Tear osmolarity measurement using the TearLab™ Osmolarity System in the assessment of dry eye treatment effectiveness

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Abstract

Purpose

To evaluate the efficacy of three commercially available lubricant eye drops for the treatment of mild, dry, irritated eyes.

Methods

Randomized, investigator-masked evaluation of 60 patients in which 20 patients used carboxymethylcellulose sodium (CMC), 0.5% (Cellufresh®, Allergan Inc., Irvine, CA) (group 1); 20 patients used a drop containing polyethylene glycol 400, 2.5% and sodium hyaluronate (Blink® Intensive Tears, Abbott Medical Optics Inc., Santa Ana, CA) (group 2); and 20 patients used HP Guar 0.18% (Systane®, Alcon Laboratories Inc., Ft. Worth, TX) (group 3). Study visits were at baseline and 1 month. Tests performed at both visits included Schirmer, tear-film break-up time (TBUT), visual acuity, fluorescein staining, tear osmolarity and wavefront aberrometry. Osmolarity testing was performed prior to instillation of the lubricant eye drops and then a final time 5 min after instillation of the drop at both day 1 and day 30. Tear osmolarity was performed only in the right eye and only one time before and after instillation of lubricant eye drops.

Results

At day 1 the mean reduction in osmolarity 5 min after instillation of the lubricant eye drop was, −5.0 ± 1.9 in group 1, −9.0 ± 4.2 in group 2 and −5.0 ± 2.2 in group 3. At day 30 the mean reduction in osmolarity 5 min after instillation of the lubricant eye drop was, −5.6 ± 2.3 mOsm/L in group 1; −9.9 ± 2.8 mOsm/L in group 2 and −4.5 ± 1.8 mOsm/L in group 3. The differences were statistically significant between groups 1 and 2, and 2 and 3. There was a reduction of osmolarity from day 1 to day 30 but the differences were not statistically significant. We feel that after a 30-day treatment with the lubricant eye drops, the lower osmolarity values could indicate that the tear film is progressing towards a more normal osmolarity value. A future study could examine the tear osmolarity value after 60 or 90 days of usage. LogMAR best-corrected visual acuity (BCVA) results showed an improvement in group 2 compared with baseline with no change in BCVA in groups 1 and 3. There was no statistically significant change from day 1 to 1 month in TBUT, while the Schirmer test showed an improvement in all groups at 1 month.

Conclusions

Assessment of tear osmolarity provides the most objective, measurable test for determining improvement in dry eye patients. The instillation of any artificial tear or lubricant eye drop should decrease the tear-film osmolarity. The results found that polyethylene glycol 400, 0.25% and sodium hyaluronate (Blink® Intensive Tears) significantly improved tear osmolarity compared with carboxymethylcellulose sodium (CMC), 0.5% (Cellufresh®) and HP Guar 0.18% (Systane®) after instillation.

Introduction

Lubricant eye drops are the accepted treatment when a patient presents with signs or symptoms of dry eye disease before more invasive treatments are employed [1]. However, as noted in the 2007 Dry Eye Workshop (DEWS) report, there has been a lack of evidence on the efficacy of many of the active ingredients used in these tears. In the DEWS Management and Therapy chapter, the authors note that this is likely the result of currently available tests or because it is not clear if the active ingredients are intended to lubricate, replace tears, improve tear osmolarity or lessen ocular surface inflammation [1]. Two points are clear from this report: there is a need for more sensitive clinical tests to assess if lubricant eye drops improve the ocular surface health and that lubricant eye drops should have active ingredients that do more than lubricate.

Hyaluronic acid (HA) has a long history of use in ophthalmic surgery since its introduction in the 1970s as a vitreous replacement and then later as a surgical tool in cataract surgery [2], [3]. Evidence also shows that HA has the ability to increase the stability of the tear film, promote corneal healing and strengthen the mucous layer of the tear film [4], [5], [6], [7].

One of the challenges in managing dry eye disease patients has long been in objectively measuring the effectiveness of a chosen treatment. Signs and symptoms often do not match with results of tests, including tear-film break-up time, Schirmer tear test or ocular surface (cornea and conjunctival) staining [1], [8], [9], [10]. As a result, there is an ongoing search for tests that can objectively diagnose dry eye disease, as well as assess treatment effectiveness. Recent studies have looked at optical coherence tomography [11], tear stress tests [12], fluorescein dye tracking with a xeroscope [13] and wavefront aberrometry [14] as methods for objectively assessing the efficacy of various lubricant eye drops solutions [15], [16], [17].

In our study presented here, we elected to use a new diagnostic test for assessment of tear osmolarity. The TearLab™ Osmolarity System (TearLab™ Corp., San Diego, CA) is described as a “lab-on-a-chip” system that uses a 50 nL tear sample in order to measure the osmolarity of the tear. The system is non-invasive, user friendly and provides a result in less than 1 min. The TearLab™ System utilizes a hand-held pen that features a non-invasive tear collection interface to decrease sampling time to less than a second. The test card is used as a measurement system as well as a tear collection device. Once the sample is collected, the pen initiates measurement and is docked onto the TearLab™ Reader, which displays a quantitative measurement from the test card analysis. The test is quick, easy to administer and the system does not require calibration [18].

As indicated in the DEWS report, osmolarity is considered to be one of the most objective assessments for dry eye disease [1]. In addition, standard dry eye assessment tests of Schirmer, tear-film break-up time (TBUT), corneal and conjunctival fluorescein staining, as well as visual acuity assessment and wavefront aberrometry were performed in order to provide a comparison for measurement of treatment effectiveness.

Section snippets

Methods

This study was a randomized, investigator-masked study involving three types of lubricant eye drops and 60 patients divided into three treatment groups: 20 patients received a carboxymethylcellulose sodium drop (CMC), 0.5% (Cellufresh®, Allergan Inc., Irvine, CA) (Group 1); 20 patients received a drop containing polyethylene glycol 400, 0.25% and sodium hyaluronate (Blink® Intensive Tears, Abbott Medical Optics Inc., Santa Ana, CA) (group 2); and 20 patients used HP Guar 0.18% (Systane®, Alcon

Tear osmolarity

Table 1 provides a summary of the osmolarity results and between-group P values at day 1 and day 30. At day 1, there was a statistically significant difference in reduction of osmolarity between groups 1 and 2 and groups 2 and 3. The difference between groups 1 and 3 was not statistically significant. At day 30, the difference in reduction of osmolarity was statistically significant between groups 1 and 2 and between groups 2 and 3. Again, the difference between groups 1 and 3 was not

Discussion

Current methods of diagnosing dry eye disease have a number of limitations. This is primarily due to the fact that these tests look at physical endpoints or parameters that are signs of late-stage disease. In addition, the basis for efficacy of commonly used diagnostic tests, such as the Schirmer tear test or Rose Bengal staining, may actually show higher rates of sensitivity and specificity because the sample population is typically selected because it has previously demonstrated dry eye

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    Financial disclosure: This study was funded by an unrestricted educational grant by Abbott Medical Optics.

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