Eur J Ophthalmol 2011 ; 21 ( 5): 538-544 DOI: 10.5301/EJO.2011.

6324

ORIGINAL ARTICLE

Efficacy of 3 different artificial tears for the treatment

of dry eye in frequent computer users and/or contact
lens users
Gil Calvo-Santos1, Cristina Borges2, Sandrina Nunes3, Jos Salgado-Borges1, Lilianne Duarte1
1
Ophthalmology Department, Centro Hospitalar de Entre o Douro e VougaUnidade de Santa Maria da Feira, Santa
Maria da Feira - Portugal
2
Biology, Universidade Fernando Pessoa, Porto - Portugal
3
Eye Sciences, AIBILI-Associao para a Investigao Biomdica e Inovao em Luz e Imagem, Coimbra - Portugal

Purpose. To compare the efficacy of 3 different artificial tears (AT) acting primarily in one of the 3 tear
film layers (Tears Again, lipidic; Opticol, aqueous; Optive, mucin) in recovering the tear film changes
in patients with dry eye symptoms due to external causes.
Methods. A total of 27 patients, with dry eye symptoms associated with extra hours of computer or
contact lenses use, were randomized to 4 treatment groups: A received Tears Again; B received Op-
tive; C received Opticol; D received no treatment (control). Patients were observed in 3 visits: day
0, day 7, and day 30. Tear break-up time (TBUT) and Schirmer tests and the Ocular Surface Disease
Index were performed. Data analysis was performed.
Results. There were no significant differences between the groups. From day 0 to day 30, there was
a decrease in the number of eyes with abnormal TBUT (not significant) and Schirmer (significant in A,
B, D; p<0.031). There was an increase in the average TBUT for all groups (significant in A, C; p<0.001)
and a decrease in the average Schirmer value in groups B, C, and D (not significant) and an increase
in group A (p=0.002). There was a decrease in the average Ocular Surface Disease Index value in all
groups (p<0.045).
Conclusions. All AT were efficient at recovering the tear film, but those acting primarily on the inter-
nal and intermediate layer led to a mild decline on lachrymal production. An association of different
kinds of AT acting on each layer can be the best treatment for corneal surface diseases affecting eye
lubrication.

Key Words. Artificial tears, Dry eye, Tear film

Accepted: January 5, 2011

INTRODUCTION evaporation is the lipid layer deficiency. Tear film consists

Dry eye syndrome is one of the most common eye diseases
worldwide. According to the National Eye Institute/Industry
workshops (1), dry eye syndrome may be caused by tear
deficiency, keratoconjunctivitis sicca, and excessive evap-
oration. About 80% of patients develop evaporative dry
eye (2-4). The most common cause of tear film excessive
of 3 layers: the inner layer, which is composed of mucin
and is stuck to the corneal and conjunctival surface; the
aqueous intermediate layer, corresponding to nearly 90%
of the tear film and which is produced by the main lacri-
mal gland and the accessory Krause and Wolfring lacrimal
glands; and an outermost lipid layer, the main function of
which is to prevent the intermediate layer to evaporate.
In a healthy subject, ocular dryness complaints are due

538 2011 Wichtig Editore - ISSN 1120-6721

Calvo-Santos et al
to ocular exogenous situations. In these cases, dry eye
is always of the evaporative type and the most common
causes include the following:
1. Decrease in blinking frequency, thus increasing the ex-
posure time (blinking, which normally occurs in a vari-
able frequency that can achieve 20 times/min, is part
of the lachrymal function, since it renews the film lay-
ers, remaining intact for 10 seconds) (5). This occurs in
those with eyestrain due to extended fixation and atten-
tion caused, for instance, by reading or by using a com-
puter (enhanced by the convergence eye positioning) or
microscope.
2. Contact lens trauma causing the lipid layer to break
down.
3. Exposure to a particularly dry and low humidity envi-
ronment (e.g., exposure to air conditioning or intense
heat).
Most artificial tears available in the market tend to preserve
the tear film, mainly acting at the aqueous layer. It has been
demonstrated that these tears, when used in a lipid layer
deficiency situation, may cause an additional increase in
the evaporation velocity (6-8). However, artificial tears con-
taining hyaluronic acid, a component of a great part of that
tear group, have shown to be effective for the treatment
of evaporative dry eye syndrome. New tears have been
launched, with a lipid composition, with the aim to restore
the tear film outer layer, thus reducing the evaporation risk.
Artificial tears acting at the innermost layer have also be-
come available, having per basis the importance of the re-
vitalization action of the corneal epithelium cells.
The goal of this study is to compare the efficacy of Tears
Again, a liposome spray, Opticol, hyaluronic acid mono-
dose eyedrops, and Optive, mucin-containing eyedrops
in bottles, in recovering the tear film of healthy subjects
with dry eye symptoms due to external causes. Each of
these 3 different artificial tears acts in one of the 3 tear film
layers (Tears Again, lipid layer; Opticol, aqueous layer;
Optive, mucous layer).
MATERIALS AND METHODS
A phase IV, open-label, observational, comparative, ran-
domized clinical study has been conducted, with the ap-
proval of the Ethics Committee of Centro Hospitalar de En-
tre o Douro e Vouga (CHEDV), as per the recommendations
of the Helsinki Declaration. The objective was to compare
2011 Wichtig Editore - ISSN 1120-6721
the efficacy of Tears Again, Opticol, and Optive in the
treatment of dry eye syndrome, in healthy individuals who
are frequent computer users and/or contact lens users.
Volunteers were selected for this study according to the
following inclusion criteria: signature on informed consent,
age ranging from 18 to 55 years, more than 4 hours of
computer work per day, and/or daily use of a disposable
contact lens. The exclusion criteria included other than
evaporative dry eye syndrome, as per the International
Classification of Dry Eye Syndrome (1); eye disease or sys-
temic disease that may affect normal eye lubrication (such
as thyroid disease, neuromuscular disease, history of re-
fractory surgery, or other eye surgery); and breastfeeding,
pregnancy, or being a woman of childbearing age using no
valid contraceptive method.
Volunteers were selected from the CHEDV administrative
staff and sequentially randomized to 1 of 4 groups:
Group A received Tears Again liposome spray
Group B received Optive eyedrops in bottles
Group C received Opticol monodose eyedrops
Group D (control group) received no product
Subjects were duly observed in 3 different periods (days 0,
7, and 30). At day 0 (D0), full clinical history data were col-
lected, eye and systemic history was recorded, and a com-
plete ophthalmology examination was performed, including
the tear break-up time (TBUT) test and the Schirmer test.
The volunteer was also provided with the Questionnaire of
Subjective ComplaintsOSDI (Ocular Surface Disease In-
dex). At days 7 (D7) and 30 (D30), both the TBUT test and
the Schirmer test were performed and the answers to the
OSDI questionnaire were provided.
The study parametersTBUT, Schirmer, and OSDIwere
analyzed and characterized at baseline (D0) and through-
out the study, based on the mean value and respective
standard deviation. In this study, parametric statistical
tests for continuous variables with normal distribution and
nonparametric statistical tests, both for the continuous
variables with no normal distribution and for the discrete
variables (nominal/ordinal), were used. Data normality and
homoscedasticity (homogeneity of variance) was previ-
ously tested. Normality of the studied variables was tested
using the Kolmogorov-Smirnov and Shapiro-Wilk normal-
ity tests and the homoscedasticity of the 4 studied groups
was tested using the Levene test.
To test statistically significant differences between groups
and/or visits, the following tests were used: parametric
tests for normal distribution variables (TBUT and Schirmer)
539
Efficacy of artificial tears for the treatment of dry eye
and nonparametric tests for no normal distribution vari-
ables (OSDI). To test statistically significant differences be-
tween groups, the following tests for independent samples
were used: the analysis of variance (ANOVA) parametric
test with Dunnett correction and the Kruskal-Wallis non-
parametric test. To test statistically significant differences
between visits, the following tests for paired samples were
used: the ANOVA parametric test for repeated measures
and/or paired t test and Friedman and/or Wilcoxon non-
parametric tests. The TBUT and Schirmer variables were
also analyzed using the chi-square test, based on the fol-
lowing cohort values: TBUT, abnormal <10 seconds, bor-
derline between 10 and 20 seconds, normal >20 seconds;
and Schirmer, abnormal <5 mm, borderline between 5 and
10 mm, normal >10 mm.
Therefore, the statistical analysis consists of variables
characterization (mean value, standard deviation, mini-
mum and maximum values); group analysis (comparison
between groups); and time analysis (comparison between
visits).
p0.050 Was considered as the significance level (the
SPSS statistical software from SPSS Inc. was used).
RESULTS
Fifty-four eyes from 27 volunteers (21 women and 6 men,
all Caucasian), aged between 24 and 53 years (mean age
36.449.17 years), were enrolled. Seven volunteers (14
540 2011 Wichtig Editore - ISSN 1120-6721
Fig. 1 - Patients randomiza-
tion (A received Tears Again,
B received Optive, C received
Opticol and D received no
product).
eyes) were assigned to groups A, B, and D, and only 6
volunteers due to one lost to follow-up after inclusion (12
eyes) to group C (Fig. 1). All volunteers completed the 3
study visits, at D0, D7, and D30. All volunteers are com-
puter users, spending from 4 to 9 hours in front of a com-
puter (mean time 6.391.64). Only 3 volunteers were wear-
ing contact lenses.
Descriptive analysis
Group characterization throughout the 3 visitsD0, D7,
and D30is shown in Table I and in Figure 2. No baseline
statistically significant difference was observed between
groups (p> 0.05).
Inferential analysis
Differences between groups. No statistically significant
differences between groups were observed, in any of the
visits. There were no differences in parameters and test re-
sults at baseline between contact lens users/nonusers, so
they were considered equally for the study analysis.
Differences between visits. TBUT variableAt D0, 22 eyes
had TBUT test abnormal values (9 eyes in group A, 4 in
groups B and D, and 5 in group C). At D30, a decrease in
the number of eyes showing TBUT test abnormal values
has been observed, with 7 eyes showing abnormal values
(1 eye in groups A and C, 2 in group B, and 3 in group D).
Calvo-Santos et al
Error Bars show Mean 1.0 SD
Value
Bars show Means
Error Bars show Mean 1.0 SD
Value
Bars show Means
Error Bars show Mean 1.0 SD
Value
Bars show Means
Fig. 2 - Mean value and standard deviation for TBUT, Schirmer and
OSDI throughout study (day 0, day 7 and day 30).
Although the number of eyes showing TBUT test abnormal
values has decreased from D0 to D30, across the 4 groups,
this improvement was not statistically significant. However,
considering the TBUT value, a statistically significant in-
crease in the mean value, in groups A and C (p<0.001),
throughout the study (i.e., considering the 3 visits), was
observed (Tab. II).
Schirmer variableAt D0, 6 eyes showed abnormal
Schirmer test values (2 eyes in every group: A, B, and C).
At D30, a reduction in the number of eyes showing abnor-
mal Schirmer test values has been observed, with 3 eyes
showing abnormal values (2 eyes in group B and 1 eye
2011 Wichtig Editore - ISSN 1120-6721
in group C). The decrease in the number of eyes show-
ing abnormal Schirmer test values and the corresponding
increase in the number of eyes showing normal Schirmer
test values is statistically significant in groups A, B, and
C (Tab. III). Considering the Schirmer value, a statistically
significant increase in the mean value has been observed
in group A (p=0.003) throughout the study (i.e., considering
the 3 visits) (Tab. II).
OSDI variableA statistically significant decrease in OSDI
mean value has been observed across all groups, through-
out the study; A (p=0.001), B (p=0.020), C (p=0.045), and D
(p <0.001) (i.e., considering the 3 visits) (Tab. IV).
DISCUSSION
No statistically significant differences were found across
the 4 groups, in terms of TBUT, Schirmer, and OSDI vari-
ables. From D0 to D30, a decrease in the number of eyes
showing abnormal TBUT values (although this decrease
has not been statistically significant) and Schirmer values
(although this decrease has been statistically significant in
groups A [Tears Again], B [Optive], and D [control], [p<
0.031]) has been observed in all 4 groups. It could also be
observed that:
1. There was an increase in the mean TBUT value, across
the 4 groups, which was statistically significant in groups
A (Tears Again) and C (Opticol) (p< 0.001). As all volun-
teers are healthy and their dry eye complaints are mainly
of the evaporative type, an early tear film break with an
abnormal TBUT test value is expected. Both group A
(Tears Again) and group C (Opticol) volunteers showed
a better TBUT recovery, which is consistent with its etio-
pathogenesis. By recovering the outermost layer integ-
rity (Tears Again) and contributing to the aqueous in-
termediate layer preservation (Opticol), evaporative dry
eye syndrome immediate effects are reduced.
2. T
 here was a decrease in the Schirmer test mean value
in groups B (Optive), C (Opticol), and D (control) (not
statistically significant) and an increase in the Schirmer
test mean value in group A (Tears Again) (p=0.002). Tear
secretory mechanism is associated to the corneal sur-
face sensors. In healthy volunteers, where this mecha-
nism is competent, a counter-regulation response with
a tear production reduction is perceived in those tear
groups acting in the innermost layers of the tear film,
541
Efficacy of artificial tears for the treatment of dry eye

TABLE I - SAMPLE DESCRIPTIVE ANALYSIS

Group A Group B Group C Group D

D0
TBUT
Average 9.21 11.79 9.33 12.79
SD 3.77 3.38 2.42 6.28
Min 4.00 7.00 5.00 6.00
Max 16.00 19.00 13.00 25.00
Schirmer
Average 16.21 16.29 20.33 20.57
SD 8.57 11.73 9.37 9.07
Min 1.00 1.00 7.00 6.00
Max 35.00 35.00 35.00 35.00
OSDI
Average 20.89 10.88 16.23 13.66
SD 25.08 10.90 8.89 11.35
Min 0.00 .00 .00 .00
Max 62.50 31.25 25.00 31.25
D7
TBUT
Average 11.29 13.21 14.25 14.21
SD 3.02 3.38 3.52 6.12
Min 7.00 7.00 7.00 7.00
Max 16.00 17.00 19.00 27.00
Schirmer
Average 13.14 15.21 16.00 21.07
SD 7.21 8.98 5.41 10.09
Min 3.00 1.00 5.00 4.00
Max 32.00 29.00 25.00 35.00
OSDI
Average 11.11 9.52 10.04 6.84
SD 15.29 11.55 9.80 7.10
Min 0.00 0.00 0.00 0.00
Max 43.75 31.25 22.92 20.83
D30
TBUT
Average 14.50 14.14 15.92 14.57
SD 3.59 4.74 4.14 5.46
Mn 8.00 8.00 8.00 8.00
Max 20.00 22.00 21.00 25.00
Schirmer
Average 17.79 14.93 17.17 18.64
SD 8.15 9.33 9.38 8.11
Min 5.00 2.00 4.00 5.00
Max 35.00 30.00 35.00 35.00
OSDI
Average 7.79 4.76 9.25 5.65
SD 14.45 5.51 10.09 5.86
Min 0.00 0.00 0.00 0.00
Max 41.67 16.67 27.08 14.58

OSDI = Ocular Surface Disease Index; TBUT = tear break-up time.

542 2011 Wichtig Editore - ISSN 1120-6721

Calvo-Santos et al

TABLE II - ANALYSIS OF VARIANCE PARAMETRIC TEST FOR REPEATED MEASURES

Variable Group

A B C D

TBUT 0.000 a
0.196 0.000 a
0.161

Schirmer 0.003 a
0.763 0.222 0.533

TBUT = tear break-up time.

a
Significant.

TABLE III - SHIRMER VARIABLE CONTINGENCY TABLE

Group D30: Schirmer Total p

Abnormal Borderline Normal

A: D0: Schirmer

Abnormal 0 2 0 2 0.001a

Normal 0 1 11 12

Total 0 3 11 14

B: D0: Schirmer

Abnormal 2 0 0 2 0.006a

Borderline 0 2 1 3

Normal 0 2 7 9

Total 2 4 8 14

C: D0: Schirmer

Borderline 0 1 1 2 0.267

Normal 1 0 9 10

Total 1 1 10 12

D: D0: Schirmer

Borderline 0 2 1 3 0.031a

Normal 0 1 10 11

Total 0 3 11 14

a
Significant.

TABLE IV - FRIEDMAN NONPARAMETRIC TEST FOR OSDI VARIABLE

Variable Group

A B C D

OSDI 0.001a 0.020a 0.045a 0.000a

OSDI = Ocular Surface Disease Index.

a
Significant.

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Efficacy of artificial tears for the treatment of dry eye
restoring them. The idea that Tears Again solely acts
superficially, in the outermost layer of the tear film, is,
therefore, strengthened.
3. There was a statistically significant decrease in OSDI
mean value across the 4 groups (p<0.045). Subjective
complaints, which are disturbing in general, lead the
patient with dry eye syndrome to seek medical advice.
Symptom improvement was seen in all subjects through-
out the study.
4. The control group also achieved positive results through-
out the study. As participants were aware of this study,
we believe these findings are due to the fact that they
are more prone to situations that exacerbate symptoms
(e.g., extended, uninterrupted time of computer fixa-
tion). Either consciously or unconsciously, they some-
how changed their behavior or were able, through nor-
mal mechanisms, to prevent higher evaporation and the
resulting complaints.
All artificial tears were effective in recovering the tear film;
however, those primarily acting both in the inner and in-
termediate layers led to a mild decrease in tear produc-
tion, possibly through a counter-regulation mechanism.
Therefore, the idea of discouraging the excessive use of
artificial tears in subjects with a normal tear film dynamic
is strengthened (9).
REFERENCES
1. Lemp MA. Report of the National Eye Institute/Industry
Workshop on clinical trials in dry eyes. CLAO J 1995; 21:
221-32.
2. Heiligenhaus A, Koch JM, Kruse FE, Schwarz C, Waubke
TN. [Diagnosis and differentiation of dry eye disorders].
Der Ophthalmologe 1995; 92: 6-11.
3. Heiligenhaus A, Koch JM, Kemper D, Kruse FE, Waubke
TN, Heiligenhaus A. [Therapy of dry eye disorders]. Klin
Monatsbl Augenheilkd 1994; 204: 162-8.
4. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes
and discomfort in patients with meibomian gland dysfunc-
tion. Arch Ophthalmol 1995; 113: 1266-70.
544 2011 Wichtig Editore - ISSN 1120-6721
Subjects exposed to environmentally aggressive situa-
tions, such as video monitors or contact lens extended
use, develop evaporative dry eye disease with early tear
film lipid layer break; consequently, this layer, in these
subjects, should be reinforced. However, this deficiency
is not limited to the outermost layer, since a change in
this layer leads to a disruption of the deepest layers;
therefore, restoring the innermost layers is also impor-
tant. A combination of the different types of artificial
tears, acting in each of the tear film layers, will be the
best treatment approach for corneal surface diseases
affecting eye lubrication.
The authors report no proprietary interest or financial support.
Address for correspondence:
Gil Calvo-Santos, MD
Centro Hospitalar de Entre o Douro e Vouga
Unidade de Santa Maria da Feira
Rua Dr. Cndido de Pinho
4520-211 Santa Maria da Feira
Portugal
gilfilipesantos@gmail.com
5. Carney LG, Hill RM. The nature of normal blink-
ing patterns. Acta Ophthalmol 1982; 60: 427-33. 6.
Mathers W. Evaporation from the ocular surface. Exp
Eye Res 2004; 78: 389-94.
7. Toda I, Shinozaki N, Tsubota K. Hydroxypropyl methyl-
cellulose for the treatment of severe dry eye associated
with Sjgrens syndrome. Cornea 1996; 15: 120-8.
8. Tomlinson A, Trees GR. Effect of preservatives in artifi-
cial tear solutions on tear film evaporation. Ophthalmic
Physiol Opt 1991; 11: 48-52.
9. DEWS Definition and Classification. The definition and
classification of dry eye disease: report of the Definition
and Classification Subcommittee of the International
Dry Eye Workshop (2007). Ocul Surf 2007; 5: 75-92.
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