Pupillary light reflex

The pupillary light reflex (PLR) or

photopupillary reflex is a reflex that
controls the diameter of the pupil, in
response to the intensity (luminance)
of light that falls on the retinal ganglion
cells of the retina in the back of the eye,
thereby assisting in adaptation of
vision to various levels of
lightness/darkness. A greater intensity Variation in the size of the pupil in bright (left) and dim (right)
of light causes the pupil to constrict environments. In this case the pupil is 3 mm in diameter on the left,
(miosis/myosis; thereby allowing less and 9 mm on the right
light in), whereas a lower intensity of
light causes the pupil to dilate
(mydriasis, expansion; thereby allowing more light in). Thus, the pupillary light reflex regulates the
intensity of light entering the eye.[1] Light shone into one eye will cause both pupils to constrict.

Terminology
The pupil is the dark circular opening in the center of the iris
and is where light enters the eye. By analogy with a camera,
the pupil is equivalent to aperture, whereas the iris is
equivalent to the diaphragm. It may be helpful to consider the
Pupillary reflex as an 'Iris' reflex, as the iris sphincter and
dilator muscles are what can be seen responding to ambient The W-shaped pupil of the cuttlefish
light.[2] Whereas, the pupil is the passive opening formed by dilating when the lights are turned off
the active iris. Pupillary reflex is synonymous with pupillary
response, which may be pupillary constriction or dilation.
Pupillary reflex is conceptually linked to the side (left or right) of the reacting pupil, and not to the
side from which light stimulation originates. Left pupillary reflex refers to the response of the left
pupil to light, regardless of which eye is exposed to a light source. Right pupillary reflex means
reaction of the right pupil, whether light is shone into the left eye, right eye, or both eyes. When light
is shone into only one eye and not the other, it is normal for both pupils to constrict simultaneously.
The terms direct and consensual refers to the side where the light source comes from, relative to the
side of the reacting pupil. A direct pupillary reflex is pupillary response to light that enters the
ipsilateral (same) eye. A consensual pupillary reflex is response of a pupil to light that enters the
contralateral (opposite) eye. Thus there are four types of pupillary light reflexes, based on this
terminology of absolute laterality (left versus right) and relative laterality (same side versus opposite
side, ipsilateral versus contralateral, direct versus consensual):

1. Left direct pupillary reflex is the left pupil's response to light entering the left eye, the ipsilateral
eye.
2. Left consensual pupillary reflex is the left pupil's indirect response to light entering the right eye,
the contralateral eye.
 3. Right direct pupillary reflex is the right pupil's response to light entering the right eye, the
ipsilateral eye.
4. Right consensual pupillary reflex is the right pupil's indirect response to light entering the left eye,
the contralateral eye.

Neural pathway anatomy

The pupillary light reflex neural pathway on each side has an afferent limb and two efferent limbs. The
afferent limb has nerve fibers running within the optic nerve (CN II). Each efferent limb has nerve
fibers running along the oculomotor nerve (CN III). The afferent limb carries sensory input.
Anatomically, the afferent limb consists of the retina, the optic nerve, and the pretectal nucleus in the
midbrain, at level of superior colliculus. Ganglion cells of the retina project fibers through the optic
nerve to the ipsilateral pretectal nucleus. The efferent limb is the pupillary motor output from the
pretectal nucleus to the ciliary sphincter muscle of the iris. The pretectal nucleus projects crossed and
uncrossed fibers to the ipsilateral and contralateral Edinger-Westphal nuclei, which are also located in
the midbrain. Each Edinger-Westphal nucleus gives rise to preganglionic parasympathetic fibers
which exit with CN III and synapse with postganglionic parasympathetic neurons in the ciliary
ganglion. Postganglionic nerve fibers leave the ciliary ganglion to innervate the ciliary sphincter.[3]
Each afferent limb has two efferent limbs, one ipsilateral and one contralateral. The ipsilateral
efferent limb transmits nerve signals for direct light reflex of the ipsilateral pupil. The contralateral
efferent limb causes consensual light reflex of the contralateral pupil.

Types of neurons

The optic nerve, or more precisely, the photosensitive ganglion cells through the retinohypothalamic
tract, is responsible for the afferent limb of the pupillary reflex; it senses the incoming light. The
oculomotor nerve is responsible for the efferent limb of the pupillary reflex; it drives the iris muscles
that constrict the pupil.[1]

1. Retina: The pupillary reflex pathway

begins with the photosensitive retinal
ganglion cells, which convey
information via the optic nerve, the
most peripheral, distal, portion of
which is the optic disc. Some axons
of the optic nerve connect to the
pretectal nucleus of the upper
midbrain instead of the cells of the
lateral geniculate nucleus (which
project to the primary visual cortex).
These intrinsic photosensitive
ganglion cells are also referred to as
melanopsin-containing cells, and Pathways in the Ciliary ganglion.
they influence circadian rhythms as Parasympathetic;
well as the pupillary light reflex. Sympathetic;
2. Pretectal nuclei: From the neuronal Sensory
cell bodies in some of the pretectal
nuclei, axons synapse on (connect
to) neurons in the Edinger-Westphal nucleus. Those neurons are the preganglionic cells with
axons that run in the oculomotor nerves to the ciliary ganglia.
 3. Edinger-Westphal nuclei: Parasympathetic neuronal axons in the oculomotor nerve synapse on
ciliary ganglion neurons.
4. Ciliary ganglia: Short post-ganglionic ciliary nerves leave the ciliary ganglion to innervate the Iris
sphincter muscle of the iris.[1]

Schematic

Referring to the neural pathway schematic diagram, the entire pupillary light reflex system can be
visualized as having eight neural segments, numbered 1 through 8. Odd-numbered segments 1, 3, 5,
and 7 are on the left. Even-numbered segments 2, 4, 6, and 8 are on the right. Segments 1 and 2 each
includes both the retina and the optic nerve (cranial Nerve #2). Segments 3 and 4 are nerve fibers that
cross from the pretectal nucleus on one side to the Edinger-Westphal nucleus on the contralateral
side. Segments 5 and 6 are fibers that connect the pretectal nucleus on one side to the Edinger-
Westphal nucleus on the same side. Segments 3, 4, 5, and 6 are all located within a compact region
within the midbrain. Segments 7 and 8 each contains parasympathetic fibers that courses from the
Edinger-Westphal nucleus, through the ciliary ganglion, along the oculomotor nerve (cranial nerve
#3), to the ciliary sphincter, the muscular structure within the iris.

Left direct light reflex involves neural segments 1, 5, and 7.

Segment 1 is the afferent limb, which includes the retina and
optic nerve. Segments 5 and 7 form the efferent limb.
Left consensual light reflex involves neural segments 2, 4, and
7. Segment 2 is the afferent limb. Segments 4 and 7 form the
efferent limb.
Right direct light reflex involves neural segments 2, 6, and 8.
Segment 2 is the afferent limb. Segments 6 and 8 form the
efferent limb.
Right consensual light reflex involves neural segments 1, 3,
and 8. Segment 1 is the afferent limb. Segments 3 and 8 form
the efferent limb.

The diagram may assist in localizing lesion within the pupillary

reflex system by process of elimination, using light reflex testing
results obtained by clinical examination.
Schematic diagram of pupillary light
reflex neural pathway
Clinical significance
Pupillary light reflex provides a useful diagnostic tool for testing
the integrity of the sensory and motor functions of the eye.[1]
Emergency physicians routinely test pupillary light reflex to assess
brain stem function. Abnormal pupillary reflex can be found in
optic nerve injury, oculomotor nerve damage, brain stem lesion
A medical halogen penlight used to
(including brain stem death), and depressant drugs, such as
observe pupillary light reflex.
barbiturates.[4][5] Examples are provided as below:

Optic nerve damage on the left (e.g. transection of left optic

nerve, CN II, somewhere between retina and optic chiasma, therefore damaging the left afferent
limb, leaving the rest of the pupillary light reflex neural pathway on both sides intact) will have the
following clinical findings:
 The left direct reflex is lost. When the left eye is stimulated by light, neither pupils constrict.
Afferent signals from the left eye cannot pass through the transected left optic nerve to reach
the intact efferent limb on the left.
The right consensual reflex is lost. When left eye is stimulated by light, afferent signals from
the left eye cannot pass through the transected left optic nerve to reach the intact efferent limb
on the right.
The right direct reflex is intact. Direct light reflex of right pupil involves the right optic nerve and
right oculomotor nerve, which are both intact.
The left consensual reflex is intact. Consensual light reflex of left pupil involves the right optic
nerve and left oculomotor nerve, which are both undamaged.
Oculomotor nerve damage on the left (e.g. transection of left oculomotor nerve, CN III, therefore
damaging the left efferent limb) will have the following clinical findings:
The left direct reflex is lost. When the left eye is stimulated by light, left pupil does not
constrict, because the efferent signals cannot pass from midbrain, through left CN III, to the
left pupillary sphincter.
The right consensual reflex is intact. When the left eye is stimulated by light, the right pupil
constricts, because the afferent limb on the left and the efferent limb on the right are both
intact.
The right direct reflex is intact. When light is shone into right eye, right pupil constricts. Direct
reflex of the right pupil is unaffected, The right afferent limb, right CN II, and the right efferent
limb, right CN III, are both intact.
The left consensual reflex is lost. When the right eye is stimulated by light, left pupil does not
constrict consensually. Right afferent limb is intact, but left efferent limb, left CN III, is
damaged.

Lesion localization example

For example, in a person with abnormal left direct reflex and abnormal right consensual reflex (with
normal left consensual and normal right direct reflexes), which would produce a left Marcus Gunn
pupil, or what is called left afferent pupillary defect, by physical examination. Location of the lesion
can be deduced as follows:

1. Left consensual reflex is normal, therefore segments 2, 4, and 7 are normal. Lesion is not located
in any of these segments.
2. Right direct reflex is normal, therefore segments 2, 6, and 8 are normal. Combining with earlier
normals, segments 2, 4, 6, 7, and 8 are all normal.
3. Remaining segments where lesion may be located are segments 1, 3, and 5. Possible
combinations and permutations are: (a) segment 1 only, (b) segment 3 only, (c) segment 5 only,
(d) combination of segments 1 and 3, (e) combination of segments 1 and 5, (f) combination of
segments 3 and 5, and (g) combination of segments 1, 3, and 5.
4. Options (b) and (c) are eliminated because isolated lesion in segment 3 alone or in segment 5
alone cannot produce the light reflex abnormalities in question.
5. A single lesion anywhere along segment 1, the left afferent limb, which includes the left retina, left
optic nerve, and left pretectal nucleus, can produce the light reflex abnormalities observed.
Examples of segment 1 pathologies include left optic neuritis (inflammation or infection of the left
optic nerve), detachment of left retina, and an isolated small stroke involving only the left pretectal
nucleus. Therefore, options (a), (d), (e), (f), and (g) are possible.
6. A combined lesion in segments 3 and 5 as cause of defect is very unlikely. Microscopically precise
strokes in the midbrain, involving the left pretectal nucleus, bilateral Edinger-Westphal nuclei, and
 their interconnecting fibers, could theoretically produce this result. Furthermore, segment 4 shares
the same anatomical space in the midbrain as segment 3, therefore segment 4 will likely be
affected if segment 3 is damaged. In this setting, it is very unlikely that left consensual reflex,
which requires an intact segment 4, would be preserved. Therefore, options (d), (f), and (g), which
all includes segment 3, are eliminated. Remaining possible options are (a) and (e).
7. Based on the above reasoning, the lesion must involve segment 1. Damage to segment 5 may
accompany a segment 1 lesion, but is unnecessary for producing the abnormal light reflex results
in this case. Option (e) involves a combined lesion of segments 1 and 5. Multiple sclerosis, which
often affects multiple neurologic sites simultaneously, could potentially cause this combination
lesion. In all probability, option (a) is the answer. Neuro-imaging, such as MRI scan, would be
useful for confirmation of clinical findings.

Cognitive influences
The pupillary response to light is not purely reflexive, but is modulated by cognitive factors, such as
attention, awareness, and the way visual input is interpreted. For example, if a bright stimulus is
presented to one eye, and a dark stimulus to the other eye, perception alternates between the two eyes
(i.e., binocular rivalry): Sometimes the dark stimulus is perceived, sometimes the bright stimulus, but
never both at the same time. Using this technique, it has been shown the pupil is smaller when a
bright stimulus dominates awareness, relative to when a dark stimulus dominates awareness.[6][7]
This shows that the pupillary light reflex is modulated by visual awareness. Similarly, it has been
shown that the pupil constricts when you covertly (i.e., without looking at) pay attention to a bright
stimulus, compared to a dark stimulus, even when visual input is identical.[8][9][10] Moreover, the
magnitude of the pupillary light reflex following a distracting probe is strongly correlated with the
extent to which the probe captures visual attention and interferes with task performance.[11] This
shows that the pupillary light reflex is modulated by visual attention and trial-by-trial variation in
visual attention. Finally, a picture that is subjectively perceived as bright (e.g. a picture of the sun),
elicits a stronger pupillary constriction than an image that is perceived as less bright (e.g. a picture of
an indoor scene), even when the objective brightness of both images is equal.[12][13] This shows that
the pupillary light reflex is modulated by subjective (as opposed to objective) brightness.

Mathematical model
Pupillary light reflex is modeled as a physiologically-based non-linear delay differential equation that
describes the changes in the pupil diameter as a function of the environment lighting:[14]

where is the pupil diameter measured in millimeters and is the luminous intensity
reaching the retina in a time , which can be described as : luminance reaching the eye in
2 2
lumens/mm times the pupil area in mm . is the pupillary latency, a time delay between the instant
in which the light pulse reaches the retina and the beginning of iridal reaction due nerve transmission,
neuro-muscular excitation and activation delays. , and are the derivatives for the
function, pupil diameter and time .
Since the pupil constriction velocity is approximately 3 times faster than (re)dilation velocity,[15]
different step sizes in the numerical solver simulation must be used:

where and are respectively the for constriction and dilation measured in milliseconds,
and are respectively the current and previous simulation times (times since the simulation started)
measured in milliseconds, is a constant that affects the constriction/dilation velocity and varies
among individuals. The higher the value, the smaller the time step used in the simulation and,
consequently, the smaller the pupil constriction/dilation velocity.

In order to improve the realism of the resulting simulations, the hippus effect can be approximated by
adding small random variations to the environment light (in the range 0.05–0.3 Hz).[16]

See also
Pupil
Pupillary response
Slit lamp

References
1. Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia,
James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates.
pp. 290–1. ISBN 978-0-87893-697-7.
2. Hall, Charlotte; Chilcott, Robert (2018). "Eyeing up the Future of the Pupillary Light Reflex in
Neurodiagnostics" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872002). Diagnostics. 8 (1):
19. doi:10.3390/diagnostics8010019 (https://doi.org/10.3390%2Fdiagnostics8010019).
PMC 5872002 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872002). PMID 29534018 (https://
pubmed.ncbi.nlm.nih.gov/29534018).
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0-323-05714-1.
4. Belliveau, A. P.; Somani, A. N.; Dossani, R. H. (2019). "Pupillary Light Reflex" (https://www.ncbi.nl
m.nih.gov/books/NBK537180/). StatPearls. StatPearls. PMID 30725865 (https://pubmed.ncbi.nlm.
nih.gov/30725865).
5. Ciuffreda, K. J.; Joshi, N. R.; Truong, J. Q. (2017). "Understanding the effects of mild traumatic
brain injury on the pupillary light reflex" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094691).
Concussion. 2 (3): CNC36. doi:10.2217/cnc-2016-0029 (https://doi.org/10.2217%2Fcnc-2016-002
9). PMC 6094691 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094691). PMID 30202579 (htt
ps://pubmed.ncbi.nlm.nih.gov/30202579).
6. Harms, H. (1937). "Ort und Wesen der Bildhemmung bei Schielenden". Graefe's Archive for
Clinical and Experimental Ophthalmology. 138 (1): 149–210. doi:10.1007/BF01854538 (https://do
i.org/10.1007%2FBF01854538). S2CID 7110752 (https://api.semanticscholar.org/CorpusID:71107
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