Comparison of two artificial tear formulations for dry eye through high ...

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RESEARCH PAPER

Comparison of two artificial tear formulations for dry eye through high-resolution optical coherence tomography Clin Exp Optom 2011; 94: 6: 549–556

DOI:10.1111/j.1444-0938.2011.00632.x

Santiago Garcia-Lázaro OD MSc Lurdes Belda-Salmerón OD MSc Teresa Ferrer-Blasco OD PhD Alejandro Cerviño OD PhD Robert Montés-Micó OD PhD Optometry Research Group (GIO), Department of Optics, University of Valencia, Valencia, Spain E-mail: [email protected]

Purpose: The aim was to determine the efficacy of two artificial eye-drop formulations by analysing the lower tear film meniscus volume through a commercial high-resolution spectral-domain optical coherence tomographer. Methods: Twenty dry eye patients (12 men, eight women, aged 57.5 ⫾ 8.4 years) with refractive errors from -2.50 to +0.75 D (mean -1.34 ⫾ 1.02 D) and cylinders lower than 1.00 D were examined. Tear meniscus volume was measured before, immediately after and 10, 30 and 60 minutes after instillation using the Copernicus high-resolution spectral-domain optical coherence tomographer (Optopol Tech SA, Zawiercie, Poland). Volume was calculated from the local area obtained from tomograms considering a regular distribution of the tear meniscus across the eyelid. Ten subjects were randomly assigned to first receive either polyethylene glycol (Blink Intensive, Abbot Medical Optics Inc, CA, USA) or hypromellose (Artific, Farma-Lepori SA, Barcelona, Spain) three times daily in both eyes for one month. Measures were then repeated and after a one-week wash-out period they were switched to the other eye-drop for another month. Results: Mean baseline volume was 0.38 ⫾ 0.10 mL, while mean baseline volume after the wash-out period was slightly higher, 0.39 ⫾ 0.10 mL (p = 0.638). Analysis of variance showed significant differences in meniscus volume with time after instillation with both formulations (p < 0.001), mean volume decreasing with time. At 30 and 60 minutes following instillation, values decreased to almost baseline (average difference 0.02 ⫾ 0.03 mL at t30, p = 0.016 and 0.01 ⫾ 0.01 mL at t60, p = 0.098). Conclusion: An increase in tear film meniscus volume in dry eyes from the use of eye-drops has been shown. High resolution imaging of lower tear film meniscus with clinical optical coherence tomography systems provides useful measures of tear volume. Both formulations assessed in the present study are efficient in increasing tear meniscus volume and reducing dry eye signs and symptoms, although results in terms of increase in meniscus volume were higher with the polyethylene glycol formulation.

Submitted: 23 January 2011 Revised: 23 March 2011 Accepted for publication: 12 April 2011

Key words: dry eye, hypromellose, optical coherence tomography, polyethylene glycol, tears

Tear volume is essential for many functions in eye health: maintenance of the regular optical surface, clear vision, corneal health and transparency, among

others. Drying of the tear film has a major impact on the quality of the optical system of any individual eye. Previous studies have pointed out that any local change in

© 2011 The Authors Clinical and Experimental Optometry © 2011 Optometrists Association Australia

tear film thickness (TFT) and regularity would introduce significant changes into the eye’s optical system, affecting visual performance.1

Clinical and Experimental Optometry 94.6 November 2011

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Eye-drop comparison in dry eye through OCT Garcia-Lázaro, Belda-Salmerón, Ferrer-Blasco, Cerviño and Montés-Micó

Dry eye syndrome refers to a spectrum of ocular conditions with diverse aetiologies,2 making diagnosis difficult due to the need for a comprehensive definition and the limitations in the clinical assessment of tears and the ocular surface. Only a percentage of symptomatic patients have been shown to have objective signs of dry eye.3,4 The Schirmer test5 is cheap and accessible, being the most common objective diagnostic clinical test for assessing lacrimal secretary function in dry eye; however, its many limitations are well known.6 Tear break-up time measurement with or without fluorescein is also a widely used technique for dry eye diagnosis in practice7 but it fails to give direct information on tear evaporation6. Ocular surface staining with rose Bengal, lissamine green or fluorescein have also been used to diagnose dry eye8,9 but they are not effective for early diagnosis and they lack specificity. Normal tear film requires an adequate balance between production, retention and elimination.10 Anything disrupting the balance between these components might result in dry eye. The tear volume is distributed among three continuous compartments: the cul-de-sac, menisci and preocular film. The main function of tear menisci is to act as a reservoir of fluid to reform the preocular film and to accommodate the excess tears from reflex tearing or after drop instillation.11 The menisci and tear film are held in place by interfacial forces. Creech and colleagues12 and Wong, Fatt and Radke13 developed mathematical models to relate tear film thickness to tear meniscus volume, predicting a relationship between tear film thickness and the initial meniscus radius and that the radius is proportional to the tear meniscus volume. The advent of new state-of-the-art, super-high resolution, non-invasive technology for assessment of the anterior segment of the eye has increased interest into finding new ways of quantifying the tear film in the search for more precise clinical alternatives to conventional invasive tests. In a recent study using a custom-made spectral-domain optical coherence tomographer (SOCT),

Wang and colleagues14 showed good repeatability for measurement of the parameters of the menisci. Tear meniscus variables, such as height, width, cross-sectional area and meniscus curvature have been reported to be of value in the diagnosis of dry eye.15–19 Wang and colleagues20 found that the upper and lower tear menisci have almost identical dimensions in healthy eyes and the lower tear meniscus seems to be correlated with the non-invasive break-up time during normal blinking.21 Using the same customised spectral-domain optical coherence tomographic device, Shen and colleagues11 have recently shown that the tear meniscus is reduced in aqueous tear deficiency patients compared with healthy subjects. In another recent study using ultra-high resolution spectral-domain optical coherence tomography, Yuan and colleagues22 reported that aqueous tear deficiency dry eye patients had reduced tear meniscus dynamics during a normal blink cycle, concluding that the analysis of tear meniscus dynamics might provide more insight in the altered tear system in dry eye patients. Topical instillation of artificial tears is known to improve the optical quality of the eye23,24 and optical quality has been used as an indicator of tear film status.1,25 Using a Hartmann-Shack wavefront aberrometer to measure ocular aberrations, MontésMicó, Cáliz and Alió24 reported that after instillation of eye-drops on dry eyes there is a significant improvement in optical quality. In a recent study analysing corneal aberrations, these results were confirmed with one of the formulations evaluated in the present report.23 After eye-drops were instilled Montes-Micó and co-workers found a significant reduction in sphericaland coma-like aberrations. This might be explained considering the change in corneal irregularity associated with the absence or lack of uniformity of the tear film in dry eye patients. Huang and colleagues26 found a significant improvement in the surface regularity and asymmetry indices in videokeratography of dry eye patients after instillation of eye-drops. Jones and colleagues27 used highresolution spectral-domain optical coher-


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ence tomography to compare changes in the lower tear meniscus when artificial tears were instilled, finding that it is easy to determinate the variation of tear meniscus when artificial tear products are instilled. The aim of the present study is to determine the efficacy of two different artificial eye-drop formulations by means of analysing the lower tear film meniscus volume using a commercial high-resolution spectral-domain optical coherence tomographer. METHODS

Sample The sample comprised 20 subjects suffering from dry eye (12 men and eight women, average age 57.5 ⫾ 8.4 years) with refractive errors ranging from -2.50 to +0.75 D (mean -1.34 ⫾ 1.02 D) and cylinders lower than 1.00 D in all cases. The clinical diagnosis of dry eye was made on the basis of significant subjective dry eye symptoms (McMonnies test score greater than 14), Schirmer I test results of less than 5.0 mm (measurement of tear secretion during five minutes of natural blinking without topical anaesthesia), and tear film break-up time shorter than five seconds. Only those fulfilling the three criteria were considered for the study. Ocular surface abnormalities were diagnosed through positive results on either corneal fluorescein staining or corneal and conjunctival rose Bengal staining scores of 3 or more.28 Exclusion criteria included patients with unilateral dry eye, pregnant or lactating females, ocular surgery of any type or ocular trauma within the previous four months prior to enrolment, abnormality of the nasolacrimal drainage apparatus, permanent occlusion of lacrimal puncta in any eye, use of a temporary punctal plug, contact lens wear or known hypersensitivity to any of the components or procedures used in the study. The two artificial tear formulations used were Blink Intensive Tears (Abbot Medical Optics Inc, Santa Ana, CA, USA), composed mainly of polyethylene glycol 400 (0.25%), sodium hyaluronate (viscos© 2011 The Authors

Clinical and Experimental Optometry © 2011 Optometrists Association Australia


ity enhancer) and Ocupure preservative, and Artific Tears (Farma-Lepori SA, Barcelona, Spain) containing hypromellose (0.3%) and cetrimide. Two drops of either type of eye-drop were instilled into the eye after baseline measurements of the tear meniscus were made. After instructing the patient to blink a few times to help spread the artificial eye-drops and after instillation of the drops, measurements were made of the tear meniscus volume immediately and then at 10, 30 and 60 minutes after instillation. Patients were randomly assigned to one of two groups. Ten subjects were randomly assigned for instillation of polyethylene glycol tears first and 10 patients were to use hypromellose tears first. All drops were instilled three times daily in both eyes for one month. After one month, the meniscus volume was measured and the patients went through a one-week washout period, after which they switched to the other drop and instilled three drops daily for another month.

Determination of lower meniscus volume The lower tear film menisci were measured using a vertical scan at the centre of the lower eyelid captured with the high-resolution spectral-domain optical coherence tomographer Copernicus HR (Optopol Tech SA, Zawiercie, Poland) and its anterior segment-coupling device. The Copernicus HR is a posterior segment SOCT using a 840 nm light source that recently launched an anterior segment coupling device that allows imaging of the anterior segment with an axial resolution up to 2.88 mm (manufacturer’s data) and around 10 mm lateral resolution. Recently, the same instrument has been used by the authors to obtain high-resolution images of the cornea-to-lens relationship, as well as the post-lens tear film and soft contact lens edge menisci.29 To get the scan, the subject was instructed to look straight ahead while the scan reference was located on the lower eyelid, around 6 o’clock from the corneal centre. A single B-scan made from up to 6,408 A-scans was obtained on three consecutive occasions per session, readjusting

the system every time. Subjects were asked to blink approximately six seconds before the scan was obtained, as after a blink in normal subjects seems to be the moment of best stability.30 All measurements were taken under the same conditions of illumination. The volume of the meniscus was calculated from the local area conformed by the tomogram obtained from the spectral-domain optical coherence tomography system and considering a regular distribution of the tear meniscus across the lower eyelid. Custom software was used to compute the area of the tear meniscus tomogram. This was carried out manually by a single masked observer. A factor of 1.294 was included into the calculation to compensate for the curvature of the eyelid, as previously suggested by Tiffany, Todd and Baker.31 Tear meniscus volume was computed as:

Volume = Area ( µm2 ) × Lower eyelid length ( µm ) × 1.294 Three scans were taken on each occasion. To avoid the possibility of interobserver differences in the determination of tear film meniscus volume with optical coherence tomography systems as reported by Bitton and colleagues,32 even though training avoids inter-observer differences, all measurements were taken by the same observer. All procedures complied with the Declaration of Helsinki and protocols were approved by the institutional Ethics Committee. A consent form was obtained from each subject after the protocol and procedures were appropriately explained. All measurements were taken in the same room where the temperature was kept constant at between 21°C and 23°C and humidity between 45 and 65 per cent.

Statistical analysis Statistical Package for Social Sciences (SPSS, v.17.0 Chicago, IL, USA) was used for statistical analysis and graphic generation. Only data from the right eye were used for analysis. To assess the mid-term benefit of artificial tear instillation, analysis of variance (ANOVA) was applied to check for differences in tear meniscus volume for the different periods following


the instillation of each of the two formulations. Paired t-tests were used to assess the differences in volume after instillation between the two types of eye-drop formulations. Plots of difference versus mean and regression plots were constructed to assess the effect of artificial tear instillation on the baseline tear meniscus volume. RESULTS Mean baseline tear meniscus volume was 0.38 ⫾ 0.10 mL, while mean baseline tear meniscus volume after the washout period (two weeks before switching between eye-drop formulations) was slightly higher at 0.39 ⫾ 0.10 mL, but this was not significant (p = 0.638). Figure 1 shows the Bland Altman plot representing the distribution of differences between the two baseline situations, as a function of the mean baseline tear film meniscus volume, showing a considerable spread of differences regardless of the actual volume value. After instillation (t0) of Intensive (with polyethylene glycol) and Artific Tears eyedrops, the tear meniscus volume increased to averages of 0.94 ⫾ 0.22 mL and 0.96 ⫾ 0.21 mL, respectively (Figure 2) and 10 minutes after instillation (t10) the tear meniscus volumes averaged 0.57 ⫾ 0.13 and 0.58 ⫾ 0.11 mL, respectively, which were still significantly increased with respect to baseline (p < 0.001). ANOVA showed statistically significant differences in the tear meniscus volume with time after instillation with both types of eyedrops (p < 0.001), with mean volume decreasing with time (mean difference 0.37 ⫾ 0.11 mL between t0 and t10), although values at t10 were significantly higher than baseline (p < 0.01, with a mean difference 0.19 ⫾ 0.02 mL). At 30 and 60 minutes following instillation, values of tear meniscus volume decreased to almost baseline (average 0.02 ⫾ 0.03 mL at t30, p = 0.016, and 0.01 ⫾ 0.01 mL at t60, p = 0.098) (Figure 3). Similar behaviour was observed after switching eye-drop formulation. By analysing data comparing the changes in tear meniscus volume induced by both eyedrop formulations over time after instilla-


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Difference in baseline prior to study and after wash-out period ( µL)


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tion, similar patterns might be observed for both, with an initial peak after instillation and a progressive decline with time. For the polyethylene glycol eye-drops, immediately after instillation there was an increase in volume by an average of 0.567 mL (p < 0.001) and then a progressive decrease by an average of 0.372 mL at 10 minutes (p < 0.001), a further 0.179 mL at 30 minutes (p < 0.001) and a decrease of only 0.011 mL on average between 30 and 60 minutes (p = 0.142). For the Artific eye-drops, the initial increase was 0.561 mL on average from baseline (p < 0.001), followed by a progressive decrease of 0.390 mL at 10 minutes (p < 0.001), a further 0.125 mL at 30 minutes (p < 0.001) and yet another 0.032 mL at 60 minutes (p < 0.001). Clinical and Experimental Optometry 94.6 November 2011

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Mean difference in tear meniscus volume from baseline

Figure 1. Plot representing the distribution of differences between the baseline values obtained at the beginning of the study and after the wash-out period between formulations as a function of mean baseline meniscus volume. The solid line represents the zero difference reference, whereas the dashed line represents a trend for the distribution of differences.

Figure 2. Tomogram of the lower tear meniscus before (A) and immediately after (B) the instillation of one of the tear formulations

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Figure 3. Variation in tear film volume after instillation of each eye-drop formulation as a function of time. Error bars represent 95% confidence intervals. © 2011 The Authors Clinical and Experimental Optometry © 2011 Optometrists Association Australia

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Figure 4. Variation in tear film volume after instillation of artificial eye-drops as a function of time. Asterisks represent statistical significance at the p = 0.05 level.

DISCUSSION The present study aimed to assess efficacy of two artificial eye-drop formulations by means of lower meniscus volume measurement by spectral-domain optical coher-

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Figure 4 shows the variation in tear film volume before and after instillation of polyethylene glycol eye-drops as a function of time. Differences between changes induced by the two eye-drop formulations are significant for t10 (p = 0.014), t30 (p = 0.002) and t60 (p = 0.015), although the clinical significance of these differences is not clear. Figure 5 shows the distribution of differences in tear meniscus volume 30 minutes after instillation of both types of eye-drop formulations, as a function of baseline tear meniscus volume. A trend might be observed for increased values of tear meniscus volume 30 minutes after instillation compared with baseline, as the baseline level of the meniscus volume decreases (solid line). Although this trend occurs with both formulations, it is more pronounced with the polyethylene glycol eye-drops (dashed line).

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Figure 5. Distribution of differences in tear meniscus volume immediately after and 30 minutes after instillation of both types of eye-drop, polyethylene glycol (full bins, dashed line) and hypromellose (empty bins, dotted line) as a function of baseline tear meniscus volume. Solid line represents the trend for the whole sample.

ence tomography. Only a few reports have been published on artificial tears measured with high-resolution non-invasive devices. To the best of the authors’ knowledge, the present study is the first assessing the efficacy of artificial eye-drops on dry eyes using this technique. For many years there has been a search for better ways of quantifying tear film in a non-invasive and accurate way. Szczesna and colleagues33 recently reported the use of non-invasive techniques such as high-speed videokeratoscopy, wavefront sensing and lateral shearing interferometry for predicting dry eye, concluding that these techniques, and particularly lateral shearing interferometry, seem to be of great use for the early detection of dry eye. Tear menisci are accessible and more easily measurable than other parts of the tear film. For this reason, many authors developed different approaches to the non-invasive quantification of tear film to both improve the determination methods and find the parameter that better represents the integrity of the whole tear film. Oguz, Yokoi and Kinoshita34 investigated the relationship between the tear menis-


cus radius of curvature (TMR) using a videomeniscometer and the tear meniscus height (TMH), concluding that there is a significant correlation between the TMR and TMH and the method proves valuable for obtaining tear meniscus parameters.14,23,24,26,35,36 The meniscometer is a non-invasive specular method for measuring TMR, which uses the tear strip as a concave mirror.37 The TMR measured by reflective meniscometry has positive correlations with fluorescein staining scores and the grading of tear film lipid layer interferometry.38,39 Johnson and Murphy40 used the optical pachymeter to measure tear meniscus height five minutes after the instillation of 5.0 mL of 2% solution of sodium fluorescein to compare TMH measurements of 25 normal subjects with five techniques, namely, optical coherence tomography in cross-section and optical pachymetry in cross-section without fluorescein and five minutes after the instillation of fluorescein, optical pachymetry en-face and in cross-section and video capture en-face. The average TMH of the five techniques gave similar results.


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Despite the clinical value of all these techniques for the quantification of tear meniscus parameters, the development of state-of-the-art high-resolution optical coherence tomography systems provided a new high-resolution method for the viewing and measurement of the tear menisci in clinical settings. Optical coherence tomography uses lowcoherence interferometry to produce a bi-dimensional image of optical scattering from tissues in a manner analogous to B-scan ultrasonography but with superior longitudinal and lateral spatial resolution.41 In recent years, optical coherence tomography has been used to image the anterior segment in different clinical conditions, as well as the tear film and menisci.11,32,42–45 Most of the studies using optical coherence tomography for tear film assessment use custom-made devices but some commercial devices were used to image lower tear menisci.32,45,46 According to Bitton and colleagues,32 the TMH seems to have no variability among observers when lower TMH is examined, provided the observers were trained. With regards to dry eye, Dogru and colleagues38 assessed the applicability of strip meniscometry for quantifying tear meniscus volume in the diagnosis of the dry eye syndromes, showing a statistically significant correlation with the Schirmer test, tear break-up time and ocular surface staining scores. The mean Schirmer test value, break-up time, vital staining, interferometry and strip meniscometry scores are significantly worse in patients with dry eye than in the control subjects. Golding, Bruce and Mainstone15 measured noninvasive break-up time and TMR, TMH, width and cross-sectional area in aqueousdeficient dry-eye and age-matched controls. They found a linear correlation between log non-invasive break-up time and TMH, in addition to the positive relationship between the TMR and TMH in agreement with Oguz, Yokoi and Kinoshita.34 This relationship is consistent with the tear-meniscus model of tear-film rupture, which predicts that the smaller the value of tear meniscus curvature, the greater the negative suction pressure and more rapid rupture of tear film. Shen and

colleagues11 measured the upper and lower tear menisci in both aqueous teardeficient patients and control subjects to determine which of the variables are most effective in the diagnosis of dry eyes. They established cut-off values for normal and dry eyes, namely, with a lower TMH of 0.164 mm and a lower TMR of 0.182 mm. The primary goals of the dry eye treatment are discomfort relief, providing a smooth optical surface and preventing damage to the cornea. Frequent instillations of drops that do not present a risk of toxicity or allergy seem to be the most successful form of therapy. Several attempts have been made to produce an artificial tear that emulates human tears and these products are currently on the market. It should be considered that the goals of therapy using these tears are to provide moisture, surface wetting, comfort and retention of the solution for as long as possible. The results of the present study show that both eye-drop formulations are effective in increasing the tear volume and remain for reasonable periods of time, following similar patterns, although the behaviour did not exactly match (Figure 4). With regards to the suitability of optical coherence tomography for assessing the efficacy of eye-drop instillation, Jones, Leech and Rahman27 compared changes in the lower tear meniscus when 35 mL of Refresh Liquid and Refresh Tears (Allergan Inc., Irvine, CA, USA) were added onto the upper conjunctiva of three healthy subjects. The results were different in that after the first drop the TMH returned to baseline values within approximately five minutes, whereas it took twice as long to return to baseline after the second drop. They concluded that it is easy to determinate the variations of TMH when artificial tear products are added using the optical coherence tomographer. More recently, Wang and colleagues14 reported that their custom-made optical coherence tomography device showed good repeatability in measuring the dynamic distribution of artificial tears on the ocular surface. Carrying out repeated measures five, 20, 40 and 60 minutes after instillation of Refresh Liquigel (Allergan,


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Irvine, CA, USA) on healthy subjects, they showed a good correlation between upper and lower tear menisci at baseline. Immediately after instillation of artificial tears, all measured variables increased significantly and remained elevated for at least five minutes. They found significant correlations between tear film thickness and the lower TMH and area when artificial tears were instilled. They also studied the dynamic distribution of artificial tears on the ocular surface using optical coherence tomography, evaluating the effects of artificial tear viscosity on tear film thickness, tear menisci and volume. Changes in central tear film thickness and lower tear meniscus dimensions were correlated with the viscosity of the artificial tear but the dimensions of the upper tear meniscus were not,35 indicating that other factors, such as specific gravity or wetting characteristics of the artificial tear, might be more important in determining the fluid held along the upper lid. These results were also in agreement with those later reported by Palakuru, Wang and Aquavella,36 who investigated the effect of blinking on tear volume after instillation of artificial tears, and also concluded that TMH increased after instillation of artificial tears but observed that baseline values re-established after five minutes. In a recent study by the authors (unpublished data) the methodology used in the present study was applied to the determination of the efficacy of an artificial tear formulation in healthy contact lenses wearers. Tear meniscus volumes increased significantly after instillation (and the patient was instructed to blink to remove tear overload), but values were still slightly higher up to 60 minutes after instillation. Wang and colleagues20 determined the difference between baseline central corneal thickness plus tear film and true corneal thickness after instillation of the artificial tears. In the same study, they report an upper tear meniscus area of 22.732 ⫾ 11.974 mm2 and a similar value for the lower tear meniscus. Over the past few years there has been a considerable number of publications applying optical coherence tomography technology to the assessment of the tear © 2011 The Authors

Clinical and Experimental Optometry © 2011 Optometrists Association Australia


film; however, very few have studied dry eye.11,22,44,46,47 Shen and colleagues11 studied the tear menisci in dry eye patients and demonstrated the diagnostic value of optical coherence tomography.11 They reported average baseline values for the lower tear meniscus area of 9.492 ⫾ 3.010 and 9.189 ⫾ 2.685 mm2 for the right and left eyes of dry eye patients, respectively. Yuan and colleagues22 reported baseline lower tear meniscus volume for the dry eye sample of 0.36 ⫾ 0.28 mL under normal blinking conditions. In the present study, average baseline values for area (and volume) were 8.777 ⫾ 2.089 mm2 (0.38 ⫾ 0.10 mL) and 8.596 ⫾ 2.210 mm2 (0.39 ⫾ 0.10 mL), corresponding to the beginning of the study and after the wash-up period before switching eye-drops, respectively. Qiu and colleagues46 used a commercially available spectral-domain optical coherence tomography system to measure meniscus area, the RTVue-100 (Optovue Inc, Fremont, CA, USA), on a large sample of dry eye and healthy control subjects to assess age-related variations in tear meniscus and the suitability of the system for dry eye diagnosis. They confirmed clinical spectral-domain optical coherence tomographers as useful tools for the diagnosis of dry eye, although more research is needed to establish its limitations. The pathogenesis of dry eye syndrome is not simply desiccation but includes ocular surface disease and inflammation, and therefore it could be expected that changes in the need for eye-drop instillation would appear after regular use for several weeks. This could explain why the second baseline values obtained after the wash-out period were slightly higher than the initial ones in the present study. The meniscus volume after one month of regular use of both types of eye-drop resulted in sustained increased values, implying that both formulations are effective in treating dry eye, although the values after one month were higher following the polyethylene glycol eye-drops. In summary, an increase in tear film meniscus volume in dry eyes occurs following the use of eye-drops. Only a few reports have been published on artificial tears measured with high-resolution, non-invasive

devices.35,36 High-resolution imaging of the lower tear film meniscus with the available clinical optical coherence tomography provides a useful measure of tear volume. The use of eye-drops on dry eyes improves the tear meniscus volume. Both formulations assessed in the present study increased the tear meniscus volume, although the results were higher with the polyethylene glycol formulation. REFERENCES 1. Montés-Micó R, Cerviño A, Ferrer-Blasco T, García-Lázaro S, Madrid-Costa D. The tear film and the optical quality of the eye. Ocul Surf 2010; 8: 185–192. 2. Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 2004; 23: 449–474. 3. Schein OD, Munoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol 1997; 124: 723–728. 4. Pflugfelder SC, Tseng SC, Sanabria O, Kell H, Garcia CG, Felix C, Feuer W et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea 1998; 17: 38–56. 5. Wright JC, Meger GE. A review of the Schirmer test for tear production. Arch Ophthalmol 1962; 67: 564–565. 6. Cedarstaff TH, Tomlinson A. Human tear volume, quality and evaporation: a comparison of Schirmer, tear break-up time and resistance hygrometry techniques. Ophthalmic Physiol Opt 1983; 3: 239–245. 7. Nichols KK, Mitchell GL, Zadnik K. The repeatability of clinical measurements of dry eye. Cornea 2004; 23: 272–285. 8. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003; 22: 640–650. 9. Khan-Lim D, Berry M. Still confused about rose bengal? Curr Eye Res 2004; 29: 311–317. 10. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006; 47: 4309–4315. 11. Shen M, Li J, Wang J, Ma H, Cai C, Li J, Cui L et al. Upper and lower tear menisci in the diagnosis of dry eye. Invest Ophthalmol Vis Sci 2009; 50: 2722– 2726. 12. Creech JL, Do LT, Fatt I, Radke CJ. In vivo tear-film thickness determination and implications for tear-film stability. Curr Eye Res 1998; 17: 1058–1066. 13. Wong H, Fatt I, Radke CJ. Deposition and thinning of the human tear film. J Colloid Interface Sci 1996; 184: 44–51. 14. Wang J, Aquavella J, Palakuru J, Chung S. Repeated measurements of dynamic tear distribution on the ocular surface after instillation of artificial tears. Invest Ophthalmol Vis Sci 2006; 47: 3325–3329. 15. Golding TR, Bruce AS, Mainstone JC. Relationship between tear-meniscus parameters and tearfilm breakup. Cornea 1997; 16: 649–661. 16. Mainstone JC, Bruce AS, Golding TR. Tear meniscus measurement in the diagnosis of dry eye. Curr Eye Res 1996; 15: 653–661.


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Corresponding author: Dr Alejandro Cerviño Department of Optics University of Valencia Dr Moliner, 50 – 46100 Burjassot Valencia SPAIN E-mail: [email protected]


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