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Objective optical assessment of tear-film
quality dynamics in normal and mildly
symptomatic dry eyes
Antonio Benito, PhD, Guillermo M. P
erez, PhD, Sandra Mirabet, MD, Meritxell Vilaseca, PhD,
Jaume Pujol, PhD, Jos
e M. Marín, MD, PhD, Pablo Artal, PhD
PURPOSE: To evaluate and compare the tear-film dynamics in normal eyes and in eyes with mild
dry-eye symptoms using a new noninvasive optical method based on a double-pass instrument.
SETTING: Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
DESIGN: Evaluation of diagnostic test or technology.
METHODS: Dynamic recording of double-pass retinal images during unforced tear-film breakup
was performed in eyes with mild dry-eye symptoms (study group) and in an asymptomatic control
group. Series of consecutive retinal images were recorded every 0.5 seconds while the patient
avoided blinking. Measurements were performed under low-light conditions to naturally increase
pupil diameter and maximize the method’s sensitivity. Additional clinical tests were performed
for comparison and included tear breakup time (TBUT), Schirmer I tests, and a normalized ques-
tionnaire (McMonnies). From the retinal images, a quality metric, the intensity distribution index,
was calculated. An objective TBUT value was estimated in each eye when the intensity distribution
index surpassed a defined threshold value compared with the initial baseline.
RESULTS: The study group comprised 20 eyes and the control group, 18 eyes. Symptomatic dry
eyes had a typical exponential increase in the intensity distribution index with time. The objective
TBUT values in the study group were comparable to the clinical TBUT estimates.
CONCLUSIONS: The new objective optical method to evaluate the quality and stability of the tear film
was sensitive in detecting mild symptoms of dry eye and differentiating from normal cases. The pro-
cedure may allow early detection and follow-up of patients’ tear film–related complaints.
Financial Disclosure: No author has a financial or proprietary interest in any material or method
mentioned.
J Cataract Refract Surg 2011; 37:1481–1487 Q2011 ASCRS and ESCRS
The optical quality of the retinal image is the result of
light passing through the ocular structures. The tear
film is the first medium that modifies the optical
path of the light that finally reaches the retina. The im-
pact of the tear film on the quality of the retinal image
depends greatly on the homogeneity of the tear pelli-
cle. The loss of homogeneity in the tear film modifies
its thickness locally,
1
and because of the refractive
index variation across the air–tear interface, this may
cause significant differences in the optical path of the
eye's wavefront.
2,3
Moreover, small local changes in
the tear film increase the light scattered in the anterior
surface of the cornea, affecting overall ocular scatter.
4,5
In some eyes with dysfunctional tear syndrome, the
epithelial opacities associated with dry eyes also affect
the scattered light.
6
The changes in ocular aberrations
and scatter degrade the retinal image quality. The in-
fluence of the tear film on the retinal image might be
especially important in eyes with pathology, such as
dry eye. In these eyes, the homogeneity of the tear
film and its temporal stability may be greatly compro-
mised by the severity of the disease.
7
The quality of the tear film may have a significant
impact on the optical quality of the retinal image.
Thus, an indirect approach can be used to quantify
tear-film quality based on dynamic analysis of retinal
images. Indirect approaches are, in fact, traditional.
Rieger
8
first evaluated the severity of diagnosed dry
eyes by quantifying visual acuity. This was followed
by other studies that analyzed visual acuity
9
or
Q2011 ASCRS and ESCRS
Published by Elsevier Inc.
0886-3350/$ - see front matter 1481
doi:10.1016/j.jcrs.2011.03.036
ARTICLE
contrast sensitivity,
10
alone or in combination with
other subjective measures such as glare disability.
11
These studies focused on the subjective evaluation of
the changes in visual performance that correlated
with the severity of different dry-eye conditions. Other
studies analyzed objective parameters related to reti-
nal image quality and affected by fluctuations in the
tear film. Most studies evaluated the changes in cor-
neal
12
or ocular
13,14
aberrations between blinks using
corneal topographers or wavefront sensors. However,
tear-film deterioration also affects intraocular scatter.
The images of Hartmann-Shack wavefront sensors
usually show a decrease in the contrast of the spots
when measuring dry eyes.
5
This is produced by the in-
crease in light scattering caused by the loss of homoge-
neity in the tear film.
4
Because the computation of the
wavefront aberrations from Hartmann-Shack images
does not take this effect into account, the isolated char-
acterization of the ocular aberration does not take into
account ocular scattering as a sign of loss of homoge-
neity of the tear film.
An alternative and complementary objective tech-
nique is the analysis of double-pass retinal images.
The double-pass technique has been widely used to
measure the eye's optical quality in the laboratory
15–17
and in clinical applications.
18,19
The interest in this
approach stems from the fact that double-pass images
are affected by both ocular aberrations and scattering.
20
In this study, we propose the use of dynamic analy-
sis of double-pass retinal images as an indirect
indicator of the relative quality of the tear film in 2
groups of patients, one with dry eye and the other
with no symptoms of dry eye.
PATIENTS AND METHODS
Patients
Patients with dry-eye symptoms were recruited at Hospi-
tal Universitario Virgen de la Arrixaca, Murcia, Spain. Ac-
cording to the tenets of the Declaration of Helsinki, all
patients signed an informed consent form after receiving
an explanation of the nature and possible consequences of
the study. The Hospital Virgen de la Arrixaca ethics commit-
tee approved the study protocol.
Patient selection was made according to the score on the
McMonnies dry-eye questionnaire.
21
Tear-film quality was
evaluated by measuring the tear breakup time (TBUT) with
a slitlamp and by performing a Schirmer I test. The study
group comprised patients with mildly symptomatic dry
eye and a McMonnies test score between 10 and 20. The con-
trol group comprised patients with known good tear-film
quality and a McMonnies test score well below 10.
The exclusion criteria in both groups were a history of
ocular surgery known to affect the tear film (eg, refractive
surgery), diagnosed conjunctival allergy, or under treatment
for dry eye while enrolled in the study.
Dynamic Retinal Imaging
The double-pass retinal images were recorded using the
Optical Quality Analysis System II (Visiometrics S.L.) with
purpose-developed analysis software. The double-pass in-
strument is based on unequal pupil configuration,
22
with
an entrance pupil diameter of 2.0 mm and an exit pupil of
variable diameter. In this study, the exit pupil diameter
was set to 7.0 mm. Figure 1 shows a schematic representation
of the double-pass instrument. An infrared diode laser is col-
limated and, after passing the entrance aperture, enters the
eye. After reflection in the retina and a double pass through
the ocular media, the light is reflected in a beam splitter,
passes the exit aperture, and is recorded by a charge-coupled
device camera. In all cases, the double-pass images were
acquired at best focus, corrected internally in the instrument
by an optometer that ranged from 8.00 diopters (D) to
C6.00 D. The patient's astigmatism was also corrected using
Figure 1. Schematic of the double-pass method. An additional lens,
hidden behind P2 in the illustration, forms the double-pass images
on the camera (CCD Zcharge-couple device camera; CL Zcollimat-
ing lens; DP Zdouble pass; IR Zinfrared; P1 Zentrance aperture;
P2 Zexit aperture).
Submitted: October 19, 2010.
Final revision submitted: March 7, 2011.
Accepted: March 21, 2011.
From Laboratorio de
Optica (Benito, P
erez, Artal), Universidad de
Murcia, Murcia, Hospital Universitario Virgen de la Arrixaca (Mar
ın,
Mirabet), Murcia, and CD6, Universidad Polit
ecnica de Catalu~
na (Vi-
laseca, Pujol), Tarrasa, Barcelona, Spain.
Additional financial disclosures: Dr. Pujol is an investor in
Visiometrics SL, the manufacturer of the Optical Quality Analysis
System instrument, and Dr. Artal holds patents on parts of the tech-
nology used in this study.
Supported by the Ministerio de Educaci
on y Ciencia, Spain (grants
FIS2007-64765, FIS2010-149260 and Consolider-Ingenio 2010,
CSD2007-00033), and Fundaci
on S
eneca (grant 04524/GERM/
06), Murcia, Spain.
Presented in part at the annual meeting of the Association for
Research in Vision and Ophthalmology, Fort Lauderdale, Florida,
USA, May 2010.
Corresponding author: Pablo Artal, PhD, Laboratorio de Optica,
Instituto Universitario de Investigaci
on en
Optica y Nanof
ısica
(IUiOyN), Universidad de Murcia, Campus de Espinardo (Edificio
34), 30100 Murcia, Spain. E-mail: pablo@um.es.
1482 OPTICAL ANALYSIS OF TEAR-FILM QUALITY
J CATARACT REFRACT SURG - VOL 37, AUGUST 2011
the appropriate cylindrical lens on a holder placed in front of
the eye. The software of the instrument was modified to al-
low recording of temporal sequences of double-pass images
while the patient fixated on a distant target. In each eye and
during each experimental session, sequences of double-pass
images were recorded every 0.5 seconds. The continuous re-
cording group lasted 20 seconds (corresponding to 40 dou-
ble-pass images) in the study group and 40 seconds (80
double-pass images) in the control group.
Although images were recorded with a 7.0 mm exit aper-
ture, not all eyes reached a natural pupil size of 7.0 mm or
larger; thus, double-pass images were recorded for different
pupil sizes, which affected the energy distribution in the re-
corded double-pass images. Before the measurements
started, patients were trained to blink freely until the regis-
tration of the double-pass images began. They were then
asked to blink twice and to not blink again to the extent pos-
sible, even if they felt uncomfortable. When 1 series of dou-
ble-pass images was completed, at least 2 minutes passed
before a new series of images was recorded. This was to pre-
vent an abnormally increased amount of tear film caused by
the itchy sensation commonly reported during the double-
pass registration; the sensation is secondary to tear-film
breakage. For each patient, between 2 to 4 series of double-
pass images were recorded. Only well-recorded double-
pass images taken between blinks were analyzed.
From each double-pass image, an image quality metric,
the intensity distribution index, was calculated. First, R1
was calculated; this is the ratio between the light recorded in-
side an annular area between 12 minutes and 20 minutes of
arc and the light recorded at the closer surroundings of the
central peak (a circular area with a radius of 1 minute of
arc). As this value increases, more light is scattered in the
outer part than in the center. Next, R2 was calculated; this
is the ratio between the intensity recorded in the central re-
gion (1 minute of arc) in the actual image and the mean value
computed for the 3 initial images of the corresponding series.
This value provides an indication of the overall degradation
of image quality.
The intensity distribution index was obtained by direct
multiplication of the 2 ratio parameters (intensity distribu-
tion index ZR1 R2). This represents an index of the
degradation in the retinal image considering small angles
(1 minute) and small eccentric areas (up to 20 minutes).
The intensity distribution index can be expressed by
IDI ZR1R2ZIð120
;200Þimage
Ið00
;10Þimage
Ið00
;10Þimage
Ið00
;10Þ1st imagesZIð120
;200Þimage
Ið00
;10Þ1st images
where IDI is the intensity distribution index and Iis the
intensity in the appropriate area of the double-pass image.
Finally, the intensity distribution index was normalized
again to the first value of the series by subtracting the initial
intensity distribution index value from the first image in the
series. In every case, the initial intensity distribution index
value would be zero. This would allow comparison between
patients by eliminating the effect of different uncontrolled,
although mainly static, factors (eg, different pupil size, reti-
nal scatter, ocular aberrations).
When the tear film is in good condition, the normalized in-
tensity distribution index would remain nearly stable
around the initial value, showing only small changes with
time. The symptomatic dry eyes commonly would present
a similar initial behavior, followed by an increase in the
intensity distribution index value; the increase would be
related to tear-film breakage.
From the temporal series of double-pass retinal images,
an objective TBUT was estimated as the elapsed time from
the beginning of the series to the moment the normalized
intensity distribution index, fitted to an exponential
ðyZy0þabxÞ, reached a predefined threshold. The thresh-
old value of 1 was obtained from the average normalized in-
tensity distribution index found in eyes with normal tear film
(see below). From the fitting data ðy0;a;bÞ, the objective
TBUT was directly estimated for each series of double-passim-
ages. For each double-pass image series recorded in every eye,
the objective TBUT was obtained when the fitting was possi-
ble; this value was compared with the standard clinical TBUT.
To interfere as little as possible with the natural dynamics
of the patients' tear film, measurements were performed in
the following order: McMonnies test, double-pass retinal im-
age measurements, Schirmer I test, and, after approximately
10 minutes, TBUT. The double-pass measurements were
taken after the patient was adapted to a dimly illuminated
room with the purpose of obtaining the largest possible
natural pupil.
RESULTS
The study group (mildly symptomatic dry eyes) com-
prised 20 eyes of 20 women with a mean age of 47.9
years G8.3 (SD). The control group (asymptomatic
eyes) comprised 18 eyes of 4 men and 14 women
with a mean age of 29.9 G7.5 years. Table 1 shows
the results for the tear-film tests by group.
Figure 2 shows an example of the temporal evolu-
tion of the double-pass images in 1 symptomatic
dry-eye patient and the corresponding intensity distri-
bution index values. In this case, the double-pass
images degraded significantly after approximately 10
seconds.
Figure 3 shows the results of the intensity distribu-
tion index as a function of time for all eyes in the con-
trol group. The threshold of normal tear film quality
was 1. This value was used to estimate the objective
TBUT, as described in the Methods section. The thresh-
old intensity distribution index of 1 was determined as
the average (0.45) plus twice the standard deviation
(SD) of the dispersion (G0.25) in the control group. Ev-
ery eye in the control group had intensity distribution
index values below this threshold (1), even in cases in
Table 1. Mean test results.
Test
Mean GSD
Study Group Control Group
McMonnies 15.8 G3.6 4.1 G2.8
Schirmer I (mm) 13.1 G5.7 19.3 G5.2
TBUT (s) 6.2 G2.8 14.1 G2.4
TBUTZtear breakup time
1483OPTICAL ANALYSIS OF TEAR-FILM QUALITY
J CATARACT REFRACT SURG - VOL 37, AUGUST 2011
which the recording lasted for more than 30 seconds.
However, in the study group, there was a systematic
increase in intensity distribution index over time that
could be modeled with an exponential function. (See
case with solid symbols in Figure 3). In the patient
with significantly degraded double-pass images after
approximately 10 seconds, the objective TBUT was
5.7 seconds, obtained as the time when the fitted expo-
nential (gray line) to the intensity distribution index
values reached the threshold value of 1 (black line).
The main purpose of Figure 3 is to show how the
threshold value of 1 was defined. The TBUT in the con-
trol group was approximately 14 seconds (Table 1).
Because not all series of double-pass images showed
the same temporal behavior, several were recorded to
obtain an average objective TBUT value in each eye.
Figure 4 shows the exponential fitting to intensity dis-
tribution index values versus time for each eye in the
study group. The regression factor (r
2
) was 0.8 or high-
er in most eyes in the study group.
In the study group, the mean clinical TBUT value
was 6.2 G2.8 seconds, which was in good agreement
with the mean objective TBUT value of 7.1 G2.7 sec-
onds. Figure 5 compares the clinical TBUT value and
the objective TBUT value. Because of the defined
threshold value, the objective TBUT was obtained in
few eyes in the control group. The correlation between
the clinical TBUT and the objective TBUT was modest
(r
2
Z0.41).
DISCUSSION
Because of the dynamic nature of the tear film, the re-
sults were variable when comparing different patients
Figure 2. A series of double-pass images from the right eye of a symptomatic dry-eye patient. A series of 40 consecutive images was recorded
every 0.5 seconds. When the system started image acquisition, the patient was told to blink twice and then keep the eyes open. The blank images
correspond to those blinks. The numbers on each image indicate the time (right) and intensity distribution index value.
Figure 3. Normalized intensity distribution index values obtained
from double-pass image series in 18 eyes with good tear film (open
circles) and 1 symptomatic dry eye (solid circles). In the control
eyes, the intensity distribution index was nearly constant, without
surpassing the threshold (black line). In study eyes, the intensity dis-
tribution index values tended to increase with time exponentially.
The objective TBUT parameter is defined as the time that the inten-
sity distribution index value is higher than the threshold (1). See inset
for details of a shorter time interval.
Figure 4. Example of the exponential fitting of the intensity distribu-
tion index results for all symptomatic dry eyes. The individual objec-
tive TBUT were estimated for each eye from the crossing of the
exponential fitting and the threshold horizontal line (black line).
1484 OPTICAL ANALYSIS OF TEAR-FILM QUALITY
J CATARACT REFRACT SURG - VOL 37, AUGUST 2011
and different series of double-pass images from the
same patient. This can be partially explained by the
fact that dry eye is a multifactorial disease.
23,24
The im-
pact of the disease on the homogeneity of the tear film
is variable, and the correlation between symptoms and
signs in dry-eye patients is still under investiga-
tion.
25,26
In particular, dry eyes might affect the optical
quality of the retinal image as a result of several differ-
ent factors. For example, an uneven optical surface
would cause local differences in the wavefront, or
epithelial opacities in more severe cases could produce
even more scattered light.
6
The area of the tear film that we evaluated was lim-
ited to that projected to the pupil area (in most cases,
around a 7.0 mm diameter central portion of the cor-
nea). As a consequence, the method would not detect
quality degradation if the tear inhomogeneities were
located in peripheral areas. However, this could help
discriminate between different types of dry-eye syn-
dromes by determining whether they affect the area
of the cornea with a direct effect on the retinal image.
Our procedure captured information on the portion
of the tear film with a direct impact on foveal vision.
The asymmetric configuration of pupils in the system
(ie, a small entrance and a larger exit pupil) would
cause random noise in the measured parameters.
Depending on the area covered by the entrance pupil,
the retinal image could be degraded differently. This
effect was reduced somewhat by the normalization
to the first recorded images. In addition, the protocol
for double-pass image collection forces the entrance
beam to be nearly centered over the eye’s pupil.
Near-infrared light is used in the double-pass
instrument, which increases patient comfort. How-
ever, the retinal image in infrared is affected by retinal
scatter, and this could produce artificially elevated in-
tensity distribution index values compared with mea-
surements with visible light.
27
However, this is not
relevant to this study because we considered only dy-
namic variations that were normalized to first images
and the effect of retinal scatter impact would be nearly
constant over time. There are some differences
between the use of wavefront sensors and the dou-
ble-pass method to evaluate tear-film quality. This
results from the different type of measurements, aber-
ration only in wavefront-sensors versus aberrations
and scatter in double-pass.
20
Dry eye is a common, yet frequently under-recog-
nized clinical condition whose etiology and manage-
ment challenge clinicians and researchers alike.
Although there are many methods to evaluate dry-
eye symptoms, there is a lack of successful, truly
noninvasive approaches in clinical practice. Different
optical-based methods have been proposed for testing
the quality of the tear film. Some studies characterize
the tear-film meniscus to estimate tear-film quality by
applying optical coherence tomography techniques.
28
Dubra et al.
29
propose a different approach based on
the interferometric analysis of tear-film homogeneity
that could be translated into a wavefront aberration
map. Other studies explore the use of the Hartmann-
Shack wavefront sensor
30
to diagnose dry-eye
syndrome by analyzing the changes in the aberrations
produced by a distorted tear film
5
or by measuring
the differences between the modal and zonal maps
obtained from Hartmann-Shack measurements.
31
The optical procedure we propose was designed to
provide a straightforward and clinically simple esti-
mation of the tear-film quality based on the dynamic
recording and analysis of double-pass images. An
image-quality parameter, the intensity distribution in-
dex, was defined as an indicator of tear-film quality
and stability. When the double-pass image is
degraded as a result of tear-film breakage and subse-
quent increases in ocular scattering and aberrations,
the intensity distribution index parameter also
increases. The relative nature of the procedure ensures
that other factors affecting the retinal image in a more
stable manner would not affect this indirect estimation
of tear-film quality. This renders the approach more
robust and relatively independent of common sources
of errors, such as uncorrected refractive errors, cataract
opacities, or elevated aberrations.
We have proposed and evaluated a new objective
optical method for the indirect evaluation of the qual-
ity of the tear film. It is based on temporal analysis of
double-pass retinal images of a point source. From
these measurements, we introduced an objective
Figure 5. Comparison between the clinical TBUT and the corre-
sponding objective TBUT. For every symptomatic dry eye (black solid
symbols), the SDs of the objective TBUTs estimated from several dou-
ble-pass series are shown an error bars. White symbols correspond
to control eyes (TBUT Ztear breakup time).
1485OPTICAL ANALYSIS OF TEAR-FILM QUALITY
J CATARACT REFRACT SURG - VOL 37, AUGUST 2011
parameter conceptually similar to the clinical TBUT.
This objective TBUT value is set when an image qual-
ity index, calculated for each image, surpasses
a defined threshold value compared with the initial
baseline value. To obtain a good correlation between
the objective TBUT and the clinical TBUT in these pa-
tients, a lower threshold value would be required.
However, our main intention was to set a value to
better discriminate between symptomatic eyes and
asymptomatic eyes. Therefore, a larger value is more
appropriate toward that end.
The modest correlation between the clinical TBUT
and the objective TBUT was expected because of the
significant differences between the procedures. The
TBUT is an invasive method in which some fluorescein
is put into the eye. Then, the observer counts the sec-
onds until the tear film, in green under the blue light
of the slitlamp, shows the typical black spaces, corre-
sponding to the corneal areas uncovered by the tear
film. In contrast, the objective TBUT is a fully noninva-
sive optical parameter.
Our procedure was sensitive in detecting mild
symptoms of dry eye and differentiating dry-eye cases
and normal cases. This promising approach may allow
early detection and follow-up of tear film–related pa-
tient complaints.
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