1
2
TITLE:
TEAR BREAK-UP TIME FOR TEAR FILM EVALUATION: ARE MOISTENING
SOLUTIONS INTERCHANGEABLE?
3
4
5
6
AUTHORS:
Carme Serés, MSc*
7
Lluïsa Quevedo, PhD*
8
Genís Cardona, PhD*
9
Estel·la Blanch, BSc Optom*
10
Montserrat Augé, MSc*
11
12
13
14
15
*Research Group of Centre Universitari de la Visió, Optics and Optometry Department,
Technical University of Catalonia, Spain
16
17
18
19
Corresponding Author:
Genís Cardona
20
Facultat d’Òptica i Optometria de Terrassa
21
Violinista Vellsolà, 37
22
E08222 Terrassa, Catalonia, Spain
23
24
25
E-mail address:
gcardona@oo.upc.edu, genis.cardona@gmail.com
26
Phone:
+34 93 739 8774
27
28
1
1
ABSTRACT
2
Purpose: It was the main purpose of this study to investigate the influence of the moistening
3
solution on TBUT measurements in an asymptomatic population.
4
Methods: An online survey was employed to determine the compliance of Spanish eye care
5
practitioners with the recommended normalized procedure to administer TBUT. For the
6
purpose of examining the clinical relevance of discrepancies from the recommended
7
procedure, a randomized, double-masked, bilateral study was designed in which a
8
micropipette was used to moisten fluorescein strips with a controlled volume of six different
9
solutions, commonly available in the contact lens office, and TBUT was measured in 58 non-dry
10
eye (OSDI<15) subjects (age from 19 to 32 years).
11
Results: Results from the online survey revealed that 64% of Spanish practitioners frequently
12
use (or have used) different solutions to moisten fluorescein strips during TBUT assessment.
13
Statistically significant differences in TBUT values were found between the various solutions as
14
a whole (χ2=198.384, p<0.001), as well as between all solutions when explored pair-wise (all
15
p<0.001), except for the two saline solutions.
16
Conclusions: The present findings support the relevance of selecting the appropriate solution
17
when conducting TBUT for the evaluation of the tear film. Deviations from the recommended
18
procedure may result in misdiagnosis of dry eye and unnecessary patient referral.
19
20
KEY WORDS
21
22
Dry eye; Moistening solution; Sodium fluorescein; Tear break-up time; Tear film
2
1
INTRODUCTION
2
Tear break-up time (TBUT) remains one of the most commonly employed tests to assess tear
3
film stability and for dry eye diagnosis [1, 2]. First introduced by Norn in 1969, TBUT was
4
defined as the time “interval between the last complete blink and the presentation of the first
5
appearance of a dry spot or disruption in the tear film” [2, 3]. While many variations exist, the
6
usual technique requires the instillation of sodium fluorescein into the tear film, whereupon
7
the ocular surface is observed with a slit-lamp and a combination of excitatory cobalt blue light
8
and a Wratten #12 yellow observation filter [4]. TBUT values may be influenced by the
9
amount, concentration, pH, presence of preservatives and type of fluorescein, among other
10
factors [5, 6].
11
Several attempts at controlling the volume of instilled fluorescein have been explored. Indeed,
12
pipetting 1 µl of 2% fluorescein solution was found to result in an improved repeatability of
13
TBUT measurements [7], although there remains debate regarding the increased risk of
14
microbial contamination associated with unpreserved fluorescein solutions and the need for
15
contact of the pipette with the ocular surface [8]. Similarly, the Dry Eye Test (DET; Amcon
16
Laboratories, Inc., USA) was developed to deliver the same small volume of fluorescein
17
solution by application of slightly modified impregnated strips to the superior temporal bulbar
18
conjunctiva [1]. More recently, a Modified Fluorescein Strip (MFS) test was described in which
19
the top 1 mm of a standard fluorescein strip is folded to ensure optimal volume of instilled
20
solution and improve repeatability [9].
21
It may also be noted that the method of instilling fluorescein solution may affect the cutoff
22
values and the predictive value of the test in the diagnosis of dry eye. Thus, while a cutoff of ≤
23
10 seconds is generally accepted with standard fluorescein impregnated strips [2, 10], a ≤ 5
24
seconds cutoff was proposed when microquantities of fluorescein are instilled [11]. Similarly,
25
whereas sensitivity and specificity values of 72% and 62%, respectively, are associated with a
3
1
10 seconds cutoff point [10], other authors describe a sensitivity of 94%, as compared with
2
OSDI scores, when the MFS test was employed with a cutoff value of 5 seconds [9].
3
The standards published by The Diagnostic Methodology Subcommittee of the International
4
Dry Eye WorkShop recommend TBUT to be performed with fluorescein impregnated strips
5
moistened with a single drop of 0.9% nonpreserved saline [12]. However, it is not exceptional
6
for practitioners to employ alternative solutions to moisten fluorescein strips, such as artificial
7
tears [13], or to instil diagnostic drops containing a mix of fluorescein and oxybuprocaine
8
(Fluotest®, Alcon, Spain) [14]. It may be speculated that other solutions commonly available in
9
the contact lens fitting room, such as multipurpose solutions, may be used by practitioners
10
instead of non-preserved saline for the purpose of moistening fluorescein strips during tear
11
film assessment.
12
It was the first aim of the present study to assess, through an online survey, the compliance of
13
Spanish eye care practitioners with the recommended normalized procedure to administer
14
TBUT. Once the survey responses were analysed and it was determined that practitioners
15
employ a variety of solutions for TBUT measurements, a study was designed to determine the
16
influence of the moistening solution on TBUT measurements. For this purpose, TBUT was
17
measured on a sample of non-symptomatic subjects (OSDI score < 15) by moistening
18
conventional fluorescein strips with a constant, controlled volume of six different solutions,
19
commonly available in any contact lens office.
4
1
SURVEY DESIGN AND RESULTS
2
A simple, user-friendly, anonymous online survey was developed, which could be completed in
3
less than 1 minute (see Figure 1). The survey form consisted of 2 questions in which
4
practitioners were first instructed to report on the type of solution they used to moisten
5
fluorescein strips by selecting one or several of the 5 different main solution categories they
6
were provided with, and then they were asked a simple dichotomous question devised to
7
determine whether they employed any means to control the volume of fluorescein instilled in
8
the tear film of their patients. A link to the survey site was sent by email to one hundred
9
registered optometrists randomly selected from the distribution list of the Faculty of Optics
10
and Optometry of Terrassa (Spain).
11
A total of 47 registered optometrists answered the web-based survey. Of all respondents, 64%
12
admitted using, or having used, one or several different solutions, apart from saline solution,
13
to moisten fluorescein strips during tear film assessment (multi-purpose solution, 26%;
14
artificial tears, 23%; wetting solution, 16%; others, 8%). In addition, 77% of the respondents
15
reported not employing any means to control de volume of fluorescein they instilled to the
16
ocular surface during TBUT.
5
1
METHODS
2
Participants
3
Fifty eight students of optometry (45 female) were enrolled on the second part of study. Mean
4
± SD age of participants was 21.74 ± 2.64 years (range from 19 to 32 years). All subjects had
5
good ocular health and were free of symptoms of dry eye, as evaluated with the Ocular
6
Surface Disease Index questionnaire (OSDI score < 15 [15]). Exclusion criteria were history of
7
ocular or corneal surgery or injury, current use of any ocular medication, ointment or artificial
8
tear substitutes and current or recent contact lens wear. In addition, pregnancy, diabetes and
9
any other systemic condition or use of medication known to influence tear film stability also
10
resulted in exclusion from the study.
11
All participants provided written informed consent after the nature of the study was explained
12
to them. The study was conducted in accordance with the Declaration of Helsinki tenets of
13
1975 (as revised in Tokyo in 2004) and received the approval of an Institutional Review Board
14
(Universitat Politècnica de Catalunya).
15
16
Moistening solutions
17
Six different solutions were employed for the purpose of moistening conventional 1 mg
18
fluorescein sodium sterile strips (Fluorets®, Chauvin Pharmaceuticals Ltd, Surrey, UK).
19
Solutions were selected from those commonly encountered in any optometric practice and
20
represent a sample of the types of solutions listed in the survey, including several with added
21
viscosity agents. A summary of the characteristics of the solutions employed in the study may
22
be found in Table 1.
23
6
1
Procedure
2
A randomized, double-masked, bilateral study was implemented to determine TBUT values
3
with each solution. All sessions took place at the same time of the day and consecutive
4
sessions were 1 to 3 days apart, with a minimum wash-out period of 24 hours between
5
sessions. The same experienced examiner conducted all clinical procedures, and solutions
6
were tested in a random order, under controlled and constant room temperature (20 °C ± 2 °C)
7
and humidity (40% ± 10%) conditions. TBUT was captured via video recording and an
8
independent observer, masked to the type of solution under evaluation, later determined the
9
time interval between the last complete blink and the first appearance of a dry spot.
10
For each solution, a micropipette was used to ensure that only 2 µl of solution was applied to
11
the fluorescein strip in order to deliver a controlled, constant volume to the ocular surface.
12
The strip was then lightly applied for 1 second to the superior-temporal bulbar conjunctiva, by
13
raising the upper eyelid while subjects were instructed to look inferior-nasally. Video capture
14
was repeated 3 times, with subjects blinking normally for about 20 seconds between each
15
recording. Both eyes were used for the study and, in each session, the same type of solution
16
was employed in both eyes. Fluorescein was first instilled in one eye, selected at random, and
17
following video capture, the same procedure was repeated in the contralateral eye.
18
TBUT was observed with a Topcon SL-D7 slit-lamp (Topcon España S.A., Barcelona, Spain) with
19
a cobalt blue light filter and a Wratten #12 yellow filter (Kodak, Rochester, NY, US) positioned
20
in front of the observation system. Slit-lamp magnification was set at 10X and a circular beam
21
of 10 mm in diameter was employed to illuminate the ocular surface. A slit-lamp mounted
22
video camera was used to capture TBUT and a frame by frame examination of recordings was
23
later performed by the independent observer. The median of the three measurements was
24
recorded as the TBUT value for that particular subject and solution. In addition, the difference
7
1
in TBUT between the maximum and minimum values for each subject and solution was
2
determined and considered an indicator of TBUT consistency.
3
4
Data analysis
5
Statistical analysis of the data was performed with the SPSS software 19.0 (IBM Corp., NY, US)
6
for Windows. Descriptive statistics were employed to summarize the answers to the online
7
survey. For TBUT and TBUT consistency values, data from right and left eyes was found to
8
present a strong positive correlation (Spearman rho = 0.92; p < 0.001). Besides, when
9
submitted to a Wilcoxon test for matched pairs, no statistically significant differences were
10
encountered between both eyes in either TBUT or consistency values between both eyes for
11
any of the solutions under study (all p > 0.05). Thus, data from only one eye (selected at
12
random) was used for statistical analysis. TBUT values were examined for normality with the
13
Kolmogorov-Smirnov test, revealing a non-Gaussian distribution of the data (in agreement
14
with published literature [4]). Therefore, all results are provided as median values. The
15
Friedman test was employed to analyse the significance of TBUT score differences between
16
solutions, whereupon the Wilcoxon test for related samples was used as a post-hoc test to
17
investigate pair-wise differences between solutions. A p-value of 0.05 or less was considered
18
to denote statistical significance throughout the study.
8
1
RESULTS
2
A summary of TBUT values for each of the moistening solutions is presented in Table 2.
3
Analysis with the Friedman test revealed a statistically significant difference in TBUT scores
4
between the six different solutions (χ2 = 198.384; p < 0.001) which, when submitted to a post-
5
hoc pair-wise analysis with the Wilcoxon test, disclosed statistically significant differences in
6
TBUT values between all pairs of solutions (all p < 0.001), with the exception of between S1
7
and S2 (Z = -0.875; p = 0.381). Solutions S3 and S2 were found to present the smallest (1.22
8
seconds) and largest (1.84 seconds) median differences between the maximum and minimum
9
TBUT measurements (TBUT consistency values), respectively. For comparison purposes, Table
10
2 also shows the number of patients with TBUT values under the cutoff of 5 seconds
11
recommended for small volumes of instilled fluorescein.
9
1
DISCUSSION
2
The results from the survey underline the fact that, even with the existence of published
3
protocols aiming at normalizing such common optometric procedures as TBUT assessment,
4
there is a lack of uniformity when performing this test. Indeed, although previous surveys of
5
the clinical practices of both Spanish and Australian optometrists revealed TBUT to be one of
6
the most commonly employed tests for tear film evaluation and dry eye diagnosis, the same
7
surveys disclosed a lack of agreement between the published recommendations and actual
8
clinical practice [16,17]. These studies, however, did not investigate in detail how optometrists
9
conducted each particular test.
10
Although many authors have acknowledged the influence of volume of instilled fluorescein on
11
TBUT values [1,5,7,9], and also noted the lack of consensus regarding what should be
12
considered a standard procedure to control this volume [1,5,18], to the best of our knowledge
13
no previous research had evaluated the influence of employing alternative solutions to
14
moisten fluorescein strips on TBUT measurements. Therefore, given that the online survey
15
revealed that many practitioners use different solutions for TBUT evaluation, it is important to
16
understand these effects.
17
Overall, TBUT values were comparable to those reported in the literature for non-dry eye
18
subjects and small volumes of instilled fluorescein [11], and were not inconsistent with those
19
documented by other authors when using conventional or modified strips [1]. The small
20
differences between the maximum and minimum TBUT measurements, defined as good TBUT
21
consistency, were also in agreement with previous reports in which small volumes of
22
fluorescein were instilled with modified fluorescein strips [1,9] or by pipetting 1 µl of 2%
23
fluorescein solution [7], but conflicted with other studies in which volume of fluorescein was
24
not found to influence measurement variability [5].
10
1
Statistically significant differences were uncovered upon comparing TBUT values with different
2
solutions. These findings may potentially be explained by the biophysical properties of each
3
particular solution such as different solution viscosity from the addition of viscosity agents.
4
Thus, for example, S1 and S2 are both saline solutions with similar TBUT values and TBUT
5
consistency, although S2 may be argued to be closer to the ideal recommendation for TBUT
6
evaluation (nonpreserved saline). On the other hand S3, which resulted in the longest TBUT
7
values, contains hyaluronic acid, which has been reported as a high-viscosity agent equivalent
8
to mucus glycoprotein, with the ability to adhere to epithelial cells [19]. Previous research on
9
surface residence time found that solutions containing sodium hyaluronate had a mean half-
10
life on the ocular surface of 321 seconds, significantly longer than others with hydroxypropyl
11
methyl cellulose, which is a viscosity agent for S4, or a buffered saline solution such as S1 and
12
S2 [20,21]. Other reports also disclosed that tear substitutes with sodium hyaluronate provide
13
better tear film stability, as determined by NIBUT values, than those with hydroxypropyl
14
methyl cellulose [22], and also resulted in better patient reported comfort [23]. In addition, in
15
the present study solutions with high or mid-viscosity agents also led to less variation between
16
the maximum and minimum TBUT measurements, that is, in better TBUT consistency, which
17
may also be a reflection of solution properties.
18
These findings, however, may be interpreted with caution. In effect, S6, which contains
19
hyaluronan, was found to result in the shortest TBUT, and the second worst consistency of all
20
solutions. Thus, it may be speculated that different concentrations of HA, as well as different
21
combinations of HA with other solution constituents, may lead to a different overall effect on
22
the tear film, which may be difficult to infer by the inspection of the composition of a
23
particular solution alone.
24
It must be noted, however, that albeit statistically significant differences were found, absolute
25
TBUT values differences were probably devoid of clinical significance (if defined as a change of
11
1
30% or more [5]). Besides, further research, with a sample of both dry eye and non-dry eye
2
patients, is required to investigate the influence of solution on the sensitivity and specificity of
3
TBUT measurements with the various solutions. In addition, it needs to be noted that although
4
all subjects were considered as normal based on an OSDI score < 15, some patients presented
5
TBUT values with S2 (the recommended solution) lower than the cutoff value of 5 seconds.
6
This finding, which is not unexpected, given the documented discrepancy between signs and
7
symptoms [24], raises the question of whether different results would have been obtained
8
with a study sample resulting from a different set of inclusion criteria (e.g. based on clinical
9
signs instead of symptoms). It was believed, however, that although absolute TBUT scores
10
would probably differ, the main goal of the study, which was to explore the effect of solution
11
selection TBUT values, should still be valid.
12
Finally, it is worth observing that in the present study a constant volume of solution was
13
employed. However, the findings from the online survey revealed that many practitioners do
14
not adhere to any protocol to control the amount of instilled fluorescein. In addition, it is
15
known that the size of a drop will depend on such properties of the solution as viscosity and
16
surface tension, that is, solution composition and drop size are interrelated variables. In
17
consequence, it may be relevant to explore the joint contribution of volume and solution
18
composition on TBUT values.
19
In conclusion, the present findings support the relevance of selecting the appropriate solution
20
when conducting TBUT for the evaluation of the tear film. Deviations from the recommended
21
procedure may result in misdiagnosis of dry eye and unnecessary referral of patients, with the
22
associate economic implications. In addition, communication and continuous education and
23
training efforts are required to encourage practitioners to revise and adhere to the published
24
recommendations for tear film evaluation.
12
1
REFERENCES
2
1. Korb DR, Greiner JV, Herman J. Comparison of fluorescein break-up time measurement
3
reproducibility using standard fluorescein strips versus the dry eye test (DET) method.
4
Cornea 2001; 20: 811-5.
5
6
7
8
9
10
11
12
13
14
2. Lemp MA. Report of the National Eye Institute/Industry Workshop on Clinical Trials in
Dry Eye. CLAO J 1995; 21: 221-32.
3. Lemp MA, Dohlman CH, Holly FJ. Corneal desiccation despite normal tear volume. Ann
Ophthalmol 1970; 2: 258-61.
4. Cho P, Douthwaite W. The relation between invasive and noninvasive tear break-up
time. Optom Vis Sci 1995; 72: 17-22.
5. Johnson ME, Murphy PJ. The effect of instilled fluorescein solution volume on the
values and repeatability of TBUT measurements. Cornea 2005; 24: 811-7.
6. Mengher LS, Bron AJ, Tonge SR, Gilbert DJ. Effect of fluorescein instillation on the precorneal tear film stability. Curr Eye Res 1985; 4: 9-12.
15
7. Marquardt R, Stodmeister R, Christ T. Modification of tear film break-up time test for
16
increased repeatability. In: Holly FJ, ed. The Precorneal Tear Film in Health, Disease,
17
and Contact Lens Wear. Lubbock, TX: Dry Eye Institute, 1986, pp: 57-63.
18
19
20
21
8. Rautenbach P, Wilson A, Gouws P. The reuse of ophthalmic Minims: an unacceptable
cross-infection risk? Eye (Lond) 2010; 24: 50-2.
9. Pult H, Riede-Pult BH. A new modified fluorescein strip: Its repeatability and usefulness
in tear film break-up time analysis. Cont Lens Anterior Eye 2012; 35: 35-8.
22
10. Vitali C, Moutsopoulos HM, Bombardieri S. The European Community Study Group on
23
diagnostic criteria for Sjögren’s syndrome. Sensitivity and specificity of tests for ocular
24
and oral involvement in Sjögren’s syndrome. Ann Rheum Dis 1994; 53: 637-47.
25
26
11. Abelson M, Ousler G, Nally L. Alternate reference values for tear film break-up time in
normal and dry eye populations. Adv Exp Med Biol 2002; 506 (Part B): 1121-5.
27
12. The Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop.
28
Methodologies to diagnose and monitor dry eye disease. Ocul Surf 2007; 5: 108-52.
29
13. Duran P, León A, Márquez M, Veloza C. Evaluación de la película lagrimal con métodos
30
diagnósticos invasivos vs método de diagnóstico no invasivo. Investigaciones Andina
31
2006; 8: 36-49.
32
14. Vico E, Quereda A, Benítez-del-Castillo JM, Fernández C, García-Sánchez J. A
33
comparative study of 0.15% sodium hyaluronate versus polyvinyl alcohol in the
34
treatment of dry eyes. Arch Soc Esp Oftalmol 2005; 80: 387-94.
13
1
2
3
4
5
6
15. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity
of the Ocular Surface Disease Index. Arch Ophthalmol 2000; 118: 615-21.
16. Cardona G, Serés C, Quevedo L, Augé M. Knowledge and use of tear film evaluation
tests by Spanish practitioners. Optom Vis Sci 2011; 88: 1106-11.
17. Downie LE, Keller PR, Vingrys AJ. An evidence-based analysis of Australian
optometrists’ dry eye practices. Optom Vis Sci 2013; 90: 1385-95.
7
18. Tomlinson A, Bron AJ, Korb DR, Amano S, Paugh JR, Pearce EI, Yee R, Yokoi N, Arita R,
8
Dogru M. The International Workshop on Meibomian gland dysfunction: report of the
9
diagnosis subcommittee. Invest Ophthalmol Vis Sci 2011; 52: 2006-49.
10
19. Mengher LS, Pandher KS, Bron AJ, Davey CC. Effect of sodium hyaluronate (0.1%) on
11
break-up time (NIBUT) in patients with dry eyes. Br J Ophthalmol 1986; 70: 442-7.
12
20. Snibson GR, Greaves JL, Soper ND, Tiffany JM, Wilson CG, Bron AJ. Ocular surface
13
residence times of artificial tear solutions. Cornea 1992; 11: 288-93.
14
21. Snibson GR, Greaves JL, Soper ND, Prydal JI, Wilson CG, Bron AJ. Precorneal residence
15
times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy.
16
Eye (Lond) 1990; 4: 594-602.
17
22. Prabhasawat P, Tesavibul N, Kasetsuwan N. Performance profile of sodium
18
hyaluronate in patients with lipid tear deficiency: randomised, double-blind,
19
controlled, exploratory study. Br J Ophthalmol 2007; 91: 47-50.
20
21
22
23
23. White CJ, Thomas CR, Byrne ME. Bringing comfort to the masses: a novel evaluation of
comfort agent solution properties. Cont Lens Anterior Eye 2014; 37: 81-91.
24. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and
symptoms in patients with dry eye disease. Cornea 2004; 23: 762-770.
14
1
TABLES
2
3
Table 1: Summary of the characteristics of the moistening solutions employed in the study
4
Commercial Name
Manufacturer
Main Type
Preserved
Composition
Sensitive Eyes® Plus Saline
Bausch & Lomb,
Rochester, NY, US
Isotonic,
buffered saline
solution
Boric acid, sodium borate, potassium chloride and
sodium chloride
Solución Fisiológica Cinfa
5 ml uni-dose drops
Acuaiss 0.35 ml uni-dose
eye drops
Laboratorios Cinfa,
S.A., Huarte, Spain
DISOP SA,
Alcobendas, Spain
Sterile, buffered
saline solution
Wetting drops
Polyaminopropyl
biguanide (0.00003%)
and disodium edetate
(0.025%)
Non-preserved
Multi-dose 15 ml Sensitive
EyesTM Lens Lubricant
Bausch & Lomb,
Rochester, NY, US
Opti-Free® Express® multipurpose solution
Alcon Laboratories,
Inc., Fort Worth, TX,
US
Isotonic and
buffered
solution
Aqueous,
sterile, isotonic
and buffered
solution
BiotrueTM multi-purpose
solution
Bausch & Lomb,
Rochester, NY, US
Aqueous,
sterile, buffered
and isotonic
solution
Non-preserved
Non-preserved
Polyquaternium-1
(0.001%) and
myristamidopropyl
dimethylamine
(0.0005%)
Polyaminopropyl
biguanide (0.00013%)
and polyquaternium
(0.0001%)
Sodium chloride (0.9%), boric acid, borax and
purified water
Hyaluronic acid, hidroxyethyl cellulose, sodium
chloride, sodium tetraborate, boric acid and 0.02%
disodium edetate
Boric acid, sodium borate, sodium chloride,
poloxamine, hidroxypropyl methyl cellulose, sorbic
acid (0.25%) and disodium edetate (0.1%)
Citrate, sodium chloride, boric acid, sorbitol,
aminomethylpropanol, poloxamine and edetate
disodium
Hyaluronan, sulfobetaine, poloxamine, boric acid,
sodium borate, edetate disodium and sodium
chloride
5
15
1
Table 2: TBUT values (in median and interquartile range) for the six different employed
2
moistening solutions. Median TBUT consistency was determined as the difference between the
3
maximum and minimum measurement for each particular subject and solution.
4
SOLUTION
CODE
Median
(seconds)
Interquartile
range
(seconds)
S1
S2
S3
S4
S5
S6
6.0
6.0
6.8
6.2
5.7
5.5
1.5
1.6
1.5
1.6
1.3
1.2
Friedman
test
χ2 = 198.384
p < 0.001
Wilcoxon test
All pair-wise
differences p <
0.001 except for
the difference
between S1 and
S2 (p = 0.381)
Median
TBUT
consistency
(seconds)
1.6
1.8
1.2
1.3
1.7
1.7
Number of
patients with
TBUT Values
under 5 s
6
6
0
2
8
8
5
6
7
8
S1: Sensitive Eyes® Plus Saline; S2: Solución Fisiológica Cinfa 5 ml uni-dose drops; S3: Acuaiss 0.35 ml uni-dose eye
drops; S4: Multi-dose 15 ml Sensitive EyesTM Lens Lubricant; S5: Opti-Free® Express® multi-purpose solution; S6:
BiotrueTM multi-purpose solution.
16
1
FIGURES
2
3
Figure 1: Web-based survey sent to 100 Spanish registered optometrists to assess habits while
4
conducting TBUT
5
6
17