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OCL • Volume 1 • No. 3 • October 2021
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1
Clinical comparison between
a newly developed prototype
method for measuring corneal
sensitivity and the current
gold standard
Tobias Bracher
1,, Daniela Nosch
2,3, Roland Joos
2,3
1 M.Sc., EurOptom • 2 Prof. Dr. • 3 Institute of Optometry, FHNW, Switzerland
Received April ; accepted July
Original Article Optometry & Contact Lenses · Vol. 1, No. 3, pp. 84-91, 2021
© 2021 Ocial journal of the VDCO · Published by DOZ-Verlag
All rights reserved · Printed in Germany
Published online in English as Open Access: 29.09.2021
Abstract
Purpose. The aim of the study was to test a newly developed
prototype for corneal sensitivity measurement (liquid jet (LJ)
with saline as stimulus) for repeatability and correlation with
the Cochet-Bonnet esthesiometer (CB). This is an excerpt of
a master thesis, which was part of a larger study.
Material and Methods. Corneal sensitivity thresholds (CST)
were determined for subjects, in a clinical trial with
subjects, with each device on two separate dates (with inter-
vals of at least one day and a maximum of fourteen days). In
addition, the pain sensitivity questionnaire (PSQ) was applied
to determine any possible correlation with corneal sensitivity.
Results. Similar standard deviations of the CSTs for LJ and
CB were obtained (LJ (M ± SD): . ± . dB; CB (M ± SD):
. ± . dB). No statistically signicant dierence in CST
was found between the two visits for LJ (mean dierence:
-.dB, p = .), however there was a statistically sig-
nificant difference for CB (mean difference: -. dB,
p = .). LJ CSTs correlated moderately positively with
CB CSTs and PSQ (LJ-CB: r = ., p < .; LJ-PSQ:
r = ., p < .).
Conclusion. LJ oers a signicantly larger stimulus bandwidth
than CB. Better reproducibility was observed for LJ, while
correlation between the results for the two instruments was
good. Signicant moderate positive correlation was found
between LJ CSTs and general pain sensitivity.
Keywords
esthesiometry, Cochet-Bonnet, Liquid Jet, prototype, PSQ
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OCL • Volume 1 • No. 3 • October 2021 2
Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
Introduction
The cornea has the highest nerve density in the body.1-4 Based
on animal models, it is estimated that the cornea is to
times more densly innervated than the skin.5 The nerves
respond to mechanical, electrical, chemical and thermal
stimuli to protect the functionality of the cornea.1,4 How-
ever, if pain is not triggered due to a defect in the nocice-
ptive system or the threshold value for triggering a reflex is
too high, there is a risk of unnoticed injuries to the cornea
and the associated possible loss of vision. An intact nerve
supply is required to regenerate the cornea after injury and
to maintain its integrity. Epithelial defects, ulcerations or
even perforations of the cornea can occur if the response
of the nervous system is interrupted for a long period of
time.6 Modern imaging methods have shown that structural
anomalies occur with certain pathological defects and vice
versa.2,7 However, the structure and function of the nerves
do not always match. Symptoms can be present without
any visible pathology and a visible pathology can arise with-
out presenting symptoms.2,7 More precise measurements of
corneal sensitivity could therefore provide additional infor-
mation about the cause and eect of pathological defects
on the corneal nerves.
Stimulus perception arises on the corneal surface,
where it is passed on by the nerves to the truncus cerebri,
interpreted by the limbic system and transmitted to the
cerebrum. At each of these stages, the signal is either ampli-
ed or weakened by nociceptive processing. How unpleas-
ant stimuli are perceived varies from person to person.8 The
Pain Sensitivity Questionnaire (PSQ) by Ruscheweyh et al.9
is a validated process to auto-evaluate the individual per-
ception of pain. This survey has already been used for eye
examinations and has shown a connection between general
pain perception and eye discomfort.8,10,11 The PSQ was also
proposed as an aid for the selection of suitable candidates
for rigid contact lenses.12
Another function of supercial nerve endings is to detect
cooling resulting from a thinned tear film and trigger the
secretion of new tears and blinking, which distributes the tear
lm evenly again.1,13 Thus, supercial, pain-sensitive nerves are
jointly responsible for the basic secretion of tears and play an
important role in the pathogenesis of dry eyes.13
Studies have shown that corneal sensitivity is not con-
stant and can change as a result of systemic diseases such
as diabetes,14–16 surgical interventions on the eye2,4 or aging
processes.17,18 Wearing contact lenses19,20 and degenerative
defects such as keratoconus also have a negative impact on
the corneal sensation.4,21,22 A change in sensitivity can explain
the increased or absent symptoms in dry eyes, which means
that symptoms may appear without any apparent reason and
signs of dryness may be present without any symptoms.1,13,23
The measurement of corneal sensitivity is therefore of great
importance in ophthalmology. This measurement is carried
out using aesthesiometry. Von Frey described aesthesiometry
for the rst time in .21 Back then, horse tail hairs of dif-
ferent lengths were used to test the sensitivity of the cornea.
This method was optimised by Francheschetti in and
then by Boberg-Ans by substituting the horse hairs with a
nylon thread of constant diameter and variable length.24 The
length of the nylon thread is constrained to eleven values
(from . cm to cm, in steps of . cm); a very limited range
with increasingly larger gaps in the measuring range as the
thread length decreases. Furthermore, the nylon thread is
susceptible to fluctuations in humidity.25 Since the stimulus
is visible, the patient’s nervous state during the examination
may also influence the threshold value. The pressure values
for longer thread lengths are relatively close to one another
and increase exponentially with decreasing thread length.
When using a thread with a diameter of . mm, there is
a risk of overlooking very high sensitivities, as the lowest
threshold value for this diameter already corresponds to
the average value of the thread with . mm in diameter.
Furthermore, in the case of larger thread diameters, the high
forces and the edges of the thread can lead to lesions on the
corneal epithelium. For these reasons, the aesthesiometer
with a thread diameter of . mm (Luneau Ophtalmologie,
Chartres, France) was used in this study. It is worth noting that
the Cochet-Bonnet aesthesiometer, with a nylon thread as a
tactile stimulus, is the only commercially available device to
measure corneal sensitivity. Due to the disadvantages of the
traditional method mentioned above, a prototype (Liquid Jet
aesthesiometer) was developed at the University of Applied
Sciences of Northwestern Switzerland (FHNW), which uses
a liquid stimulus consisting of saline solution.
The aim of this study was to compare the threshold value
measurements of the corneal sensitivity obtained using the
Liquid Jet aesthesiometer with those of the Cochet-Bonnet
aesthesiometer and to test their repeatability. Additionally,
the threshold values for corneal sensitivity were tested for
correlation with the results from the Pain Sensitivity Ques-
tionnaire (PSQ). This article is a subanalysis of a larger study
at the Institute for Optometry of the FHNW.
Material and Methods
Test subjects
The participating test subjects were recruited from the pa-
tient pool of the Institute of Optometry of the FHNW and
by advertisement. Subjects aged between and years
(Group A) or and years (Group B) were admitted to the
study (Table ). The division into two age groups was based
on the decreasing density of nerve cells and the associated
reduction in the sensitivity of the cornea with age.17,18 Ac-
cording to Acosta et al., gender has no signicant influence
corneal sensitivity.18 However, wearing rigid contact lenses
was an exclusion criterion from the study due to their lasting
influence on corneal sensitivity, whereas soft contact lenses
were allowed to be worn but had to be removed at least
hours before the examination.19,20 Subjects could not present
any systemic diseases that may have an impact on eye health,
such as diabetes. Subjects, who have experienced trauma or
operations, as well as acute inflammatory processes aecting
the anterior eye segment and with symptoms of dry eye (OSDI
OCL • Volume 1 • No. 3 • October 2021
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Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
score > ) were also excluded. Furthermore, and especially
on the day of the examination, no systemic drugs or eye drops
which could influence the tear lm, were allowed to be used.
This study is a subanalysis of a larger study, which was
carried out in accordance with the Declaration of Helsinki
and approved by the Ethics Committee of Northwestern and
Central Switzerland (project ID -).26
Devices for measuring corneal sensitivity
Cochet-Bonnet aesthesiometer
In the s, Cochet and Bonnet improved the existing
aesthesiometer by developing two models with different
thread diameters (. and . mm). The length of the nylon
thread is variable and adjustable in . cm increments. The
procedure foresees the application of the thread perpen-
dicular to the central cornea until it bends ve degrees. For
the measurement, the test subject concentrates on a distant
xation target and states whether the stimulus caused by the
thread was felt. The length of the thread that caused the last
stimulus felt by the test subject is noted in centimetres (cm).24
The aesthesiometer used in this study had a thread diameter
of . mm (Luneau Ophtalmologie, Chartres, France).
Liquid Jet aesthesiometer prototype
The newly developed Liquid Jet aesthesiometer prototype
(LJ) (self-made by FHNW, updated version as of September
) consists of a camera-centring device, a peristaltic
pressure pump, a pressure transmitter, a valve (with a dia-
meter of . mm) with a connected heating foil and two
release buttons. In this case, the stimulus consists of an iso-
tonic saline solution released during a valve-opening period
of ms. The isotonic saline solution reaches the valve in a
sterile manner through an infusion kit and from there is pro-
jected onto the cornea with a predened intensity and tem-
perature. The volume of the saline solution is so small, that it
is absorbed by the tear lm immediately after hitting the front
surface of the eye and does not overflow beyond the eyelid
margin (.ml for mbar to . ml for mbar).
Measurements conducted by Bistoletti and Mauchle within
the scope of a Bachelor thesis at the Institute of Optometry
of the FHNW showed that a maximum cooling of the surface
of the cornea of . °C can be assumed.27 Thus, for this study,
stimulus temperature was set at .°C warmer than ocular
surface temperature of the cornea to ensure that any cooling
occurred below the tolerance level. A cooling of as little as
. °C may trigger excitation of the cold-sensitive receptors,
whereas the sensitivity to an increase in ocular surface tem-
perature is much lower.1,28,29 The mean stimulus temperature
was . ± . °C. By controlling the temperature of the
stimulus to attain a similar temperature to that of the surface
of the cornea, it was aimed to present a pure tactile stimulus.
The measurement procedure took place as follows. The
test subject xates a point light source while the opposite eye
is occluded. Two laterally oset cameras enable the correct
centring of the device and its required distancing of mm
from the eye. The measurement is carried out in a darkened
room so that the test subject cannot visually perceive the
stimulus, as this may influence the response (felt/not felt).
The required settings are configured using a laptop
connected to the aesthesiometer. The pre-programmed
algorithm searches for the corneal sensitivity threshold
in a step-by-step process. This is achieved by alternating
between continuously reducing clearly perceptible stimuli
and continuously increasing stimuli that are not perceptible.
This prevents any possible bias of the examiner. After the
stimulus was released, the test subject indicates by pushing
a button whether he or she felt the stimulus on the eye. The
device is cleaned after each test subject using a rinsing pro-
cess and ultrasonic cleaning of the valve.
OSDI
The Ocular Surface Disease Index (OSDI) is determined with
the help of the Allergan questionnaire, specially developed
and validated for this purpose.30 The test subject lls in the
survey and the answers are used to assess whether a person
has subjectively dry eyes or not. The questionnaire consists of
twelve questions related to the everyday routine of the last
week and covers the most common activities that typically
involve dry eye symptoms. The OSDI score is calculated on
the basis of the sum of the values of all answered questions.
An OSDI score of represents the lower limit for dry eyes.
Pain Sensitivity Questionnaire (PSQ)
The questionnaire consists of questions about everyday
situations, which are to be rated on a scale from zero (not
painful at all), one (barely perceptible) to ten (the strongest
imaginable pain). This results in a Painscore ranging from
zero to ten.9
Table 1: Age distribution of the study participants
General Age group A Age group B
Men Women Men Women Men Women
Number
Age [years] Mean . . . . . .
Standard deviation ±. ±. ±. ±. ±. ±.
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Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
Study design and examinations
The present study is designed as a prospective clinical trial
with repeated measurements. Two threshold values were
measured with the LJ and CB techniques respectively dur-
ing both subject visits. All measurements were performed
exclusively on the right eye, with the last measurement of
each appointment being the one with the Cochet-Bonnet
aesthesiometer, since this procedure may cause supercial
epithelial corneal defects and, thus, falsify any following
measurements.
Each test subject attended for two visits of approximate-
ly minutes. During the rst visit, the test subjects were
informed in detail about the procedure. After signing a dec-
laration of consent, the test subjects completed the OSDI
questionnaire and the Pain Sensitivity Questionnaire (PSQ).
Both eyes were checked for acute inflammation or previous
trauma/operations by checking the medical history of the
patient and via a slit lamp examination of the anterior eye
segment.
A subliminal and a clearly noticeable stimulus were
demonstrated in the left eye using both measuring devices
so that the test subjects knew what to expect. This was fol-
lowed by the two determinations of the corneal sensitivity
threshold value. At the end of the measurements, the an-
terior eye segment was examined again with the slit lamp,
now with the additional use of fluorescein. The threshold
value determinations and the completion of the question-
naire were repeated at intervals of at least hours and a
maximum of days.
Statistical analysis
The data were processed with Microsoft Excel ,
con verted, and then evaluated with IBM SPSS .. The
data were then checked for normal distribution with the
Shapiro- Wilk test. The mean values for normally distribut-
ed data were compared using either the t-test for paired
samples or the t-test for independent samples. The non-
normally distributed data were tested with a non-paramet-
ric test for dependent samples (Wilcoxon test) or a non-
parametric test for independent samples (Mann-Whitney
U test). The linear regressions were calculated using the
Pearson correlation.
Method repeatability was assessed with use of Bland-
Altman plots (Figure and Figure).31 First, the dierence
between the threshold values from the rst and the second
visit was calculated. The mean values, the standard deviations
and the % condence intervals were also determined. The
condence interval is calculated by multiplying the standard
deviation by ± . and adding it to the mean. The x-axes
of the plots correspond to the mean and the y-axes to the
dierences. The red line represents the mean, and the green
lines reflect the upper and lower ends of the % confi-
dence interval. The width of the condence intervals shows
the reproducibility of the respective procedures. The closer
the condence intervals are to one another and the less the
mean deviates from zero, the better the reproducibility of the
respective method.
In natural sciences, the signal-to-noise ratio is used to
assess the quality of a measured variable. The mean of the
threshold values of the rst and second visit was taken as the
signal and the standard deviation was calculated. The noise
was calculated from the standard deviation of the dierence
between the threshold values of the rst and second visit. The
signal-to-noise ratio is a measure of the usability of the method.
The calculations presented here are general, i.e., the data
was not subdivided according to age. Furthermore, we used
a signicance level of α = .. Values of . < p < . were
taken as presenting a strong or a less strong trend respec-
tively. The correlation coecients were interpreted according
to Cohen, where r = . corresponds to a weak, r = . to a
moderate and r = . to a strong correlation.32
Data transformation
Data with dierent units of measurement cannot be directly
compared without undergoing a prior transformation. There-
fore, the threshold values were transformed into a logarithmic
scale. Decibel (dB) is a ratio of two numbers based on a log-
arithmic scale. This unit of measurement allows very large or
very small values to be displayed and processed more easily.
In order to avoid negative values, mbar or N respectively
were selected as zero values of the dB scale.
Results
Testing for normal distribution
Differences between the measured values from the first
and second appointments were tested for normality, us-
ing the Shapiro-Wilk test. After transforming the thresh-
old values into decibels, the null hypothesis of normal dis-
tribution for LJ could be accepted (p = .). However,
the null hypothesis of normal distribution was rejected for
the CB thresholds (p = .). The null hypothesis of nor-
mal distribution was also rejected for OSDI and Painscore
(OSDI: p < .; Painscore: p = .).
Overview of the threshold values
The means (M) of the threshold values and their standard de-
viation (SD), as well as the median (MD) over all test subjects,
are summarised in Table . The threshold values are listed
in mbar or N, and dB. Additionally, Table also shows the
rst and third quartiles, which describe the magnitude of the
interquartile range. LJ has higher mean values than CB, with
the SD being very similar for both methods.
Comparison of visits
The threshold values of the rst and second visits were an-
alysed with the t-test for paired samples for the LJ method
and with the non-parametric test for dependent samples
(Wilcoxon test) for the CB method.
OCL • Volume 1 • No. 3 • October 2021
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Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
For LJ, there was no significant difference be-
tween the visits for any of the age groups (LJ general:
M dierence = -. dB, p = .; group A: M dierence
= +. dB, p = .; group B: M dierence = -. dB,
p = .). In the case of CB, however, there was a sig-
nificant difference between the threshold values of the
two visits when considering all test subjects and when
only considering age group A (CB general: M difference
= -. dB, p = .; group A: M dierence = -. dB,
p = .). For age group B, there was a strong tendency
towards dierent threshold values between the two visits
(M dierence = -. dB, p = .) (Figure ).
Comparison of the age groups
The means of the threshold values were slightly higher in age
group B than in age group A. In the case of LJ, this dierence
between the two age groups was not signicant (p = .).
For CB, the dierence between the two groups showed a
slight trend towards higher measured values in the older
group (p = .) (Figure ).
Correlations
The correlations were calculated using the Pearson prod-
uct-moment correlation coecient and checked for signi-
cance. The LJ measurements correlate moderately positively
with the CB and Painscore measurements (Figure ).
Repeatability
Both LJ and CB showed slight fluctuations in their signal
quality and a slightly weaker noise for CB. This leads to a low
signal-to-noise ratio, both with and without subdivision into
age groups (see Table ). The dierences between the two
visits were not signicantly dierent for LJ, whereas there
was a signicant dierence for CB (LJ general: p = .;
CB general: p = .). The difference between the two
measurements averaged to -. ± . dB for LJ and
-. ± . dB for CB (Figure and Figure).
Table 2: Threshold values for the Liquid Jet and Cochet-Bonnet esthesiometers
Liquid Jet Cochet-Bonnet
dB mbar dB µN
Median . . . .
Mean . . .
Standard deviation . .
First quartile . .
Third quartile . . .
Figure 1: Box plots of the threshold values grouped by appointment Figure 2: Box plots of the threshold values grouped by age group
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Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
Discussion
The aim of this work was to nd out whether the Liquid Jet
aesthesiometer prototype delivers repeatable values and
correlates with the values of the Cochet-Bonnet aesthesio-
meter. In addition, we also tested a clinical application of the
prototype.
General comparison
The fluctuations in the measurements with the Liquid Jet
and the Cochet-Bonnet aesthesiometer turned out to be
similar when considering the overall subject group and when
considering the two age groups.
Table 3: Signal and noise of the two measurement methods
General Group A Group B
Standard
deviation [dB]
Ratio Standard
deviation [dB]
Ratio Standard
deviation [dB]
Ratio
Liquid Jet Signal , , , , ,
Noise , , ,
Cochet-Bonnet Signal , , , , , ,
Noise , , ,
Figure 4: Bland-Altman plot for the Liquid Jet esthesiometer
Figure 5: Bland-Altman plot for the Cochet-Bonnet esthesio meter
Comparing the two age groups, a tendency towards a
higher threshold value in the older group was observed, which
however, was not statistically signicant. This trend was only
statistically signicant in the measurements obtained with
the Cochet-Bonnet aesthesiometer. Roszkowska, et al. also
found signicant dierences between the age groups in their
analysis with the Cochet-Bonnet aesthesiometer.33 However,
this dierence was not signicant for the Liquid Jet aesthe-
siometer, probably due to the large dierence in sample size
(Roszkowska et al. eyes versus eyes). The age groups
in this subanalysis are not homogeneous, which makes a
comparison difficult. However, due to changes in corneal
sensitivity with age, it was considered important to maintain
Figure 3: Scatter plots of the measured parameters
OCL • Volume 1 • No. 3 • October 2021
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Clinical comparison of a newly developed prototype for measuring corneal sensitivity to the current gold standard • Tobias Bracher et al.
this division. In the larger study with sample size determina-
tion, which has not yet been published, this dierence was
also signicant for LJ.
With the Liquid Jet aesthesiometer, the pressure between
the stimuli is regulated by a peristaltic pump, a process which
takes a relatively long time. Even if a successful measurement
can be carried out within three to ve minutes with appro-
priate compliance of the test subjects, this time interval is
much longer than the one required with the Cochet-Bonnet
aesthesiometer. The installation of an irrigation pump would
be a possible optimisation to accelerate the build-up of the
required pressure.
Correlations
The threshold values of the Liquid Jet aesthesiometer have
a moderately signicant positive correlation with those of
the Cochet-Bonnet aesthesiometer (r = ., p < .).
This suggests that these two methods can measure similar
values.
On the other hand, OSDI and Painscore hardly correlate
with the other variables. This is possibly due to the fact that
only subjects with a low OSDI, i.e., with no dry-eye symptoms
and healthy eyes, were admitted to the study. Only the Liquid
Jet had a moderately signicant positive correlation with the
general pain sensitivity from the PSQ (r = ., p < .).
Since the Cochet-Bonnet aesthesiometer correlates with
Liquid Jet, but not with Painscore, these correlations would
have to be examined more closely with a larger sample.
According to Ruscheweyh et al., PSQ scores significantly
correlated with the assessment of perceived pain, but not
with the individual threshold values. They found no signicant
dierences in gender or age in their validation of the PSQ.9
Repeatability
When comparing sensivitiy thresholds from the first and
second visit, signicant dierences were observed with the
Cochet-Bonnet aesthesiometer (p = .). This was not the
case with the measurements performed with the Liquid Jet
prototype (p = .). These observations apply both with and
without a subdivision into the two age groups. The reasons for
the dierences between the two visits may, on the one hand,
be due to the fact that these are psychophysical measure-
ments at the limit of perception, which generates variability,
and, on the other hand, to the fact that physiological daily
dierences are, indeed, possible. There is signicant noise
in the measurements obtained using both devices. This high
level of noise leads to a very low signal-to-noise ratio for both
measurement methods. However, it cannot be conclusively
stated whether the noise has a physiological source stemming
from the fact that all test subjects had healthy eyes, or it is
due to the measurement inaccuracy of the devices.
The authors of this study believe that the repeatability
of measurements obtained using the Cochet-Bonnet aes-
thesiometer is very likely overestimated. Due to the limited
stimulus range and the uneven intensity distribution of the
stimuli, this measurement method is a lot more tolerant to
fluctuations than the innite number of intensity levels of
the prototype.
Conclusion
By controlling the temperature of the stimulus to attain a simi-
lar temperature to that of the surface of the cornea, the Liquid
Jet aesthesiometer aims to deliver a true tactile stimulus. The
measurements were found to be repeatable and correlated
with the Cochet-Bonnet aesthesiometer, which is currently
still used as the gold standard. The Liquid Jet aesthesiometer
has a signicantly larger stimulus rage, making it possible to
recognise smaller sensitivity fluctuations and to determine
the corneal sensitivity in a more repeatable manner.
The Liquid Jet aesthesiometer has a moderately sig-
nificant positive correlation with general pain perception
(r = ., p < .). This potential connection would have to
be examined more closely in the future with a larger sample.
Further studies with optimised prototypes and a larger
test sample with balanced age groups and, if necessary, test
subjects with dry-eye symptoms should be conducted in
the future.
Corresponding Author
Tobias Bracher
M.Sc., EurOptom
E-Mail:
t.bracher@gmx.ch
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