- Author: Eric R Eggenberger, MS, DO, FAAN; Chief Editor: Edsel Ing, MD, FRCSC more...
Anisocoria, or unequal pupil sizes, is a common condition. The varied causes have implications ranging from life-threatening to completely benign, and a clinically guided history and examination is the first step in establishing a diagnosis.
Pupil size depends on the effects of the autonomic nervous system and the iris muscle, and numerous pathophysiological processes can cause anisocoria.
From the autonomic nerve standpoint, the parasympathetic system constricts the iris, while the anatomically distinct sympathetic channels dilate the iris. The sympathetic system begins in the hypothalamus, descends through the brain stem (including the lateral medulla) and into the cervical cord to synapse in the ciliospinal center of Budge-Waller at the C8-T1 level. The second-order neuron then exits the C8-T1 nerve root, travels over the lung apex, and ascends to the superior cervical ganglia with the carotid artery. The third-order neuron leaves the superior cervical ganglia to ascend as a plexus around the internal carotid artery through the cavernous sinus, where fibers destined for the pupil dilator and the Mueller muscle of the eyelid travel with the trigeminal nerve through the superior orbital fissure to their orbital targets. Fibers destined to modulate sweating of the face travel with the external carotid artery.
The parasympathetic fibers begin in the Edinger-Westphal subnucleus of cranial nerve III in the midbrain. Parasympathetic fibers travel with the oculomotor (cranial III) nerve, traverse the cavernous sinus, and enter the orbit via the superior orbital fissure to synapse in the ciliary ganglia. The short ciliary nerves then innervate the iris sphincter and muscles of accommodation.
Anisocoria is common, although no overall prevalence statistics are available. The incidence and prevalence data for anisocoria depend on the specific pathophysiology and population. The presence of physiologic anisocoria has been estimated at 20% of the normal population, so some degree of pupil difference may be expected in at least 1 in 5 clinic patients.
Mortality and morbidity rates associated with anisocoria depend entirely upon the specific pathophysiology.
Several causes of anisocoria are life threatening, including Horner syndrome due to carotid dissection or third nerve palsy due to an aneurysm or uncal herniation.
Other causes of anisocoria are completely benign (eg, simple or physiologic anisocoria), although the unnecessary evaluation of these disorders may produce morbidity inadvertently.
Levin LA. The perils of PERRLA. Ann Intern Med. 2007 Apr 17. 146(8):615-6. [Medline].
Fan X, Miles JH, Takahashi N, Yao G. Sex-specific lateralization of contraction anisocoria in transient pupillary light reflex. Invest Ophthalmol Vis Sci. 2009 Mar. 50(3):1137-44. [Medline].
Thompson S, Pilley SF. Unequal pupils. A flow chart for sorting out the anisocorias. Surv Ophthalmol. 1976 Jul-Aug. 21(1):45-8. [Medline].
Freedman KA, Brown SM. Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. 2005 Jun. 25(2):83-5. [Medline].
Martin TJ. Horner's syndrome, Pseudo-Horner's syndrome, and simple anisocoria. Curr Neurol Neurosci Rep. 2007 Sep. 7(5):397-406. [Medline].
Kawasaki A, Borruat FX. False negative apraclonidine test in two patients with Horner syndrome. Klin Monbl Augenheilkd. 2008 May. 225(5):520-2. [Medline].
Wehbe E, Antoun SA, Moussa J, Nassif I. Transient anisocoria caused by aerosolized ipratropium bromide exposure from an ill-fitting face mask. J Neuroophthalmol. 2008 Sep. 28(3):236-7. [Medline].
Andreola B, Piovan A, Da Dalt L, Filippini R, Cappelletti E. Unilateral mydriasis due to Angel's trumpet. Clin Toxicol (Phila). 2008 Apr. 46(4):329-31. [Medline].
Cremer SA, Thompson HS, Digre KB, Kardon RH. Hydroxyamphetamine mydriasis in Horner's syndrome. Am J Ophthalmol. 1990 Jul 15. 110(1):71-6. [Medline].
Harle DE, Wolffsohn JS, Evans BJ. The pupillary light reflex in migraine. Ophthalmic Physiol Opt. 2005 May. 25(3):240-5. [Medline].
Kardon RH, Denison CE, Brown CK, Thompson HS. Critical evaluation of the cocaine test in the diagnosis of Horner's syndrome. Arch Ophthalmol. 1990 Mar. 108(3):384-7. [Medline].
Lowenfeld IE. The Pupil. Anatomy, Physiology, and Clinical Application. 1993.
Miller NR, Newman NJ, eds. Walsh & Hoyt's Clinical Neuro-ophthalmology. 1998. Vol 1:
Moster ML, Galiani D, Garfinkle W. False negative hydroxyamphetamine test in horner syndrome caused by acute internal carotid artery dissection. J Neuroophthalmol. 2003 Mar. 23(1):22-3. [Medline].
Pishdad GR, Pishdad P, Pishdad R. Pupillary autonomic neuropathy simulating partial Horner syndrome in diabetes mellitus and its reversal with control of blood glucose. J Neuroophthalmol. 2008 Sep. 28(3):241-2. [Medline].