The mydriatic effect of tropicamide
on light and dark Iricies
...
ABSTRACT -Tropicamide 0. 59 wAF topically
applied to the eyes of thirteen subjects to study its
effectiumess as a mydriatic. A amiparison was
made between the subjects with light colored irides
and those with dark broum irides, and also betzvern
1.hose who had worn contact lenses prezlimis to dita-
Lion rind those who had not. Resultx indicate that a
minimum pupil size of 6 min uns achin,ed within
25 minutes after instillation and this dilation was
independent of iris pigmentation. Typically, IOP
was reduced during dilation with tropicamide.
ABOUT OUR AUTHORS-James R. Dillon,
O.D., rereired his degree from the Pacific Univer-
Introduction
Recently, several states have legalized the
use of certain diagnostic pharmaceuticals
by O.D.s. Hence, it has become necessary
for the optometric community to better
understand the actions of these various
drugs. While many of these drugs have un-
dergone considerable research with the re-
sulting publication of the data, there does
not seem to be an overabundance of litera-
ture on the mydriatic tropicamide. A search
of the literature indicates that there are
very few articles quantifying the rate and
depth of mydriasis of tropicamide. Most
studies that have been done have dealt
primarily with Caucasians and light irides,
simply stating that dark highly pigmented
irides were more difficult to dilate and
could not be satisfactorily dilated with the
same minimal dosages and concentra-
tions.1.2,3 Gettes4, however, noted that the
eyes of Negroes were more difficult to di-
late with .05,.10 and .25% solutions of
tropicamide but stated that the maximum
JAMES R. DILLON, O.D.,
CHARLES W. TYHURST, B.S.,
AND ROBERT L. YOLTON, O.D., PH.D.
sity College of Optoinetry in 1976, (ind is nmi,
practicing with the U.S. Navy at Norfolk Naval
Station, Norfolk, Virginia.
Charles W. Tyhurst receiz,ed his B.S. degree at
Pacific Unil,ersity, and is a folirth year stildent at
the Pacific Uniz, ersity College of Optometry.
Robert L. Yotton, O.D., Ph.D., B Director of
Research at Patif ic University College of OP-
tometry. He rec e iz,ed his Ph.D. from the Uniz,ersity
if Texas and his O.D. from the New England
College of Optometry.
dilatation was approximately the same for
all subjects using 0.5% tropicamide.
Several reasons have been postulated for
mydriatics being less effective on dark
irides. Howard and Lees felt that pigment
cells in the limbal conjunctiva and sclera
and additional chromatophores in the iris
had a destructive action upon the drug.
Obianwu and Rand6 felt that subjects with
dark irides had a stronger reflex miosis.
Angenent and Koelle7 examined the
differential destructive effects of enzymes
upon certain chemical mediators, using
both pigmented and albino rabbit iris-
ciliary bodies. They postulated that a simi-
lar enzyme mechanism in human dark
irides may exert a destructive effect upon
mydriatics.
A general belief that dark heavily pig-
mented irides are more difficult to dilate
may lead to the use of larger dosages,
stronger concentrations or stronger drugs
on patients with such irides, thus increasing
the risk and severity of possible side effects
or reactions.
Volume 48, Number 5, May 1977 653
 . 1 > 11.39,1 li.,33'c , :,t:~d'
--

~WI<:':z
I .-
~~~ f ~ There have been very few reports of ad-
verse reactions with tropicamide. In one
. Cast, a subject, described as being emo-
: ist M tionally labile , was found to have become
addicted to the topical application of cy-

At.
clopentolate and tropicamide. He de-
veloped a drug induced epithelial keratitis
which reversed within four days after he
ceased the application of up to 200 drops of
*v~. - 1 A-/F, ., . . *fr
. thedrugs per day. The patient experienced
apparent physiological and psychological
withdrawal symptoms after discontinuing
the use of the drugs. Since the patient was
using both tropicamide and cyclopentolate,
it was not knoivn whether the tropicamide,
,4
.... cyclopentolate or the combination of the
two were responsible for the keratitis and
james R. Dillon
the addiction. The reporting author sug-
gested that the keratitis could have been
15 caused by the preservatives,
In another case: a ten year old male de-
veloped an apparent anaphylactic reaction
following one drop of 0.5% tropicami(le in
14' each eye. He immediately became uncon-
IS. scious, and exhibited generalized muscular
rigidity, opisthotonos, pallor and cyanosis.
Without treatment, he shortly became flac-
cid, and about an hour after onset, his vital
signs were normal and he had recovered
except for residual drowsiness. No inconti-
nence, psychotic behavior, ataxia, hyper-
sensitivity, flushing or fever was experi-
enced. By the next morning he had fully
/\ recovered. Wahl stated that "adverse sys-
temic reactions to this preparation have not
been previously reported" and felt that the
child was possibly pre-sensitized from ap-
plication of atropine at the age of five, since
atropine and tropicainide are both similar
Charles W. Tyhurst derivatives.
N. DeNosagno, in january 1969, re-
Robert L. Yolton ported to WahP one documented report of
an acute explosive type of' local reaction in
I.
an adult. Severe edema of the eyelids and
rhinitis occurred following instillation of
one drop in each eye. E. Maxwell also re-
ported a reaction after instillation of
tropicamideand cyclopentolate, but the pa-

1 tient was later found to be sensitive to cy-

clopentolate.
According to Gettes,4 animal studies have
- shown that prolonged applications of
tropicami(le produced no evidence of
damage to any part of the eye upon biomi-
croscopIc examination.

'11*140/ZE'h
 Tropicamide is chemically designated as
N-ethyl-2-phenyl-N-(4-pyridylmethyl)-
hydracrylamide.10 It is a synthetically pre-
pared derivative of tropic acid which is a
constitutent of the belladonna alkaloids.
Tropicamide is pharmacologically related
to the parasympatholytic group of drugs. It
is an antimuscarinic drug which acts as a
competitive antagonist to acetylcholine and
other muscarinic agents. It inhibits the ac-
tions of acetylcholine on structures inner-
vated by postganglionic cholinergic nerves
and on certain smooth muscles. The an-
timuscarinic drugs, such as topicamide,
block the actions of the sphinctor muscle of
the iris and the ciliary muscle of the lens to
cholinergic stimulation, dilating the iris
(mydriasis) and paralyzing accommodation
(cycloplegia).
Cycloplegics and mydriatics are con-
traindicated in general in closed angle
glaucoma. Elevation of intraocular pres-
sure has also been reported to occur in
some cases of open angle glaucoma.
O'Connor-Davisll states that tropicamide
does not elevate the intraocular pressure in
normal eyes. A tonometric study by Vilmar
and Buchman12 with gonioscopically con-
.
firmed cases of wide-angle" glaucoma
found no recorded elevation in the intra-
ocular pressure. Portney and Purcell,13 in a
study of 1% tropicamide on 50 normal and
50 open angle glaucoma patients, found
little effect on both normal eyes and eyes
with untreated open angle glaucoma al-
though some effect was found on eyes of
open angle glaucoma patients under
pilocarpine therapy. A study by Harris14
found that 11 patients experiencing intra-
ocular pressure increases with the use of
1% cyclopentolate experienced no such in-
crease with the use of .5% tropicamide. Of
these 11 patients nine were open angle
glaucoma patients and two were normal.
Tropicamide has many properties which
appear to be of benefit to the O.D. such as a
very short lag time, fast action and fast re-
covery time.Since an O.D. would primarily
be using a mydriatic for ophthalmoscopic
examining purposes, the short duration of
action of this drug should be no problem.
Tropicamide is considered to be a rela-
tively safe mydriatic because of its short
duration and fast recovery time. Although
there have been adverse reactions with this
class of drugs, relatively few side effects or
adverse reactions have been reported with
tropicamide. Since any possible side effect
would probably be dose dependent, it
would be of benefit to both the practitioner
and the patient to use the smallest dosages
and concentration practical to produce an
effective mydriasis.
The purpose of this study was to deter-
mine and quantify the mydriatic effects of
0.5% tropicamide on both light irides and
dark, heavily pigmented irides and to de-
termine if tropicamide is effective at nor-
mal dosage levels on dark irides.
Methods
Thirteen subjects participated including
three blacks, two orientals, four Caucasians
with dark brown irides and four Caucasians
with light irides. Each subject was carefully
screened to avoid risks of angle-closure
glaucoma or drug hypersensitivity. The
screening included a history of drug reac-
tions, the use of ocular pharmaceuticals or
any other drugs being presently used,
measurements of visual acuity, ophthal-
moscopy, anterior chamber angle evalua-
tion with the slit lamp, and measurement of
intraocular pressure. The amplitude of ac-
commodation was measured by the push-
up method using a .62M reading para-
graph before instillation of the drug and
during dilation to determine the cyclo-
plegic effect of 0.5% tropicamide. The
American Optical Non-Contact Tonome-
ter was used to measure the intraocular
pressure before instillation and during
maximum mydriasis to monitor IOP
changes.
Pupillary size measurements were made
photographically using a 35mm Yashica
camera with a 135mm Vivitar telephoto
lens and a + 3.00 D lens to reduce the focal
distance. The unit was mounted on a slit
lamp base. The focal distance was critical
within *2mm thus insuring a constant eye
to camera distance. A 7X magnifier reticule
was photographed in the same plane as the
iris thus giving a reference photograph
calibrated in .1mm steps. The photograph
negatives were projected on a microfilm
reader over which the measurement scale
was superimposed, allowing measurement
of iris diameters within .05mm. To allow
for the variability of unequal dilatation in
the horizontal and vertical meridians, both
meridians were measured with the average
Volume 48, Number 5, May 1977 655
 e- of the two being used for the data. The
f T subjects were photographed prior to instil-
7 -
lation of 1 drop of .5% tropicamide and at
6- five minute intervals for the first 60 min-
utes and at fifteen minute intervals for the
5-
EE next 60 minutes. Standard instillation pro-
4- SD LIGHT
_~ LSD DARK cedure was followed with the patient com-
2 3- pressing the lacrimal sac for one minute
after instillation to minimize systemic ab-
2-
sorption. Although only the pupil diameter
of the left eye was photographed and re-
corded, both eyes were dilated to avoid any
O111
20 40
lilli
60 75 90 105 120 consensual pupillary responses, to avoid
TIME(min) discomfort to the patient by having one eye
Figure 1 light sensitive and the other eye not, and to
Curves showing the mean dilation and standard de- prevent Pulfrich phenomenon.
viation for nine subjects with dark brown irides and Standard room lighting was used be-
four subjects with light irides. tween measurements. During photographs
9-
a 100 watt study lamp was positioned 6.5
inches from the patient's eyes with a con-
8- stant 750 footcandles of light incident on
the eye at the time of measurement. The
7-
photographs were taken as soon as constric-
6- tion had occurred after turning on the
light. This procedure was used to ensure
that the measurements recorded would be
i 9- valid whenever a stimulus to constriction
-f,P-C
WEAR ~SD-NON n
WEAR was present since in direct or indirect
ophthalmoscopy, biomicroscopy, and fun-
2- dus photography, a bright light is directed
into the eye. With ambient room illumina-
1-
tion only, impressive dilation may occur,
11111111 but it also may disappear when a stronger
0 20 40 60 75 90 105 120
stimulation is present.
TIME (min)
A comparison was made of the extent
Figure 2 and time of maximum mydriasis between
Curves showing the mean dilation and standard de- light and dark irides and between contact
viation for five subjects who wore contact lenses
prior to dilation and eight subjects who did not. lens and non contact lens wearers. Since
contact lens wear can affect corneal integ-
•2 -
rity, it was hypothesized that the drug
would have a significantly more rapid ef-
fect on contact lens wearers.
IOP (mrn Hg)

•1- _ -

Results
0-
CHANGE IN

Newell and Ernest15 indicate that a dila-

tion to at least 6mm with failure to constrict
-1 -
when stimulated by light is expected after
SD - topical application of a mydriatic. With a
-2 - 6mm pupil as an arbitrary criterion for use-
0 25 50 75
ful dilation, all subjects reached this crite-
rion with one drop of 0.5% tropicamide. In
TIME Imin)
fact, all but one subject dilated beyond
Figure 3 7mm.
Mean and standard deviation of changes in intraocu- Figure 1 compares the mean dilation ver-
lar pressure for 13 subjects during mydriasis. sus time curves for subjects with light irides
and dark irides. It can be seen that the

656 Journal of the American Optometric Association

greatest amount of mydriasis took place
within the first 25 minutes after instillation,
and that mydriasis was maintained for
another 25 to 50 minutes before recovery
began. Using a Student's t test, no signifi-
cant difference was found at the 0.01 level
of significance for amount of dilation with
respect to iris pigmentation at 25 minutes
after instillation or at maximum dilation.
Figure 2 shows the mean dilation curves
for subjects who had been wearing contact
lenses prior to instillation of the drug, and
for those who had not. Again, the Student's
t test showed no significant difference at
the 0.01 level.
The mean change in intraocular pres-
sure is plotted in Figure 3. For all but one
subject there was no increase in IOP at max-
imum mydriasis. One subject did have an
increase of +2.3mm (average increase for
both eyes). However, upon redilation at a
later date no increase was found to occur.
For eleven of the thirteen subjects a slight
decrease in IOP occurred.
Although there was a considerable range
of variability even for each individual sub-
ject in measurement of amplitude of ac-
commodation , all but one of the subjects
could easily read the .62 M paragraph at
50cm or less atall times duringthe dilation.
Three of the subjects were re-dilated at
least two weeks after the initial dilation in
order to confirm the reliability and re-
peatability of the measurements. The three
subjects consisted of two with light irides
and one with darkbrownirides. The results
of the re-dilation were found to be nearly
the same in each case as in the previous
trial.
Discussion
All subjects were effectively dilated using
one drop of 0.5% tropicamide. Hence, evi-
dence is given that the average young adult
patient who is to be dilated for ophthalmos-
copy or fundus pictures will normally
achieve useful mydriasis with the minimum
dosage of tropicamide. Useful mydriasis
was obtained in all subjects within an aver-
age of 25 minutes after instillation , showing
that the onset with minimum dosage is
rapid enough for practical clinical use.
It has been commonly held that dark
irides are more difficult to dilate than are
light irides. This was not found to be true
with 0.5% tropicamide. Variations in max-
imum mydriasis and rate of mydriasis ap-
peared to be individual characteristics
rather than related to iris pigmentation.
Conclusions
Tropicamide (0.5%) has many advan-
tages for O.D.s thus making it the agent of
choice for mydriasis with many patients.
1. It is rapid acting with approximately
25 minutes to useful dilation.
2. The mydriatic effect dissipates
rapidly.
3. Very few adverse reactions have been
reported.
4. It has little effect on IOP.
5. It is a poor cycloplegic.
6. Previous contact lens wear does not
alter the mydriasis significantly.
7. A minimal dosage appears to be effec-
tive on most patients, including those
with darkly pigmented irides. AOA
Submitted for publication in the JAOA in July,
1976.
Pacific University
College of Optometry
Forest Grove, Oregon 97116
ACKNOWLEDGMENT
The authors wish to express their apprecia-
tic,n to the Oregon Optometric Association for
the grant which made this study possible, and to
Lec,nard Levine, Ph.D. for suggesting this study.
REFERENCES
1. Gettes, B. C., Tropicamide: comparative
mydriatic effects, Am. 1. Ophth., 55: 84-87,
January, 1963.
2. Gambill, Ogle and Kearns, Mydriatic effect
of four drugs determined with pupillo-
graph,Arch. Ophth., 77: 740-746,June, 1967.
3. Smith, S. E., Mydriatic drugs for routine
fundal inspection, The Lancet., 2(7729):
837-839,1971.
4. Gettes, B. C., Tropicamide: a new' cyclo-
plegic mydriatic , Aych. Ophth ., 65 : 48 , 1961 .
5. Howard, H. J. and T. Lee, The effect of
instillation of ephedrine solution upon the
eye, Proc. Soc. Exp. Bio. Med., 24. 700- 702 ,
April, 1972.
6. Obianwu, H. O. and M. Rand,The relation-
ship between the mydriatic effect of ephe-
drine and the colour of the iris , B rit. J
Opht/tai., 49:264-270, May, 1965.
7. Angenent, W. j. and G. B. Koelle, A possi-
ble enzymatic basis for the differential ac-
Volume 48, Number 5, May 1977 657