Contact Lens & Anterior Eye 37 (2014) 7780

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Contact Lens & Anterior Eye

journal homepage: www.elsevier.com/locate/clae

Comparison of corneal hysteresis and corneal resistance factor after

small incision lenticule extraction and femtosecond laser-assisted
LASIK: A prospective fellow eye study
Alper Agca a , Engin Bilge Ozgurhan a , Ahmet Demirok b , Ercument Bozkurt a , Ugur Celik a, ,
Abdullah Ozkaya a , Ilker Cankaya a , Omer Faruk Yilmaz a
a
Beyoglu Eye Research and Training Hospital, Istanbul, Turkey
b
Istanbul Medeniyet University, Department of Ophthalmology, Istanbul, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: To compare corneal hysteresis (CH) and corneal resistance factor (CRF) between eyes treated with
Received 24 January 2013 small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis
Received in revised form 10 April 2013 (femto-LASIK).
Accepted 31 May 2013
Setting: Beyoglu Eye Training and Research Hospital.
Design: Prospective comparative case series.
Keywords:
Methods: Sixty eyes from 30 patients with bilateral myopia or myopic astigmatism were studied. Inclusion
Small incision lenticule extraction
criteria were spherical equivalent of subjective manifest refraction (SE) <10 diopters (D) and a difference
SMILE
LASIK
0.50 D between the SEs of both eyes. One eye of each patient was treated with SMILE, and the fellow
Corneal hysteresis eye underwent femto-LASIK. Randomization was performed using a sealed envelope system. The main
Corneal resistance factor outcome measures were CH and CRF measured preoperatively and postoperatively (1 and 6 months).
Biomechanics Results: Preoperative SE was similar in both groups (p = 0.852). CH and CRF values were reduced post-
operatively in both groups compared to their corresponding preoperative values (p < 0.001). At the
6-month follow-up visit, the mean CH values in the SMILE and femto-LASIK groups were 8.95 1.47
and 9.02 1.27, respectively (p = 0.852), and the mean CRF values were 7.77 1.37 and 8.07 1.26,
respectively (p = 0.380).
Conclusion: CH and CRF decreased after SMILE. There were no differences between SMILE and femto-LASIK
treatments in postoperative CH or CRF values.
Crown Copyright 2013 Published by Elsevier Ltd on behalf of British Contact Lens Association. All
rights reserved.

1. Introduction and safe surgical procedure with refractive results comparable to

Femtosecond lenticule extraction is a new method for refrac-
tive correction of myopia and myopic astigmatism. The procedure
involves the creation of an intrastromal lenticule between two
photodisruption planes that is mechanically removed for refrac-
tive correction. If the procedure involves creating and lifting a
hinged ap above the lenticule, it is called femtosecond lenticule
extraction (FLEX) [1]. If a ap is not created, and the lenticule is
extracted from a 3- to 4-mm arcuate side cut close to the edge
of the lenticule, the procedure is referred to as small incision
lenticule extraction (SMILE) [2]. These procedures can only be car-
ried out with the Visumax femtosecond laser platform (Carl Zeiss
Meditec AG, Jena, Germany). Lenticule extraction is an efcient
Corresponding author. Tel.: +90 5359651740.
E-mail address: h.ugurcelik@gmail.com (U. Celik).
those achieved with laser-assisted in situ keratomileusis (LASIK)
[3].
LASIK alters corneal biomechanical properties that are thought
to play an important role in the development of post-LASIK ectasia
[4]. SMILE may have biomechanical benets over LASIK because it
does not involve the creation of a ap and leaves the stroma over
the lenticule untouched. However, there are no published studies
regarding the biomechanical effects of SMILE.
The ocular response analyzer (ORA; Reichert Inc., Buffalo, NY,
USA) is designed to obtain in vivo measurements of corneal
biomechanical properties [5]. Corneal hysteresis (CH) and corneal
resistance factor (CRF) are two metrics used in this device to
describe the biomechanical properties of the cornea. Previous stud-
ies reported that CH and CRF signicantly decrease after LASIK
surgery [68,5]. Here, we performed the rst analysis of CH and
CRF values after SMILE and compared them with the results of
femtosecond LASIK (femto-LASIK) in fellow eyes.

1367-0484/$ see front matter. Crown Copyright 2013 Published by Elsevier Ltd on behalf of British Contact Lens Association. All rights reserved.
http://dx.doi.org/10.1016/j.clae.2013.05.003
78 A. Agca et al. / Contact Lens & Anterior Eye 37 (2014) 7780
2. Patients and methods
This prospective pilot study was approved by the ethics commit-
tee of Beyoglu Training and Research Hospital. All patients provided
informed consent, and the study complied with the Declaration of
Helsinki.
Patients with bilateral myopia or myopic astigmatism were
included in the study if the spherical equivalent of subjective man-
ifest refraction (SE) was <10 diopters (D) and if the difference in
SEs between both eyes was 0.50 D. Other inclusion criteria were
mesopic (4 lux) pupil size 6.5 mm and a calculated residual stro-
mal bed thickness >300 m. Patients who had an accompanying
ocular disease, prior history of ocular surgery, or any contraindica-
tion to LASIK surgery were not included.
One eye of each patient was assigned to the SMILE group and
the fellow eye was assigned to the femto-LASIK group using a ran-
dom number table. The random numbers were placed in sealed
envelopes to ensure allocation concealment. The envelopes were
shufed and sequentially numbered. The surgeon opened the next
available envelope before the surgery. If the random number in the
envelope was odd, then the right eye was allocated to the SMILE
group, and if the number was even, the left eye was allocated to
the SMILE group.
2.1. Sample size calculation
A sample estimate of the correlation between the two eyes of
a person in the population was calculated to be r = 0.75 for CH
and r = 0.77 for CRF based on a pilot study in our clinic (unpub-
lished information). Because this was a pilot study, it was designed
to reveal a medium-sized effect that was set at Cohens d = 0.5
(representing half the standard deviation of the variable to be
tested). Under these circumstances and with the two-sided alpha
set at 0.05, a sample size of 30 subjects per group was calculated
to yield statistical powers of 96% and 97% to detect differences
in CH and CRF, respectively, between the groups. Power anal-
ysis was performed using G Power 2 version 3.1.5 (available
at http://www.psycho.uni-duesseldorf.de/aap/projects/gpower/),
and the study was designed to include 60 eyes from 30 patients.
2.2. Pre- and postoperative examinations
All patients underwent the clinics standard detailed preop-
erative examination procedure to plan the surgical procedures.
Uncorrected distance visual acuity (UDVA) and best-corrected
visual acuity (CDVA) measurements were performed with an illu-
minated ETDRS chart (Ophtec 3500, Stereo Optical Co, Chicago, IL,
USA). Corneal topography, dynamic infrared pupillography, and
ocular and corneal wavefront analyses were performed with the
Sirius corneal topography and aberrometry system (Costruzioni
Strumenti, Oftalmici, Italy). Horizontal corneal diameter was mea-
sured with the IOL master (Carl Zeiss Meditec). Schirmers test with
topical anesthesia and intraocular pressure measurements (Gold-
mann applanation tonometer) were performed. Detailed anterior
and posterior segment examinations were performed using a slit
lamp. CH and CRF were preoperatively measured in all eyes using
the ORA.
Preoperative SE, maximum calculated ablation depths, mean
preoperative central corneal thickness (CCT), and mean simulated
keratometry (simK) were determined. CH and CRF measurements
performed 1 and 6 months after the procedure were compared
between the groups. CH and CRF were also compared to their cor-
responding preoperative values in both the SMILE and femto-LASIK
groups.
2.3. Statistical analysis
The average CH and CRF values calculated from four ORA mea-
surements were used in the statistical analysis. Mean, standard
deviation, frequency, and percentage were used for descrip-
tive statistics. Variable distributions were checked with the
KolmogorovSmirnov test. Students t-tests were used to com-
pare quantitative data. Repeated measures analysis of variance
(rANOVA) and paired sample t-tests with Bonferroni corrections
were used for the repeated measurement analysis. Chi-squared
tests were used to compare qualitative data. SPSS 20.0 (IBM Corp,
Armonk, NY, USA) was used for all statistical analyses.
2.4. Surgical technique
The same surgeons (A.D. and O.F.Y.) performed all surgeries in
the study. The eyes in the SMILE and femto-LASIK groups were
treated with SMILE and femto-LASIK, respectively. Both eyes under-
went surgery on the same day and by the same surgeon. After
adding one drop of topical anesthetic to both eyes and application
of sterile draping, an eyelid speculum was inserted. The eye in the
SMILE group was treated rst. The ap of the other eye was created
before transporting the patient to an excimer laser. An antibiotic
drop was added at the end of the operation.
2.5. SMILE
Visumax (Carl Zeiss Meditec) femtosecond laser platform was
used for the surgeries. The surgeries were performed as described
by Shah and Shah [3]. The same parameters were used in all cases.
The spot distance was 3 m for lamellar cuts and 2 m for side cuts.
The spot energy was set to 140 nJ. The minimum lenticule side cut
thickness was set to 15 m. The lenticule side cut angle was 120 ,
and the optical zone was 6.5 mm. The optical zone diameter was
equal to the lenticule diameter in patients with purely spherical
refractive error. However, if the patient had astigmatism, the soft-
ware added a transition zone to convert the oval lenticule into a
circle. As a result, the lenticule diameter was 6.56.6 mm, depend-
ing on the presence or absence of astigmatism. The cap diameter
was 7.5 mm with a 50 superior side cut and a side cut angle of 90 .
A small-sized (Size S) patient interface was used in all patients.
2.6. Femto-LASIK
Flaps were created using the Visumax femtosecond laser plat-
form (Carl Zeiss Meditec). The spot energy was set to 140 nJ. The
spot distance was 3 m for the lamellar ap cut and 2 m for the
ap side cut, which was 90 , and the ap diameter was set at 8.5 mm
in all patients. A medium-sized (Size M) patient interface was used
in all patients. After the ap was created, the patient was trans-
ported to the Schwind Amaris 750S (Schwind eye-tech-solutions,
Kleinostheim, Germany) excimer laser platform. The ap was lifted
with a blunt spatula (Katena Products, Inc., Denville, NJ, USA), and
excimer laser photoablation was performed. The residual stromal
bed was washed with a balanced salt solution, and the ap was
repositioned.
3. Results
Preoperative patient characteristics are shown in Table 1. Pre-
operative SE of manifest refraction and maximum thickness of the
removed tissue were not statistically different between the SMILE
and LASIK groups (p > 0.05).
There were no statistically signicant differences in CH and CRF
values between the SMILE and LASIK groups in any pre- or postop-
erative measurements (Tables 2 and 3).
 A. Agca et al. / Contact Lens & Anterior Eye 37 (2014) 7780 79

Table 1
Preoperative patient characteristics.

Operation p

SMILE LASIK

Mean SD/n (%) Mean SD/n (%)

Age 26.63 4.57 26.63 4.57 1

Gender
Female 16 53.3% 16 53.3% 1
Male 14 46.7% 14 46.7%
Eye
Right 16 53.3% 16 53.3% 0.796
Left 14 46.7% 14 46.7%
Mean simulated 44.46 1.38 44.56 1.56 0.840
keratometry
Central corneal 539 28 542 37 0.763
thickness
Preoperative SE 3.62 1.79 3.71 1.83 0.852
Optical zone 6.5 6.5 1
Flap/cap thickness 120 120 1 Fig. 1. Pre- and postoperative corneal hysteresis (CH).
Removed tissue 82.67 19.85 73.40 24.18 0.110
thicknessa
In both groups, postoperative CH values at 1 and 6 months
Chi-square test/student t-test; SE: spherical equivalent; SMILE: small incision lentic-
were signicantly lower than the preoperative values (Fig. 1 and
ule extraction; LASIK: laser in situ keratomileusis.
a
Maximum lenticule thickness in SMILE group and maximum ablation depth in
Table 2, all p < 0.001). However, the difference between the 1-
femto-LASIK group. and 6-month postoperative values was not statistically signicant
(Table 2, p = 0.242 and p = 0.164 in the SMILE and LASIK groups,
respectively).
Postoperative CRF values at months 1 and 6 were signicantly
Table 2 lower than the preoperative values in both groups (Fig. 2 and
Pre- and postoperative corneal hysteresis (CH) values by group. Table 3, all p < 0.001). However, the difference between the 1- and
Operation p 6-month postoperative measurements was not statistically signi-
cant (Table 3, p = 0.587 and p = 0.609 in the SMILE and LASIK groups,
SMILE LASIK
respectively).
Mean SD Mean SD

CH 4. Discussion
Preoperative 10.89 1.79 11.00 1.53 0.811
Month 1 8.70 1.31 8.80 1.51 0.792 The ORA device measures the biomechanical parameters CH and
Month 6 8.95 1.47 9.02 1.27 0.852
CRF; the manufacturer claims that these values characterize the
Change by month viscoelastic properties of the cornea. Previous studies found that
Month 1preoperative CH 2.19 1.30 2.20 1.34 0.984
CH and CRF were signicantly decreased after LASIK surgery, and
p 0.000 0.000
Month 6preoperative CH 1.94 1.52 1.98 1.50 0.925 greater attempted corrections correlated with greater reductions in
p 0.000 0.000 CH and CRF [68,5]. In addition, eyes with keratokonus have lower
Month 6month 1 CH 0.25 1.15 0.22 0.84 0.909 CH and CRF values compared to normal eyes [6]. These facts suggest
p 0.242 0.164 that CH and CRF are lower in biomechanically weaker corneas.
Student t-test (paired samples); CH: corneal hysteresis; SMILE: small incision lentic- In this study, we compared CH and CRF after SMILE and femto-
ule extraction; LASIK: laser in situ keratomileusis. LASIK. Our aim was to compare outcomes in similar corrections.
Hence, we limited the maximum preoperative difference between
the SE of the eyes to 0.50 D and used the same optical zone (6.5 mm)
in both groups. Cap thickness in the SMILE group was set to be
Table 3
Pre- and postoperative corneal resistance factor (CRF) values by group.

Operation p

SMILE LASIK

Mean SD Mean SD

CRF
Preop 10.73 1.71 10.76 1.45 0.942
Month 1 7.89 1.57 7.98 1.58 0.838
Month 6 7.77 1.37 8.07 1.26 0.380

Change by month
Month 1preoperative CRF 2.84 1.93 2.79 1.69 0.910
p 0.000 0.000
Month 6preoperative CRF 2.96 1.69 2.69 1.44 0.508
p 0.000 0.000
Month 6month 1 CRF 0.12 1.20 0.10 1.02 0.454
p 0.587 0.609

Student t-test (paired samples); CRF: corneal resistance factor; SMILE: small incision
lenticule extraction; LASIK: laser in situ keratomileusis.

Fig. 2. Pre- and postoperative corneal resistance factors (CRFs).

80 A. Agca et al. / Contact Lens & Anterior Eye 37 (2014) 7780
similar to ap thickness in the femto-LASIK group. Furthermore, we
randomized the eyes between the groups, using sealed envelopes
to ensure allocation concealment. As a result, the preoperative dif-
ference between the mean SE of the groups was not statistically
signicant (Table 1). Removal of more tissue in one group could
have affected the outcome because it has been shown that higher
attempted corrections correlate with greater reductions in CH and
CRF [6,8,9]. To identify any possible differences in the amount of
removed tissue, we recorded the maximum ablation depth in the
femto-LASIK group and the maximum lenticule thickness in the
SMILE group. However, no statistically signicant differences were
found (Table 1). There is no other published study comparing the
amount of removed tissue for a given refractive correction in LASIK
and SMILE. Our results suggest that a similar amount of tissue is
removed in SMILE and femto-LASIK surgeries, when the attempted
correction and optical zones are similar.
We found statistically signicant reductions in CH and CRF val-
ues in both groups. The amount of reduction in the femto-LASIK
group was consistent with that described in previous studies [59].
On the other hand, the reduction of CH and CRF values following
SMILE is a novel nding, and there are no previously published
results for comparison.
When we compared the values between the SMILE and femto-
LASIK groups, the differences were not statistically signicant at
any time point. Larger sample sizes would be needed to identify
smaller differences between the groups, but there are no other
studies in the literature comparing these two groups. It is not pos-
sible to know what the smallest clinically interesting difference in
either biomechanical parameter is; however, this pilot study shows
(with a power greater than 95%) that even if there is a difference
between the two groups, it is smaller than half of the standard
deviations of CH and CRF values.
The postoperative measurements were taken after 1 and 6
months. In our opinion, any possible advantage related to SMILE
would be more evident at an early postoperative period when the
aps in the femto-LASIK eyes are weaker. However, there was no
difference, even in the rst month.
Although we did not nd statistically signicant differences in
postoperative CH and CRF values between the femto-LASIK and
SMILE groups, this does not mean that the corneas in both groups
were biomechanically similar to each other after these operations.
We would like to emphasize the fact that CH and CRF measure-
ments only reect some clinically signicant aspects of corneal
biomechanical structure. Results from corneal collagen crosslink-
ing studies are examples of this fact; although it is clear from in vitro
and in vivo studies that corneal collagen crosslinking leads to statis-
tically (and clinically) signicant changes in corneal biomechanical
properties, CH and CRF measurements do not change signicantly
after crosslinking [1012]. In conclusion, a difference between the
two groups in our study would conrm a biomechanical difference
in structure; however, the absence of difference does not mean that
the corneas in both groups are biomechanically similar. Nonethe-
less, this study clearly provides the rst evidence that femto-LASIK
and SMILE surgeries affect CH and CRF in a similar way.
One weakness of our study was that we removed the lentic-
ules from the same depth (120 m) in all patients. It is possible
to increase the cap thickness (lenticule depth) in SMILE surgery,
which may have important consequences. Removing the lenticule
from deeper stroma would preserve more of the anterior stroma
by sacricing the posterior stroma. This trade-off may have bene-
cial biomechanic effects because the anterior stroma is stronger.
On the other hand, removal of a very deep lenticule may be less
effective in changing the shape of the anterior corneal surface,
which may result in reduced refractive effect. In addition, a deep
lenticule would necessitate a deeper arcuate side cut to reach the
lenticule for removal, and this could produce an astigmatic effect.
Moreover, accuracy of the device in creating the lenticule surface
may be different in deeper dissection planes. SMILE is a new sur-
gical procedure, and in all the SMILE cases published to date, the
lenticule depth has been 100120 m. We used a depth of 120 m
because we knew from our own experience and published stud-
ies that SMILE performed with these parameters was efcient and
safe and produced results comparable to those achieved with LASIK.
Future studies that employ deeper lenticule extractions may yield
different results.
In conclusion, we found no signicant differences in CRF and CH
in fellow eyes treated with SMILE and femto-LASIK. Studies com-
paring biomechanical differences in eyes that underwent LASIK or
SMILE should compare parameters other than CH and CRF. In addi-
tion, they should explore the effects of different lenticule extraction
depths.
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