CLINICAL SCIENCE
The Effects of Eye Drops on Corneal Thickness
in Adult Myopia
Lei Gao, MD,* Huijun Fan, MD,* Arthur C. K. Cheng, MRCS,† Zhonghao Wang, MD,*
and Dennis S. C. Lam, MD, FRCOphth†
Purpose: To study the effects of Complex Tropicamide (0.5%
Tropicamide and 0.5% phenylephrine HCI) and Saline solution on
corneal thickness in adult myopic patients with the Orbscan II system.
Setting: Department of Ophthalmology, Yantai Yuhuangding Hospital.
Design: Prospective, nonrandomized, clinical trial.
Methods: The thinnest pachymetry of the cornea was obtained
before and 1.5 hours after administration of three drops of Complex
Tropicamide to the left eyes of 58 patients (58 eyes) and Saline
solution to their 31 right eyes, respectively. The corneal thickness of
the other 27 right eyes before and 1.5 hours after eyelid closure
without exposure to eye drops was used as the control group.
Results: The thinnest pachymetry of the cornea was significantly
higher after exposure to eye drops in the Tropicamide group (23.36 T
15.01 Km; t = j11.855, P G 0.001). Similar findings were also noted
in the Saline group (7.13 T 8.11 Km, t = j4.894, P G 0.001). The
difference between the two groups was also significant (t = 6.737,
P G 0.001). There were no statistically changes in corneal thickness
in control group. The drops tested have no effect on the location of
the thinnest corneal site and its distance form the visual axis.
Conclusion: Eye drops including Saline solutions may have
significant effects on the corneal thickness in myopia, and this
may have implications for corneal refractive surgery.
Key Words: complex Bistropamide, Sodium chloride injection,
Orbsacn, corneal thickness, myopia
(Cornea 2006;25:404Y407)
C entral corneal thickness (CCT) has become an area of
research interest due to the advancement of excimer
laser corneal refractive surgery, particularly in laser in situ
keratomileusis (LASIK). It was considered to be one of
the most important factor for stability of refractive surgeries
and correlated to the occurrence of corneal ectasia and
From the *Department of Ophthalmology, Yantai Yuhuangding Hospital,
Affiliated Hospital of Medical College, Qingdao University, Yantai, Shan-
dong 26400, PR China; and †Department of Ophthalmology and Visual
Sciences, The Chinese University of Hong Kong, Hong Kong, PR China.
Received for publication March 1, 2005; revision received September 14, 2005;
accepted September 16, 2005.
Presented in part at the 5th Hong Kong International Symposium of
Ophthalmology, Hong Kong, October 2003.
The authors do not have any commercial or proprietary interest in any of the
products mentioned in this article.
Reprints: Lei Gao, MD, Department of Ophthalmology, Yantai Yuhuangding
Hospital, Affiliated Hospital of Medical College, Qingdao University,
Yantai, Shandong 26400, P.R. China (e-mail:gl6365@yahoo.com.cn).
Copyright * 2006 by Lippincott Williams & Wilkins
404
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keratoconus.1 However, corneal shape or thickness can be
affected by various factors such as mechanical forces,2 atropine
sulphate ointment 1%,3 topical anesthetic,4,5 and long-term
contact lens wear.6 In addition, human corneal thickness also
displays diurnal variation.7,8 Accurate assessment of the cor-
neal thickness is, therefore, important to allow safe surgery.
This study evaluates the effects of some eye drops on corneal
thickness. The role of Orbscan system in determining the
corneal thickness for refractive surgery was also discussed.
METHODS
Subjects
The prospective study involved 58 adult (above 18 years
old) myopic patients from April to October 2004. All left eyes
were chosen into the Tropicamide group. Right eyes were
divided into two groups: the first 31 consecutive eyes for
Saline solution group and the remaining 27 eyes for control
groupVcorneal thickness measured before and 1.5 hours
after eyelid closed without any eye drops intervention. The
patients underwent an ophthalmic examination that included
the best corrected visual acuity, manifest refraction, slit-
lamp examination, and noncontact applanation measure-
ment. All the patients enrolled had no complaints of ocular
irritation, no history of contact lens use, no anterior segment
abnormality, and no eye drops administration on the day of
examination except those in this study. Informed consents
were obtained from all participating patients. All experi-
ments were performed in compliance with the tenets of the
Declaration of Helsinki.
Apparatus and Procedure
The Orbscan II corneal topography system (Orbscan,
Inc, Salt Lake City, UT, USA, Version 3.00E) was performed
before and 1.5 hours after administration of three drops (about
10 minutes of interval) of Complex Tropicamide (0.5%
Tropicamide and 0.5% phenylephrine HCI; Beijing Shuanghe
pharmacy Ltd, China) or 0.9% Saline solutions (Yangzhou
Zhongbao pharmacy Ltd, China) depending on their groups.
Patients were asked to keep their both eyes closed before the
final examination. Each patient was asked to blink before
corneal thickness measurement to avoid any bias because of
corneal drying. Three consecutive corneal measurements of
each eye (right eyes firstly) before and 1.5 hours later were
recorded, respectively.
The corneal thickness measurements were made using
the noncontact Orbscan II system following the procedures
recommended by the manufacturer. The procedure was
Cornea & Volume 25, Number 4, May 2006
Cornea & Volume 25, Number 4, May 2006 Effects of Eye Drops on Corneal Thickness in Adult Myopia

TABLE 1. Patient Demographics and Refractive Status TABLE 3. Maximum Increases and Decreases of the Corneal
of All Subjects (116 Eyes) Thickness Observed With Orbscan
Saline Tropicamide Saline Solution Control
Tropicamide Solution Control Variable Group (n = 58) Group (n = 31) Group (n = 27)
Group Group Group
Maximum 52 26 21
No. eyes 58 31 27 increase, Km
Male/Female (eyes) 34/24 17/14 15/12 Maximum 8 6 23
Age, y (mean T SD) 22.9 T 4.9 22.5 T 5.0 22.6 T 5.1 decrease, Km
Refractive state, j4.30 T 2.59D j4.26 T 2.27 j4.04 T 2.60D Increased 37 (63.79) 4 (12.90) 1 (3.70)
(Diopter) Q20 Km (eyes, %)
(mean T SD)
Intraocular pressure, 15.75 T 1.98 15.55 T 2.16 15.63 T 2.06
mm Hg (mean T SD)
Corneal thinnest values (THN) were significantly increased
in the Tropicamide group by 22.48 T 18.06 Km (t = j9.48,
performed by the same investigator. Pachymetry is deter- P G 0.001). Similar finding was also noted with the Saline
mined by this Orbscan from the difference in elevation group by 7.13 T 8.11 Km (t = j4.89, P G 0.001). The
between the anterior and posterior surfaces of the cornea. differences in THN alteration between the two groups were
This instrument can recognize the thinnest point of the cornea significant (t = 5.625, P G 0.001), although the differences
(THN) and marks its distance from the visual axial and its between the two groups before eye drops were not
quadrant location. Acoustic factor for the Orbscan was set as significant (F = 0.108, P = 0.897). However, there were no
0.92 in all performances. statistically significant changes in THN for the control
Noncycloplegic refractive state was recorded with groups (t = j1.337, P = 0.180).
Canon RK-5 automated refractor (Canon Inc, Japan). Myopia The maximum increase and the maximum decrease in
was defined as spherical equivalent refraction greater than THN happened within the 1.5 hours for each groups can be
j0.75D. Calibration and verification were performed weekly seen in Table 3. Increase in corneal thickness was found
both for the Orbscan system and Canon RK-5 automated in 55 eyes (94.83%), 24 eyes (77.42%), and 16 eyes (59.26%)
refractor to ensure their repeatability of readings. for Tropicamide, Saline solution, and control groups,
respectively. The thinnest site on the entire cornea was
Statistical Analysis located at an average of 0.61 T 0.27 mm from the visual axis
Statistical data analysis was performed with SPSS for all cases before instillation of any drops. This site
for Windows, version 11.0 (SPSS Inc, Chicago, IL, USA) was most commonly located in the inferotemporal quadrant
using analysis of variance chi-square test and paired (63.4%), followed by the superotemporal (15.9%), infer-
sample t test. P value of less than 0.05 was considered onasal (14.6%), and superonasal quadrants (6.1%). However,
statistically significant. the instillation of the tropicamide and saline solution seems to
have no effect on the location of the thinnest corneal site and
RESULTS its distance from the visual axis. (Tables 4 and 5).
Fifty-eight healthy myopic patients (116 eyes) were
recruited in the study. The patients’ demographics and DISCUSSION
refractive status are shown in Table 1. Findings of the mean LASIK is the most popular refractive procedure in
corneal thinnest values with their corresponding paired China. It involves the creation of anterior corneal flap and
sample t test were presented in Table 2. The results of a removal of midstromal tissue by excimer laser photoablation.
normality test showed that the distribution of all variables As residual bed thickness is an independent significant
before and after administration of eye drops was normal determinant for posterior corneal ectasia, CCT had to be
(j1 G Skewness G 1). One-way analysis of variance analysis sufficient to ensure at least 250 Km in the posterior stroma
revealed no difference in THN for three groups before and after keratorefractive surgery.9
after the instillation of the eye drops tested (P 9 0.05). Corneal thickness has been evaluated by various
methods. Ultrasound pachymetry has been used to measure
corneal thickness worldwide. It is also the reference against
which the more sophisticated devices are currently tested and
TABLE 2. Corneal Thickness Values Observed Between the
First and the Second Orbscan Assessment (116 Eyes)
was regarded as Bgold standard[ in this field.1 However, recent
studies demonstrated the Orbscan II pachymetry measurements
Variable Tropicamide Saline Solution Control
(Mean T S. D.) Group (n = 58) Group (n = 31) Group (n = 27)
correlated well with the ultrasound measurements in eyes
with clear corneas, and it is the most repeatable technique
THN (Km) 525 T 42 528 T 40 530 T 41 for measuring corneal thickness as well.10,11
THN* (Km) 549 T 44 535 T 42 533 T 46 We previously demonstrated that the corneal refractive
t test (THN-THN*) P G 0.001 P G 0.001 P = 0.180 power in myopic children measured with topography was sig-
*Data obtained from the second examination, t test: paired sample t test. nificantly decreased after 5 days of ointment atropine 1%.3
THN indicates corneal thickness at the thinnest point.
Complex Tropicamide is widely used for clinical examination,

* 2006 Lippincott Williams & Wilkins 405

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Gao et al
TABLE 4. The Location of the Thinnest Corneal Site Before and After Instillation of Two Drops
Tropicamide Group (n = 30)
Variable 1 2
Before 18 (60%) 7 (23.3%)
After 18 (60%) 7 (23.3%)
Chi-square test P 9 0.05
1: inferotemporal quadrant, 2: superotemporal, 3: inferonasal, 4: superonasal quadrants.
and the active ingredients are tropicamide and epinephrine.
The former has cycloplegic effect and the latter has mydriatic
effect. We have shown that the corneal thickness increased
after administration of Complex Tropicamide, and the causes
could be many. It is possible that this increase is due to the
disruption of corneal physiological metabolism or epithelial
barrier function from the active or inactive ingredient such as
?-aminocaproic acid and benzalkonium chloride within the
Complex Tropicamide. This may also be confirmed by the
difference in corneal alteration between Tropicamide and sa-
line solution groups. However, we cannot explain the increase
in thickness in patients receiving saline solution alone as
saline does not contain any preservatives and is similar to the
tear film in pH and osmotic pressure. The 1.5-hour closed eye-
lid may have similar Bdiurnal effects[ on the corneal thickness
as studies indicate that the corneal thickness was slightly
increased overnight and gradually return to baseline measure-
ments after eye opening.7,8 However, the results from our
control group deny the above-mentioned Bhypothesis[ as no
significant changes were noted in the control group. One
possible explanation is that the Saline solution is not human
tears after all. The microenvironmental differences in every
aspect between Saline solution and nature tear film could be the
explanation for the changeable measurements of corneal
thickness. Furthermore, no visual blur or corneal edema was
noted in the subject analyzed following the instillation.
Further analysis from total 58 left eyes before eye
drops instillation (mean age, 23.9 T 4.9 years) revealed that
the mean corneal thinnest value was 525.96 T 42.93 Km
(normal range from 441.82 to 610.10 Km). Considering the
mean increase of 22.48 Km for Tropicamide group, we can
conclude that approximately 3.68% to 5.09% of the total
corneal thickness increased 1.5 hours after administrating
complex Tropicamide solution.
Corneal thickness can be evaluated by a number of
methods including ultrasonic pachymetry, optical slit lamp
pachymetry, confocal microscopy, and optical coherence
TABLE 5. The Thinnest Site From the Visual Axis Before
and After Instillation of Drops
Tropicamide
Variable Group (n = 30)
Distance, mm 0.65 T 0.28
Distance,* mm 0.67 T 0.27
t test (THN-THN*) P = 0.685
*Data obtained from the second examination, t test: paired sample t test.
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Cornea & Volume 25, Number 4, May 2006
Saline Solution Group (n = 31)
3 4 1 2 3 4
4 (13.3%) 1 (3.3%) 18 (58.1%) 6 (19.4%) 5 (16.1%) 2 (6.5%)
3 (10%) 2 (6.7%) 17 (54.8%) 8 (25.8%) 4 (12.9%) 2 (6.5%)
P 9 0.05
tomography.12,13 Ultrasonic pachymetry is believed to be
the most reliable and was considered as BGold Standard[ in
determining the CCT.1 Although it is a widely used, accurate
assessment of the corneal thickness cannot be made without
disturbing the anterior cornea. The tip of the probe may
disturb the precorneal tear film14 and even disrupt the epi-
thelium.15 It is also difficult to control patient’s gaze during
repeated measurements, and the placement of the probe is
difficult to reproduce. Furthermore, it can only be carried out
in anesthetized eyes. Topical anesthesia seems to have more
effects on cornea than saline solution. Asensio et al4 have
found that some individuals can present important increases
and decreases in corneal thickness values only 3 minutes
after administration of two drops of oxybuprocaine 0.4% to
26 patients (26 eyes), although the changes were no
significant differences. The dramatic changes on corneal
topography 20 minutes after 4 drops of Benoxil (Oxybu-
procaine) 0.4% solution were also detected by Do et al.16 In
our recent study with Orbscan II, both THN and CCT of 2
mm in diameter were dramatically increased 5 minutes later
after the instillation of one drop of the topical anesthetic
Benoxil (Oxybuprocaine) 0.4% solution.5
It is known that corneal thickness increases peripher-
ally. For the maximal safety of LASIK, the purpose of
corneal thickness measurement is to find the exact values at
the thinnest point for the whole cornea. However, ultrasonic
probe is unable to locate and kept accurately at the thinnest
point in serial examinations, and this may result in large
variation in corneal thickness measurement. Some investi-
gators did not measure in the exact center of the cornea. The
probe tip was placed 1.5 mm temporal to the cornea light
reflex.17 In fact, the thinnest site on the entire cornea was
located at an average of 0.90 (0.51) mm from the visual axis.
This site was most commonly located in the inferotemporal
quadrant (69.57%), followed by the superotemporal, infer-
onasal, and superonasal quadrants.12
None of these problems exists with the described
Orbscan technique. The instrument’s software analyses up to
240 data points per slit and calculates the elevation of
the anterior and posterior surface of the cornea as well as the
entire corneal thickness. The system can also identifies the
Saline Solution thinnest point location and display its actual values (THN)
Group (n = 31) simultaneously even if the examined eye happened to move
0.60 T 0.24
slightly but within the permit range of the system. It is a
0.68 T 0.42
noninvasive, noncontact, well-controlled method of excellent
P = 0.273
reproducibility both in clinical and in research studies.11,18
In summary, our study demonstrated thickening of
cornea after instillation of Saline solution as well as Complex
* 2006 Lippincott Williams & Wilkins
Cornea & Volume 25, Number 4, May 2006
Tropicamide in the adult myopia. Furthermore, it is possible
that other eye drops commonly used in our clinical would
have similar effects based on the finding with Saline solution.
To our understanding, it could be advisable to calculate a
greater preoperative residual bed depth than usual if
preoperative corneal thickness is measured using corneal
anesthetic eye drops or any other eye drops, and this, in
return, may also have implications for the outcome of corneal
refractive surgery and even for the accuracy of applanation
tonometry,13,19 considering that more than 60% of the eyes in
Tropicamide group would suffer 20-Km increase in corneal
thickness. The values of corneal thinnest, rather than that of
mean CCT, should be taken into account by refractive
surgeons for the maximum safety of performance. As
Orbscan allows an exact measurement of corneal thickness
without the multiple sources of bias known from ultrasonic
pachymetry and it is the only available device which can
identify the thinnest point location and display its actual
values, its role in corneal refraction surgery should be
reassessed and be emphasized.
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