We use our eyes to monitor our external environment and depend on our ocular motor systems to protect

and guide our eyes. The ocular motor systems control eye lid closure, the amount of light that enters the
eye, the refractive properties of the eye, and eye movements. The visual system provides afferent input to
ocular motor circuits that use visual stimuli to initiate and guide the motor responses. Neuromuscular
systems control the muscles within the eye (intraocular muscles); the muscles attached to the eye
(extraocular muscles) and the muscles in the eyelid. Ocular motor responses include ocular reflexes and
voluntary motor responses to visual and other stimuli.

The ocular reflexes are the simplest ocular motor responses. Ocular reflexes compensate for the condition
of the cornea and for changes in the visual stimulus. For example, the eye blink reflex protects the cornea
from drying out and from contact with foreign objects. The pupillary light reflex compensates for changes
in illumination level, whereas the accommodation responses compensate for changes in eye-to-object-
viewed distance. Note that reflex responses are initiated by sensory stimuli that activate afferent neurons
(e.g., somatosensory stimuli for the eye blink reflex and visual stimuli for the pupillary light reflex and
accommodation responses). In general, ocular reflexes are consensual (i.e., the response is bilateral
involving both eyes). Consequently, a light directed in one eye elicits responses, pupillary constriction, in
both eyes.

PUPILLARY LIGHT REFLEX / PHOTOPUPILLARY REFLEX

This reflex involves adjustments in pupil size with changes in light levels. The reflex is consensual meaning
when a light is directed in one eye, it produces pupil constriction in both eyes. The direct response is the
change in pupil size in the eye to which the light is directed (e.g., if the light is shone in the right eye, the
right pupil constricts). The consensual response is the change in pupil size in the eye opposite to the eye
to which the light is directed (e.g., if the light is shone in the right eye, the left pupil also constricts
consensually). The pupillary light reflex allows the eye to adjust the amount of light reaching the retina and
protects the photoreceptors from bright lights. The iris contains two sets of smooth muscles that control the
size of the pupil: The sphincter muscle fibers form a ring at the pupil margin so that when the sphincter
contracts, it decreases (constricts) pupil size. Then, the dilator muscle fibers which radiate from the pupil
aperture so that when the dilator contracts, it increases (dilates) pupil size. Both muscles act to control the
amount of light entering the eye and the depth of field of the eye. The iris sphincter is controlled by the
parasympathetic system, whereas the iris dilator is controlled by the sympathetic system. The action of the
dilator is antagonistic to that of the sphincter and the dilator must relax to allow the sphincter to decrease
pupil size. Normally the sphincter action dominates during the pupillary light reflex.

Figure 1. Iris dilator and Sphincter muscles of the Iris

The pupillary light reflex allows for the constriction of the pupil when exposed to bright light. This reflex
serves to regulate the amount of light the retina receives under varying illuminations. The pupillary light
reflex two main parts: an afferent limb and an efferent limb.

Afferent Pathway of Pupillary Light Reflex

When light enters the pupil, it stimulates the retina. The retinal ganglion cells transmit the light signal to the
optic nerve and this optic nerve will enter the optic chiasm where the nasal retinal fibers cross to
contralateral optic tract, while the temporal retinal fibers stay in the ipsilateral optic tract. Fibers from the
optic tracts project and synapse in the pretectal nuclei in the dorsal midbrain in the collicular region. The
pretectal nuclei project fibers to the ipsilateral Edinger-Westphal nuclei and also to the contralateral
Edinger-Westphal nucleus via the posterior commissure.

Efferent Pathway of Pupillary Light Reflex

The Edinger-Westphal nucleus projects pre-ganglionic parasympathetic fibers, which exit the midbrain and
travel along the oculomotor nerve (CN III) and then synapse on post-ganglionic parasympathetic fibers in
the ciliary ganglion. The ciliary ganglion post-ganglionic parasympathetic fibers (short ciliary nerves)
innervate the sphincter muscle of the pupils resulting in pupillary constriction.

The physiological result of the neuroanatomical pathways is that light shined in one eye will result in
pupillary constriction in both the ipsilateral pupil (direct pupillary light reflex) and the contralateral pupil
(consensual pupillary light reflex).

Figure 2. The Afferent and Efferent Pathway

PUPILLARY ABNORMALITIES

Pupillary disorders may involve the afferent pathways (RAPD) or the efferent pathways. Anisocoria, where
not physiological, indicates a problem of the efferent pupillary pathway, either parasympathetic or
sympathetic (Horner's syndrome). Disorders of the parasympathetic system impair the light response and
they include third nerve palsy and tonic pupil. Disorders of the iris, including application of cholinergic
agents, also need to be considered in impaired pupillary light reaction.

Aniscoria

Refers to the asymmetric sizes of pupils.

Many cases of mild anisocoria are normal
and do not have any underlying pathology
or history of trauma. Generally, these
cases of anisocoria where one pupil is
bigger than the other by less than 1.0 mm
with no apparent cause are called simple
anisocoria, benign anisocoria or
physiologic anisocoria. Physiologic
anisocoria can be very common and a
normal variant in up to 20% of the
population. The variation should be no
more than 1mm and both eyes should
react to light normally. Can be dangerous
if a manifestation Horner's syndrome (e.g.
carotid dissection) or from damage to the
third nerve (e.g. aneurysmal expansion).

Significant aniscoria can have a number

of causes and some can be medical
problems. Causes may be: Eye trauma,
Eye medications (e.g. pilocarpine eye
drops used to treat glaucoma may cause
the pupil of the treated eye to be smaller
than the other pupil.) Inflammation of
Iris or Iritis may also cause aniscoria that
is usually accompanied by eye pain.
Adie’s tonic pupil, and Neurological
disorders.
Relative Afferent Pupillary Defect
(RAPD, Marcus Gunn Pupil)

An RAPD is a defect in the direct

response. It is due to damage in optic
nerve or severe retinal disease. In case of
RAPD, the affected pupil will not constrict
to light when light is shone in the pupil
during the swinging flashlight test.
However, it will constrict if light is shone
in the other eye (consensual response).
The swinging flashlight test is helpful in
separating these two etiologies as only
patients with optic nerve damage will
have a positive RAPD. This decrease in
constriction or widening of the pupil is due
to reduced stimulation of the visual
pathway by the pupil on the affected side.
By not being able to relay the intensity of
the light as accurately as the healthy pupil
and visual pathway, the diseased side
causes the visual pathway to mistakenly
respond to the decrease in stimulation as
if the flashlight itself were less luminous.
This explains the healthy eye is able to
undergo both direct and consensual
dilatation seen on the swinging flashlight
test.

Some causes of a RAPD include:

1. optic neuritis
2. ischemic optic disease or retinal
disease
3. severe glaucoma causing
trauma to optic nerve
4. direct optic nerve damage
(trauma, radiation, tumor)
5. retinal detachment
6. very severe macular
degeneration
7. retinal infection (CMV, herpes)
Adie’s (Tonic) Pupil

is a neurological disorder that causes one

or both pupils to be abnormally dilated
(mydriasis) with either no or sluggish
response to light (both direct and
consensual responses). A tonic pupil is
caused by postganglionic
parasympathetic pupillomotor damage.
Common clinical findings associated with
Adie’s syndrome beyond mydriasis
include hypersensitivity to muscarinic
receptor agonists (e.g. pilocarpine),
reduced tendon reflexes, and
occasionally hypohidrosis.
Histopathologic examination of the ciliary
ganglion in patients with Adie tonic pupil
has shown a reduction in the number of
ganglion cells. Pilocarpine drops can be
applied multiple times per day in order to
constrict the pupil. Prescription reading
glasses may be necessary to correct
impaired vision.

Argyll Robertson Pupil

Argyll Robertson pupil describes the

physical exam finding of small bilateral
pupils that do not constrict when exposed
to bright light but do constrict when
focused on a nearby object. This finding
is highly specific for late-stage syphilis.
Neurosyphilis occurs due to an invasion
of the cerebrospinal fluid (CSF) by the
spirochete which likely occurs soon after
the initial acquisition of the disease. The
exact pathophysiology leading to the AR
pupil, however, remains unknown. The
patient with AR pupil will show small,
irregular pupils with light-near
dissociation: absent light reflex, prompt
constriction with near accommodation.
Symptoms are usually bilateral and have
a gradual onset of months to years. The
pupils will initially have a sluggish
response to light, progressing eventually
to a complete absence of the light reflex.
Horner’s Syndrome

Loss of sympathetic innervation causing

the clinical triad of:

1. Ptosis (drooping eyelid): The

superior tarsal muscle requires
sympathetic innervation to keep
the eyelid retracted
2. Miosis (pupillary constriction): A
loss of sympathetic input causes
unopposed parasympathetic
stimulation which leads to
pupillary constriction. This
degree of miosis may be subtle
and require a dark room.
3. Anhidrosis (decreased
sweating): Also caused by a loss
of sympathetic activity. The
pattern of anihidrosis may help
identify the lesion. Anhidrosis of
the entire face is often
associated with a lesion at the
level of the carotid artery. Partial
anhidrosis involving only the
medial aspect of the forehead
ipsilateral side of the nose is
associated with a lesion distal to
the carotid bulb.

Causes of Horner's Syndrome include:

1. carotid artery dissection

2. pancoast tumors,
nasopharyngial tumors
3. lymphoproliferative disorders
4. brachial plexus injury
5. cavernous sinus thrombosis
6. fibromuscular dysplasia
REFERENCES

Dichter, S.L. and Shubert, G.S. (2019). Argyll Robertson Pupil. Retrieved on October 14, 2019. Retrieved
from < https://www.ncbi.nlm.nih.gov/books/NBK537179/>

Dragoi, V. (n.d.). Chapter 7: Ocular Motor System. Retrieved on October 13, 2019. Retrieved from
<https://nba.uth.tmc.edu/neuroscience/m/s3/chapter07.html#>

Heiting, G. (2017). Aniscoria: Why is one pupil bigger than the other? Retrieved on October 14, 2019.
Retrieved from <https://www.allaboutvision.com/conditions/anisocoria.htm>

Lowth, M. and Tidy, C. (2017). Pupillary Abnormalities. Retrieved on October 14, 2019. Retrieved from
<https://patient.info/doctor/pupillary-abnormalities>

Neuroscience Clerkship. (2006). NEUROANATOMY OF THE PUPILLARY LIGHT REFLEX. Retrieved on

October 13, 2019. Retrieved from
<http://casemed.case.edu/clerkships/neurology/NeurLrngObjectives/Pupil.htm?fbclid=IwAR0KdsF9kgfFsi
B21B5fjCNHWH90x_LZImgqbGyUZ8Btj1AOs3Gi5p__Bno>

Ringeisen, A.L. and Rolnick, K. (2015). Adie’s Pupil. Retrieved on October 14, 2019. Retrieved from
<https://eyewiki.aao.org/Adie%27s_Pupil

Standord Medicine. (n.d.). Pupillary Responses. Retrieved on October 14, 2019. Retrieved from
<https://stanfordmedicine25.stanford.edu/the25/pupillary.html>

Images

Figure 1: https://nba.uth.tmc.edu/neuroscience/m/s3/chapter07.html#

Figure 2:
http://casemed.case.edu/clerkships/neurology/NeurLrngObjectives/Pupil.htm?fbclid=IwAR0KdsF9kgfFsiB
21B5fjCNHWH90x_LZImgqbGyUZ8Btj1AOs3Gi5p__Bno

Aniscoria: https://www.allaboutvision.com/conditions/anisocoria.htm

Relative Afferent Pupillary Defect: https://stanfordmedicine25.stanford.edu/the25/pupillary.html

Adie’s Tonic Pupil: https://media.springernature.com/original/springer-static/image/prt%3A978-3-540-

69000-9%2F20/MediaObjects/978-3-540-69000-9_20_Part_Fig1-1230_HTML.jpg

Argyll Robertson Pupil: https://image.slidesharecdn.com/pseudo-

180403171647/95/pseudoophthalmology-34-638.jpg?cb=1564318795

Horner’s Syndrome:
https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=2ahUKEwiV2M-
LiZ3lAhVDL6YKHSutDUsQjRx6BAgBEAQ&url=%2Furl%3Fsa%3Di%26rct%3Dj%26q%3D%26esrc%3Ds
%26source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps%253A%252F%252Fwww.physio-
pedia.com%252FHorner%252527s_Syndrome%26psig%3DAOvVaw2Q9SgwUICEwZqsGPv_9gk9%26u
st%3D1571187625535009&psig=AOvVaw2Q9SgwUICEwZqsGPv_9gk9&ust=1571187625535009