801163

research-article2018
EJO0010.1177/1120672118801163European Journal of OphthalmologyTojo et al.

EJO European
Journal of
Ophthalmology
Original Research Article

European Journal of Ophthalmology

Comparison of intraocular pressure

1­–8
© The Author(s) 2018
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fluctuation before and after cataract sagepub.com/journals-permissions
https://doi.org/10.1177/1120672118801163
DOI: 10.1177/1120672118801163

surgeries in normal-tension glaucoma journals.sagepub.com/home/ejo

patients

Naoki Tojo, Mitsuya Otsuka and Atsushi Hayashi

Abstract
Purpose: Cataract surgeries have been shown to reduce intraocular pressure. We used a Sensimed Triggerfish® contact
lens sensor to compare intraocular pressure levels and their fluctuation between before and after cataract surgeries in
patients with normal-tension glaucoma.
Methods: This was a prospective open-label study. Thirteen patients with normal-tension glaucoma were included. All
patients underwent a 1-month washout and discontinued glaucoma medications during this study. In each eye, intraocular
pressure fluctuations over 24 h were measured with the contact lens sensor before and at 3 months after the cataract
surgery. We compared intraocular pressure levels and their fluctuation between before and after cataract surgeries. We
used two approaches to evaluate the amplitude of intraocular pressure fluctuations: dual-harmonic regression analysis,
and measurement of the difference between the maximum and the minimum value.
Results: The mean pre-operative intraocular pressure was 14.7 ± 2.2 mm Hg and mean post-operative intraocular
pressure was 11.4 ± 2.2 mm Hg. Cataract surgery significantly decreased intraocular pressure (p = 0.0005). In both
methods, the post-operative fluctuations in intraocular pressure over 24 h were significantly smaller than their pre-
operative counterparts (dual-harmonic regression analysis: p = 0.0171; difference between the maximum and the
minimum: p = 0.0398).
Conclusion: Cataract surgery decreased both intraocular pressure values and intraocular pressure fluctuations in
normal-tension glaucoma patients.

Keywords
Normal-tension glaucoma, intraocular pressure, contact lens sensor, Triggerfish, fluctuation, cataract surgery

Date received: 17 December 2017; accepted: 28 August 2018

Introduction
Glaucoma is a neurodegenerative disease of the eye and
the leading cause of blindness in Japan.1 Normal-tension
glaucoma (NTG) is typically defined as optic disk and/or
visual field glaucomatous changes in an individual who
has never shown an untreated intraocular pressure (IOP)
value above 21 mm Hg.2 High IOP is a well-known signifi-
cant risk factor for the progression of glaucoma.3,4
In the Tajimi Study, the average IOP for eyes with primary
open-angle glaucoma (POAG) was 15.4 ± 2.8 mm Hg.5
It has been estimated that NTG is present in almost 70% of
all glaucoma patients in Japan, and the lack of an effective
treatment other than lowering the IOP is a significant
problem. In the Collaborative Normal Tension Glaucoma
Study,3 20% of NTG subjects showed visual field progres-
sion despite a reduction in their IOP by more than 30%
from baseline. These results suggest that non-IOP-related
elements may be involved in the progression of NTG.
Department of Ophthalmology, Graduate School of Medicine and
Pharmaceutical Sciences for Education, University of Toyama, Toyama,
Japan
Corresponding author:
Naoki Tojo, Department of Ophthalmology, Graduate School of
Medicine and Pharmaceutical Sciences for Education, University of
Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Email: tojo-naoki@umin.ac.jp
2 European Journal of Ophthalmology 00(0)
The IOP is known to fluctuate, and several studies have
shown that large IOP fluctuation might be one of the causes
of glaucoma progression.6–11 In support of these findings,
other studies have reported that large IOP fluctuations con-
tribute to fast glaucoma progression.6,9,12,13 The determina-
tion of IOP fluctuations over the course of a full 24 h may
thus provide better information for clinical decision-making
than discrete measurements of IOP in a single day.
A contact lens sensor (CLS) was developed to continu-
ously monitor habitual IOP fluctuations over a period of
24 h.14,15 Cataract surgery has been shown to reduce the
IOP and the number of anti-glaucoma medications in glau-
coma patients.16–18 The purpose of this study was thus to
use a CLS to compare the IOP value and IOP fluctuations
before and after cataract surgery in patients with NTG.
Material and methods
Subjects
This was a prospective, open-label study. Thirteen con-
secutive patients who were diagnosed with NTG by two
glaucoma specialists (N.T and M.O) at Toyama
University Hospital were enrolled. All subjects were
recruited during the period from April 2016 to January
2017. All patients underwent a comprehensive ophthal-
mic examination including refraction, Goldmann goni-
oscopy, fundus examination, anterior segment optical
coherence tomography (AS-OCT) (CASIA SS-1000;
Tomey, Nagoya, Japan), and automated perimetry
(Humphrey Field Analyzer; Carl Zeiss Meditec, Dublin,
CA, USA). We measured IOP with Goldmann applana-
tion tonometry (GAT), we did not use correction IOP
value with central corneal thickness (CCT).
Glaucoma medications had already been used in all
patients, but additional treatment was needed to lower
their IOP due to the progression of their visual field disor-
der. The research protocol was approved by the Institutional
Review Board of the University of Toyama, and the proce-
dures used conformed to the tenets of the Declaration of
Helsinki. After the nature and possible consequences of
the study were explained to the patients, written informed
consent was obtained from each.
Inclusion and exclusion criteria
The diagnosis of NTG was made if all three of the follow-
ing criteria were satisfied. (1) Untreated IOP had never
been above 21 mm Hg. We measured untreated IOP at least
two times on separate occasions, and we clinically defined
NTG as an untreated IOP value of less than 21 mm Hg. (2)
Glaucomatous optic disk neuropathy (a cup/disk ratio of
⩾0.7, or the presence of notching) was present, accompa-
nied by corresponding visual field defects. (3) In a thresh-
old examination using the Swedish Interactive Threshold
Algorithm (SITA) 30-2 program, the scores on the
Glaucoma Hemifield Test (GHT) were “outside normal
limits,” and a cluster of three contiguous points on the pat-
tern deviation plot that were depressed at the p < 0.05 level
(occurring in age-matched normal subjects) did not cross
the horizontal meridian and were compatible with
glaucoma.
The inclusion criteria for the subjects were (1) the
case was appropriate for cataract surgery; (2) the best-
corrected visual acuity was ⩾0.2 and <0.8; (3) spherical
equivalent was >−6 and <+6 diopters; and (4) mean
deviation (MD) was >−20  dB. For patients with
advanced glaucoma, other surgical treatments might be
also considered, so we excluded advanced glaucoma
patients (<−20 dB). When both eyes were indicated,
we choose the eye of the severe visual field. The exclu-
sion criteria were (1) primary angle closure glaucoma,
(2) neovascular glaucoma, (3) steroid glaucoma, (4)
history of ocular trauma, (5) retinal disease, (6) post-
photocoagulation, (7) post-vitrectomy, (8) ocular inflam-
matory disease, (9) prior laser trabeculoplasty or other
prior glaucoma surgery, (10) IOP of more than 21 mm Hg
after washout of glaucoma medications, and (11) case of
intraoperative complications.
Measurement of IOP with GAT
All patients underwent a 1-month washout of glaucoma
medications. The untreated IOP was obtained at two read-
ings on separate occasions prior to the cataract surgeries.
We confirmed that untreated IOP was less than 21 mm Hg.
We measured the post-operative IOP at 3 months after the
cataract surgeries in each patient. Since this study is con-
ducted under conditions excluding the effect of glaucoma
medications, it is aimed to investigate the effects of pure
cataract surgery. We adopted the IOP value at about 10
a.m., just before the start of the 24-h continuous IOP meas-
urement with the CLS.
Surgical techniques
All patients were operated on by a single surgeon (N.T.)
using the same surgical protocol under local (peribulbar)
anesthesia. A temporal clear cornel incision was made
(2.8 mm), and conventional phacoemulsification (PEA)
and intraocular lens implantation were then performed.
PEA was performed with a WHITESTAR SIGNATURE
System (Abbott Medical Optics, Santa Ana, CA, USA).
Post-operative medications
The post-operative treatments consisted of topical steroids
and antibiotics that were reduced over 4 weeks following
the intervention. Topical non-steroidal anti-inflammatory
drugs were used for 3 months. All anti-glaucoma medi-
cations were discontinued for the duration of the study
period.
Tojo et al. 3
Figure 1.  Representative results of IOP fluctuation measurement using a contact lens sensor over a 24-h period before and after
cataract surgery.
Gray line: the IOP fluctuation before cataract surgery.
Black line: the IOP fluctuation after cataract surgery. After the surgery, the range of IOP fluctuation was decreased. The two gently sloping lines
show the results of the dual-harmonic regression analysis.
Measurement of IOP fluctuation with the CLS
We measured the IOP fluctuation using the CLS at about
10 a.m. the day before and the day 3 months after cataract
surgery. Two doctors trained (N.T and M.O) in CLS meas-
urement inserted and removed the CLS in the hospital.
Monitoring was performed in one eye of each subject; if
both eyes had NTG, we inserted the CLS in the eye with
the worse visual field.
The 24-h IOP was monitored using a Triggerfish® CLS
(Sensimed, Lausanne, Switzerland). This CLS consists of
a highly oxygen-permeable soft contact lens whose key
elements are two sensing-resistive strain gauges that can
record circumferential changes in the area of the corneo-
scleral junction.14,15 The device is based on a novel
approach to IOP monitoring in which changes in corneal
curvature and circumference are assumed to correspond
to changes in IOP. The unit of measurement used in moni-
toring the IOP fluctuation with the Triggerfish is not
mm Hg but mVeq (millivolt equivalents), which is unique
to the Triggerfish. The median values were monitored for
30 s every 5 min, providing 288 points over the 24-h
period. The subjects were instructed to record the time
when they went to bed, and the time when they woke up.
Subjects were not restricted in their posture during the
measurement.
We compared IOP fluctuation before and after cataract
surgery using two methods: dual-harmonic regression anal-
ysis, and manual calculation of the difference between the
maximum and minimum values. A sample result from dual-
harmonic regression analysis is shown in Figure 1. The
shapes of these approximate curves were generated by com-
bining two sine curves from raw IOP data over 24 h. This
method was used to model the 24-h IOP rhythms19,20 as
 2π   2π 
IOPt = M + A1 cos  t + φ1  + A2 cos  2 t + φ2 
 τ   τ 
where A1 is the amplitude of the fundamental cosine fit, A2
is the amplitude of the first harmonic cosine fit, φ1 is the
acrophase of the fundamental cosine fit, φ2 is the acrophase
of the first harmonic cosine fit, τ is the endogenous circa-
dian period (set at 24 h because of the entrained condi-
tions), M is the midline estimating statistic of rhythm
(MESOR), and τ is time. Unbiased estimates and confi-
dence limits of amplitude (half the difference between the
highest and lowest IOP values in a 24-h cycle), MESOR
(average IOP values in a 24-h cycle), acrophase (time of
the highest IOP value in a 24-h cycle), and bathyphase
(time of the lowest IOP value in a 24-h cycle) were
obtained from modeling each IOP curve.21 The amplitude
of the IOP curve was calculated automatically using the
software provided with the Sensimed CLS.
The other method was based on manual calculation of
the difference between the maximum value (mVeq) and
the minimum value during the course of the 24 h. This
method was used in previous reports.10,11,22 We also evalu-
ated the IOP fluctuations separately: diurnal IOP and noc-
turnal IOP. The nocturnal/sleep periods were defined based
on the observation of blink cessation. Eye blink was iden-
tified as short and high-amplitude spikes in the CLS sig-
nals that were displayed by the software’s zoom function.
We also verified diurnal/wakefulness periods and noctur-
nal/sleep periods during the 24-h assessment based on
each subject’s log; subjects were instructed to record the
time when they returned home, installed their eye drops,
went to bed, and woke up. We also evaluated the relation-
ship between systemic disease and IOP change.
4 European Journal of Ophthalmology 00(0)

Evaluation of the changes in corneal thickness Table 1.  Ophthalmic data.

and meridians Gender (male) 53.8% (7/13)
Age (years) 70.9 ± 6.2
The CCT and corneal meridians, which may influence
Axial length (mm) 24.0 ± 1.5
IOP measurement, were measured with AS-OCT before CCT (µm) 514 ± 16
and after a 24-h IOP measurement in each eye. All Medications 2.9 ± 1.3
patients were measured with CLS twice (once before and Treated IOP (mm Hg) 12.0 ± 2.0
once after their surgeries), we used the results obtained Baseline IOP (mm Hg) (washout medication) 14.7 ± 2.2
before the surgeries. We measured the differences
between the total corneal meridians and anterior corneal CCT: central corneal thickness; IOP: intraocular pressure.
meridians.
Table 2.  Comparison of the results of IOP and IOP
fluctuations between pre- and post-cataract surgery for
Statistics normal-tension glaucoma.
The Wilcoxon signed-rank test was used to compare the
Pre-operation Post-operation p value
values between before and after IOP and to assess the fluc-
tuation of IOP. Assuming that the standard deviation of the IOP (mm Hg) 14.7 ± 2.2 11.4 ± 2.2 0.0005
IOP daily variation with respect to a paired difference IOP fluctuation (mVeq)
between before and after surgery was 50 mVeq according  Dual-harmonic 174.5 ± 63.9 137.8 ± 48.8 0.0171
to the data to have been collected in a previous study,22 we   24 h 519.6 ± 122.0 433.2 ± 107.0 0.0398
found that a total of eight pairs of values were needed to   Diurnal period 439.0 ± 115.7 389.5 ± 117.0 0.147
detect a meaningful difference of 50 mVeq with respect to   Nocturnal period 265.4 ± 83.6 183.0 ± 54.7 0.0105
the IOP daily variation with 80% power and a two-sided IOP: intraocular pressure.
significance level of 0.05. All statistical analyses were per-
formed using the JMP Pro 11 software program (SAS,
Cary, NC, USA). Statistical significance was defined at the NTG patients (p = 0.0005). Only one patient had an
p < 0.05. IOP at 3 months after surgery that was higher than the pre-
operative IOP.

Results
Ophthalmic data
Table 1 shows the baseline data of the subjects, and Table 2
shows the IOP fluctuation data. The study was performed
on 13 eyes of 13 patients (7 males and 6 females). The
mean (±standard deviation) age at the time of surgery,
axial length, CCT, and amount of glaucoma medication
were 70.9 ± 6.2 years, 24.0 ± 1.5 mm, 514 ± 16 µm, and
2.9 ± 1.3 drops, respectively. No patients took oral aceta-
zolamide. Regarding systemic diseases, there were three
patients with hypertension and two patients with diabetes.
All cataract surgeries were performed successfully, and
no intraoperative complications occurred. After the surger-
ies, there were no severe post-operative complications
such as hypertonia, hypotony, maculopathy, choroidal
effusion or hemorrhage, and endophthalmitis.
Measurement of IOP with GAT
The average IOPs before and after the washout of glau-
coma medications were 12.0 ± 2.0 and 14.7 ± 2.2 mm Hg,
respectively. Washout of glaucoma medication increased
the IOP significantly (p = 0.0009). The average IOP at
3 months after cataract surgery was 11.4 ± 2.2 mm Hg.
Cataract surgery was shown to significantly lower IOP in
Measurement of IOP fluctuations
We were able to successfully measure the 24-h IOP in
all 13 NTG patients. There were no serious complica-
tions related to wearing the CLS. Figure 1 shows an
example of IOP result with dual-harmonic regression
analysis. The mean of pre-operative IOP fluctuations was
174.5 ± 63.9 mVeq, and the mean post-operative IOP fluc-
tuation was 137.8 ± 48.8 mVeq. The amplitudes of IOP
fluctuation are shown in Figure 2. As shown in Figure 2,
the mean amplitude of IOP fluctuations was significantly
decreased (p = 0.0171). The peak IOP (the time of peak
amplitude) occurred during the nocturnal period in all
patients. 10 of 13 patients had smaller IOP fluctuations
than before the cataract surgery with this method.
The results for the second method, that is, the analysis
of differences between the maximum and minimum IOP,
are shown in Figure 3. The mean range of IOP fluctuations
over 24 h and the nocturnal period were significantly
smaller than before the surgery (p = 0.0398, p = 0.0105).
The number of patients who had greater IOP fluctuations
after cataract surgery over 24 h, the diurnal period, and the
nocturnal period were 2, 4, and 3, respectively.
There was no correlation between the presence or
absence of systemic disease and post-operative IOP
decrease.
Tojo et al. 5

Corneal effects of the CLS

To examine the effects of the CLS on the cornea, we meas-
ured the corneal curvature and CCT with the AS-OCT just
before insertion of the contact lens with the CLS, and
again just after its removal. Table 3 shows the changes of
corneal curvature, thickness, and IOP value. The mean
steeper meridian was significantly changed (p = 0.0332),
and the mean of the flatter meridian was not significantly
changed (p = 0.348). The mean CCT was not significantly
changed (p = 0.172). We measured the corneal curvature
and CCT with the AS-OCT before and 3 months after cata-
ract surgeries. There was no significant change of CCT
and corneal curvature between before and after cataract
surgeries (Table 4).

Discussion
We used a CLS to measure IOP fluctuations in 13 NTG
patients before and after cataract surgery and found that there
were significant decreases in the IOP values and the ampli-
tude of 24-h IOP fluctuation at 3 months after surgery.
Previous studies reported that cataract surgery could
reduce the IOP to within the range of 1.1–4.0 mm Hg.17,23–28
Figure 2.  Range of IOP fluctuation before and after cataract
surgery (dual-harmonic regression analysis).
Boxplots of the amplitude of IOP fluctuation with dual-harmonic
regression analysis before and after cataract surgery are shown. Cata-
ract surgery significantly decreased the amplitude of IOP fluctuation
(p = 0.0171).

Figure 3.  Range of IOP fluctuation before and after cataract surgery (the difference between the maximum and minimum).
Boxplots of the range of IOP fluctuation (a) over 24 h, (b) during the diurnal period, and (c) during the nocturnal period before and after
cataract surgery. Cataract surgery significantly decreased the range of IOP fluctuation over 24 h and during the nocturnal periods (p = 0.0398,
p = 0.0105).
6 European Journal of Ophthalmology 00(0)
Table 3.  Change in the CCT and corneal curvature before and after the 24-h measurement with contact lens sensor.
Before measurement
CCT (µm) 514 ± 16
Steeper meridian (D) 44.8 ± 2.3
Flatter meridian (D) 43.7 ± 1.6
CCT: central corneal thickness; D: diopter
Table 4.  Change in the CCT and corneal curvature before and after cataract surgeries.
Pre-operation
CCT (µm) 514 ± 16
Steeper meridian (D) 44.75 ± 2.27
Flatter meridian (D) 43.65 ± 1.57
CCT: central corneal thickness; D: diopter.
However, there were some reports that cataract surgery
could not affect for lowering IOP.29,30 In this study, cataract
surgery was found to reduce the IOP by 3.3 mm Hg in our
NTG patients, which constituted an improvement over the
previous reports. We considered that this was due to the
difference in the number of glaucoma medications. Most of
the previous studies reported that cataract surgery reduced
the number of glaucoma medications. In this study, how-
ever, we did not use glaucoma medications.
There are some reports that IOP fluctuation is one of
factors for glaucoma progression and some reports that it
is not so, and it is controversial.31–33 In general, however,
because the existing studies on IOP fluctuation can be
divided into the short-term studies (with measurements
throughout a single day) and the long-term studies (with
measurements over several years), it has been difficult to
determine the significance of these variations due to the
lack of standardization regarding the time between assess-
ments, the methods of measurement, and the definition of
fluctuation itself.
Using GAT, Kim et al.34 reported that the 24-h IOP fluc-
tuation in NTG eyes was significantly larger than that in
healthy eyes. Their method could not adequately account
for the variations in IOP throughout the day, because their
methods might overlook the IOP fluctuations at interval
between IOP measurements. However, methods for meas-
uring IOP more frequently must overcome the burdens of
hospitalization and sleep disturbance. The new method of
measuring IOP fluctuation with a CLS overcomes these
problems and provides a clearer assessment of circadian
patterns of IOP. We also expect that it will lessen the pos-
sibility of bias in the measurement of IOP fluctuation,
since the CLS provides objective measurements. Using the
CLS method, some studies have reported that the IOP
fluctuation in the eyes of patients with NTG was greater
than that in healthy eyes.11,35 In this regard, larger IOP
After measurement p value
511 ± 19 0.172
45.3 ± 2.6 0.0332
43.8 ± 2.1 0.348
Post-operation p value
517 ± 17 0.106
45.05 ± 2.44 0.178
44.12 ± 1.83 0.223
fluctuation might have possibility to contribute progres-
sion glaucoma.
There was no significant relationship between system-
atic disease and IOP lowering or IOP fluctuation change.
To state the relationship between systemic diseases and
IOP, the number of subjects was too small.
All our patients experienced their peak IOP during the
night. This result is in accord with the previous reports.11,35
In our study, cataract surgery was found to significantly
reduce IOP fluctuations. We suspect that there are two rea-
sons for the reductions in IOP and IOP fluctuation after
cataract surgery. First, the opening of the anterior chamber
angle would be expected to reduce these parameters.
Second, when patients undergo cataract surgery, the irriga-
tion and aspiration could washout some materials that
obstructed the outflow though the trabecular meshwork.
Our study has several weaknesses. First, it was not pos-
sible to convert the recorded units of mVeq to units of
mm Hg. The CLS recorded relative IOP from the initial
IOP, not the absolute IOP. Moreover, the relationship
between the CLS device output and IOP as measured with
a tonometer is unknown. Therefore, further investigations
will be needed into the usefulness of CLS for use in meas-
uring IOP fluctuation. Leonardi et al.15 demonstrated that
the IOP and the output by CLS were directly proportional.
Some studies have reported that the reproducibility with
CLS was good.21,36–38 In light of the existing data, we con-
sidered that the plotted data with CLS were reliable.
A second limitation is that changes in the corneal curva-
tures may have affected the values of mVeq during the
24-h measurement of IOP fluctuations with CLS. Further
improvement in the CLS will be expected to reduce stress
on the cornea during the measurement. Cataract surgery
makes some changes in morphology.39 Measurement IOP
with CLS results in the presence of artifacts due to the cor-
neal incision. In our study, there was no significant change
Tojo et al. 7
of corneal curvature between pre-op and post-op, but these
small changes might not be negligible. Previous studies
reported that cataract surgery increased IOP with dynamic
contour tonometry, and the phaco-induced GAT-measured
IOP drop has been questioned.40,41
A third limitation is that the methods for evaluating IOP
fluctuation with CLS have not been standardized. The pre-
vious studies on IOP fluctuation used a variety of slightly
different evaluation methods. Some studies evaluated the
range of IOP fluctuations as the difference between the
maximum value (mVeq) and the minimum value during
the course of the 24 h recording.10,11 This method is simple,
and the calculations are easily made. However, if the plot-
ted IOP has some spikes, it might not be suitable for depict-
ing the overall IOP fluctuations. Mottet et al.21 reported the
method of dual-harmonic regression analysis. Their
method yields a sophisticated curve of IOP fluctuation, but
it can fail to capture the real IOP peak. Other reports have
evaluated IOP fluctuations using various calculation
methods.42–44 Given this wide range of approaches, the
CLS-based methods for evaluating IOP fluctuation will
need further study.
The forth limitation is very small number of subjects
and short term of follow-up period. Only 3 months is
probably too short in a chronic disease as glaucoma.
Furthermore, it is desirable to follow-up for long term
and to measure IOP fluctuation multiple times with CLS.
This fifth limitation is lack a control group to compare
with NTG patients. It desirable to compare IOP and IOP
fluctuations between NTG patients and normal subjects
before and after cataract surgery. The sixth limitation is to
ignore the influence of glaucoma medications. The aver-
age IOP before washout glaucoma medication period
(12.0 ± 2.0 mm Hg) is quite similar to the average IOP
at 3 months after cataract surgery (11.4 ± 2.2 mm Hg). It
desirable to compare IOP when resuming glaucoma medi-
cations after cataract surgery. Whether cataract surgery is
better than glaucoma medications treatment is unknown in
this study.
Treatment for glaucoma may be needed not only to
reduce a temporary IOP but also to lessen IOP fluctuation.
IOP measurement with a CLS might therefore becomes an
essential test for glaucoma patients. Even though there are
some limitations regarding the use of a CLS, habitual IOP
fluctuation can provide useful information. Our study
clearly showed that cataract surgeries decreased both IOP
values and IOP fluctuations in our patients with NTG.
Cataract surgery might thus be one of the treatment strate-
gies for NTG. In addition, the improvement of IOP fluc-
tuations might be important for the prevention of glaucoma
progression.
Acknowledgement
The authors thank Professor Hideki Orikasa for his guidance on
statistics.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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