Question 1 of 10

    Anisocoria (Unequal Pupils)

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

    Presentation

    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].

    Eyes
    Anisocoria
    • Concepts Finding ( T033 ) MSH D015875 ICD9 379.41 ICD10 H57.02 SnomedCT 194165001 , 103270007 , 13045009 English Anisocoria , ANISOCORIA , anisocoria (physical finding) , anisocoria , unequal pupils , Anisocoria-unequal pupil diam. , Pupil unequal , Pupils[fpnotebook.com]
    • Intermittent Anisocoria If the anisocoria is episodic, it may be intermittent.[hxbenefit.com]
    • A14 Anisocoria anisocoria unequal or asymmetric pupils. prechiasmal anisocoria mydriasis caused by disorders of the retina or optic nerve.[medical-dictionary.thefreedictionary.com]
    • The prevalence of simple anisocoria.[umem.org]
    Marcus Gunn Pupil
    • A relative afferent pupillary defect (RAPD) also known as a Marcus Gunn pupil does not cause anisocoria.[en.wikipedia.org]
    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]
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  • cardiovascular
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  • neurologic
    Intracranial Hemorrhage
    • Zum Verlinken/Zitieren: Englisch Objective: Patients showing anisocoria due to head trauma (HT) or spontaneous intracranial hemorrhage (SIH) require immediate evaluation and neurosurgical intervention.[ediss.uni-goettingen.de]
    • 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]
    Confusion
    • Confusion may also be present, which may indicate head trauma or internal pressure.[petmd.com]
    • Anisocoria in the presence of confusion, decreased mental status, severe headache, or other neurological symptoms can forewarn a neurosurgical emergency.[en.wikipedia.org]
    • Head trauma is a common cause of anisocoria (unequal pupil size) and may cause confusion, pacing and other problems.[vetary.com]
    • Sebaceous Cell Carcinoma of the Lid – Cancers derived from the glands within the eyelids that may confused with recurrent chalazion or stye and often associated with eyelash loss.[eye.keckmedicine.org]
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  • Face, Head & Neck
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  • Entire body system
    Hunting
    • As Kevin Hunt reports for the Conversation, some people mistakenly assume it was caused by heterochromia , a condition in which a person has two different iris colors.[nymag.com]
    • Hunt, Kevin (January 11, 2016).[en.wikipedia.org]
    • This gave the illusion of a difference in colour, explains Kevin Hunt, senior lecturer in design and visual culture at Nottingham Trent University, Here, writing for The Conversation , he explains what anisocoria is, and tells the remarkable story of[dailymail.co.uk]
    • […] carotid artery – dissection – trauma – thrombosis – tumor – cluster headache Base of skull/carotid canal – tumor (nasopharyngeal CA) – trauma Middle ear – tumor (cholesteatoma) – infection Cavernous sinus – tumor (pituitary adenoma) – inflammation (Tolosa Hunt[lifeinthefastlane.com]
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  • Workup

    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].

    Laboratory

    Serum
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  • Treatment

    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

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

    Complications

    Cluster Headache
    • Other conditions that cause anisocoria include migraines and cluster headaches, trauma, ocular inflammation (either previous or current), multiple sclerosis, ischemic optic neuropathy, significant retinal disease, certain eye drops, certain medications[baltimorewashingtoneyecenter.blogspot.com]
    • Medical causes include Horner’s syndrome, Argyll Robertson pupil, and cluster headaches.[healthcentral.com]
    • While there are benign things that can cause Horner's, such as cluster headaches( ), you need to rule out the more serious causes.[forums.studentdoctor.net]
    • […] central catheter) – infection (eg. apical TB) Anterior neck – iatrogenic (thyroid or neck surgery) – trauma – tumor Superior cervical ganglion – iatrogenic (tonsillectomy) – trauma Internal carotid artery – dissection – trauma – thrombosis – tumor – cluster[lifeinthefastlane.com]
    Intracranial Hypertension
    • Idiopathic Intracranial Hypertension – raised intracranial pressure in the absence of a brain tumor, meningitis, or hydrocephalus.[eye.keckmedicine.org]
    Multiple Sclerosis
    • There are a number of other systemic diseases and conditions that may show themselves in the eyes, including an overactive thyroid , multiple sclerosis and infectious diseases such as HIV /AIDS.[m.webmd.boots.com]
    • ., multiple sclerosis ), head trauma, and brain tumors are the most common causes of oculomotor nerve palsy in adults.[en.wikipedia.org]
    • DO, MS, FAAN Professor, Vice-Chairman, Department of Neurology and Ophthalmology, Colleges of Osteopathic Medicine and Human Medicine, Michigan State University; Director of Michigan State University Ocular Motility Laboratory; Director of National Multiple[emedicine.medscape.com]
    • Other conditions that cause anisocoria include migraines and cluster headaches, trauma, ocular inflammation (either previous or current), multiple sclerosis, ischemic optic neuropathy, significant retinal disease, certain eye drops, certain medications[baltimorewashingtoneyecenter.blogspot.com]
    • However, if multiple sclerosis has caused damage to the 2nd or 3rd cranial nerves, then you may show anisocoria.[healthcentral.com]
    Parinaud Syndrome
    • Adie’s tonic pupil) or a midbrain lesion limited to the pre-tectal area of the dorsal midbrain (Parinaud’s syndrome) – causes of Parinaud’s syndrome include pinealomas, brainstem encephalitis, brainstem infarction and multiple sclerosis – the pupil in[lifeinthefastlane.com]
    • See also [ edit ] Cycloplegia Miosis Mydriasis Parinaud's syndrome References [ edit ] Lam, BL; Thompson, HS; Corbett, JJ (Jul 15, 1987).[en.wikipedia.org]
    • Some other cause of a large pupil include: Iris trauma, Parinauds syndrome, Migraine.[cataract.org.uk]
    Carotid Artery Aneurysm

    Etiology

    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]

    Causes

    Epidemiology

    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

    Pathophysiology

    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].

    Prevention

    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.

    Summary

    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.

    Other symptoms

    Pilocarpine
    • […] eyedrops (two drops of 0.1% solution dilute the standard 1% solution 1:10 with water) and then, if no response to dilute pilocarpine within 30 minutes use standard dose (1% solution) pilocarpine eyedrops – 0.1% pilocarpine eyedrops pupillary constriction[lifeinthefastlane.com]
    • 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.[en.wikipedia.org]
    • Differentiation between paralytic and pharmacologic mydriasis can be made by using a 1% pilocarpine eye drops test.[ijponline.biomedcentral.com]
    • Pilocarpine) Mydriasis (pupil dilatation) of one, but not the other mydriatic drug (e.g.[gpnotebook.co.uk]
    • If extraocular movements are intact, an ophthalmologist can further differentiate among causes by instilling a drop of a pupillary constrictor (eg, 0.1% pilocarpine ).[merckmanuals.com]
    Anticholinergic
    • […] properties the condition is then referred to as anticholinergic mydriasis or 'atropine' mydriasis ).[medical-dictionary.thefreedictionary.com]
    • […] drop or misplaced nebulizer : Unilateral mydriasis, caused by direct anticholinergic drug effect on iris because of a badly fitting face mask.[mmcneuro.wordpress.com]
    • Correct me if I'm wrong but I seem to recall that if the iris dilator is stimulated with a drug like epinephrine and the iris sphincter is NOT blocked by an anticholinergic drug, then you should get some constriction of the pupil if you shine a light[forums.studentdoctor.net]
    • The differential diagnosis included intracranial haemorrhage or other space-occupying lesion causing oculomotor nerve compression, impaired venous return from the head, ocular trauma, ocular exposure to sympathomimetic or anticholinergic agents, and pre-existing[onlinelibrary.wiley.com]
    • Pharmacological agents with anticholinergic or sympathomimetic properties will cause anisocoria, particularly if instilled in one eye.[en.wikipedia.org]
    Scopolamine
    • All Brugmansia and Datura plants contain, primarily in their seeds and flowers, tropane alkaloids such as scopolamine, hyoscyamine and atropine.[ijponline.biomedcentral.com]
    • […] drugs may be drops intended to treat eye disorders (for example, homatropine used for certain inflammatory disorders or injuries or pilocarpine used for glaucoma), or they may be drugs or other substances that accidentally get into the eye (for example, scopolamine[merckmanuals.com]
    • Some examples of pharmacological agents which may affect the pupils include pilocarpine , cocaine , tropicamide , MDMA , dextromethorphan , and ergolines . [4] Alkaloids present in plants of the genera Brugmansia and Datura , such as scopolamine , may[en.wikipedia.org]
    • […] pupil (due to syphilis) Pupils that respond more to accommodation than to light; possibly findings suggesting syphilis Congenital iris defects Associated ocular abnormalities, chromosomal disorder, nonocular congenital defects, chronicity Drugs (eg, scopolamine[merckmanuals.com]
    • Atropine, scopolamine, and spray perfumes containing belladonna are well known to cause pharmacologic pupillary dilation by direct or indirect contamination of the eye.[journals.lww.com]
    Sympathomimetic
    • Also, Sympathomimetics probably will not cause distortion or vision or affect the ability to accommodate.[forums.studentdoctor.net]
    • The differential diagnosis included intracranial haemorrhage or other space-occupying lesion causing oculomotor nerve compression, impaired venous return from the head, ocular trauma, ocular exposure to sympathomimetic or anticholinergic agents, and pre-existing[onlinelibrary.wiley.com]
    • Pharmacological agents with anticholinergic or sympathomimetic properties will cause anisocoria, particularly if instilled in one eye.[en.wikipedia.org]
    • […] drugs (-) (-) (* topical sympathomimetic drugs may also cause conjunctival blanching and eyelid retraction, and strong light can still induce a pupillary constrictor response; atropinic mydriasis may last 1 – 2 weeks and strong light may only induce[lifeinthefastlane.com]
    Carotid Artery Dissection
    • Horner’s syndrome is important to diagnosis, because it can indicate a lesion in the brain stem ( stroke ), neck ( carotid artery dissection ) or lung apex ( Pancoast’s tumor ).[mmcneuro.wordpress.com]
    • Some of the causes of anisocoria are life-threatening, including Horner's syndrome (which may be due to carotid artery dissection ) and oculomotor nerve palsy (due to a brain aneurysm, uncal herniation , or head trauma).[en.wikipedia.org]
    Ischemia
    • 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.[en.wikipedia.org]
    • The differential diagnosis of this disease involves: Adie’s Syndrome Botulism Alcohol intoxication Cerebral Aneurysm Brain tumor Diabetes mellitus Encephalitis Herpes zoster Injury on the iris Iridocyclitis Ischemia Lead Poisoning Intracranial Hemmorage[hxbenefit.com]
    • […] external carotid artery to the face – the superior cervical ganglion is situated at the bifurcation of the carotid artery in the upper neck) Causes of Horner’s syndrome Central Preganglionic Postganglionic Hypothalamus – infarct – tumor Brainstem – ischemia[lifeinthefastlane.com]
    Demyelinization
    • 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.[en.wikipedia.org]
    • […] face – the superior cervical ganglion is situated at the bifurcation of the carotid artery in the upper neck) Causes of Horner’s syndrome Central Preganglionic Postganglionic Hypothalamus – infarct – tumor Brainstem – ischemia – hemorrhage – tumor – demyelination[lifeinthefastlane.com]
    Fibromuscular Dysplasia
    • dysplasia, Ehlers–Danlos syndrome type IV (vascular type), Marfan syndrome, cystic medial necrosis, polycystic kidney disease, α 1 -antitrypsin deficiency and osteogenesis imperfecta type I. 3 , 8 However, people with connective tissue disorders account[cmaj.ca]
    Dextromethorphan
    • Some examples of pharmacological agents which may affect the pupils include pilocarpine , cocaine , tropicamide , MDMA , dextromethorphan , and ergolines . [4] Alkaloids present in plants of the genera Brugmansia and Datura , such as scopolamine , may[en.wikipedia.org]
    Demyelinating Disease
    • 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.[en.wikipedia.org]
    Adolescence
    No Language
    • Etymology [ edit ] Anisocoria is composed of prefix, root and suffix: prefix: aniso- from the Greek language (meaning: unequal ), which in turn comes from an : meaning not and iso : meaning equal the root word: cor , from the Greek word "korē" meaning[en.wikipedia.org]
    Benign Condition

    Self-assessment

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    References

    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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