Anisokoria

Ketidaksamaan lebar pupil antara kedua mata

dengan pebedaan 0,4mm atau lebih
Anisokoria patologis terjadi karena defek aferen
parasimpatis atau simpatis pada satu mata atau
dua mata secara asimetris
Anisokoria lebih nyata pada keadaan gelap
kelemahan otot dilator pupil atau saraf simpatis
pada mata yang pupilnya tidak mau lebar
Anisokoria lebih nyata pada keadaan terang
kelemahan sfingter pupil atau parasimpatis pada
mata yang pupilnya tidak mau mengecil

Anisocoria with normally

reactive pupils
Differential diagnosis
physiologic anisocoria
Horners syndrome
- intermittent pupillary mydriasis of young (some
cases)

Physiologic anisocoria

present in 1520% of normal people

present at birth
may be very obvious or very subtle
may change both size and side by hour
no visual effects
if the patient is asymptomatic and there is
normal motility and no ptosis, no pharmacologic
testing or other investigations are required
occasionally, however, if by coincidence there is
a mild ptosis of another cause, there can be
concern that the patient could have Horners
syndrome

 pharmacologic testing to differentiate physiologic

anisocoria from Horners syndrome:
the transmitter substance at the neuromuscular
junction of the sympathetic pathway is
norepinephrine
10% cocaine blocks the reuptake of norepinephrine
patients with physiologic anisocoria have normal
release of norepinephrine at the junction of the
sympathetic neuron and the iris dilator
a patient with physiologic anisocoria will show
dilation of both pupils 45 minutes after 2 drops of
10% cocaine are instilled in both eyes (compared
with Horners syndrome in which there is no dilation)

Horners syndrome
anisocoria with smaller pupil on side of lesion
pupils normally reactive to light (actually,
Horners pupil is hyperreactive to light)
ipsilateral upper eyelid ptosis (from involvement
of Muller muscle)
upside-down ptosis of ipsilateral lower lid (lower
lid slightly higher)
apparent enophthalmos (from ptosis of upper and
lower lids)

Pharmacologic testing to confirm

the diagnosis of Horners
syndrome

regardless of the location of the lesion along the sympathetic

pathway, patients with Horners syndrome have a reduced rate of
norepinephrine release at the iris dilator neuromuscular junction
10% cocaine will not dilate a Horners pupil (or will dilate it minimally)
place two drops of 10% cocaine in each eye
place cocaine in the eye with the smaller pupil first why? Because
topical cocaine is a major ocular irritant. If cocaine drops are put in the
eye with the larger pupil first, the patient may squeeze the lids tightly
while you are trying to put drops in the other eye. Then, if the smaller
pupil fails to dilate, it could be because it is a Horners pupil OR because
the drops didnt get into the eye because of squeezing of the eyelids. If
the cocaine drops are placed first in the eye with the smaller pupil, the
latter argument cannot be made
wait 45 minutes
examine the pupils in dim light or a dark room why? Because
cocaine affects only the sympathetic system, not the parasympathetic
system. If the pupils are examined in bright light, they may constrict
and the effects of the cocaine may not be appreciated

 why bother with a cocaine test if the patient has

anisocoria and ipsilateral ptosis?
because 1520% of normal people have physiologic
anisocoria and if such a patient has unilateral ptosis
from another condition (e.g. age-related levator
dehiscence), there is a 50% chance that the ptosis
and the miotic pupil will be on the same side
is there an alternative to the cocaine test?
cocaine drops may be hard or impossible to obtain
one can use apraclonidine instead
apraclonidine is an alpha-adrenergic receptor
agonist
it reduces aqueous production and lowers IOP
a 1% solution will dilate a Horners pupil (1.04.5
mm), with no change in the normal pupil (often
reversing anisocoria!)
a 0.5% solution will work just as well

 central (first order)

head or neck
brainstem stroke
brainstem tumor
spinal cord tumor
cervical spondylosis
preganglionic (second order)
neck or chest
apical lung tumor
internal carotid artery dissection
iatrogenic (from neck or chest surgery)
postganglionic (third order)
head or neck
internal carotid artery dissection
cavernous sinus tumor or inflammation
Raeder paratrigeminal neuralgia
iatrogenic (neck surgery)

Pharmacologic testing to
determine the location of the
lesion

paredrine (1% hydroxyamphetamine) stimulates

release of norepinephrine from the presynaptic
portion of the neuromuscular junction; it
dilates a normal pupil
dilates central and preganglionic Horners
pupils
will not dilate a postganglionic Horners
phenylephrine (1%) will dilate a postganglionic
Horners syndrome (due to denervation sensitivity)
but not a preganglionic Horners syndrome

Summary of
pharmacologic testing for
Horners syndrome

Investigations
central or preganglionic
cervical spine films in flexion and extension
chest CT scan
MRI brain (with detailed views of brainstem);
MRI/MRA or CT/CTA of neck
postganglionic
MRI brain (with detailed views of skull base and
cavernous sinus); MRI/MRA of neck

Anisocoria with one pupil that is

poorly reactive or non-reactive to
light
Differential diagnosis
iris sphincter damage (traumatic mydriasis)
pharmacologic blockade
tonic pupil
third nerve palsy
intermittent unilateral pupillary mydriasis
(parasympathetic form)

Evaluation
perform slit-lamp examination to look for iris
sphincter damage
check for other evidence of third nerve paresis
(e.g. ptosis, exodeviation, hyper- or hypotropia or
phoria)
the diagnosis is usually clinically apparent.
However, in a minority of cases pharmacologic
testing is required:
use 1% pilocarpine for a widely dilated, nonreactive pupil (possible pharmacologic dilation)
use 1% tropicamide for a markedly constricted,
non-reactive
pupil
(possible
pharmacologic
constriction)
use 0.1% pilocarpine for a moderately dilated
pupil with sector paralysis, vermiform movements or
light-near dissociation with tonic redilation (possible

Iris sphincter damage

(traumatic mydriasis)
pupil usually irregularly dilated
some reaction usually present
easily detected using slit-lamp biomicroscopy

Pharmacologic blockade
Topical parasympatholytic agents (causing dilated
pupil/s)
atropine
scopolamine (patch for
seasickness/postoperative nausea)
anticholinergic nasal sprays (inhalants)
ipratropium bromide (e.g. in Atrovent)
plants, e.g. datura (cornpickers pupil)
testing for parsympatholytic pharmacologic blockade:
place two drops of 1% pilocarpine in each lower
cul-de-sac wait 45 minutes and observe
anything less than full constriction is a positive
test for pharmacologic blockade

Pharmacologic blockade
Topical parasympathomimetic agents (causing
constricted pupil/s)
organophosphate pesticide (causes non-reactive
miotic pupil)
testing for parasympathomimetic pharmacologic
blockade:
place two drops of 1% tropicamide in each lower culde-sac wait 45 minutes and observe
anything less than full dilation is a positive test for
pharmacologic blockade

Tonic pupil
dilated pupil
sluggish or no reaction to light
sluggish or no reaction to near (but when present,
reaction to near better than to light)
slow redilation after constriction (very important)
sector iris paralysis
vermiform movements of iris
constricts to 0.1% pilocarpine

Etiology
features based on:
number of fibers for pupillary constriction versus accommodation in
the ciliary ganglion
aberrant regeneration in the peripheral nervous system
denervation supersensitivity
number of fibers for pupillary constriction versus accommodation in the
ciliary ganglion
about 95% of fibers in the ciliary ganglion are for accommodation
accommodation is more likely to be spared in ciliary ganglion damage
regeneration more likely to occur from fibers destined for ciliary body for
accommodation
aberrant regeneration
after injury to a peripheral nerve, both injured and uninjured fibers
regenerate
fibers originally intended for the ciliary body may regenerate to the iris
sphincter; the pupil will constrict during near viewing but not to light
denervation supersensitivity
an organ deprived of its postganglionic nerve supply becomes
supersensitive to the transmitter substance
the iris sphincter becomes supersensitive to acetylcholine and similar
substances (e.g. pilocarpine) once constriction of the pupil is achieved,
supersensitivity of the iris sphincter prevents normal, rapid redilation

Causes
classification of tonic pupil syndromes
local
with systemic or neurologic dysfunction
Adies (HolmesAdie) syndrome
local tonic pupils
tumor
trauma
inflammation (especially herpes zoster)
iatrogenic (lateral orbital exploration)
amyloid
systemic/neuropathic tonic pupils
more often bilateral than other syndromes
diabetes mellitus
myotonic dystrophy
dysautonomic syndromes
RileyDay
ShyDrager
acute pandysautonomia
HIV autonomic neuropathy
paraneoplastic

Causes
Adies (HolmesAdie) syndrome
usually unilateral (4% become bilateral each
year)
women more often affected than men (5:1)
usually occurs in early adulthood or middle
age (2050 years)
accommodation reduced or absent
absent deep tendon reflexes in 5075%
natural history is for pupil to become smaller
and accommodation to improve
etiology unknown: possibly viral or
autoimmune

Pharmacologic testing for

tonic pupil
In most cases of tonic pupil, the diagnosis is
obvious clinically and no pharmacologic testing is
required. However, if the diagnosis is unclear,
dilute pilocarpine testing can be performed:
place two drops of 0.1% pilocarpine in lower cul-desac of each eye
wait 45 minutes and assess
tonic pupil will constrict (markedly)
normal pupil will not constrict
some third nerve palsy pupils will also constrict to
this strength of pilocarpine why? It is thought that
some efferent pupillomotor fibers either bypass the
ciliary ganglion or pass through it without synapsing

Third nerve palsy

Isolated anisocoria from third nerve palsy:
the pupil is never widely dilated and nonreactive
in a patient with a mildly dilated, less reactive
pupil
ask about episodic eyelid droop or diplopia
check position of lids
test for exodeviation on gaze toward opposite
side
test for ipsilateral hypotropia in upgaze and
hypertropia in downgaze

Intermittent unilateral pupillary

mydriasis (parasympathetic form)
one pupil transiently becomes large and poorly
reactive to light
may be associated with migraine or occur as an
isolated event, usually in young adults
even when not associated with migraine, 50% of
patients have a history of migraines
poor reaction of the dilated pupil and reduced (or
absent) accommodation
no ocular motor dysfunction or ptosis
lasts 15 minutes to several hours
MRI may show enhancement of the third nerve