapy vs. anticoagulation in cervical artery dissection: rationale and design of the Cervical Artery Dissection in Stroke Study (CADISS). Int J Stroke 2007 ; 2 : 292 – 6. ↵ ↵ [cmaj.ca]

  Identification of nonischemic stroke mimics among 411 code strokes at the University of California, San Diego, Stroke Center. J Stroke Cerebrovasc Dis. 2008; 17: 23-25 Merino JG Luby M Benson RT et al. [strokejournal.org]

  The sooner treatment of stroke is begun, the better the outcome. Anisocoria can be one of the first symptoms of a stroke. It may be seen when a stroke is about to happen. Third Nerve Palsy (TNP). [webmd.com]

  Anisocoria is known to result from strokes, depending on where the stroke is located in the brain. Anisocoria is often found in strokes of the pons. The pons is a part of the brainstem that is very important for sleep and arousal. [medfriendly.com]

• Meningism

  Infectious conditions, such as meningitis and encephalitis, are often treated with fluid, electrolyte and oxygen therapies. [wagwalking.com]

  They can also point to meningitis, other types of infections, or bleeding somewhere in the body. Imaging tests may be performed to look for injuries or abnormalities, such as a brain tumor. [nvisioncenters.com]

  This can happen as a result of taking certain medications; however, more serious causes can include brain tumors, meningitis, migraines, seizures, bleeding in the skull, aneurysm, or an abscess in the brain. [study.com]

  […] tumor or abscess (such as, pontine lesions) Excess pressure in one eye caused by glaucoma Increased intracranial pressure, because of brain swelling, intracranial hemorrhage, acute stroke, or intracranial tumor Infection of membranes around the brain ( meningitis [nlm.nih.gov]

• Intracranial Hemorrhage

  […] of brain swelling, intracranial hemorrhage, acute stroke, or intracranial tumor Infection of membranes around the brain ( meningitis or encephalitis ) Migraine headache Seizure (pupil size difference may remain long after seizure is over) Tumor, mass [nlm.nih.gov]

  hemorrhage (SIH) require immediate evaluation and neurosurgical intervention. [ediss.uni-goettingen.de]

  […] of brain swelling, intracranial hemorrhage, acute stroke, or intracranial tumor Infection of membranes around the brain (meningitis or encephalitis) Migraine headache Seizure (pupil size difference may remain long after seizure is over) Tumor, mass, [pennstatehershey.adam.com]

  However, anisocoria can be a result of serious trauma or conditions, such as: A brain abscess or tumor Intracranial hemorrhaging Brain swelling An aneurysm A stroke Inflamed membranes surrounding the brain Anisocoria can also be caused by migraines or [allabouteyes.com]

• Dizziness

  These include: Anticholinergics, a class of medication for conditions including: COPD gastrointestinal symptoms Parkinson’s disease treatment of poisoning asthma dizziness motion sickness Oral pilocarpine, which treats dry mouth or damaged saliva glands [medicalnewstoday.com]

  Other important symptoms that do not involve the eyes include headache, dizziness or loss of balance, cough, chest pain, or shortness of breath. [msdmanuals.com]

• Vertigo

  Scopolamine, a belladonna alkaloid, a frequently used medication in the hospital setting, is most commonly used for motion sickness, prevention of postoperative nausea/vomiting, vertigo, dizziness and drooling, 2 4 5 acts as a competitive antagonist to [casereports.bmj.com]

  […] patches (“cruise ship” anisocoria) – neosynephrine nasal sprays or eyedrops – flea collar powders (anti-cholinesterases) – inquire about abnormal neurological symtoms – focal weakness or sensory deficits – dysarthria or dysphagia or diploplia – ataxia or vertigo [lifeinthefastlane.com]

First the affected pupil is identified by using the method as detailed above. If the anisocoria is greater in the dark, then the dilation lag cocaine test is done. Cocaine dilates the normal pupil but not the affected pupil, in syndromes such as Horner’s syndrome. If the test show no lag and there are no other features then it is most likely diagnosis is physiological.

If the anisocoria is greater in light then the number of differentials is increased. Conditions such as third nerve palsy have to be examined. The pharmacologic pupil is larger than most other causes of anisocoria and there is poor response to light. The rest of the exam may be normal. Possible exposures should be found. Mechanical cause have an obvious history such as trauma and surgery.

Imaging studies will dependent on the possible cause. For suspected Horner’s syndrome a magnetic resonance imaging (MRI) or angiography may be required. Third nerve palsies should be presumed compressive if there is a pupillary involvement. The imaging modality will depend on the suspected etiology [7] [8] [9] [10].

This is highly dependent on the cause of the anisocoria. The benign causes do not warrant treatment. Life-threatening causes will require immediate attention.

Prognosis is dependent on the cause and which may be totally benign or life threatening.

Structural defects can cause anisocoria. Congenital defects such ectopic pupils and lenses, Rieger’s syndrome and other defects may cause the pupils to be unequal. Other causes may be trauma and glaucoma.

Physiologic anisocoria is seen in about twenty percent of the population. The anisocoria is usually less than 0.4mm, and there is no lag in the dilation or constriction. The physiologic anisocoria is usually persistent.

If the small pupil is abnormal it means the pupil is not dilated well. The cause include:

• Previous ocular surgery
• Iridocyclitis
• Drugs such as some eye drops. 
• Horner’s syndrome

If the large pupil is abnormal, this occurs when the pupil doesn’t respond well to light when there is an ipsilateral parasympathetic pathway. Causes include:

• Trauma
• Synechia 
• Chronic medication use
• Third nerve palsy
• Tonic pupil [4] [5]

This condition is common, but the true prevalence is unknown. Physiological anisocoria is noted in over 20% of the general population. The mortality depends on the underlying causes. These causes may be life threatening like Horner’s syndrome which may be due to neck injury or carotid dissection, and herniation [4].

The pathophysiology depends on the underlying cause and an injury in either the dilator or constrictor pathway may cause anisocoria.

Pupillary size is determined by a balance between the dilator and sphincter muscles and by reflex actions that are responsive to light. Other factors such as the sympathetic tone and may also influence the pupil size.

Constriction is mediated by increasing light and near vision. This is primarily transferred via parasympathetic fibres that originate from the Edinger-Westphal subnucleus of cranial nerve III in the midbrain. Dilatation is mediated by sympathetic outflows that originate from the hypothalamus. The first order neuron descends down to the spinal cord to the T2 level. The second order neuron travels upward the cervical spine via the brachial plexus and over the apex of the lung to the cervical (superior) ganglion, near the bifurcation of the carotid. The third order neuron then ascends with the carotid artery to the lateral sellar compartment, where it travels near the sixth nerve. The fibres then travel with the fifth cranial nerve and innervate the dilator muscle and the Mueller muscle [1] [2] [3].

Due to the large number of differential diagnosis, the prevention strategies will be determined by the underlying etiologies. In many of the cause such as trauma, protective gear and eye wear should be worn in potentially dangerous environments.

Anisocoria is a condition characterized by an unequal size of the pupils. It is a common disorder with causes ranging from benign to life-threatening. It is defined by a difference of more than 0.4mm between the pupils. A systematic approach is required to identify patients with serious conditions.

• Definition: Anisocoria is the presence of unequal pupils. The causes a numerous from non-life threatening to threatening ones. There is a large proportion of the population that has a benign form which is usually noticed incidentally. 
• Cause: The causes are numerous, but there is usually damage to the nerve that supplys the muscle that either make pupil bigger or smaller. This can range from infections of the nerves to masses pushing on the nerve. A common cause could be inside the eye, due to previous surgery or trauma. 
• Symptoms: The may be no symptoms. If symptoms are present they are usually of the associated cause, such as a brain tumour. There may also be double vision or a droopy eye lid.
• Diagnosis: This will depend on the history and presentation. In the benign type it is advisable to look at older pictures, such as drivers licences (with a magnifying glass) to see if it has always been there (and it usually is). 
• Treatment: This is highly dependent on the cause of the anisocoria. The benign causes require no treatment at all.
• Prevention: There are many causes, of which some are unpreventable, but traumatic causes may be prevented with appropriate protective gear.

1. Biousse, V, Newman, NJ. Neuro-Ophthalmology Illustrated, Thieme Verlag, Germany 2009.
2. Johnston JA, Parkinson D. Intracranial sympathetic pathways associated with the sixth cranial nerve. J Neurosurg 1974; 40:236
3. Digre, KB. Principles and techniques of examination of the pupils, accommodation and lacrimation. In: Walsh and Hoyt Clinical Neuro-ophthalmology, 6th ed, Miller, NR, Newman, NJ, Biousse, V, Kerrison, JB (Eds), Williams & Wilkins, Baltimore 2005. p.715.
4. Lam BL, Thompson HS, Corbett JJ. The prevalence of simple anisocoria. Am J Ophthalmol 1987; 104:69.
5. Biousse V, Newman NJ. Third nerve palsies. Semin Neurol 2000; 20:55.
6. Martin TJ. Horner's syndrome, Pseudo-Horner's syndrome, and simple anisocoria. Curr Neurol Neurosci Rep. Sep 2007;7(5):397-406.
7. Thompson S, Pilley SF. Unequal pupils. A flow chart for sorting out the anisocorias. Surv Ophthalmol. Jul-Aug 1976;21(1):45-8
8. Miller NR, Newman NJ, eds. Walsh & Hoyt's Clinical Neuro-ophthalmology. Vol 1. 1998.
9. Kardon RH, Denison CE, Brown CK, Thompson HS. Critical evaluation of the cocaine test in the diagnosis of Horner's syndrome. Arch Ophthalmol. Mar 1990;108(3):384-7
10. Kawasaki, A. Disorders of pupillary function, accommodation and lacrimation. In: Walsh and Hoyt Clinical Neuro-ophthalmology, 6th ed, Miller, NR, Newman, NJ, Biousse, V, Kerrison, JB (Eds), Williams & Wilkins, Baltimore 2005. p.739.