Varying tear osmolarity readings may be hard to interpret

By David Douglas

NEW YORK (Reuters Health) - Measurements of tear osmolarity taken with the TearLab Osmolarity System vary highly in individuals with and without dry eye, according to a new study.

"This variability could be due to a combination of the variability of the osmolarity in the tear film itself, the sampling of a small volume of tears, and variability in the measurement process," Dr. Vatinee Y. Bunya, of the Scheie Eye Institute at the University of Pennsylvania, Philadelphia, told Reuters Health by email. "Nonetheless, because of this large degree of variation, TearLab osmolarity readings are difficult to interpret when following patients over time."

In a March 26 online paper in JAMA Ophthalmology, Dr. Bunya and colleagues note that they came to these conclusions after studying 74 eyes in 37 subjects between June 13, 2012 and March 21, 2013. Their study involved 18 patients with Sjögren syndrome (SS), 11 patients with blepharitis, and eight controls. Most of the patients and none of the controls were taking systemic or topical dry eye medications at the time of enrollment.

Using the TearLab system, clinicians took three consecutive osmolarity measurements at 1-minute intervals in each eye of each participant. A subgroup of 15 patients had three measurements per eye taken at each of three sessions a few hours apart on the same day to assess intersession variability.

Mean tear osmolarity came to 307 milliosmoles per liter (mOsm/L) in the SS group, 304mOsm/L in the blepharitis patients, and 301mOsm/L in controls, but the differences did not reach statistical significance.

The error associated with repeated measurements within a session in the patients without dry eye (10.5mOsm/L) was significantly lower than in the blepharitis group (14.6mOsm/L, p=0.006) and in SS patients (15.8mOsm/L, p<0.001).

Researchers found no difference in measurement error between patients with blepharitis and patients with SS.

The researchers concede that limitations of the study include the relatively small sample size. Nevertheless, they conclude, "The high variability among TearLab osmolarity readings calls into question its clinical utility."

Commenting on the findings, Stephen J. Kilmer of the TearLab Corporation, San Diego, told Reuters Health by email, "While we are pleased to see a paper cover the importance of 'variability' in dry eye patients, it is unfortunate that the study design, analytical methods, and conclusions were all significantly compromised."

Among such shortcomings, said Kilmer, citing Dr. Manoj S. Venkiteshwar, vice president of medical affairs at TearLab, were that:

- Most patients in both test groups were on dry eye disease treatment, which would lower their osmolarity measurements.

-Control subjects showed a series of measurements that demonstrated signs of mild dry eye disease, which would increase their osmolarity measurements.

-Researchers did not factor in the difference between the two eyes, which is a measure of tear film instability. The DEWS [Dry Eyes Workshop] definition of core mechanisms of dry eye disease are hyperosmolarity, tear film instability, and inflammation.

-All groups had small numbers and the groups were not age-matched.

"Dr. Venkiteshwar's points," Kilmer continued "are just the quick high-level limitations of the study design that are some of the primary drivers that resulted in the conclusions that are so inconsistent with the much larger body of work that exists in this area."

"In summary," he added, "there are important flaws in the study design and conclusions drawn. There is a body of work that spans over 40 years that supports both the importance of osmolarity as a global marker for dry eye disease, as well as TearLab's osmolarity test as a clinically useful test for the diagnosis and management of dry eye."

One from 2013, for example (http://bit.ly/1I7lOBo), Kilmer said, is in direct conflict with the current study's outcomes.

The National Eye Institute and Research to Prevent Blindness funded this research. Dr. Bunya received research supplies from TearLab for the study; the authors reported no other disclosures.

SOURCE: http://bit.ly/1DrkbgK

JAMA Ophthalmol 2015.

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