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Unequal Pupils

Anisocoria is a condition, characterized by unequal pupil sizes. The causes can range from benign to life-threatening. 


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].

  • In room light, three children had anisocoria of 0.1 to 0.5 mm (9.4%), 14 had anisocoria of 0.6 to 1.2 mm (43.8%), and 15 had anisocoria of 1.3 mm or greater (46.9%).[ncbi.nlm.nih.gov]
  • Anisocoria is usually a benign finding, unaccompanied by other symptoms (physiological anisocoria). Old face photographs of patients often help to diagnose and establish the type of anisocoria.[en.wikipedia.org]
  • Group 1 included 52 patients who had normal or impaired consciousness, group 2 included 27 patients who had coma with no anisocoria and group 3 consisted of 39 patients who had coma with anisocoria.[ncbi.nlm.nih.gov]
  • Abstract Variations in anisocoria in light and dark conditions are used to help diagnose normal and pathologic conditions; however, there have been few observations of anisocoria in different lighting and accommodative conditions.[ncbi.nlm.nih.gov]
  • By the time of MRI, anisocoria had been diagnosed in 45 (32%) patients. Mortality was highest, at 58%, in patients with anisocoria and a midbrain lesion, whilst it was 23% in those with anisocoria and no lesion in the midbrain.[ncbi.nlm.nih.gov]
Pupillary Abnormality
  • Finally, an abnormality of the third cranial nerve (a nerve that comes from the brain to the eye socket and controls eyelid position, eye movement, and pupil size) can cause a pupillary abnormality.[aapos.org]
Corneal Edema
  • The presentation may be confused with aneurysmal oculomotor nerve palsy owing to the pain and fixed pupil, but corneal edema and normal motility with angle closure help separate these entities.[emedicine.medscape.com]
Neck Mass
  • Other associated signs/symptoms included ptosis (100%), heterochromia (28.1%), anhidrosis (9.4%), straight hair on affected/curly on unaffected side (9.4%), and neck mass (6.3%).[ncbi.nlm.nih.gov]
Intracranial Hemorrhage
  • 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, or lymph node in the upper chest[nlm.nih.gov]
  • Zum Verlinken/Zitieren: Dateien Name: Dissertation_FINAL Sebastian Haus.pdf Größe: 1,9 MB Format: PDF Zusammenfassung Englisch Objective: Patients showing anisocoria due to head trauma (HT) or spontaneous intracranial hemorrhage (SIH) require immediate[ediss.uni-goettingen.de]


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].

Sex distribution
Age distribution


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.

Patient Information

  • 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.

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Last updated: 2017-08-09 17:55