VIEWPOINT

The Argyll Robertson Pupil

H. Stanley Thompson, MD and Randy H. Kardon, MD, PhD

Abstract: The Argyll Robertson (AR) pupil has

been defined as a pupil that is small and constricts
poorly to direct light but briskly when a target within
reading distance is viewed (light-near dissociation).
Most descriptions of the AR pupil do not mention
segmental iris sphincter constriction, or slow, sustained
constriction with a near vision effort. Such features
are considered typical of the light-near dissociation of
Adie syndrome and of neuropathic tonic pupils,
where damage to the ciliary ganglion or ciliary nerves
is believed to be the mechanism. Because the AR
pupil lacks these features, it has been attributed to a
dorsal midbrain lesion that interrupts the pupillary
light reflex pathway but spares the more ventral
pupillary near reflex pathway. However, lesions in
this region have not been reliably demonstrated in
syphilis. Resolving the issue about the location of
the syphilitic lesion that produces the AR pupil will
depend on careful examination of patients with techniques designed to disclose segmental palsy of the
iris. If segmental iris sphincter palsy is found and the
light-near dissociation has tonic features, one must
conclude that the mechanism of the pupil disorder is
a ciliary (peripheral) rather than a midbrain (central)
denervation. Until better evidence settles the localization of the AR pupil, it is appropriate to screen
patients with bilateral tonic pupils for syphilis.
(J Neuro-Ophthalmol 2006;26:134138)

early a century and a half ago, Argyll Robertson

pointed out that some patients with tabes dorsalis had
small pupils that constricted poorly if at all to light yet
constricted promptly when the patients viewed a near object
(light-near dissociation). This observation was soon
confirmed at a rate of three to four publications per year and
was pronounced a useful clinical sign for syphilis (1). After
1908, when Wassermanns serologic test for syphilis

Neuro-ophthalmology Unit, Department of Ophthalmology and Visual

Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Address correspondence to H. Stanley Thompson, MD, Ginniff
Brooks 2096 Krestel Ridge SW, Oxford, IA 52322; E-mail: thompson@
ginniff.com

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became available and was found to be frequently positive

in patients with Argyll Robertson (AR) pupils, the popularity of Argyll Robertsons pupillary sign increased.
In the twentieth century, it became apparent to Adie
and others (2) that some young patients without clinical or
serologic signs of syphilis had this pupillary light-near
dissociation and also an abnormally slow (tonic) pupillary constriction when changing fixation from a distant
to a near target and back again. By mid-century, many of
the tonic light-near dissociated pupils that had previously
been called AR pupils (3) were being called Adies tonic
pupils.

TWO TYPES OF LIGHT-NEAR

DISSOCIATION
There appeared to be two different kinds of pupillary
light-near dissociation in patients with good vision and
normal eye movements and alignmentAR pupils and
tonic pupils:
1. AR pupils. These were frequently associated with
syphilis, tended to be small, almost always bilateral,
with little or no constriction to direct light, but prompt,
apparently normal, pupil constriction to near targets.
2. Tonic pupils. The tonic response to near came in three
varieties, all apparently orbital:
a) Adie tonic pupil. These were not clinically associated
with syphilis. Usually at first, only one pupil was
affected. The pupil was large, and accommodative power
was diminished. Close examination showed segmental
paralysis of the iris sphincter with the intact segments
constricting to light, a feature that ruled out pharmacologic mydriasis. After some weeks, the constriction to
a near stimulus would return, but it was strong and longlasting (tonic), and with time the second eye would
often become involved with the same process. Both
pupils would eventually become small. When the ciliary
ganglia of some of these patients with Adie syndrome
were examined, a loss of ciliary ganglion cells was
demonstrated (4).
b) Neuropathic tonic pupils (5). Patients with various
kinds of peripheral neuropathy also damage the innervation of their intraocular muscles in both eyes, including the sympathetic innervation to the dilator muscle (6).
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The Argyll Robertson Pupil

J Neuro-Ophthalmol, Vol. 26, No. 2, 2006

FIG. 1. Pupillogram of Argyll Robertson pupils showing a weak (low

amplitude) light reaction and a strong
near pupil constriction, which dilates
promptly with a change in focus to
a far object. Adapted from Reference 1.

c) Local tonic pupils (5). These were associated with

local damage to orbital nerves (penetrating wounds,
surgery, hemorrhage, orbital tumors, or infections).
It was eventually recognized that the tonicity of the
pupil reaction to a near target seen in these three groups of
patients was the result of aberrant regeneration into the iris
sphincter of fibers that had been originally destined for
the ciliary muscle (7). The slowness and tonicity of this
restored near response could be taken as an indicator of
aberrant regeneration of orbital peripheral nerves (7).

LOCALIZING THE LESION CAUSING THE

ARGYLL ROBERTSON PUPIL
There are two schools of thought about the location
of the lesion that causes the AR pupil. The first school
suggests that a lesion in the midbrain knocks out the light
reaction by damaging the interneuron that bridges the connection between the retinal ganglion cells and the EdingerWestphal nucleus but does not affect the more ventral
pathway mediating the near reaction. The second school
suggests that the lesion lies in the ciliary ganglion or nerves
in the orbit and that we have been fixating on the midbrain
and searching there in vain for pathology for a hundred
years because little was known of peripheral misdirection
syndromes when the AR pupil was first described.

THE CASE FOR A MIDBRAIN CAUSE FOR

THE ARGYLL ROBERTSON PUPIL
Loewenfeld (8,9) has strongly favored the idea that
syphilis usually produces a pupillary light-near dissociation
of a central (midbrain) variety by damaging the pupillary
light reaction pathway and sparing the near reaction
pathway and that the resulting light-near dissociation

without tonicity of the near reaction was what we called the

AR pupil. Using pupillography, Lowenstein (10) documented a number of such cases in patients with syphilis and
argued that it was natural to think that different kinds of
light-near dissociation should have different mechanisms,
probably in different locations.
In 1921, Kinnier Wilson started using the term
dissociation to refer to the pupil reactions in syphilis and
clearly favored a midbrain mechanism for AR pupils
because he had seen pupillary light-near dissociation in
patients with dorsal midbrain tumors (11) and, during the
1918 influenza pandemic, in patients with an acute
encephalitis (12). Unfortunately, he called every light-near
dissociated pupil an AR pupil and did not look closely at
the iris sphincter. Because he made no effort to distinguish
between tonic and normal constriction to a near target,
his rich clinical experience with neurosyphilis and AR
pupils is not relevant to our discussion of the location of the
lesion.

THE CASE FOR AN ORBITAL CAUSE FOR

THE ARGYLL ROBERTSON PUPIL
The counter argument suggests that Treponema
pallidum, or the bodys immune reaction to it, has a predilection for the meninges and blood vessels and that in
tabes dorsalis, the target is the dorsal root ganglion (part
of the peripheral nervous system). Peripheral nervous
system damage leads to the radiculopathy that accounts
for the typical symptoms in tabes. Since syphilis is
a famously versatile disease, why cant it also damage the
ciliary ganglion or short ciliary nerves? The aberrant
regeneration process would then produce a tonic pupillary light-near dissociation. This hypothesis would

FIG. 2. Aqueduct of Sylvius in a normal patient (A) and in a patient with

tabes dorsalis and Argyll Robertson
pupils (B) showing subependymal
gliosis as a dark line around the lining
of the aqueduct. Adapted from
Reference 20.

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Thompson and Kardon

FIG. 3. Pupillary light-near dissociation in a patient with neurosyphilis

who had smallish pupils in dark (top)
and light (bottom). There was very
prompt miosis with a near effort.
Inset shows that this patient had
a normal iris sphincter with no signs
of sector palsy.

eliminate the need to invoke an anatomically murky midbrain cause for pupillary light-near dissociation in the
AR pupil.
However, a traditionally strong argument against
a peripheral origin for the abnormal pupil in syphilis is that
syphilis does not commonly produce tonic pupils because it
does not produce a peripheral neuropathy. Yet, two studies
(5,13) have shown that a small number of patients with
tonic pupils in both eyes have (or have had) syphilis. One
series (5), published in 1977, followed 150 patients with
tonic pupils and segmental iris palsy. Of these patients, 21
had bilateral tonic pupils in the context of a widespread
peripheral neuropathy. This subgroup (neuropathic tonic
pupils) was older (63 years old at time of examination) than
the group of Adie tonic pupils without the neuropathy (32
years old at onset of symptoms). Seventy-seven of these
150 patients were tested for syphilis (VDRL, FTA-ABS).
No patient with only one eye involved was positive, but
one-third of the older group with both eyes involved (7/21)
were positive.
The other series (13) involved 60 patients with tonic
pupils and segmental iris palsy. Five of the 29 patients
tested (VDRL, FTA-ABS) had a positive serology (17%).
All five patients had bilateral tonic pupils and were
appropriately pursued for evidence of treatable neurosyphilis. In four of these five patients, the same tests were
positive in the spinal fluid.
Although the authors of these series of tonic pupils
suggested that the syphilis caused the orbital damage to the

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pupillary pathways, we now think it more likely that the

tonic pupils were merely an expression of the patients
established peripheral neuropathy.
Certain features of a peripherally denervated iris
sphincterirregularity of the pupil margin and segmental
damagehave occasionally appeared in older descriptions
of the AR pupil. For example, the Hamblin drawings in
McGraths 1932 paper, reprinted in Duke-Elder (1416),
show a tight miosis with some wrinkling of the pupillary
margin in one patient and an apparent segmental iris
atrophy of the stroma in another. These iris abnormalities
were blamed on the patients syphilis, but they are the very
features often seen in old Adie tonic pupils.
Another strong argument against a peripheral (orbital) cause of the AR pupil in syphilis is that pathologic
study of the ciliary ganglia in these patients has invariably
been normal. After Marina (17) argued for a peripheral
cause in 1910, there appeared a cluster of five publications
on postmortem studies of the ciliary ganglia in 40 syphilitic
patients with AR pupils and age-matched controls (18). The
ciliary ganglia were invariably normal.

OUR POSITION
We believe that the evidence supports a midbrain
cause of the AR pupil, provided one follows Loewenfelds
definition of the AR pupil as small pupils that react very
poorly to light and yet seem to retain a normal pupillary
near response that is definitely not tonic.
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The Argyll Robertson Pupil

We support our position with the following

arguments:
1. A tumor growing in the dorsal midbrain is known to be
capable of producing pupillary light-near dissociation,
although usually in association with upgaze difficulties;
2. The increased third ventricle pressure that occurs when
a ventricular drain or shunt has failed can also produce
a pupillary light-near dissociation.
3. Tonic pupils are common in patients with a widespread
peripheral neuropathy. They are usually bilateral and
have sector sphincter palsies and a tonic light-near
dissociation. If a patient with a diabetic neuropathy is
found to have bilateral tonic pupils, it would be wise to
assume that this is simply a manifestation of the diabetic
neuropathy. A minority of such patients may also have
syphilis (5,13), and their unrelated peripheral neuropathy might obscure a midbrain mechanism for the AR
pupils. For this reason, we favor checking the blood for
syphilis in patients with bilateral neuropathic tonic
pupils.
4. There is a very long and well-established tradition,
dating from the late nineteenth century when neurosyphilis was common, that syphilis does not cause a
polyneuritis.
5. Patients with AR pupils often have a considerable
amount of subependymal gliosis in the area where the
third ventricle narrows into the Sylvian aqueduct, at or
near the posterior commissure. Loewenfeld (19) cites
20 papers remarking on a combination of ependymitis
and subependymal gliosis. For example, Warkany (20),
in 1924, studied the brains of 10 tabetic patients with
a pupillary light-near dissociation and compared them
with non-syphilitic patients of a similar age. All of
the patients with syphilis and a light-near dissociation
had a striking gliosis just outside the ependyma that
lined the top end of the aqueduct of Sylvius. Could this
kind of periaqueductal subependymal gliosis and
associated nerve fiber loss, by itself, be enough to
interfere with the pupillary light reflex pathways from
both eyes while sparing the pupil response to a near
effort as suggested by Warkany (20)? The iris sphincter
is a very small muscle, and it probably does not take very
many nerve fibers to make it contract. It is not known
whether these few fibers of the interneuron controlling the
pupillary light reflex in both eyes could be taken out of
action by subependymal gliosis in the right location,
leaving the pupillary near reaction intact.

DETECTING SEGMENTAL IRIS

SPHINCTER PALSY
In our slit-lamp (21) and infrared iris transillumination (2224) examinations of the iris sphincter in patients
with Adie tonic pupil, we have consistently found evidence

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of segmental iris sphincter palsies. When the lights are

turned on, the video monitor will show segmental iris
sphincter palsy as a darkening of the parts of the iris
sphincter that are still wired up to the pupillary light reflex
(see boxed text below). With a near effort, there will often
be a thickening/darkening of other parts of the iris sphincter, sometimes in the very sectors that failed to darken in
light.
Even if examiners lack the equipment for iris infrared
transillumination, they should inspect the remaining movements of the iris sphincter at the slit-lamp, looking for
sectoral sphincter palsies. Our working assumption is that
when a patient has a sectoral sphincter palsy, light-near
dissociation is of orbital origin.
To settle the question of whether the AR pupil is of
central or peripheral origin, it will be necessary to perform
iris transillumination (or a magnified slit-lamp examination) in a substantial number of patients who have a pupillary light-near dissociation (with and without tonicity of the
near reaction), perhaps in many parts of the world.

REFERENCES
1. Loewenfeld IE. The Pupil: Anatomy, Physiology, and Clinical
Applications. Ames, Iowa: Iowa State University Press; 1993:9778.
2. Lowenstein O, Loewenfeld IE. Pupillotonic pseudotabes: the syndrome of Markus-Weill & Reys-Holmes-Adie: a critical review of
the literature. Surv Ophthalmol 1965;10:12985.
3. Loewenfeld IE. The Pupil: Anatomy, Physiology, and Clinical
Applications. Ames, Iowa: Iowa State University Press; 1993:984.
4. Harriman DG, Garland H. The pathology of Adie syndrome. Brain
1968;91:40118.
5. Thompson HS. Adie syndrome: some new observations. Trans Am
Ophthalmol Soc 1977;75:587626.
6. Koc F, Kansu T, Kavuncu S, et al. Topical apraclonidine testing
discloses pupillary sympathetic denervation in diabetic patients.
J Neuroophthalmol 2006;26:259.
7. Loewenfeld IE, Thompson HS. The tonic pupil: a re-evaluation.
Am J Ophthalmol 1967;63:4687.
8. Loewenfeld IE. Midbrain syndrome: Argyll Robertson pupils. In:
Loewenfeld IE. The Pupil. Ames, Iowa: Iowa State University Press;
1993:9561001
9. Loewenfeld IE. Lesions in the ciliary ganglion and short ciliary
nerves: the tonic pupil Adie syndrome. In: Loewenfeld IE.
The Pupil. Ames, Iowa: Iowa State University Press; 1993:1080
130.
10. Lowenstein O. The Argyll Robertson pupillary syndrome: mechanism and localization. Am J Ophthalmol 1956;42:10521.
11. Wilson SAK, Gerstle M Jr. The Argyll Robertson sign in
mesen-cephalic tumors. Arch Neurol Psychiat (Chicago) 1929;
22:918.
12. Kinnier Wilson SA. Some problems in neurology: the Argyll
Robertson pupil. J Neurol Psychpath 1921;2:125.
13. Fletcher WA, Sharpe JA. Tonic pupils in neurosyphilis. Neurology
1986;36:18892.
14. Duke-Elder WS. Text-Book of Ophthalmology, vol. IV. St. Louis:
C.V. Mosby Co.; 1949:3785.
15. Duke-Elder WS, Scott GI. System of Ophthalmology, vol XII. St.
Louis: C.V. Mosby Co.; 1971:663.
16. McGrath WM. Observations on abnormalities of the pupils and iris in
tabes dorsalis, general paralysis and tabo-paresis. J Ment Sci 1932;78:
36273.

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17. Marina A. Le ganglion ciliare comme centre peripherique de la

reaction pupillaire a` la lumiere et la phenomene dArgyll Robertson.
Presse Med 1910;18:4801.
18. Loewenfeld IE. The Pupil: Anatomy, Physiology, and Clinical
Applications. Ames, Iowa: Iowa State University Press; 1993:994.
19. Loewenfeld IE. The Pupil: Anatomy, Physiology, and Clinical
Applications. Ames, Iowa: Iowa State University Press; 1993:997.
20. Warkany J. Studien ueber das Verhalten der Glia im Mittelhirn
bei reflektorischer Pupillenstarre. Arbeit Neurol Inst Wien Univ
(Obersteiner) 1924;26:45569.

Thompson and Kardon

21. Thompson HS. Segmental palsy of the iris sphincter in Adie

syndrome. Arch Ophthalmol 1978;96:161520.
22. Kardon RH, Corbett JJ, Thompson HS. Segmental denervation and
reinnervation of the iris sphincter as shown by infrared videographic
transillumination. Ophthalmology 1998;105;31321.
23. Alward WL, Munden PM, Verdick RE, et al. Use of infrared videography to detect and record iris transillumination defects. Arch
Ophthalmol 1990;108:74850.
24. Verdick RE, Thompson HS. Infrared videography of the eyes.
J Ophthalmic Photography 1991;13:1921.

HOW TO TRANSILLUMINATE THE IRIS

The image on the screen shows the typical segmental iris sphincter palsy of Adie syndrome. The patients head is
supported by the chin rest. The sensitive camera is focused on the iris. The transilluminating light shines into the globe
through the lower lid and uvea, and the reflected light emerges through the iris, outlining its structures. Even an eye with
a heavily pigmented uvea can be penetrated with sufficient light to show the sphincter muscle. By turning the
transilluminating light off and on at a remote switch, one can obtain a sense of the mobility of various iris sphincter
segments. The resting position of the muscles in the dark can be seen during the latent period of the light reaction
(2224).

Equipment Used
1. A small, low-light video camera. These security cameras have been greatly improved in the last few years. Choose one
that is sensitive to near infrared wavelengths and very sensitive to low light levels. We have clamped this camera to
a table with a Bogen No. 3265 tripod head.
2. A macro close-up zoom lens that has no coated elements designed to block infrared wavelengths can focus on the eye
from just a few inches away and still leave enough room to move the transilluminator in front of the patients face.
3. A monitor on which the image can be displayed.
4. A recording device (S-VHS tape recorder, DVD recorder, or a digital tape).
5. A transilluminating light source. Since this hand light is applied to the patients skin, it should not become
uncomfortably hot. We use a standard Welch-Allyn Finhof transilluminator with a halogen source, which produces
a bright, visible light that is rich in infrared. It is held on the lower lid laterally and aimed at the posterior pole of the
eye.

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