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Assessment of condition-induced changes on the ocular surface using novel methods to assess the tear film dynamics and the lipid layer

Open AccessPublished:December 26, 2022DOI:https://doi.org/10.1016/j.clae.2022.101799

      Abstract

      Objectives

      To assess the effects of different condition-induced changes on current and novel ocular surface metrics.

      Methods

      Eighty-four healthy volunteers (22.4 ± 2.6 years) participated in this study. The ocular surface and tear film response to (1) computer use, (2) contact lens insertion and (3) tear film instillation during computer use with contact lenses were assessed. Current metrics included the ocular surface disease (OSDI) questionnaire, 5-item dry eye questionnaire (DEQ-5), bulbar redness, tear meniscus height (TMH) and non-invasive keratograph break-up time (NIKBUT). Novel metrics included the lipid layer thickness obtained from the intensity of the reflected Placido disk and the speed of tear film particles post-blink.

      Results

      Higher dry eye symptoms, TMH and bulbar redness, and lower values in metrics related to the intensity of the Placido disk pattern and to particle speed were found after the computer reading task (p < 0.036). When a contact lens was fitted, lower TMH, NIKBUT and particle speed metrics were obtained (p < 0.044). Mixed ANOVA revealed that artificial tears significantly ameliorated the effect of computer reading on OSDI, DEQ-5, NIKBUT, metrics related to the intensity of the Placido disk pattern and metrics related to particle speed (p < 0.033).

      Conclusions

      Computer use and contact lens wear worsened dry eye signs and symptoms, but artificial tears ameliorated this effect. Newly developed methods can serve as a tool to detect changes in the tear film triggered by different ocular surface-disturbing conditions.

      Keywords

      1. Introduction

      Dry eye disease was defined in 2017 by the Tear Film and Ocular Surface Society in the Dry Eye Workshop II (TFOS DEWS II) as a multifactorial disease characterised by the loss of homeostasis in the tear film [
      • Wolffsohn J.S.
      • Arita R.
      • Chalmers R.
      • Djalilian A.
      • Dogru M.
      • Dumbleton K.
      • et al.
      TFOS DEWS II Diagnostic Methodology report.
      ]. The report also acknowledged the challenging nature of dry eye disease diagnosis because of its multifactorial aetiology, the lack of a gold standard metric and the low agreement between dry eye signs and symptoms. Thus, it has been acknowledged that there is a need for new, non-invasive and objective metrics to assess the tear film [
      • Wolffsohn J.S.
      • Arita R.
      • Chalmers R.
      • Djalilian A.
      • Dogru M.
      • Dumbleton K.
      • et al.
      TFOS DEWS II Diagnostic Methodology report.
      ].
      Recently, two methods have been validated to non-invasively assess the tear film objectively [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ,
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. The first method tried to overcome the issues of the Non-Invasive Keratograph Break-Up Time (NIKBUT) procedure. NIKBUT does not allow the tear film assessment under entirely natural conditions because subjects must keep their eyes open forcefully, which might cause reflex tearing [
      • Lai H.-Y.
      • Kuo M.-T.
      • Fang P.-C.
      • Lin C.-C.
      • Chien C.-C.
      • Cho W.-H.
      • et al.
      Tracking the reflective light particles spreading on the cornea: An emerging assessment for tear film homeostasis.
      ]. Thus, a method was developed to assess tear film dynamics in natural conditions. The method is based on the in vivo measurement of the speed of tear film particles post-blink [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ]. These particles are a combination of eroded epithelial corneal cells, tarsal conjunctival cells, mucin-contaminated lipid particles and small air bubbles [
      • Owens H.
      • Phillips J.
      Spreading of the tears after a blink: Velocity and stabilization time in healthy eyes.
      ,
      • Varikooty J.
      • Keir N.
      • Simpson T.
      Estimating tear film spread and stability through tear hydrodynamics.
      ]. It was found to provide emerging parameters related to the speed of tear film particles post-blink for indirectly assessing the tear film quality in natural conditions with acceptable repeatability [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ].
      On the other hand, the second method attempted to measure the lipid layer thickness in an objective way, without the need for an interferometer, through the analysis of the grey scale intensity values obtained from the Placido disk pattern reflected onto the tear film. The authors found that lipid layer thickness can be objectively measured with acceptable repeatability, accuracy and diagnostic capability [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ].
      The present work goes one step further by assessing the effect of computer use, contact lens wear and artificial tears on the tear film using these new and current metrics. It is widely known that the tear film and ocular surface parameters are affected by digital devices [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cervino A.
      • García-Lázaro S.
      Use of digital displays and ocular surface alterations: A review.
      ,
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ] and contact lenses [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ,
      • Gomes J.A.P.
      • Azar D.T.
      • Baudouin C.
      • Efron N.
      • Hirayama M.
      • Horwath-Winter J.
      • et al.
      TFOS DEWS II iatrogenic report.
      ,
      • García-Marqués J.V.
      • Macedo-de-Araújo R.
      • Lopes-Ferreira D.
      • Cerviño A.
      • García-Lázaro S.
      • González-Méijome J.M.
      Tear film stability over a myopia control contact lens compared to a monofocal design.
      ]. Thus, both have been identified as potential risk factors for dry eye disease, according to the TFOS DEWS II Epidemiology Report [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ]. Moreover, the instillation of artificial tears is generally accepted as one of the main management strategies for dry eye disease [
      • Jones L.
      • Downie L.E.
      • Korb D.
      • Benitez-del-Castillo J.M.
      • Dana R.
      • Deng S.X.
      • et al.
      TFOS DEWS II Management and Therapy Report.
      ].
      The present study aims to assess the effect of computer use, contact lenses and artificial tears on the tear film using newly developed and current metrics. The hypothesis is that new metrics are able to detect changes in the tear film and the ocular surface in a non-invasive and objective way. The present study might help to validate these metrics further and find clinical applications for them, such as assessing the ocular surface in contact lens wearers, computer users or subjects under artificial tears treatment.

      2. Material and methods

      Eighty-four healthy Caucasian volunteers ranging in age from 18 to 27 years (22.4 ± 2.6 years) participated in this study. Participants had no prior history of ocular disease or injury in the last three months. Refraction and visual acuity were obtained, and participants with an astigmatism > 0.75 dioptres (D) or with a best-corrected monocular or binocular near and distance visual acuity > 0.00 logMAR were excluded from the study due to the link between visual performance and the computer vision syndrome [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cervino A.
      • García-Lázaro S.
      Use of digital displays and ocular surface alterations: A review.
      ]. Contact lens users were instructed not to wear their contact lenses a day before the first visit. The duration of contact lens wear and the time of use were not considered. Current contact lens wearers were chosen as a sample, to ensure they would be familiar with management and handling procedures since they were required to put in the study contact lenses 1 h before the second visit. Only the right eye of the participants was measured to avoid data duplication. The study was performed following the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the University of Valencia. Written consent from each participant was obtained after verbally explaining the study protocol.

      2.1 Experimental design

      Fig. 1 summarizes the experimental design of the study in both visits. The ocular surface and tear film of participants were assessed at (1) baseline, (2) after reading on a modern laptop computer for 20 min, (3) after the insertion of a contact lens and (4) after reading on a computer with contact lenses and initial artificial tear instillation. Participants completed a total of two visits. In the first visit, the participants’ ocular surface and tear film were assessed at baseline. A 15-minute acclimatization period was left between the entry into the room of the participants and the measurements to minimize the effects of outdoor conditions on the way to the laboratory. Then participants performed a reading task on a modern laptop computer for 20 min. Twenty minutes of reading time was established based on previous studies of similar nature [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cerviño A.
      • García-Lázaro S.
      Digital display use and contact lens wear: Effects on dry eye signs and symptoms.
      ]. During the task, the device was placed at a 10° angle below the eye level of the participants and with an inclination angle of 100° from the desk’s surface. The ocular surface area exposed during the computer task was 138 ± 35 mm2.
      After the 20-minute reading task, the battery of standard clinical tests was repeated. After the visit, contact lens wearers were fitted with contact lenses and instructed to put in the study contact lenses 1 h before the second visit. In the second visit, baseline measurements were repeated, but on this occasion, during CL wear. After that, participants were instructed to read on the computer for 20 min while wearing the CLs and after the initial instillation of artificial tears. One drop of Systane® Ultra (Alcon SL, Geneva, Switzerland) single-dose artificial tears were instilled on each eye 2 min before the reading. Finally, after the 20-minute reading task, ocular surface and tear film measurements were repeated (Fig. 1). Participants were instructed not to use other digital devices 30 min before the visits. A rest period of 7 days between sessions was established. The approximate duration of each session was 45 min. Moreover, each session was performed at the same time of the day and the same day of the week.
      The text material was Allan Poe's full stories, displayed using Kindle (2021) reading application (Amazon Inc., Seattle, WA). The font style was Georgia with black letters on a white background, with a 0.15 logMAR visual acuity and an angular line spacing of 0.23°. The maximum number of words per line and per page was of 23 and 897, respectively. Page angular width was 25°, and the text was left-justified. The display was a MacBook Air Retina 2020 laptop computer (Apple Inc., Cupertino, CA) with a 13-inch screen, a resolution of 227 pixels per inch, a refresh rate of 60 Hz and a contrast ratio of 1350:1. The device was placed at 60 cm and a 10° angle below the eyes since it is the usual distance to work with a computer. Participants performed the task with the head fixed on a chin and forehead to minimize head movements. The room’s illuminance, temperature and humidity were maintained at 200 lx, 24.4 ± 1.3 °C and 44.7 ± 5.2 %, respectively.

      2.2 Contact lenses

      After the first visit, participants who were contact lens wearers were binocularly fitted with a daily-disposable contact lens (Dailies Total One®, Alcon Laboratories Inc. Fort Worth TX, USA), according to the manufacturer’s guidelines for the initial lens selection. These contact lenses are made of Delefilcon A with a water content of 33 % in the nucleus and > 80 % on the surface. After a set period of 5 min, distance and near logMAR visual acuity were assessed, and contact lens correct movement and centration were checked using a slit-lamp.

      2.3 Measurements

      The ocular surface was assessed using Oculus Keratograph 5 M (K5 M; Oculus GmbH, Wetzlar, Germany). Measurements were obtained by the same masked and experienced examiner following the guidelines of the TFOS DEWS II Diagnostic Methodology report [
      • Wolffsohn J.S.
      • Arita R.
      • Chalmers R.
      • Djalilian A.
      • Dogru M.
      • Dumbleton K.
      • et al.
      TFOS DEWS II Diagnostic Methodology report.
      ] in the following order to prevent the tear film from destabilization: Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 (DEQ-5), total bulbar redness, Tear Meniscus Height (TMH), tear film-dynamic and NIKBUT.
      The Keratograph 5 M measured bulbar redness from a picture of the ocular surface. The software detects the bulbar conjunctiva and measures the ratio between conjunctival vessels (red) and sclera (white) in steps of 0.1 units. Total bulbar redness score ranges from 0.0 to 4.0 [
      • Koprowski R.
      • Tian L.
      • Olczyk P.
      A clinical utility assessment of the automatic measurement method of the quality of Meibomian glands.
      ]. Tear meniscus was captured post-blink immediately in primary gaze, and TMH was measured on the centre of the eyelid using digital callipers as the distance between the upper limit of the reflective zone and the lower eyelid margin [
      • Wolffsohn J.S.
      • Arita R.
      • Chalmers R.
      • Djalilian A.
      • Dogru M.
      • Dumbleton K.
      • et al.
      TFOS DEWS II Diagnostic Methodology report.
      ].
      The Keratograph 5 M provides a tool to record the movement of tear film particles after blinking. A video at up to 32 frames per second with a resolution of 1360 × 1024 pixels was recorded, while two white LED spots illuminated the eye. A complete, natural and spontaneous blink was recorded, and the post-blink distribution of light particles spreading over the cornea was observed using high magnifications. Fig. 2 shows one video frame with the light particles spreading after a blink. Once the video was obtained, particles were tracked through a previously developed method using Matlab R2018a® (MathWorks, Natick, MA) to calculate the particles’ speed within 1.75 s post-blink. At least 8 different particles were tracked, and the average speed for each second was calculated.
      Figure thumbnail gr2
      Fig. 2Particles spread after blinking in one frame. Light particles spread over the cornea (blue circles). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
      Multicollinearity between variables was assessed, and the metrics with the highest diagnostic capability, according to previous work [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ], were included in the analysis to avoid the inclusion of inter-related variables. Thus, “median particle speed” and “time for particle speed to decrease to 1.20 mm/second” were calculated. It was previously reported that these metrics, related to the speed of tear film particles post-blink, can be used as emerging parameters for the indirect assessment of the tear film quality in natural conditions with acceptable repeatability [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ]. Further details on these parameters and their rationale can be found in a previous report [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ].
      The first NIKBUT of the tear film was measured three consecutive times, and the mean value was calculated [
      • Wolffsohn J.S.
      • Arita R.
      • Chalmers R.
      • Djalilian A.
      • Dogru M.
      • Dumbleton K.
      • et al.
      TFOS DEWS II Diagnostic Methodology report.
      ]. The Keratograph 5 M was also used to record a video of the NIKBUT at up to 32 frames per second with a spatial resolution of 680 × 512 pixels. The video was analysed through a previously developed software using Matlab R2019a. Software decomposed the video into frames and processed the images to calculate metrics from the grey intensity values of the Placido disk ring pattern reflected onto the tear film. Fig. 3 shows the distribution of Placido disk pixels intensity in one frame. As before, multicollinearity was assessed, and the metrics with the highest diagnostic capability, according to previous work [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ], were included. Thus, “entropy” and “median pixels intensity” were calculated. Moderate positive significant correlations were found between grey level intensities of the Placido disk pattern and lipid layer thickness and NIKBUT.
      Figure thumbnail gr3
      Fig. 3Histogram of the distribution of Placido disk pixels intensity in one frame. In the histogram, axe “x” represents the grey level intensities (0–255), while axe “y” shows the number of pixels.
      Moreover, multiple linear regression showed that lipid layer thickness was the only parameter associated with new metrics [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. It was previously reported that metrics at 5.33 s after blinking were correlated with lipid layer thickness and achieved a good diagnostic capability to assess the lipid layer thickness in an easy, repeatable, objective and accessible way without the need for an interferometer [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. Further details on these parameters and their rationale can be found in a previous report [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ].

      2.4 Statistical analysis

      Statistical analysis was performed using SPSS v26.0 for Windows (IBM Corp, Armonk, New York, USA). Results were reported as mean ± SD. Normality distribution was tested using the Kolmogorov-Smirnov or Shapiro-Wilk test, depending on the sample.
      Differences in parameters between before and after reading with a computer were assessed with the paired t-test or Wilcoxon signed-rank test, depending on sample distribution. Moreover, the effect of the contact lens on ocular surface parameters was also assessed through the aforementioned statistical tests. Finally, mixed ANOVA was performed to evidence which parameters improved after using artificial tears while performing the computer task, without considering differences in baselines (pre-task measurements) between visits. A p-value<0.05 was defined as statistically significant.

      3. Results

      Eighty-four right eyes from 84 participants were included in this study, out of which 52 were females (61.9 %) and 32 males (38.1 %). The mean age was 22.4 ± 2.6 years, ranging from 18 to 27 years.

      3.1 Computer use

      All participants complied with the instructions of the computer reading task. Table 1 shows the mean values for the pre-computer task, post-computer task and the difference between them for the dry eye questionnaires and ocular surface metrics. Statistical analysis revealed an increase in dry eye symptoms, TMH and bulbar redness; and a decrease in metrics related to the intensity of the reflected Placido disk pattern and in metrics related to particle speed after blinking. This fact suggests that computer use decreased lipid layer thickness and altered the distribution of the tear film after blinking.
      Table 1Mean values and statistical comparison for the pre-computer task, post-computer task and the difference between them.
      MetricPre-task (Mean ± SD)Post-task (Mean ± SD)Difference

      post-task – pre-task
      Significance level

      (p-value)
      OSDI6.9 ± 9.615.6 ± 15.78.6 ± 12.0<0.0012*
      DEQ-53.8 ± 4.56.9 ± 5.43.1 ± 5.0<0.0012*
      TMH (mm)0.2 ± 0.10.3 ± 0.10.1 ± 0.1<0.0012*
      Bulbar redness0.5 ± 0.30.6 ± 0.30.1 ± 0.20.0312*
      NIKBUT (seconds)15.7 ± 8.214.9 ± 7.5−0.8 ± 5.80.1442
      Entropy (a.u.)1.5 × 10-4 ± 4.5 × 10-51.5 × 10-4 ± 3.9 × 10-5−6.2 × 10-6 ± 2.9 × 10-50.0082*
      Median pixels intensity (a.u.)159.4 ± 26.5131.3 ± 12.1−28.1 ± 23.6<0.0012*
      Median particle speed (mm/second)1.1 ± 0.40.9 ± 0.4−0.2 ± 0.40.0041*
      Time for particle speed to decrease to < 1.20 mm/second (seconds)1.1 ± 0.40.8 ± 0.4−0.3 ± 0.4<0.0011*
      Where: DEQ-5 = 5-item Dry Eye Questionnaire; NIKBUT = Non-Invasive Keratograph Break-Up Time; OSDI = Ocular Surface Disease Index; SD = Standard Deviation; TMH = Tear Meniscus Height; *Statistically significant; 1T-Test.; 2Wilcoxon Signed Rank test.

      3.2 Contact lens wear

      Out of the total sample, 30 participants were contact lens wearers (22.8 ± 2.4 years, ranging in age from 18 to 26 years) and these individuals were fitted with contact lenses on the second visit. Contact lenses had correct movement, centration and coverage in all participants. Table 2 shows the comparison between the pre-task of the first visit (naked eye) and the pre-task of the second visit (with the contact lens). Statistical analysis revealed that contact lens use causes lower TMH, NIKBUT, and particle speed metrics values. Likewise, contact lens use increased entropy of the reflected Placido disk pattern. This fact suggests that contact lens wear decreased the lipid layer thickness and altered the dynamics and distribution of the tear film across the ocular surface.
      Table 2Comparison between the pre-task of the first visit (naked eye) and the pre-task of the second visit (with the contact lens).
      MetricContact lens effect

      Difference pre-task (Pre computer, contact lens and artificial tears – pre computer) (Mean ± SD)
      Significance level

      (p-value)
      OSDI−0.9 ± 7.20.6562
      DEQ-5−0.8 ± 4.80.1852
      TMH (mm)−0.04 ± 0.050.0092*
      Bulbar redness−0.04 ± 0.190.0882
      NIKBUT (seconds)−5.7 ± 7.70.0012*
      Entropy (a.u.)2.1 × 10-5 ± 5.4 × 10-50.0102*
      Median pixels intensity (a.u.)−7.2 ± 19.70.0742
      Median particle speed (mm/second)−0.4 ± 0.40.0142*
      Time for particle speed to decrease to < 1.20 mm/second (seconds)−0.6 ± 0.40.0022*
      Where: DEQ-5 = 5-item Dry Eye Questionnaire; NIKBUT = Non-Invasive Keratograph Break-Up Time; OSDI = Ocular Surface Disease Index; SD = Standard Deviation; TMH = Tear Meniscus Height; *Statistically significant; 1T-Test.; 2Wilcoxon Signed Rank test.

      3.3 Computer use, contact lens and artificial tears

      Table 3 shows the mean values for the pre-computer task (with the contact lens), post-computer task (with the contact lens and artificial tears) and the difference between them for the dry eye questionnaires and ocular surface metrics. Statistical analysis revealed an increase in TMH and in metrics related to particle speed after blinking. This fact suggests that after computer use with a contact lens and artificial tears, lipid layer thickness did not decrease, and the distribution of the tear film after blinking improved. Moreover, dry eye symptoms and the rest of the ocular surface parameters remained unaltered, which might be caused by the use of artificial tears.
      Table 3Mean values and statistical comparison for the pre-computer task (with the contact lens), post-computer task (with the contact lens and artificial tears) and the difference between them.
      MetricPre-task (Mean ± SD)Post-task (Mean ± SD)Difference

      post-task – pre-task
      Significance level

      (p-value)
      OSDI6.0 ± 9.46.5 ± 9.30.4 ± 4.90.6832
      DEQ-53.0 ± 3.93.0 ± 3.7−0.03 ± 2.550.8652
      TMH (mm)0.19 ± 0.040.2 ± 0.10.04 ± 0.05<0.0012*
      Bulbar redness0.5 ± 0.20.5 ± 0.2−0.003 ± 0.1240.7732
      NIKBUT (seconds)10.0 ± 6.311.4 ± 6.21.5 ± 4.20.0522
      Entropy (a.u.)1.5 × 10-4 ± 6.9 × 10-51.5 × 10-4 ± 5.6 × 10-5−4.9 × 10-6 ± 4.6 × 10-50.3672
      Median pixels intensity (a.u.)152.2 ± 15.7152.9 ± 12.90.7 ± 13.10.9651
      Median particle speed (mm/second)0.7 ± 0.41.1 ± 0.40.4 ± 0.40.0052*
      Time for particle speed to decrease to < 1.20 mm/second (seconds)0.5 ± 0.40.9 ± 0.40.4 ± 0.40.0032*
      Where: DEQ-5 = 5-item Dry Eye Questionnaire; NIKBUT = Non-Invasive Keratograph Break-Up Time; OSDI = Ocular Surface Disease Index; SD = Standard Deviation; TMH = Tear Meniscus Height; *Statistically significant; 1T-Test.; 2Wilcoxon Signed Rank test.

      3.4 Computer use and artificial tears

      Mixed ANOVA analysis (Table 4) was performed to evidence which parameters improved after using artificial tears while performing the computer task, without considering differences in baselines (pre-task measurements) between visits. It showed statistically significant differences between conditions (computer versus computer + contact lens + artificial tears) for all ocular surface parameters except for bulbar redness and the entropy of the reflected Placido disk pattern. However, some parameters differed in pre-task measurements due to the contact lens. The interaction between conditions (computer versus computer + contact lens + artificial tears) and the time (pre and post-task) had a significant effect on OSDI, DEQ-5, NIKBUT, median pixel intensity, median particle speed, and time for particle speed to decrease to < 1.20 mm/second. This fact suggests that artificial tears help to ameliorate the deterioration of these ocular surface parameters after reading with a computer.
      Table 4Analysis of the interaction between the time (pre-task versus post-task) and the condition (computer versus computer + contact lens + artificial tears) for each dependent variable through a mixed ANOVA.
      MeasurementInteraction between time (pre versus post-task) and the condition (computer versus computer + contact lens + artificial tears)

      (Significance level)
      Differences between conditions (computer versus computer + contact lens + artificial tears)

      (Significance level)
      OSDI<0.001*0.026*
      DEQ-50.001*0.005*
      TMH0.3430.001*
      Bulbar redness0.1820.142
      NIKBUT0.033*0.001*
      Entropy0.8310.070
      Median pixels intensity<0.001*<0.001*
      Median particle speed<0.001*0.042*
      Time for particle speed to decrease to < 1.20 mm/second<0.001*0.012*
      Where: DEQ-5 = 5-item Dry Eye Questionnaire; NIKBUT = Non-Invasive Keratograph Break-Up Time; OSDI = Ocular Surface Disease Index; SD = Standard Deviation; TMH = Tear Meniscus Height; *Statistically significant.

      4. Discussion

      The use of digital displays and contact lens wear have been previously found to increase dry eye signs and symptoms [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ,
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cervino A.
      • García-Lázaro S.
      Online Vs In-person Education: Evaluating the Potential Influence of Teaching Modality on Dry Eye Symptoms and Risk Factors During the COVID-19 Pandemic.
      ,
      • Yazici A.
      • Sari E.S.
      • Sahin G.
      • Kilic A.
      • Cakmak H.
      • Ayar O.
      • et al.
      Change in tear film characteristics in visual display terminal users.
      ,
      • Tan L.L.
      • Morgan P.
      • Cai Z.Q.
      • Straughan R.A.
      Prevalence of and risk factors for symptomatic dry eye disease in Singapore.
      ,
      • Paulsen A.J.
      • Cruickshanks K.J.
      • Fischer M.E.
      • Huang G.-H.
      • Klein B.E.K.
      • Klein R.
      • et al.
      Dry eye in the beaver dam offspring study: Prevalence, risk factors, and health-related quality of life.
      ]. Moreover, the TFOS DEWS II Epidemiology Report recognized both conditions as potential risk factors for dry eye disease [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ], and contact lens wearers have been found to suffer higher symptoms of dryness while using digital displays [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ]. The present work confirmed these previous findings and included new, objective and non-invasive methods in the analysis, that might be used to assess the variations in the tear film induced by several condition-induced changes.

      4.1 Computer use

      Ocular surface and tear film alterations such as reduced tear stability, changes in tear volume and composition, oxidative stress, ocular surface inflammation and meibomian gland abnormalities have been found in computer users in previous studies [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cervino A.
      • García-Lázaro S.
      Use of digital displays and ocular surface alterations: A review.
      ,
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cervino A.
      • García-Lázaro S.
      Online Vs In-person Education: Evaluating the Potential Influence of Teaching Modality on Dry Eye Symptoms and Risk Factors During the COVID-19 Pandemic.
      ,
      • Yazici A.
      • Sari E.S.
      • Sahin G.
      • Kilic A.
      • Cakmak H.
      • Ayar O.
      • et al.
      Change in tear film characteristics in visual display terminal users.
      ,
      • Paulsen A.J.
      • Cruickshanks K.J.
      • Fischer M.E.
      • Huang G.-H.
      • Klein B.E.K.
      • Klein R.
      • et al.
      Dry eye in the beaver dam offspring study: Prevalence, risk factors, and health-related quality of life.
      ,
      • Choi J.H.
      • Li Y.
      • Kim S.H.
      • Jin R.
      • Kim Y.H.
      • Choi W.
      • et al.
      The influences of smartphone use on the status of the tear film and ocular surface.
      ,
      • Ribelles A.
      • Galbis-Estrada C.
      • Parras M.A.
      • Vivar-Llopis B.
      • Marco-Ramírez C.
      • Diaz-Llopis M.
      Ocular Surface and Tear Film Changes in Older Women Working with Computers.
      ,
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ]. According to these studies, reading with a computer for 20 min increased dry eye symptoms, TMH and bulbar redness in this work, indicating tear film alterations and ocular surface stress. Furthermore, the intensity of the reflected Placido disk pattern and the speed of particles after blink decreased. Nevertheless, NIKBUT was not statistically altered. As the intensity of the reflected Placido disk pattern is an objective indicator of lipid layer thickness [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ], these results suggest that computer use decreased lipid layer thickness and altered the dynamics of the tear film after blinking. Aligned with these results, Talens-Esterelles et al. [
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ] also found differences in OSDI, TMH and bulbar redness after a 15 min task with a computer; however, they found a decrease in NIKBUT.
      The reduction in entropy after the computer task might be attributable to the increases in bulbar redness, TMH and OSDI, since entropy has been found to inversely correlate with these parameters [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. In addition, TMH increased in this study, probably due to a burst of blinks such as has been observed right after a digital display task [
      • Nielsen P.K.
      • Søgaard K.
      • Skotte J.
      • Wolkoff P.
      Ocular surface area and human eye blink frequency during VDU work: The effect of monitor position and task.
      ]. This might be a compensation phenomenon to wet the ocular surface after blinking suppression during the task. Conversely, some authors previously reported lower TMH and Schirmer test values in long-term office workers, while others found no difference [
      • Choi J.H.
      • Li Y.
      • Kim S.H.
      • Jin R.
      • Kim Y.H.
      • Choi W.
      • et al.
      The influences of smartphone use on the status of the tear film and ocular surface.
      ,
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ,
      • Cardona G.
      • García C.
      • Serés C.
      • Vilaseca M.
      • Gispets J.
      Blink rate, blink amplitude, and tear film integrity during dynamic visual display terminal tasks.
      ].

      4.2 Contact lens wear

      Contact lens wear impacts ocular surface homeostasis [
      • Stapleton F.
      • Alves M.
      • Bunya V.Y.
      • Jalbert I.
      • Lekhanont K.
      • Malet F.
      • et al.
      TFOS DEWS II Epidemiology Report.
      ]. When a contact lens is inserted into the eye, the tear film destabilizes because the contact lens divides it into two layers: pre-lens and post-lens tear film [
      • Korb D.R.
      • Greiner J.V.
      • Glonek T.
      Tear film lipid layer formation: Implications for contact lens wear.
      ]. Approximately 50 % of contact lens wearers suffer from dryness and ocular discomfort, both problems being the major causes of contact lens intolerance [
      • Gomes J.A.P.
      • Azar D.T.
      • Baudouin C.
      • Efron N.
      • Hirayama M.
      • Horwath-Winter J.
      • et al.
      TFOS DEWS II iatrogenic report.
      ,
      • Doughty M.J.
      • Fonn D.
      • Richter D.
      • Simpson T.
      • Caffery B.
      • Gordon K.
      A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada.
      ]. Thus, it has been found that contact lens wear causes a reduction in tear volume [
      • Chen Q.
      • Wang J.
      • Shen M.
      • Cui L.
      • Cai C.
      • Li M.
      • et al.
      Tear menisci and ocular discomfort during daily contact lens wear in symptomatic wearers.
      ,
      • Del Águila-Carrasco A.J.
      • Ferrer-Blasco T.
      • García-Lázaro S.
      • Esteve-Taboada J.J.
      • Montés-Micó R.
      Assessment of corneal thickness and tear meniscus during contact-lens wear.
      ], lipid layer thickness and alterations in tear spreading [
      • Yokoi N.
      • Yamada H.
      • Mizukusa Y.
      • Bron A.J.
      • Tiffany J.M.
      • Kato T.
      • et al.
      Rheology of tear film lipid layer spread in normal and aqueous tear-deficient dry eyes.
      ]; and higher tear film instability [
      • Santodomingo-Rubido J.
      • Wolffsohn J.S.
      • Gilmartin B.
      Changes in ocular physiology, tear film characteristics, and symptomatology with 18 months silicone hydrogel contact lens wear.
      ] and tear osmolarity [

      Hori Y. Secreted mucins on the ocular surface. Investig Ophthalmol Vis Sci 2018; 59:DES151–6. 10.1167/iovs.17-23623.

      ].
      Despite the optimal properties of the contact lens used in the present study [
      • Pérez-Gómez I.
      • Giles T.
      European survey of contact lens wearers and eye care professionals on satisfaction with a new water gradient daily disposable contact lens.
      ], contact lens wear decreased TMH, NIKBUT and particle speed after blinking, whilst entropy increased. Despite some metrics related to the intensity of the Placido disk pattern not being statistically significant, they show a tendency to decrease after contact lens wear. Therefore, contact lens wear also affected lipid layer thickness and the dynamics of the tear film after blinking. The results of the present study are aligned with previous ones that also found a relationship between contact lens wear and alterations in the tear film and the ocular surface [
      • García-Marqués J.V.
      • Macedo-de-Araújo R.
      • Lopes-Ferreira D.
      • Cerviño A.
      • García-Lázaro S.
      • González-Méijome J.M.
      Tear film stability over a myopia control contact lens compared to a monofocal design.
      ,
      • Yang W.-J.
      • Yang Y.-N.
      • Cao J.
      • Man Z.-H.
      • Yuan J.
      • Xiao X.
      • et al.
      Risk factors for dry eye syndrome: A retrospective case-control study.
      ,
      • Uchino M.
      • Schaumberg D.A.
      • Dogru M.
      • Uchino Y.
      • Fukagawa K.
      • Shimmura S.
      • et al.
      Prevalence of Dry Eye Disease among Japanese Visual Display Terminal Users.
      ,
      • Rico-del-Viejo L.
      • Lorente-Velázquez A.
      • Hernández-Verdejo J.L.
      • García-Mata R.
      • Benítez-del-Castillo J.M.
      • Madrid-Costa D.
      The effect of ageing on the ocular surface parameters.
      ].
      The higher entropy found with contact lens use might be a consequence of the lower TMH since entropy and TMH are inversely correlated [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. A previous study also found that tear volume decreased 20 min after the insertion of soft contact lenses [
      • Wang J.
      • Cox I.
      • Reindel W.T.
      Upper and lower tear menisci on contact lenses.
      ]. Furthermore, it was previously reported that contact lenses with high-water content may absorb tear fluid into the contact lens, decreasing pre- and post-tear film thickness [

      Kojima T. Contact lens-associated dry eye disease: Recent advances worldwide and in Japan. Investig Ophthalmol Vis Sci 2018;59:DES102–8. 10.1167/iovs.17-23685.

      ,
      • Nichols J.J.
      • Sinnott L.T.
      Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye.
      ].
      Dry eye symptoms did not increase after contact lens wear in the present study, which might be explained as discomfort and lens dryness usually occurring late in the day [
      • Chalmers R.L.
      • Begley C.G.
      Dryness symptoms among an unselected clinical population with and without contact lens wear.
      ]. Thus, the results of this study represent the short-term effects of a daily disposable lens on the ocular surface.

      4.3 Computer use, contact lens wear and artificial tears.

      Artificial tears are an effective strategy to ameliorate dry eye symptoms and signs [
      • Jones L.
      • Downie L.E.
      • Korb D.
      • Benitez-del-Castillo J.M.
      • Dana R.
      • Deng S.X.
      • et al.
      TFOS DEWS II Management and Therapy Report.
      ]. In this regard, sodium hyaluronate artificial tears have a prolonged residence time in the eye and have been reported to significantly increase TMH, improve tear film stability and decrease higher-order aberrations 30 min after instillation [
      • Montés-Micó R.
      Role of the tear film in the optical quality of the human eye.
      ,
      • Montés-Micó R.
      • Cerviño A.
      • Ferrer-Blasco T.
      • García-Lázaro S.
      • Ortí-Navarro S.
      Optical quality after instillation of eyedrops in dry-eye syndrome.
      ,
      • Kobashi H.
      • Kamiya K.
      • Igarashi A.
      • Miyake T.
      • Shimizu K.
      Intraocular scattering after instillation of diquafosol ophthalmic solution.
      ,
      • Igarashi A.
      • Kamiya K.
      • Kobashi H.
      • Shimizu K.
      Effect of Rebamipide Ophthalmic Suspension on Intraocular Light Scattering for Dry Eye after Corneal Refractive Surgery.
      ,
      • Diaz-Valle D.
      • Arriola-Villalobos P.
      • García-Vidal S.E.
      • Sánchez-Pulgarín M.
      • Borrego Sanz L.
      • Gegúndez-Fernández J.A.
      • et al.
      Effect of lubricating eyedrops on ocular light scattering as a measure of vision quality in patients with dry eye.
      ,
      • Vandermeer G.
      • Chamy Y.
      • Pisella P.-J.
      Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study.
      ,
      • Schafer J.
      • Reindel W.
      • Steffen R.
      • Mosehauer G.
      • Chinn J.
      Use of a novel extended blink test to evaluate the performance of two polyvinylpyrrolidone-containing, silicone hydrogel contact lenses.
      ]. Moreover, previous studies with the same artificial tears, found that they were effective for ameliorating symptoms of dryness and increasing tear film stability [
      • Benelli U.
      Systane® lubricant eye drops in the management of ocular dryness.
      ,
      • Belalcázar-Rey S.
      • Sánchez Huerta V.
      • Ochoa-Tabares J.C.
      • Altamirano Vallejo S.
      • Soto-Gómez A.
      • Suárez-Velasco R.
      • et al.
      Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial.
      ,
      • Gokul A.
      • Wang M.T.M.
      • Craig J.P.
      Tear lipid supplement prophylaxis against dry eye in adverse environments.
      ]. Although in this and previous studies, both contact lens wear and the use of digital displays increase dry eye signs and symptoms, this can be prevented by the use of artificial tears, since no increase was found in dry eye symptoms and bulbar redness after the computer task. NIKBUT increased after the task, but the magnitude was not statistically significant. Likewise, lipid layer thickness did not decrease after the task, given that metrics related to the intensity of the reflected Placido disk pattern were unaltered. This might be caused by using artificial tears before computer use. Moreover, TMH increased, probably due to the instillation of artificial tears, and particle speed increased after the task, suggesting that not only does the use of artificial tears prevent the increase of dry eye signs and symptoms after computer use, but it also improves the tear film dynamics after blinking.
      Mixed ANOVA was performed to identify which parameters improved after using artificial tears while performing the computer task, without considering differences in baselines (pre-task measurements) between visits. The analysis confirmed that artificial tears help prevent the deterioration of dry eye signs and symptoms after reading with a computer. In opposition to these results, Talens-Estarelles et al. [
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ] did not find an improvement in ocular surface parameters after the instillation of artificial tears.
      The present study had some limitations to consider. First, a one-day wash-out period for contact lens wearers might not be sufficient. Nevertheless, some previous studies used this period [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cerviño A.
      • García-Lázaro S.
      Digital display use and contact lens wear: Effects on dry eye signs and symptoms.
      ,
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      The Effects of Soft Contact Lens Wear on The Tear Film and Meibomian Gland Drop-Out and Visibility.
      ]. This fact is not expected to influence the comparison between conditions since all subjects in this study had the same wash-out period. Furthermore, placing subjects on a headrest is an unrealistic situation. Nevertheless, this methodology was similar to those found in previous studies [
      • Talens-Estarelles C.
      • García-Marqués J.V.
      • Cerviño A.
      • García-Lázaro S.
      Digital display use and contact lens wear: Effects on dry eye signs and symptoms.
      ,
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ] to ensure that all subjects had the same downgaze and head position in all visits. It has been previously reported that greater gaze angles associated with computer use result in a wider palpebral fissure, which increases tear evaporation and tear film instability [
      • Talens-Estarelles C.
      • Sanchis-Jurado V.
      • Esteve-Taboada J.J.
      • Pons Á.M.
      • García-Lázaro S.
      How Do Different Digital Displays Affect the Ocular Surface?.
      ,
      • Tsubota K.
      • Nakamori K.
      Effects of Ocular Surface Area and Blink Rate on Tear Dynamics.
      ,
      • Pansell T.
      • Porsblad M.
      • Abdi S.
      The effect of vertical gaze position on ocular tear film stability.
      ].
      The lipid layer thickness was not directly measured. Nevertheless, it was previously reported that the intensity of the reflected Placido disk pattern could be used as an objective method to measure the lipid layer thickness with acceptable repeatability and accuracy [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. In addition, the novel methods are semiautomatic, and have acceptable repeatability (Coefficient of variation < 6.24 % for metrics related to the intensity of the reflected placid disk, and coefficient of variation < 9.73 % for metrics related to the speed of the particles) [
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • Martínez-Albert N.
      • García-Lázaro S.
      • Cerviño A.
      An Emerging Method to Assess Tear Film Spread and Dynamics as Possible Tear Film Homeostasis Markers.
      ,
      • García-Marqués J.V.
      • Talens-Estarelles C.
      • García-Lázaro S.
      • Cerviño A.
      Validation of a new objective method to assess lipid layer thickness without the need of an interferometer.
      ]. Furthermore, no control group was used to assess the effect of the contact lens. Assessment of the pre-task condition of both visits was compared and some variability between visits was evident. Therefore, these results should be confirmed in future studies with a control group to find whether new metrics are able to detect changes in the ocular surface due to the contact lens.
      This issue is not expected to influence the analysis regarding the effect of computer use and artificial tears because the former was performed by comparing the measurements pre- and post-reading, independently of the visit. Likewise, mixed-ANOVA was applied to show which parameters improved after using artificial tears while performing the computer task, without considering differences in baselines (pre-task measurements) between visits. It is also important to comment that the variability between visits was minimized by the fact that each session was performed at the same time of the day and the same day of the week under the constant temperature and humidity of the room. Moreover, subjects were not asked how many hours they used their contact lenses during the 7-day break between visits, which might affect the results on the second visit. They were instructed to use their contact lenses regularly as they usually do.
      Overall, the present work adds information regarding the effect of computer use, contact lens wear and artificial tears on the ocular surface. Computer use and contact lens wear worsened dry eye signs and symptoms, including lipid layer thickness and tear film dynamics. Moreover, artificial tears ameliorate the deterioration of these ocular surface parameters after reading with a computer and are an effective strategy for preventing the impact of display use on the ocular surface. Newly developed methods can serve as a tool to detect changes in the tear film triggered by different ocular surface-disturbing conditions. In this way, the present work further helps to validate these novel methods as a reliable tool to quickly, non-invasively and objectively assess the changes in the tear film induced by different conditions. Therefore, they could be included in a battery of tests to improve the detection and monitoring of dry eye disease and meibomian gland dysfunction in clinical practice. Further research is needed to assess the effects of computer reading for more extended periods, to make methods fully automatic and to assess the performance of these metrics in participants diagnosed with dry eye disease or meibomian gland dysfunction.
      Funding
      This work was supported by the University of Valencia [“Atracció de Talent” scholarship, UV-INV-PREDOC18F2-886420] awarded to José Vicente García-Marqués; and the Ministerio de Educación, Cultura y Deporte [“Formación de Profesorado Universitario” scholarship, FPU17/03665] awarded to Cristian Talens-Estarelles. The funding sources had no role in the design of the study.

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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