Kim et al.

BMC Ophthalmology 2012, 12:53

http://www.biomedcentral.com/1471-2415/12/53

RESEARCH ARTICLE Open Access

Changes in intraocular pressure after

pharmacologic pupil dilation
Joon Mo Kim1, Ki Ho Park2*, So Young Han1, Kwan Soo Kim1, Dong Myung Kim2,
Tae Woo Kim3 and Joseph Caprioli4

Abstract
Background: Intraocular pressure (IOP) may vary according to the change of ocular conditions. In this study, we
want to assess the effect and mechanism of pupil dilation on IOP in normal subjects.
Methods: We prospectively evaluated 32 eyes of 32 patients (age; 61.7 ± 8.2 years) with normal open angles under
diurnal IOP. IOP was measured every two hours from 9 AM to 11 PM for one day to establish baseline values and
was measured again for one day to assess the differences after dilation. To induce dilation, we administered 2.5%
phenylephrine and 1% tropicamide every 5 minutes from 8:30 AM to 8:45 AM and for every two hours from 11 AM
to 9 PM to keep the pupil dilated. Diurnal IOP, biometry, Visante OCT, and laser flare photometry were measured
before and after dilation.
Results: We observed a significant increase in IOP after dilation, 1.85 ± 2.01 mmHg (p = 0.002). IOP elevation
remained significant until about four hours after dilation. Thereafter, IOP decreased slowly and eventually reached
pre-dilation level (p > 0.05). Flare values decreased, and the anterior chamber angle became wider after mydriasis.
Conclusions: Dilation of the pupil significantly and incidentally elevated IOP in normal subjects. Further related
studies are warranted to characterize the mechanism of the increased IOP after dilation.
Keywords: Mydriasis, Flare, Anterior chamber angle, IOP variation

Background dilation with topical application of both parasympatholy-

Like many biological parameters, IOP is a dynamic par- tic and sympathomimetic mydriatics [5-7]. However, the
ameter and varies throughout the course of 24 hours, mechanism of IOP elevation after dilation is not clear.
possibly following circadian rhythms. The mean range of This prospective study was performed to investigate
diurnal IOP variation is approximately 2 to 6 mmHg in the effect and mechanism of dilation on IOP in normal
the normal population and 5 to 18 mmHg in glaucoma subjects.
patients [1,2]. IOP variation can be affected by many fac-
tors such as medication, posture, exercise, blinking, eye
movements, and Valsalva manoeuvres [3,4]. As such, Methods
clinicians are advised to conduct multiple measurements This study adhered to the tenets of the Declaration of
over 24 hours to assess the IOP profiles of at-risk Helsinki and was approved by the institutional review
patients. board of Kangbuk Samsung Hospital in Seoul, Korea.
Mydriatics are regularly used to dilate pupils in We examined 32 eyes of 32 patients (17 women and 15
patients presenting to ophthalmology clinics for assess- men, age; 61.7 ± 8.2 years) who provided informed con-
ment and follow-up of a wide variety of ophthalmic con- sent. All subjects were patients scheduled for a bilateral
ditions. An increase in IOP has been observed after cataract operation who underwent a full ophthalmic
examination including visual acuity, Goldmann applana-
tion tonometry, gonioscopy, slit lamp evaluation, fundus
* Correspondence: [email protected] biomicroscopy, auto refractometry (RK-F1, Canon,
2
Department of Ophthalmology, Seoul National University College of
Medicine, Seoul National University Hospital, Seoul, Korea Japan), and pachymetry (4000APW, SonomedW, USA).
Full list of author information is available at the end of the article All eyes presented as normal (except cataract) with an
© 2012 Kim et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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open angle by Goldmann three-mirror gonioscopy. Ex- change was statistically significant (p = 0.005). The max-
clusion criteria included the following: high IOP (>20 imum IOP also significantly increased from a mean pre-
mmHg) on the visit before dilation; preoperative ocular dilation level of 13.10 mmHg ± 2.91 to a post-dilation level
medication that could influence IOP level; pre-existing of 14.96 ± 3.25 mmHg (p < 0.001). However, there was no
ocular pathology such as glaucoma, uveitis, or high my- significant difference between the minimum IOP before
opia; and previous ocular surgery. (10.50 ± 2.74 mmHg) and after (10.50 ± 2.35 mmHg)
IOP was measured in both eyes of each patient by dilation (p = 0.978).
experienced personnel using a Goldmann applanation Regarding diurnal IOP variation, the mean pre-dilation
tonometer every two hours from 9 AM to 11 PM to es- value was 2.60 ± 1.14 mmHg, and the mean post-dilation
tablish baseline values. On another day (1 ~ 3 months value was 4.45 ± 2.01 mmHg. The difference in the mean
after the baseline test), we induced mydriasis by admin- change of diurnal IOP variation was 1.85 ± 2.01 mmHg,
istering one drop of Mydrin-P (fixed combination of and this change was statistically significant (p = 0.002).
2.5% phenylephrine and 1% tropicamide, Santen Phar- Diurnal IOP was elevated in 22 eyes (68.9%), decreased
maceuticals, Osaka, Japan) in the conjunctival sac every in two, and unchanged in eight. We noted a non-
5 minutes from 8:30 AM to 8:45 AM and every two significant IOP increase at 9 AM, 30 minutes after dila-
hours from 11 AM to 9 PM to maintain a dilated state. tion. IOP was significantly increased at 11 AM and
IOP was measured every two hours from 9 AM to 1 PM (Table 1). Maximum IOP levels were reached at
11 PM. 11 AM, and after 3 PM, the IOP did not significantly dif-
The following variables were assessed before and after fer (p > 0.05) from pre-dilation levels.
dilation: diurnal IOP, anterior segment examination, The flare value decreased after dilation and remained
axial length (AL), anterior chamber depth (ACD), central constant (Figure 1). The width of the anterior chamber
corneal thickness (CCT), anterior chamber flare with angle increased significantly after dilation, and this state
laser flare photometer (FM-500, Kowa, Tokyo, Japan), was maintained while the pupil was dilated (p < 0.001)
and anterior chamber angle with Visante OCT (Carl (Figure 2). After dilation, we noted significantly
Zeiss Meditec, Dubin, CA, USA). AL and ACD were increased ACD values (3.20 ± 0.45 mm), as compared
measured with an IOL Master (Carl Zeiss Meditec, with initial values (3.09 ± 0.48 mm) (p < 0.001). Mean
Dubin, CA, USA). CCT was measured with a hand-held pupil diameter increased from 2.975 ± 0.498 mm to
ultrasonic pachymeter, and the average of three readings 6.725 ± 0.717 mm 2 hours after dilation and
was recorded. 6.793 ± 0.616 mm after 8 hours, but these changes were
The Visante OCT was used to perform anterior cham- not statistically significant (p > 0.05). There was no sig-
ber angle width measurements every two hours before nificant variation of pupil size in either time interval
mydriasis and after instillation of mydriatics from 9 AM (p > 0.05).
to 9 PM. The average of three consecutive readings of IOP measurements after dilation were not related to
the mean angle value at 3 and 9 o’clock was included in the mean pre-dilation IOP, AL, or diurnal IOP value
analysis. Laser flare photometry was performed once be- according to the results of multivariate analysis (range of
fore mydriasis and every two hours after instillation of p-values: 0.232-0.966). Changes in the mean CCT and
mydriatics, from 9 AM to 5 PM. The laser flare photom- axial length measurements before and after dilation were
eter quantifies anterior chamber protein (flare) and par- not statistically significant.
ticles (cells) by measuring light scattering of a helium-
neon laser beam projected into the anterior chamber [8].
A single experienced investigator examined each subject Table 1 The variation of intraocular pressure (IOP) before
five times in series and recorded the mean value of the and after pupil dilation
five measurements. All examinations were performed in Time IOP before IOP after p-value
a hospital setting. To reduce bias, a different measuring dilation(mmHg) dilation(mmHg)
technician, data collector, and statistical analyst partici- 9 12.35 ± 3.06 12.54 ± 2.82 0.898
pated in a masked fashion. The data were analyzed using 11 12.25 ± 3.12 14.33 ± 3.65 0.001*
PASW statistics 17.0 (SPSS, Inc., Chicago, IL, USA), and
13 11.49 ± 2.68 13.42 ± 3.30 <0.001*
differences in values were assessed by paired t-test. A p-
16 11.57 ± 2.95 12.29 ± 2.58 0.051
value of less than 0.05 was considered statistically
17 11.70 ± 2.83 11.85 ± 2.30 0.604
significant.
19 11.42 ± 2.96 11.80 ± 2.82 0.372
Results 21 11.39 ± 2.97 11.39 ± 2.46 0.799
The mean pre-dilation IOP was 11.48 ± 2.85 mmHg. The 23 11.32 ± 2.76 11.32 ± 2.58 0.944
mean post-dilation IOP was 12.36 ± 2.58 mmHg. This * : p-value < 0.05.
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Figure 1 Laser flare photometry values. Flare values decreased significantly after dilation and remained low. The arrows indicate the time
mydriatics were given. Intraocular pressure (IOP) at 9A.M. was measured before the mydriatics were instilled. To maintain pupil dilation, mydriatics
were instilled every 2 hours until 9 PM, just after IOP measurement.

No patients developed clinically significant (>10 mmHg) angle glaucoma respond to cycloplegics with a pressure
sustained increases in IOP. Only one patient experienced elevation [12]. Blake et al. found that significant pressure
a rise in IOP to a level greater than 21 mmHg after elevation occurred in 32% of open angle glaucoma
dilation. The patient’s pressure dropped after an add- patients following dilation with 2.5% phenylephrine and
itional two hours with no medical intervention. This 1% tropicamide [13].
patient exhibited the highest pre-dilation IOP level of The mechanism responsible for IOP elevation after
all of our patients but did not have any other distinctive dilation is unclear. Mydriatic agents can cause increases
findings. in IOP that may be related to decreasing aqueous out-
flow resulting from decreased traction on the trabecular
Discussion meshwork due to ciliary muscle paralysis [14,15]. Under
Tropicamide is an anticholinergic drug, and phenyleph- the previously mentioned conditions, we can presume, if
rine is an alpha-1-adrenergic agent. These agents are the dilated state is maintained, increased IOP may be
commonly used together to achieve mydriasis for fundus preserved. The results of our study suggest a different
examination [9-11]. It has previously been recognized explanation. IOP was found to be significantly increased
that pharmacologic mydriasis can cause an elevation in at four hours and six hours after pupil dilation during
IOP. According to one study, 1-2% of healthy persons preserved pharmacologic mydriasis and slowly decreased
display a pressure elevation of 6 mmHg or more after after that time. After dilation, the ACD deepened, the
treatment with 1% cyclopentolate [5]. Harris and Galin anterior chamber angles widened, and the anterior
showed that 33% of miotic-treated patients with open chamber flare decreased. Harris showed that a narrow

Figure 2 Anterior chamber angle widths measured by Visante OCT. Anterior chamber angles increased significantly after dilation.
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angle was a crucial factor that predisposed patients to the trabecular meshwork can explain the elevation of
acute IOP elevation, but IOP elevation has been found intraocular pressure. Jewelewicz et al. reported similar
to occur in eyes that do not have narrow angles [16]. results in pigment dispersion syndrome cases [22]. The
Valle reported that the key characteristic separating maximal pigment liberation was reached 30 to 60 min-
responders to cyclopentolate from non-responders was utes after mydriasis, but peak IOP was reached about
a difference in the inflow rate, [17] whereas the outflow 90 minutes after mydriasis, when the anterior chamber
rate through the trabecular meshwork decreased with pigment was decreasing. Our cases have some differ-
cyclopentolate in all patients studied. The only statisti- ences. The flare decreased 30 minutes after instillation
cally significant difference between the two groups was of mydriatics. This might be because the subjects of
that the inflow decreased in non-responders but increased our study were normal, and normal subjects may have
slightly in responders. In our study, the mean IOP a different response to dilation than pigment dispersion
values decreased in two patients after dilation. Tem- syndrome patients. Another possibility was that we
porary imbalance of aqueous flow may have an effect used a combination drug. The included phenylephrine
on these patients. Also, dilation can cause a greater could increase the clearance of flare/pigment. Racial
anterior chamber depth and a wider contact region differences (only Koreans were included in our study)
between the trabecular meshwork and the aqueous. should also be considered. Also, we took measure-
There may be small amount of flare before the dila- ments of fully dilated eyes, which can explain why we
tion, and a small amount of flare may also occur due did not observe more iris pigment liberation due to
to rubbing between iris and lens when the pupil begins lack of contact between the iris and lens. The my-
dilation. Thus, IOP may not increase after dilation. Fur- driasis effect may have increased vessel stability and
ther evaluation with a larger population based study may decreased flare.
be needed. Laser flare photometry is an objective, quantitative
Iris pigment liberation into the anterior chamber and method that enables accurate measurement with very
subsequent obstruction of the trabecular meshwork high sensitivity and reproducibility. Guillen-Monterrubio
has also been noted as a possible mechanism respon- et al. reported no significant differences in flare values
sible for the increase in IOP [18-20]. Kristensen showed measured by flare photometer between right and left
that 48% of eyes with open angle glaucoma showed a eyes or between men and women [23].
rise in pressure of 8 mmHg or more after dilation, There are some limitations in this study. Ocular para-
and all elevations were associated with marked pig- meters, such as corneal thickness and shape, [24,25] an-
ment elevation [19]. Valle demonstrated IOP elevations of terior chamber depth, [26] and axial length [25] are
up to 20 mmHg after dilation with 1% cyclopento- known to undergo significant diurnal changes. We did
late, all of which were accompanied by pigment liber- not control these factors. Angle and ACD are affected by
ation [20]. many external influences such as near vision or distance
In our study, we investigated aqueous flare and an- vision, so it is difficult to measure the diurnal effect.
terior chamber angles before and after mydriasis to Also, corneal thickness may be changed due to epithelial
help determine the aetiology of increased IOP. We oedema by the repeated application of eye drops causing
demonstrated that anterior chamber angles widened the possible under measurement of IOP. This can affect
with dilation, which is possibly due to the posterior the decreased IOP of late diurnal measurements, but it
pull of the dilated iris-lens diaphragm, leading to a is difficult to calculate the cushion effect caused by epi-
deep anterior chamber. The reduction in IOP after thelial oedema. Further study is needed. IOP may change
3 pm may be explained by the widened anterior cham- as either diurnal variation or seasonal change. Qureshi
ber angle and improvement of the aqueous outflow fa- IA et al. reported that IOP tends to increase in the win-
cility. A decreased resistance to aqueous outflow may ter [27]. The longest time interval of IOP measurement
be expected from deepening of the anterior chamber, among the patients was three months, which could pos-
which creates a larger surface area between the tra- sibly affect the variability.
becular meshwork and the aqueous humour [21]. How-
ever, IOP increased just after dilation, and we assessed Conclusions
the variation in flare after dilation. Flare values According to the results of this study, pupil dilation
decreased after mydriasis (p < 0.01). The flare value caused an elevation of IOP. The elevation of IOP was
decreased just after dilation and remained decreased significant until four to six hours after dilation. After-
while the pupil was dilated. It is possible that, just after wards, IOP decreased slowly until it reached pre-dilation
mydriasis, the flare may be increased by iris pigment level. Further related studies in glaucoma patients are
liberation or by protein, but crowding in the angle and warranted to characterize the mechanism of increased
subsequent interruption through the outflow facility of IOP after dilation in a diseased state.
Kim et al. BMC Ophthalmology 2012, 12:53 Page 5 of 5
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