Pupillary Disorders


Pupillary abnormalities range from benign isolated findings to harbingers of significant, even life‐threatening, conditions. A complete understanding of the neuroanatomy underlying the innervations to the antagonistic pupillary sphincter and dilator muscles is essential to detecting, and discerning the importance of, a particular pupillary abnormality. The sphincter muscle receives neuronal input from the parasympathetic division of the autonomic nervous system, whereas the dilator muscle receives input from the sympathetic division. Afferent input carrying light information to the brain is transmitted by retinal ganglion cell axons via the optic nerves, chiasm, and tracts. The parasympathetic innervation to the pupil originates in the Edinger‐Westphal nucleus in the midbrain. The sympathetic innervation to the pupil consists of a three‐neuron pathway originating in the hypothalamus. Important pupillary disorders include physiologic anisocoria, relative afferent pupillary defect, amaurotic pupil, Argyll Robertson pupils, cranial nerve III palsy, pharmacologic mydriasis, tonic pupil, and Horner syndrome.

Key Concepts:

  • Examination of the pupil is an important part of the physician's neurological and ophthalmological evaluation of a patient.

  • The size of the pupil is controlled by the actions of antagonistic muscles located within the iris: the pupillary sphincter and dilator.

  • Constriction of the pupils is mediated by the parasympathetic nervous system, whereas dilation of the pupils is mediated by the sympathetic nervous system.

  • Pupillary constriction to light occurs via an involuntary reflex arc.

  • Retinal ganglion cell axons involved in carrying light information for the pupillary light reflex exit the optic tract (proximal to the lateral geniculate nucleus) to synapse in the midbrain pretectal nucleus.

  • The parasympathetic output controlling pupillary constriction originates in the Edinger‐Westphal nucleus in the midbrain and terminates at the pupil sphincter muscle.

  • Pupillary dilation involves a ‘three‐neuron’ sympathetic pathway, which originates in the posterolateral hypothalamus and terminates at the pupil dilator muscle.

  • A relative afferent pupillary defect is caused by a decreased amount of light information from the affected eye reaching the pretectal nuclei in the midbrain and is most commonly a sign of ipsilateral optic nerve pathology.

  • Damage to cranial nerve III can result in injury to the parasympathetic fibres travelling to the pupillary sphincter muscle, thus disrupting the efferent arc of the pupillary light reflex, resulting in deficient pupillary constriction on the involved side.

  • Horner syndrome, characterised by miosis, ptosis, and facial anhidrosis, results from disruption of the oculosympathetic pathway.

Keywords: pupil; pupillary disorders; anisocoria; miosis; mydriasis; Horner syndrome; afferent pupillary defect; cranial nerve III palsy; sympathetic; parasympathetic

Figure 1.

A normal left eye. The pupil is the round dark area in the middle of the eye. The iris surrounds the pupil and is brown in this person.

Figure 2.

Parasympathetic pathway for pupil constriction to light. Light entering one eye (orange arrows, bottom right) leads to stimulation of retinal ganglion cells whose axons project through the optic nerve (ON). Some of these axons cross at the optic chiasm (OC) to travel within the contralateral optic tract (OT) whereas others continue to travel through the ipsilateral optic tract. The fibres then leave the optic tract, bypass the lateral geniculate nucleus (LGN), travel through the brachium of the superior colliculus (SC), and synapse at the pretectal nucleus (PTN). Interneurons then connect bilaterally to the cranial nerve III nuclear complex (III Nuc) at the Edinger‐Westphal nuclei (EW). The Edinger‐Westphal nuclei then issue parasympathetic fibres, which travel within cranial nerve III (CN III) ipsilaterally and synapse at the ciliary ganglion (CG). Post‐ganglionic fibres then travel from the ciliary ganglion to synapse at the pupil sphincter muscle causing pupil constriction. Light entering one eye causes both pupils to constrict.

Figure 3.

Sympathetic pathway for pupil dilation. The oculosympathetic pathway is a ‘three‐neuron’ pathway. The first‐order neuron travels from the posterolateral hypothalamus through the brainstem and cervical spinal cord to synapse in the intermediolateral cell column (ciliospinal centre of Budge) at spinal cord level C8‐T2. Axons of the second‐order neuron exit the spinal cord via C8, T1, and T2 nerve roots and ascend to join the paravertebral sympathetic chain and synapse in the superior cervical ganglion. Axons of the third‐order neuron ascend along the internal carotid artery and eventually into the orbit to reach the pupil dilator muscle to cause pupil dilation.

Figure 4.

Large unreactive pupil due to a right third nerve palsy. (a) This patient had complete third nerve palsy on the right and a partial third nerve palsy on the left. Note the bilateral eyelid drooping (ptosis), right much more than left. (b) A large pupil on the right and deviation of the right eye downward and outward are seen after manual elevation of both eyelids. This is typical of complete third nerve palsy. (c) The large pupil on the right does not constrict despite a bright light directed at the right eye, again typical for a complete third nerve palsy.

Figure 5.

Left Horner syndrome due to carotid dissection. (a) Horner syndrome manifested by slight ptosis and miosis (small pupil) on the left. (b) Magnetic resonance imaging (MRI), axial T1‐weighted with fat saturation, through the neck of the patient in (a) demonstrating high signal around the left carotid artery (arrow), consistent with internal carotid artery dissection.



Almog Y, Gepstein R and Kesler A (2010) Diagnostic value of imaging in Horner syndrome in adults. Journal of Neuro‐Ophthalmology 30(1): 7–11.

Antonio‐Santos AA, Santos RN and Eggenberger ER (2005) Pharmacological testing of anisocoria. Expert Opinion on Pharmacotherapy 6(12): 2007–2013.

Billie JD, Wetzel WJ and Suen JY (1982) Thyroid lymphoma with adjacent nerve paralysis. Archives of Otolaryngology 108(8): 517–519.

Biousse V, D'Anglejan‐Chatillon J, Touboul PJ, Amarenco P and Bousser MG (1995) Time course of symptoms in extracranial artery dissections: a series of 80 patients. Stroke 26(2): 235–239.

Biousse V, Touboul PJ, D'Anglejan‐Chatillon J et al. (1998) Ophthalmologic manifestations of internal carotid artery dissection. American Journal of Ophthalmology 126(4): 565–577.

Blumenfeld H (2002) Neuroanatomy through Clinical Cases. Sunderland: Sinauer Associates.

Brazis P (2009) Isolated palsies of cranial nerves III, IV, and VI. Seminars in Neurology 29(1): 14–28.

Brazis PW (1992) Ocular motor abnormalities in Wallenberg's lateral medullary syndrome. Mayo Clinic Proceedings 67(4): 365–368.

Cavazza S, Bocciolini C, Gasparrini E and Tassinari G (2005) Iatrogenic Horner's syndrome. European Journal of Ophthalmology 15(4): 504–506.

Chan CCK, Paine M and O'Day J (2001) Carotid dissection: a common cause of Horner's syndrome. Clinical and Experimental Ophthalmology 29: 411–415.

Drummond PD (1988) Dysfunction of the sympathetic nervous system in cluster headache. Cephalgia 8(3): 181–186.

Drummond PD (2006) Mechanisms of autonomic disturbance in the face during and between attacks of cluster headache. Cephalgia 26(6): 633–641.

Goldstein JB, Biousse V and Newman NJ (1997) Unilateral pharmacologic mydriasis in a patient with respiratory compromise. Archives of Ophthalmology 115(6): 806.

Jett JR (2003) Superior sulcus tumors and Pancoast's syndrome. Lung Cancer 42(Suppl 2): S17–21.

Kawasaki A and Kardon RH (2001) Disorders of the pupil. Ophthalmology Clinics of North America 14(1): 149–168.

Keane JR (1996) Cavernous sinus syndrome. Analysis of 151 cases. Archives of Neurology 53: 967–971.

Kelly‐Sell M and Liu GT (2011) ‘Tonic’ but not ‘Adie’ pupils. Journal of Neuro‐Ophthalmology 31: 393–395.

Lee AG and Brazis PW (2003) Clinical Pathways in Neuro‐Ophthalmology: An Evidence‐Based Approach, 2nd edn. New York: Thieme.

Levatin P (1959) Pupillary escape in disease of the retina or optic nerve. Archives of Ophthalmology 62: 768–779.

Levy M and Newman‐Toker D (2008) Reversible chest tube Horner syndrome. Journal of Neuro‐Ophthalmology 28(3): 212–213.

Liu GT, Volpe NJ and Galetta SL (2010) Neuro‐Ophthalmology Diagnosis and Management, 2nd edn. Philadelphia: Saunders‐Elsevier.

Mahoney NR, Liu GT, Menacker SJ et al. (2006) Pediatric Horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. American Journal of Ophthalmology 142: 651–659.

Maloney WF, Younge BR and Moyer NJ (1980) Evaluation of the causes and accuracy of pharmacologic localization in Horner's syndrome. American Journal of Ophthalmology 90(3): 394–402.

Martin TJ (2007) Horner's syndrome, pseudo‐Horner's syndrome, and simple anisocoria. Current Neurology and Neuroscience Reports 7: 397–406.

May A and Jurgens TP (2006) Trigeminal‐autonomic headaches in daily clinical practice. Expert Review of Neurotherapeutics 6(10): 1531–1543.

McCrary JA 3rd and Webb NR (1982) Anisocoria from scopolamine patches. Journal of the American Medical Association 248(3): 353–354.

Monaco S, Freddi N, Francavilla E et al. (1998) Transient tonic pupils in botulism type B. Journal of the Neurological Sciences 156(1): 96–98.

Mughal M and Longmuir R (2009) Current pharmacologic testing for Horner syndrome. Current Neurology and Neuroscience Reports 9: 384–389.

Mylius V, Braune HJ and Schepelmann K (2003) Dysfunction of the pupillary light reflex following migraine headache. Clinical Autonomic Research 13(1): 16–21.

Nadgir RN, Loevner LA, Ahmed T et al. (2003) Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature. Neuroradiology 45(5): 311–314.

Reede DL, Garcon E, Smoker WRK and Kardon R (2008) Horner's syndrome: clinical and radiographic evaluation. Neuroimaging Clinics of North America 18: 369–385.

Renowden SA, Harris KM and Hourihan MD (1993) Isolated atraumatic third nerve palsy: clinical features and imaging techniques. British Journal of Radiology 66(792): 1111–1117.

Talks SJ, Shah P and Sinha PA (1994) Horner's syndrome following central line insertion. Anaesthesia 49(6): 553.

Thompson HS and Kardon RH (2006) The Argyll Robertson pupil. Journal of Neuro‐Ophthalmology 26(2): 134–138.

White HD, White BA, Boethel C and Arroliga AC (2011) Pancoast's syndrome secondary to infectious etiologies: a not so uncommon occurrence. American Journal of the Medical Sciences 341(4): 333–336.

Zafeiriou DI and Psychogiou K (2008) Obstetrical brachial plexus palsy. Pediatric Neurology 38(4): 235–242.

Further Reading

Brazis PW, Masdeu JC and Biller J (2011) Localization in Clinical Neurology, 6th edn. Philadelphia: Lippincott Williams and Wilkins.

George A, Haydar AA and Adams WM (2008) Imaging of Horner's syndrome. Clinical Radiology 63(5): 499–505.

Prasad S and Galetta SL (2011) Anatomy and physiology of the afferent visual system. Handbook of Clinical Neurology 102: 3–19.

Wilhelm H (2011) Disorders of the pupil. Handbook of Clinical Neurology 102: 427–466.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Walsh, Ryan D, and Liu, Grant T(May 2012) Pupillary Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024016]