Testing platform yields point-of-care osmolarity measure

Key Points

Washington, DC-Quick and accurate point-of-care osmolarity testing is the goal of a tear-testing platform being developed by a San Diego-based in vitro diagnostics company (TearLab, OcuSense). The platform measures highly sensitive and specific biomarkers related to ocular physiology and accomplishes this with less than 50 nl of tear fluid.

The testing system, which has not yet received FDA approval, uses a hand-held pen and a disposable test card to produce results in seconds, according to Michael A. Lemp, MD, clinical professor, George Washington and Georgetown Universities, Washington, DC.

A practical testing system based on osmolarity is lacking in ophthalmology, he said.

Staining of the ocular surface, one of the most widely used techniques, is problematic because it occurs relatively late in dry eye disease. Even among patients with a moderate level of dry eye, staining occurs in a minority of cases.

As a result, clinical trials of dry eye using staining as an endpoint-which is most of them-have been limited to patients with moderate to severe disease.

"It means that you not only had to have staining but have enough staining that you can show improvement in it," Dr. Lemp said.

From a clinical point of view, because neither staining nor other tests such as Schirmer tests are highly specific, they are only very reproducible in advanced forms of the disease, he added. Consequently, a substantial number of patients who have mild to moderate dry eye lack an objective method to characterize their disease.

Why osmolarity?

Osmolarity was chosen as the first application for the new platform based on extensive evidence.

"In the literature of the past 40 years, tear osmolarity has been recognized as a good diagnostic measure for dry eye," Dr. Lemp said. "When the tear film becomes abnormal in dry eye disease, you get a breakdown in the stability of the tear film in all forms of dry eye. Concomitant with that is an increase in the osmolarity of the tear film, caused by an increased concentration of the electrolytes.

"[Osmolarity] is a key feature of dry eye of all forms. It's seen in all stages of dry eye disease, is objective and quantitative, and is a marker for dry eye disease recognized in the recent Dry Eye Workshop Report," he said.

Studies using osmolarity, however, typically have been performed in a clinical laboratory setting because the standard methods of measuring tear film osmolarity-including freezing point depression analysis and vapor pressure osmometry-are available there. Those techniques were designed for large volume measurements, such as the osmolarity of serum or other bodily fluids, and are less reliable when applied to small volumes of tears.

In addition, equipment for measuring osmolarity is expensive, not very reproducible, and requires a high degree of expertise, making it impractical in the average practice setting. The new testing platform should overcome those hurdles, Dr. Lemp said.

The system measures impedance of the electric charge in tears, which is directly related to the concentration of electrolytes, in turn the dominant cause of the osmolarity of tears.

Impedance can be measured in extremely small volumes of fluid, said Dr. Lemp. The new tear-testing platform can measure osmolarity in tear samples less than 50 nl, or approximately a drop the size of a dot made with a ballpoint pen.

The second objective for designing the platform was to improve the method of tear collection. Although tears can be collected in a glass microcapillary tube in an experimental setting by well-trained technicians, personnel in a typical practice may lack the skills to handle the delicate tubes.

The new system uses a hand-held tear collection pen that integrates with a disposable, noninvasive "lab-on-a-chip" collection and measurement system. As soon as the marginal tear strip is touched by the soft tip of the card, tears wick to it instantaneously, and the pen emits an alert indicating that the sample has been obtained.

Other methods of sampling cause irritation and induce reflex tearing, but the new platform works so quickly that the reflex tearing response cannot occur, Dr. Lemp said.

The measurement occurs in the pen at 100,000 cycles per second; that takes 5 seconds to complete. The pen is placed in a reader, which displays a quantitative measurement from the analysis to the operator.

Trials with the first units have been conducted in normal and dry eye subjects and in office settings, where administrative staff members with no medical training were asked to read instructions, then measure their coworkers' tears.

"Everybody's been able to do it," Dr. Lemp said. Although they were tentative at first about approaching the eye, once they saw how readily the test was performed, they wanted to test the other eye, he added.

The manufacture of the testing system is performing regulatory studies that will support approval from the FDA, according to Dr. Lemp. If approved, the system could be launched in the United States in the first quarter 2009. The company will pursue a CE Mark in Europe within a few months, targeting a late summer launch. Studies are also in the planning stage in Japan, he added.