A N D R E W

S .

G U RW O O D ,

O D ,

FA A O

A N D

L A U R A

E .

L E H N ,

O D

Diagrams of the pupillary light reflex

Left - The pupillary impulses
originate in the retina. The axons of
retinal ganglion cells pass into the
optic nerve, decussate in the
chiasm, and pass with the optic tract
to the mid-brain. The pupillary fibres
do not synapse with visual fibres in
the lateral geniculate body but pass
to the pretectal nuclei
Right - Pupillary axons synapse in
the pretectal nuclei with the
intercalated neurons that pass to the
Edinger-Westphal nuclei of the
oculomotor nerve (N III) on each
side. Pre-ganglionic pupillary motor
axons (parasympathetic) in the
inferior branch of the oculomotor
nerve synapse in each ciliary
ganglion. Post-ganglionic fibres in
the short ciliary nerves are
distributed to the sphincter pupillae
muscle of each eye

Figure 1

Tonic pupils
A tonic pupil, sometimes referred to as internal ophthalmoplegia, is the result of
damage to the parasympathetic innervation to the eye, resulting in decreased
function of the iris sphincter as well as the ciliary body1-10.

The tonic pupil responds to both light and

near stimuli with extremely slow
constriction and re-dilation. Patients
typically present with a chief complaint of
unilaterally reduced near vision and
anisocoria (asymmetry of pupil size). When
first noted by the patient in ambient light,
the tonic pupil is often the larger of the two.
However, if viewed in dim illumination, it
becomes the smaller1,2. Interestingly, the
anisocoria may diminish as the tonic pupil
becomes more miotic over time1-3,5-7,9. The
tonic pupil is typically unilateral (90%), but
may become bilateral at a rate of 4% per
year1-3,7.
Along with the pupil anomaly,
parasympathetic damage may result in
dysfunction of the ciliary body causing
accommodative spasm, accommodative
insufficiency and induced astigmatism,
generating complaints of blur at both
distance and near1,2. Accommodation, like
pupillary constriction and re-dilation, is
tonic as the patient changes fixation from
distance to near and back again. As a result,
tonic pupil patients often complain that
vision transiently blurs (until the ciliary

muscle catches up or relaxes) during

focusing. Accommodation is also found to be
reduced in amplitude1,2. Over time, the
tonicity of both the accommodative and
pupillary responses increase.
Tonic pupils can be found at any age and
in both sexes, however 70% are found in
females between the ages of 20 and 501-7.
PATHOPHYSIOLOGY
Afferent input to the parasympathetic
pathway results in pupillary constriction (the
direct light reaction). The pathway
originates in the photoreceptors and retinal
ganglion cells and travels via the optic nerve,
chiasm and optic tract (Figure 1). Some
fibres leave the tract prior to the lateral
geniculate body via the superior colliculus
and the brachium conjunctivum. These
fibres synapse in the pretectum and are
distributed bilaterally to the EdingerWestphal nucleus (EWN) of the oculomotor
nerve in the mid-brain1-7. Parasympathetic
tone of the irides originates in this complex
group of paired mid-line nuclei. The efferent
fibres travel with the third cranial nerve,
entering the orbit and synapsing in the
JULY 2 1999 OPTOMETRY TODAY

ciliary ganglion (CG)1-7. Post-synaptic fibres

leave the ganglion travelling past the short
ciliary nerves, piercing the sclera to arrive at
their end organ destinations, the iris and
ciliary body1,2; 93-97% of these
parasympathetic fibres go on to supply the
ciliary body resulting in the stimulation of
accommodation. The remaining 3-7%
innervate the pupillary sphincter, allowing
constriction of the pupil in response to
light1,2,5-7. The hypothesised reason for this
uneven distribution is the unequal masses of
the ciliary muscle and the sphincter1,2,5,6.
Interruption of the above pathway
anywhere along its route can result in
incomplete parasympathetic innervation,
causing pupillary dilation, decreased speed
and amplitude of constriction and decreased
speed and amplitude of accommodation.
Since the input to the EWN is crossed and
innervation of the pupillary sphincters is
bilateral, the pupils are expected to be equal
in size5. Acquired anisocoria indicates a
lesion in one of the efferent pathways or the
iris muscle.
Also playing a role in pupillary
constriction are three synkinetic reactions
including: (1) the near reflex (miosis,
accommodation and convergence);
(2) Bells phenomenon (levator inhibition,
superior rectus activation and miosis); and
(3) the Westphal-Piltz reaction (orbicularis
contraction and miosis)2,3,5,7.
37

TO N I C

Following injury to the ciliary ganglion or

the short ciliary, observations may include:
(1) light near dissociation (LND);
(2) tonicity of both the pupillary light
reaction and accommodation; (3) segmental
palsy of the iris sphincter; and
(4) denervation hypersensitivity to dilute
cholinergic agents1-10.
In the eight to 12 weeks following injury
to the CG, surviving ganglion cells sprout
collaterals to re-innervate both the ciliary
body and the pupil1,2,4,6. Because of the
previously mentioned 30:1 out-numbering of
fibres originally intended for the ciliary
muscle, this re-innervation results in a pupil
that constricts more to near stimulation
than to light1-7. This is LND.
In addition, the re-established
connections are less efficient, further
contributing to the latency and slow
pupillary constriction1,2. The tonic pupil also
dilates poorly due to inappropriate tone
secondary to aberrant reinnervation5,6. The
tonic characteristic of constriction/
re-dilation is also in part due to the
decreased number of intact neuromuscular
junctions following injury.
Segmental palsy results from the fact
that the sphincter is made up of 70 to 80
separate motor units, each served by a
separate parasympathetic nerve fibre8.
Partial denervation will then result in partial
or segmental constriction of the iris in
response to both light and near stimuli.
Unlike light near dissociation, which
takes weeks to months to develop,
hypersensitivity can be observed in days to
weeks1,2,5,6.
DIAGNOSIS
The first step in proper diagnosis is
determining if the anisocoria is benign and
physiologic, or acquired and pathologic; this
can be done by comparing the amount of
anisocoria in bright and then dim
illumination. Pupils which possess
physiological anisocoria will show a relative
size difference which does not vary from one
illumination level to the next. Pupils
suffering from sympathetic pathway lesions
(Horners syndrome) will possess anisocoria
which is greater in dim illumination, due to
failure of the iris dilator1-5,9,10. Pupils suffering
from parasympathetic pathway interruptions
will demonstrate anisocoria which measures
larger in bright light1-5,9,10. Secondly, the
pupils ability to react to light (both the
direct and consensual response) should be
observed and graded. Thirdly, the amount of
constriction accompanying accommodative
effort should be assessed and compared to
38

JULY 2 1999 OPTOMETRY TODAY

P U P I L S

the light response, checking for LND. It is

also helpful to know how long the anisocoria
has been present, as a more acute onset is
more likely to herald a true neurological
emergency. If the patient cannot offer a time
frame, a high plus power condensing lens can
be used to examine old photographs.
The tonic pupil can be diagnosed upon
examination with the biomicroscope8. With
the slit beam opened wide and directed from
a 60 angle, the details of the iris can be
easily observed. When tonic pupils are
present, as the lamp is turned on and off, the
practitioner will observe large sectors of the
iris that do not constrict to light, but rather
are dragged by neighbouring functional
segments8.
This phenomenon, referred to as stromal
streaming, is due to sectoral palsy of the
sphincter muscle1,2,4,6-9. Thompson observed
122 patients with Adies tonic pupil8; every
pupil exhibited this sectoral paralysis. He
also observed the tendency for sphincter
function to decrease over time8. The near
reaction in tonic pupils is often segmental as
well. Interestingly, segments which are
reactive during accommodation may not be
the same segments that react to light8. The
pupillary constriction that accompanies
accommodation is slow and after the near
effort is relaxed, re-dilation may take
minutes to hours2.
Pharmacological testing also helps in the
diagnosis of a tonic pupil. In 80-90% of
patients with a tonic pupil, dilute pilocarpine
(0.125%) or methacholine (2.5%) will cause
constriction1,2,5-7. Normal pupils do not
respond. To test accurately for
hypersensitivity, the corneal epithelium must
be intact. Any pathology, procedure (i.e.
tonometry) or medication that compromises
corneal integrity may produce a false positive
result. Alternatively, profuse tearing or
blinking may dilute the already weak
pilocarpine, resulting in false negative
findings1-3. Observations of pupil diameter
should be made while fixation is directed at
distance to eliminate any contribution of the
near synkinetic response1,2. One drop of
0.125% pilocarpine should be instilled into
the inferior fornix of both eyes and the pupil
diameters re-evaluated 45 minutes later1-3.
If denervation hypersensitivity is present:
(1) the involved pupil will constrict more
than 0.5mm relative to the fellow eye; or
(2) the suspicious pupil, larger in size prior to
the instillation of the drop, will become the
smaller pupil following instillation1,2. It is
important to note that hypersensitivity is not
limited to post-ganglionic lesions of the CG.
It may also occur in both pre and post-

Table 1
Aetiology summary for Aides tonic pupil
1.
2.
3.
4.
5.

Idiopathic
Orbital trauma
Herpes zoster infection
Diabetes mellitus
Autonomic neuropathies
(i.e. Riley Day syndrome)
6. Guillain Barre syndrome

Table 2
Characteristics of Aides tonic pupil
1.
2.
3.
4.
5.

6.
7.

8.
9.
10.
11.

Occurs most frequently in young women

Asymptomatic anisocoria
Antecedent upper respiratory infection
Blurred vision in affected eyes
Dilated pupil with poor reaction to light
and to near. Pupil may get smaller with
time
Opposite pupil becomes involved
in 4 % of cases
Segmental pupil response with classic
signs of stromal streaming, stromal
spread and sector paralysis
Slow near response that is greater than
the light response
Variable effect on accommodation
Diminished deep tendon reflexes
Diminished corneal sensation in the
affected eyes

ganglionic lesions of the third nerve1,2,4.

Jacobsen found cholinergic supersensitivity
in his study of oculomotor palsy, noting the
phenomenon in four out of five traumatic
palsies, two out of two congenital palsies, five
out of 11 compressive palsies and in none of
13 ischaemic palsies5,6. If the pupil fails to
constrict to 0.125% pilocarpine, the next
step is to instill a 1% solution. If the pupil
also fails to constrict to 1% pilocarpine, the
dilation is likely due to pharmacological
mydriasis
(atropine,
scopolomine,
cyclopentolate or homatropine), traumatic
iridoplegia, sphincter ischaemia secondary to
angle closure or has been iatrogenically
induced during intraocular surgery1,2,4-6,10.

TO N I C

P U P I L S

DIFFERENTIAL DIAGNOSIS
Anything that causes damage to the ciliary
ganglion or short ciliary nerves will result in
a tonic pupil. This includes, but is not
limited to, neurotropic viral infection
(varicella), orbital tumour, diffuse peripheral
neuropathy (diabetes mellitus) and
neurosyphillis1-7. Giant cell arteritis may
result in ciliary ganglion ischaemia resulting
in a tonic pupil1,2. Transient unilateral
dilation with decreased light reaction and
reduced accommodation have also been
found in association with migraine
headaches2,7,8,10,13.
Blunt trauma to the globe may cause
segmental iridoplegia in a variety of ways:
(1) the branches of the short ciliary nerves
may be torn in angle recession or become
disconnected from their insertion on the iris
sphincter; (2) the sphincter muscle itself
may be mechanically damaged; or (3) the
ciliary ganglion may be damaged by
retrobulbar haemorrhage8. Interruption of
the parasympathetic innervation may also
occur during anterior segment surgery or
extensive cryotherapy of the retina and
choroid, diffuse laser photocoagulation of
the retina and choroid or following
retrobulbar alcohol injections7.
Damage to the oculomotor nerve along
its course from the mid-brain to the eye can
result in a partial loss of the light reaction,
often in a segmental fashion4,8. Segmental
palsy and light near dissociation have also
been observed in Parinauds syndrome (loss
of conjugate up-gaze secondary to mid-brain
lesions, frequently the result of tumours of
the pineal gland)8,11. Bilateral tonic pupils
have been found in association with other
dysfunctions of the autonomic nervous
system including Rosss syndrome
(hyporeflexia, tonic pupil and progressive
segmental
anhidrosis)12,
orthostatic
hypotension and Riley Day syndrome
(familial dysautonomia)1,2,11.
Most cases of isolated internal
ophthalmoplegia are found to be idiopathic
and can appropriately be referred to as
Adies tonic pupil7. Ninety percent of these
patients will also have reduced deep tendon
reflexes (for reasons unknown) and regional
corneal hypesthesia due to disruption of
fibres in the ophthalmic division of the
trigeminal nerve as it passes through the
ciliary ganglion7.

aetiologies have been ruled out, it is

inappropriate to refer to the tonic pupil as
an Adies tonic pupil. Each case should be
handled individually. Gathering a complete
history is the first step. An acute tonic
pupil in patients over 60 years of age
warrants an erythrocyte sedimentation rate
to rule out giant cell arteritis. Tonic pupils,
especially if bilateral, should be tested for
syphillitic infection (FTA-Abs and
VDRL)2,7,10. A pupil with a weak light
reaction but no segmental palsy usually
indicates drug-induced mydriasis.
The differential diagnosis of a tonic
pupil must always include compressive
lesions of the oculomotor nerve2,8.
Although possible in theory, it is highly
unlikely that a patient with a posterior
communicating artery aneurysm or other
basal tumours will present with only an
abnormal pupil and no other oculomotor or
sensory disturbance2,6,7,9. However, two
cases were found in which isolated internal
ophthalmoplegia were the sole presenting
sign of intracranial aneurysm7. Therefore,
the finding of an isolated tonic pupil, in an
otherwise normal ambulatory individual,
merits at the very least close follow-up
monitoring for the development of other
neurological deficits. The role of neuroimaging in the evaluation of tonic pupils
remains controversial. While some authors
are comfortable with careful follow-up,
others recommend an MRI in all cases of
isolated internal ophthalmoplgeia2,6,7,9.
It is important to note that LND is not
pathoneumonic of a tonic pupil. It may also
be found in neurosyphillis (ArgyllRobertson pupil), amaurosis (blindness),
aberrant
regeneration
following
oculomotor nerve palsy, pretectal midbrain lesions, myotonic dystrophy, tabes
diabetica, tabes pituitaria and familial
amyloidosis2-5. Therefore, when observed,
LND must provoke investigation of these
disorders.
No definitive treatment for the tonic
pupil exists. Patients may seek relief from
glare caused by mydriasis and to improve
the appearance of the anisocoria. In these
cases, a specialty contact lens may provide
a solution. Visual complaints associated
with ciliary body dysfunction occasionally
respond to low concentrations of
cholinergic drugs.

MANAGEMENT
In the absence of other signs and
symptoms, a tonic pupil is a benign finding
and heralds no systemic or neurological
disease emergency1,2. Until other

ACKNOWLEDGEMENTS
Figure 1 is reproduced from Newell, F.W.
(1996) Ophthalmology Principles and
Concepts (8th edition) with permission
from Mosby Year Book, St Louis.
JULY 2 1999 OPTOMETRY TODAY

ABOUT THE AUTHOR

Dr Andrew Gurwood is Associate Professor
of Clinical Sciences at the Eye Institute of
the Pennsylvania College of Optometry.
Dr Laura Lehn is a staff optometrist at the
institute and is also in private practice in
Philadelphia.
REFERENCES
1.

Slamovits, T.L. and Glaser, J.S. (1998)

The pupils and accommodation. In: Tasman,
W. and Jaeger, E.A. Duanes Clinical
Ophthalmology CD ROM. J.B. Lippincott,
Philadelphia.

2.

Slamovits, T.L. and Glaser, J.S. (1990)

The pupils and accommodation. In: Glaser, J.S.
Neuro-Ophthalmology. J.B.Lippincott,
Philadelphia.

3.

Tantum, L.A. (1994)

Pupil anomalies. In: Onofrey, B.E. Clinical
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Kardon, R.H. (1999)

The pupils. In: Yanoff, M. and Duker, J.S.
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Newman, N.M. (1992)

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6.

Kardon, R.H. and Thompson, H.S. (1998)

The pupil. In: Rosen, E.S., Thompson, H.S.,
Cumming, W.J.K. and Eustace, P. NeuroOphthalmology. Mosby International,
Philadelphia.

7.

Burde, R.M., Savino,P.J. and Trobe,J.D.

Anisocoria and abnormal pupillary light
reactions. In: Burde, R.M., Savino,P.J. and
Trobe,J.D. Clinical Decisions in NeuroOphthalmology. Mosby Year Book, Philadelphia.

8.

Thompson, H.S. (1978)

Segmental palsy of the iris sphincter in Adies
syndrome. Archives of Ophthalmology 96(9):
1615-1620.

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Thompson, H.S. and Pilley, S.F.J. (1976)

Unequal pupils - a flow chart for sorting out the
anisocorias. Survey of Ophthalmology 21(1):
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10. Lee, A.G., Taber, K.H., Hayman, L.A. and Tang,

R.A. (1997) A guide to the isolated dilated
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11. Friel, J.P. Ed. (1994) Dorlands Illustrated
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dysfunction in a patient with Rosss syndrome
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39