Pupillary Light Reflex

Article Author:
Alison Belliveau
Anisha Somani

Article Editor:
Rimal Dossani

Editors In Chief:
William Gossman

Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi

7/13/2019 3:41:30 PM


Eyes allow visualization of the world by receiving and processing the energy of light as it enters the eye. This light interacts with the structures and nerves of the eye to create images. Adjustments via the muscles connected to the lens, ciliary bodies, and muscles that make up the iris are stimulated by several nerves, known as the pupillary light reflex.


Light traveling through the cornea, anterior chamber, through the iris via the pupil, refracting through the lens, posterior chamber and hitting the retina initiates vision. As the light travels to the posterior aspect of the eye, it first goes through the pigmented and neural layers of the retina. The light will pass through the ganglion and bipolar cell layers of the retina before reaching the photoreceptor layer, made up of rods and cones, where the light is converted into nerve impulses. This signal then goes back through the bipolar and ganglion cell layers before officially traveling to the optic nerve (CN II) and the brain for further processing and image recognition.[1] This is the first step to the pupillary light reflex. The afferent pathway via the optic nerve travels back to the optic chiasm where there are two sets of tracts coming from each eye. These are nasal and temporal retinal fibers. At the optic chiasm, nasal retinal fibers will cross to the contralateral side of the optic tract, and the temporal retinal fibers continue on the ipsilateral side. These tracts synapse in the lateral geniculate nucleus of the thalamus before continuing to the preganglionic parasympathetic nucleus in the midbrain called Edinger-Westphal nuclei.[2][3] There are a minority of axons that go to the hypothalamus and the olivary pretectal nucleus (OPN).[4] Efferent projections from these nuclei reach ciliary ganglion where post-ganglionic axons of the oculomotor nerve extend to innervate the pupillary sphincter muscles, leading to pupillary constriction (miosis).[3] There is also the nasociliary nerve that had branched off the ophthalmic branch of the trigeminal nerve (CN V). Off of the nasociliary nerve are 2 or 3, long, ciliary nerves that will innervate the eyeball for sensory innervation and also contains sympathetic fibers that go to the dilator pupillae muscle. The short ciliary nerves, usually 6 to 10 nerve branches, provide sympathetic and parasympathetic input to the ciliary body, iris, and cornea, thus influencing the pupillary light reflex.[1] This extensive pathway is being tested when a light is shined in the eyes. And, because of the crossing fibers, there is not only a direct pupillary reflex but also a consensual pupillary light reflex.

Clinical Significance

Pupillary light reflexes are measured based on a 0-4+ gradient that considers the amount and speed of the light response. In a normal, healthy adult patient 4+ indicating a brisk, large response is expected. Being graded 3+ indicates a moderate response, 2+ a small, slowed response, 1+ representing a tiny/just visible response, and a 0 shows unresponsive pupils. Commonly clinicians document PERRL–saying the pupils are equal, round, and reactive to light.

In standard clinical testing conditions, the diameter of the pupils will usually range from two to five millimeters. Per decade of aging that occurs, there is a 0.3mm decrease in the standard pupil diameter that has been associated with iris stiffening. Pupillary light response exhibits chromatic spectral sensitivities, indicating that the process of light recognition is significantly more complex than there is light or there is no light. While there is a baseline fluctuation in the steady-state conditions for pupillary dilation, a concern for neurological abnormalities is considered for marked changes whether it be in constriction or dilation. One such condition is anisocoria, estimated at 4% of the general population having the condition at greater than 1 millimeter in which neurological compromise is considered. There is also pupillary latency to be considered, where the reaction time of the pupil is inversely related to the increase in light intensity from the stimulus. Latency also increases by approximately 1 millisecond per year with aging. Overall, pupillary response times associated with dynamic phases include one second for initial constriction and approximately 5 seconds for the dilation phase.[4]

Direct and consensual pupillary light reflexes are checked on most patients for appropriate neurological pathway connections and functioning of both cranial nerve II and III. Not only does the eye have to take in the light, but also has to process it and direct the signal back out to the sphincter to control the amount of light let into both eyes which represents both a direct and consensual response. While there are other reasons, such as arousal or stress related to the balance of parasympathetic and sympathetic nervous systems, for changes in pupillary dilation, here we will focus on the relation to light exposure. Pupils can become mydriatic, where they sustain dilation in relation to potential disease, drug toxicity, trauma, possible increased intracranial pressure, brainstem damage, or possible nerve damage to cranial nerve II and/or III.[5] Abnormalities also depend on where in the track the damage has been done. In the event of optic nerve damage, visual field defects or complete vision loss can occur. If this damage is before the optic chiasm, in the optic nerve, then there are deficits noted to bilateral ipsilateral monocular vision loss. This damage leads to a relative afferent pupillary defect (RAPD), known as a Marcus Gunn pupil, which is examined using the swinging flashlight test. Causes of a Marcus Gunn pupil include ischemic optic neuropathy, optic neuritis, nerve compression, trauma or through asymmetric glaucoma.

Unilateral optic neuropathies, most notably optic neuritis, can cause RAPDs. Optic neuritis is an anterior or posterior inflammatory demyelination of the optic nerve, leading to atrophy of optic nerve fibers and a RAPD. A RAPD can be detected in 96% of acute unilateral cases of optic neuritis.[4] Ischemic optic neuropathies, such as NAION and AION, can cause RAPDs via optic nerve ischemia and infarction secondary to optic nerve edema.[5][6] Asymmetric glaucoma can result in a RAPD, secondary to retinal nerve fiber layer loss.

RAPDs can occur due to ischemic retinal diseases such as BRVO, CRVO, BRAO, and CRAO secondary to death of photoreceptors and viable retina, ultimately leading to an uneven pupillary response.[2] Via the same mechanism of significant retinal cell death, retinal detachments can cause RAPDs. In 1987, a prediction model quantified the correlation between the sizes of RAPD to the amount of retina detached. Detachment of each peripheral quadrant correlated to 0.36 log units of pupillary defect. The detachment of the macula caused 0.68 log units of pupillary defect.

Argyll Robertson pupil, noted in tabes dorsalis from neurosyphilis, is the notable very weak to absent pupillary light reflex bilaterally, though the pupils will still constrict for the near response. With the near response (accommodation) intact it can be assumed that the afferent and efferent pathways are grossly intact and that the deficit is related to degeneration in bilateral olivary pretectal nuclei or their projections.[6]

Compression damage to the optic chiasm leads to bitemporal hemianopia and is frequently related to a pituitary adenoma. After the optic chiasm is the optic tract where with damage there is what is considered contralateral homonymous hemianopia, for example, if there is damage to the left optic tract, there are right visual field deficits to both eyes. In the case of comatose patients, it has been noted that a majority of the patients.[4][7] had non-reactive dilated pupils, and the one patient that had pinpoint pupils became vegetative–resulting in an assumption of an unfavorable outcome for the patient.[7] Uncal herniation where the uncus comes over the edge of the tentorium leading to compression of CN III suggesting current or impending brainstem compromise. Lesions within the efferent pathway, specifically the preganglionic fibers of the oculomotor nerve, can cause ipsilateral mydriasis and accommodation paralysis. One syndrome noted to have this finding is Weber Syndrome. If there is damage to the postganglionic fibers, tonic dilated pupil or Adie syndrome develops so that the constrictor muscles are hypersensitive to a cholinergic stimulus. If there is a disruption between the balance of parasympathetic and sympathetic innervation, such as in Horner syndrome where there is a loss of sympathetic stimulation, leading to miosis of the ipsilateral pupil.[6]

Transient mydriasis, dilation, can be associated with tricyclic antidepressants, typical antipsychotics and selective serotonin reuptake inhibitors, but usually, this is not long-term consequences. Topiramate, used for migraines, has been associated with acquired myopia and angle-closure glaucoma.[8] The fixed dilation of pupils noted in coma patients was related to the increased intracranial pressure (ICP) in which an association was noted in 1866 from Von Leyden’s animal experiments. Through continued research over the next 50 years or so, it was noted that the fixed dilation of pupils was noted to be a sign of acute mass effect in relation to in the ICP.[9]

Tumors in the retina, optic nerve and brain can also cause RAPDs. In children, the most common intraocular tumors are benign, developmental cysts. The most common malignant intraocular tumor is retinoblastoma.[9] Tumors or lesions affecting the optic chiasm or midbrain causes a decrease in the amount of signal that can reach the Edinger-Westphal nuclei, leading to pupillary constriction. In children, the most common intracranial tumor detected is a glioma. They account for 75% of intracranial tumors in children. Also common in children are astrocytomas, medulloblastomas, and ependymomas.

Another cause of RAPD is severe amblyopia, characterized as amblyopia of 20/100 to 20/400. Clinically, RAPDs are found in severe amblyopia with BCVA 20/400 or worse. While the etiology of a RAPD in amblyopia is poorly understood, significant risk factors include anisometropia, early age of onset with a history of strabismus, level of visual acuity at the conclusion of treatment, and extended periods of occlusion therapy.[10]

Enhancing Healthcare Team Outcomes

Emergency physicians often encounter patients with the triad of pinpoint pupils, respiratory depression, and coma related to opioid overuse. Opioids are used for pain relief by interacting with opioid receptors, including mu, delta, and kappa. With significant respiratory depression resulting in hypoxia, pupils can become dilated. Oxygenation causes the pupils to revert to the original pinpoint presentation caused by the opioid. For stabilization, one of the medications given to these patients is Naloxone, an opioid antagonist, which has a peak effect at approximately 10 minutes. Repeated dosing is frequently required and can be given up to 5 mg per hour. If there is a dilation of the pupil with the administration of naloxone, this also eliminates organophosphate poisoning, which can present similarly. Pupillary changes are used to recognize when the effects of Naloxone are waning because of how the pupils will begin to constrict again, indicating that the opioid has not yet been metabolized out of the body. There is also the concern in the event of minimal reaction that the patient may have other central nervous system depressants on board or has had hypoxic brain damage.[10]

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Pupillary Light Reflex - Questions

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In a patient who has been resuscitated by CPR, which of the following is highly recommended to determine effectiveness of resuscitation?

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Which of the following is part of the near reflex that allows the eye to focus on near objects?

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A patient presents with his right eye looking down and lateral with a dilated pupil that is not reactive to light, while the left eye appears unaffected. What structure has been compromised leading to the pupillary change?

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Which of the following events would not lead to dysfunction of the pupillary light reflex?

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Pupillary Light Reflex - References


Pupillary light reflex as a new prognostic marker in patients with heart failure., Nozaki K,Kamiya K,Matsue Y,Hamazaki N,Matsuzawa R,Tanaka S,Maekawa E,Kishi T,Matsunaga A,Masuda T,Izumi T,Ako J,, Journal of cardiac failure, 2018 Sep 20     [PubMed]
Understanding the effects of mild traumatic brain injury on the pupillary light reflex., Ciuffreda KJ,Joshi NR,Truong JQ,, Concussion (London, England), 2017 Nov     [PubMed]
Neurological Prognostications for the Therapeutic Hypothermia among Comatose Survivors of Cardiac Arrest., Kongpolprom N,Cholkraisuwat J,, Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 2018 Jul     [PubMed]
Shumway CL,Wade M, Anatomy, Head and Neck, Eye Extraocular Muscles 2018 Jan;     [PubMed]
Smith AM,Czyz CN, Neuroanatomy, Cranial Nerve 2 (Optic) 2018 Jan;     [PubMed]
Lynch G, Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD. Behavioral sciences (Basel, Switzerland). 2018 Nov 21;     [PubMed]
Bloom J,Czyz CN, Anatomy, Head and Neck, Eye Iris Sphincter Muscle 2018 Jan;     [PubMed]
Richa S,Yazbek JC, Ocular adverse effects of common psychotropic agents: a review. CNS drugs. 2010 Jun;     [PubMed]
Koehler PJ,Wijdicks EF, Fixed and dilated: the history of a classic pupil abnormality. Journal of neurosurgery. 2015 Feb;     [PubMed]
Henry J,Volans G, ABC of poisoning. Analgesics: opioids. British medical journal (Clinical research ed.). 1984 Oct 13;     [PubMed]


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