A Guide to the Isolated Dilated Pupil

Abstract

The poorly reactive and dilated pupil observed in a comatose patient is often thought to represent an acute third nerve palsy owing to brain herniation or aneurysm. In the well patient, however, the isolated dilated pupil is unlikely to be owing to a third nerve palsy. It is more commonly owing to other benign causes such as local iris sphincter abnormalities, pharmacologic dilation, tonic pupil syndrome, or sympathetic irritation. This article presents a diagnostic flowchart to help the primary care physician analyze this problem and prevent costly and unnecessary imaging of these patients.

Full text

A
Guide
to
the
Isolated
Dilated
Pupil
Andrew
G.
Lee,
MD;
Katherine
H.
Taber,
PhD;
L.
Anne
Hayman,
MD;
Rosa
A.
Tang,
MD
The
poorly
reactive
and
dilated
pupil
observed
in
a
comatose
patient
is
often
thought
to
represent
an
acute
third
nerve
palsy
owing
to
brain
herniation
or
aneurysm.
In
the
well
patient,
however,
the
isolated
dilated
pupil
is
unlikely
to
be
owing
to
a
third
nerve
palsy.
It
is
more
commonly
owing
to
other
benign
causes
such
as
local
iris
sphincter
abnormalities,
pharmacologic
dilation,
tonic
pupil
syndrome,
or
sympathetic
irritation.
This
ar-
ticle
presents
a
diagnostic
flowchart
to
help
the
primary
care
physician
analyze
this
problem
and
prevent
costly
and
unnecessary
imaging
of
these
patients.
ArchFamMed.
1997;6:385-388
Several
articles
in
the
ophthalmologic
lit¬
erature
have
reviewed
the
management
of
anisocoria,116
but
little
emphasis
has
been
placed
on
the
evaluation
of
the
isolated
di¬
lated
pupil.
This
is
unfortunate
because
many
of
these
patients
initially
present
to
the
primary
care
physician
and
may
un¬
dergo
many
unnecessary,
expensive,
and
potentially
hazardous
tests.5
This
article
outlines
a
simple
stepwise
diagnostic
sche¬
matic
(Figure)
to
guide
the
assessment
of
a
patient
with
an
isolated
dilated
pupil.
The
tests
that
need
to
be
performed
are
shown
as
steps
1
through
7
in
the
Figure.
STEP
1:
EXAMINATION
OF
LIGHT
REACTION
(FLASHLIGHT
TEST)
Pupillary
parasympathetic
constriction
to
light
is
mediated
by
the
third
nerve
as
pre-
ganglionic
efferent
fibers
to
the
ciliary
gan¬
glion
and
then
as
postganglionic
fibers
to
the
iris.
Pupil
dilation
is
mediated
by
the
oculosympathetic
pathway,
which
is
not
dis¬
cussed
in
detail
in
this
article.
Therefore,
careful
examination
of
the
pupillary
re¬
sponse
to
light
allows
the
clinician
to
de¬
termine
whether
the
larger
or
the
smaller
pupil
is
abnormal.
This
is
important
be¬
cause
a
difference
in
pupil
size
(anisoco¬
ria)
is
not
always
caused
by
an
enlarged
pu-
pil
(ie,
the
smaller
pupil
may
be
the
abnormal
pupil).
If
the
larger
pupil
dis¬
plays
a
poor
light
reaction,
it
is
likely
to
be
the
abnormal
pupil.9·1213
This
finding
sug¬
gests
damage
to
either
the
iris
or
parasym-
pathetic
innervation
to
the
iris.
If,
how¬
ever,
the
light
reaction
is
normal
in
both
eyes,
then
the
differential
diagnosis
in¬
cludes
physiological
anisocoria,
a
contra-
lateral
oculosympathetic
pathway
disrup¬
tion
(ie,
Horner
syndrome
involving
the
smaller
pupil)
or
ipsilateral
sympathetic
overaction.
Testing
for
the
amount
of
rela¬
tive
anisocoria
in
bright
or
dim
illumina¬
tion
gives
similar
information.
Specifi¬
cally,
if
the
anisocoria
is
greater
in
bright
light,
then
the
larger
pupil
is
abnormal
be¬
cause
it
is
not
constricting
appropriately
rela¬
tive
to
the
fellow
eye.
Conversely,
if
the
an¬
isocoria
is
greater
in
dim
illumination,
then
the
smaller
pupil
is
abnormal
because
it
is
not
dilating
appropriately
relative
to
the
fel¬
low
eye.
Abnormal
pupillary
light
reaction
may
be
subtle
and
difficult
to
recognize
by
the
inexperienced
examiner
and
appropri¬
ate
ophthalmologic
consultation
should
be
considered
in
questionable
cases.
STEP
2:
EVALUATION
OF
EXTRAOCULAR
MOTILITY
In
theory,
an
extra-axial
compressive
lesion
of
the
third
nerve
may
cause
an
iso¬
lated
dilated
pupil
without
an
extraocu-
lar
motility
deficit.10
In
practice,
this
rarely
occurs.
Intracranial
aneurysms,
espe-
From
the
Departments
of
Ophthalmology,
Neurology,
and
Neurosurgery
(Dr
Lee)
and
the
Department
of
Radiology
(Drs
Taber
and
Hayman),
Baylor
College
of
Medicine,
Houston,
Tex;
and
the
Departments
of
Ophthalmology
and
Neurology
(Dr
Tang),
University
of
Texas
Medical
Branch,
Galveston.
at STANFORD Univ Med Center, on November 5, 2009 www.archfammed.comDownloaded from

A
guide
to
the
isolated
dilated
pupil.
cially
those
involving
the
posterior
communicating
artery-internal
ca¬
rotid
artery
junction,
often
pro¬
duce
a
fixed
and
dilated
pupil
and
almost
always
produce
other
eyelid
or
extraocular
motility
signs
of
a
third
nerve
palsy.
Wilhelm
et
al17
re¬
viewed
the
literature
on
6
cases
with
isolated
dilated
pupils
owing
to
a
third
nerve
palsy.
Three
patients
had
headaches
and
1
patient
had
a
sei¬
zure
and
headache.
In
2
patients,
signs
or
additional
signs
of
a
third
nerve
palsy
developed
early
in
the
course
of
their
illness,
but
in
1
pa¬
tient
these
signs
developed
1
year
later.
Rare
cases
of
cryptococcal
or
tuberculous
basal
meningitis
have
also
been
described
as
presenting
with
an
isolated
dilated
pupil,
but
other
concomitant
neurologic
signs
were
present
or
additional
features
of
a
third
nerve
palsy
appeared
over
time
in
most
of
these
patients.17
Thus,
the
patient
with
an
isolated
di-
lated
pupil,
without
evidence
of
pto-
sis
or
extraocular
motility
deficit,
is
unlikely
to
have
a
third
nerve
palsy.
Nevertheless,
close
follow-up
for
the
development
of
additional
signs
of
a
third
nerve
palsy
is
mandatory
and
patients
in
the
appropriate
clinical
setting,
such
as
those
in
the
inten¬
sive
care
unit
with
severe
or
acute
onset
headache,
should
have
their
condition
evaluated
immediately.
STEP
3:
EVALUATION
OF
THIRD
NERVE
PALSY
In
general,
patients
with
a
nontrau-
matic
pupil-involved
third
nerve
palsy
should
undergo
screening
for
signs
of
subarachnoid
hemorrhage
(computed
tomographic
scan,
lum¬
bar
puncture,
or
both)
and
subse¬
quent
cerebral
arteriography
to
ex¬
clude
aneurysm.
The
Figure
shows
that
a
third
nerve
palsy
involves
the
preganglionic
efferent
lesion.
STEP
4:
DIFFERENTIATE
INTERMITTENT
FROM
PERSISTENT
PUPIL
DILATION
Transient
dilation
has
been
de¬
scribed
in
patients
with
migraine
headaches7·8·15
and
even
in
other¬
wise
normal
individuals.7·8
Tadpole-
shaped
pupils,
owing
to
segmental
spasm
of
the
iris,
may
also
be
related
to
migraine
phenomenon.11
Some
of
these
episodes
may
represent
sympa¬
thetic
irritation
or
excess,
but
there
is
still
some
controversy
as
to
whether
this
is
the
true
mechanism.
Dysauto-
nomic
cephalgia
after
neck
trauma
may
also
result
in
sympathetic
hyper¬
activity
involving
the
pupil,
sweat¬
ing,
and
eyelid
retraction.18
If
the
tran¬
sient
or
intermittent
nature
of
the
dilation
can
be
established
firmly
by
patient
medical
history
or
physical
ex¬
amination
findings
and
the
episodes
occur
in
isolation
in
an
otherwise
healthy
patient
(or
only
with
mi-
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graine
headaches),
these
patients
should
not
undergo
emergency
arte-
riography.
In
addition,
other
neuro-
imaging
may
be
deferred
and
the
pa¬
tient's
condition
should
simply
be
followed
up
for
improvement
dur¬
ing
the
next
24
to
48
hours.
Resolu¬
tion
of
all
signs
suggests
a
benign
ori¬
gin
for
the
pupil
dilation.
STEP
5:
EXCLUDE
PHARMACOLOGIC
DILATION
In
cases
with
persistent
pupil
dila¬
tion,
a
careful
patient
history
is
of¬
ten
all
that
is
required
to
detect
inad¬
vertent
or
intentional
exposure
to
topical
dilating
agents
(mydriatics).
Specific
questioning
should
be
di¬
rected
toward
the
use
of
topical
medi¬
cations
by
the
patient
or
patient's
fam¬
ily
members
(especially
postcataract
drops)
or
the
use
of
transdermal
sco¬
polamine
patches
for
motion
sick¬
ness
(which
have
been
unavailable
re¬
cently,
but
will
be
reintroduced
in
1997).
Nurses,
physicians,
and
other
health
care
workers,
in
particular,
may
be
inadvertently
or
intentionally
ex¬
posed
to
topical
mydriatics.9·12·13
To
establish
this
diagnosis,
the
dilated
pupil
may
be
tested
for
a
pharmaco¬
logie
blockade
with
topical
1%
pilo¬
carpine.1·14
A
pupil
that
is
dilated
ow¬
ing
to
a
third
nerve
palsy
will
constrict,
but
a
pupil
with
a
parasym-
pathetic
pharmacologie
blockade
(such
as
with
topical
atropine)
will
not.
Adrenergic
pharmacologie
dila¬
tion
(such
as
with
topical
phenyleph-
rine
hydrochloride)
often
may
be
clinically
distinguished
from
para-
sympatholytic
blockade
by
blanched
conjunctival
vessels,
residual
light
re¬
action,
and
a
retracted
upper
eyelid
owing
to
sympathetic
stimulation
of
the
upper
eyelid
retractor
muscle.
Convergence
effect
and
0.063%
pi¬
locarpine
also
will
not
constrict
a
pharmacologically
dilated
pupil.
In
most
cases,
the
patient
his¬
tory
and
a
simple
confirmatory
phar¬
macologie
test
result
are
all
that
are
required
for
the
diagnosis.
Reassur¬
ing
the
patient
along
with
close
fol¬
low-up
as
the
dilatory
effect
wears
off
are
sufficient.912·13
An
acute
tonic
pu¬
pil
may
be
unreactive
to
either
light
or
near
stimuli
and
may
be
difficult
to
distinguish
from
a
pharmacologi¬
cally
dilated
pupil
or
a
case
of
acute
traumatic
iridoplegia.9·12·13
STEP
6:
EXCLUDE
STRUCTURAL
IRIS
ABNORMALITIES
Ophthalmologic
consultation
is
par¬
ticularly
helpful
in
patients
with
a
suspected
orbital
or
intraocular
pathologic
condition.
Patients
may
present
with
a
history
of
ocular
trauma,
loss
of
vision,
a
red
eye,
or
ocular
pain.
Slit-lamp
biomicros-
copy
is
far
superior
to
gross
inspec¬
tion
with
a
handlight
for
the
detec¬
tion
of
iris
transillumination
defects
and
sphincter
tears
at
the
pupillary
margin,
which
may
cause
a
dilated
pupil.
Increased
intraocular
pressure
owing
to
angle-closure
glaucoma
may
also
cause
an
acute
sphincter
pare¬
sis
and
a
unilateral
dilation.
These
pa¬
tients
often
have
ocular
pain,
con-
junctival
hyperemia,
or
corneal
edema,
but
these
features
are
vari¬
able
and
may
be
missed
without
a
complete
ophthalmologic
examina¬
tion.9·12'13
Finally,
iris
ischemia
such
as
carotid
occlusion
may
also
result
in
a
dilated
pupil.19
STEP
7:
CONSIDER
TONIC
PUPIL
SYNDROME
The
clinical
features
of
the
tonic
pu¬
pil
include
a
diminished
or
absent
pu¬
pillary
reaction
to
light
stimulus,
seg¬
mentai
palsy
of
the
iris
sphincter,
a
tonic
pupillary
near
response
pro¬
ducing
a
"light-near
dissociation"
of
the
pupil,
cholinergic
supersensitiv-
ity
to
low-dose
(0.125%-0.063%)
topical
pilocarpine
of
the
dener-
vated
sphincter,
and
a
variable
ac¬
commodation
paresis.2"4'6'16
The
pathophysiological
feature
of
the
Adie
tonic
pupil
is
most
likely
damage
to
the
ciliary
ganglion
or
postgangli-
onic
efferent
nerves.2·3·61116
More
than
90%
of
the
ciliary
ganglion
cells
serve
the
ciliary
body
and
only
3%
serve
the
iris
sphincter.
After
damage
to
the
ciliary
ganglion,
aberrant
regenera¬
tion
of
fibers
originally
destined
for
the
ciliary
body
now
innervate
the
iris
sphincter.
Accommodative
effort
stimulates
these
fibers
and
pro¬
duces
a
tonic
near
response.2·3·6·11·16
Some
patients
may
have
decreased
limb
deep
tendon
reflexes.
The
syn¬
drome
is
benign
and
does
not
usu¬
ally
require
further
evaluation
or
treatment.
STEP
8:
CONSIDER
SYPHILIS
Fletcher
and
Sharpe4
reported
that
5
of
60
consecutive
patients
with
tonic
pupils
had
positive
serologie
results
for
syphilis.
Of
these
patients,
all
had
a
bilateral
tonic
pupil
and
none
pre¬
sented
with
acute
mydriasis
or
cy-
cloplegia.
We,
therefore,
perform
syphilis
serologie
testing
on
all
pa¬
tients
with
a
bilateral
tonic
pupil
and
on
patients
with
a
monocular
tonic
pupil.
CONCLUSIONS
The
primary
care
physician
should
be
familiar
with
the
most
common
causes
for
the
isolated
dilated
pupil
in
the
ambulatory
setting.
Neuroim-
aging
and
other
laboratory
studies
are
usually
unnecessary
in
the
evaluation
of
the
isolated
dilated
and
poorly
re¬
active
pupil.
A
careful
stepwise
patient
medical
history
and
physical
examination,
as
well
as
prompt
oph¬
thalmologic
consultation,
may
spare
the
patient
unnecessary,
expensive,
and
potentially
hazardous
or
invasive
diagnostic
testing.
Accepted
for
publication
August
9,
1996.
This
research
was
supported
in
part
by
an
unrestricted
grant
(Depart¬
ment
of
Ophthalmology,
Baylor
Col¬
lege
of
Medicine)
from
Research
to
Pre¬
vent
Blindness
Ine,
New
York,
NY.
Corresponding
author:
Andrew
G.
Lee,
MD,
Cullen
Eye
Institute,
6501
Fannin,
NC-200,
Houston,
TX
77030.
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