Measuring Tear Film Osmolarity

Measuring Tear Film Osmolarity

Measuring Tear Film Osmolarity
By Gary N. Foulks, MD, FACS
   
One of the enduring challenges in dry eye disease management has been the lack of a convenient laboratory test that could aid in diagnosis. While diagnosis can usually be achieved from signs and symptoms, patients with mild dry eye disease can sometimes be difficult to diagnose based on clinical presentation alone. Also, signs and symptoms are not always a sensitive indicator of a patient’s response to treatment.
   
Tear film osmolarity has been proposed as a biomarker that could be used to diagnose and monitor dry eye disease, but until recently there has been no practical way to measure osmolarity in the clinical setting. Now, however, the upcoming release of the TearLab™ Osmolarity System may soon allow tear film osmolarity measurement to become a standard tool in dry eye management.

Measuring Osmolarity
   
A measure of the concentration of solutes in the tear film, tear film osmolarity is elevated in both evaporative and aqueous deficient dry eye disease. In addition to being an indicator of disease, hyperosmolarity also contributes directly to patients’ signs and symptoms. For example, hyperosmolarity can affect the stability of the tear film by changing the way some tear film lipids and proteins interact with each other, as well as by damaging epithelial cell membranes, triggering inflammation, and stimulating corneal nerves.
   
The gold standard for measuring osmolarity in the laboratory is freezing point depression. Because solutes interfere with a solvent’s ability to form a more ordered structure, concentrated solutions freeze at lower temperatures than dilute solutions. Thus, the temperature at which a solution freezes is a function of its osmolarity. It is hard to apply this methodology to tear film osmolarity measurement, however, because it requires relatively large sample volumes.
   
For similar reasons, a high concentration of solutes also raises a solution’s vapor pressure, so the temperature at which a solution vaporizes is also a function of osmolarity. As with freezing point depression, however, large sample volumes are required to perform such a measurement.
   
Electrical conductivity is another physical property that correlates with osmolarity. Since the presence of charged particles in a fluid will increase the fluid’s electrical conductivity, a higher concentration of charged particles (ie, higher osmolarity) correlates with increased conductivity.
   
Unlike with freezing point depression and vapor pressure elevation, conductivity can be measured in nanoliter samples. Micro-scale conductivity measurement is therefore the technology used in the new TearLab System. Offering simple sample collection and fully automated osmolarity determination, this new device can produce quick and accurate results, making it suitable for clinical settings.

Applying Osmolarity Data
   
Now that there is a simple osmolarity measurement device, clinicians must answer an important question: how do specific osmolarity values correlate with the presence or absence of disease? A meta-analysis by Tomlinson and coworkers reviewed osmolarity values in patients with and without dry eye disease and suggested a referent (cutoff) value of 316 mOsmol/L, with values above this level being diagnostic of dry eye disease.1
   
Now that the TearLab device has entered the clinical realm, additional data is becoming available, and it appears that diagnosing dry eye disease may require more than simply determining a cutoff value. In addition to the osmolarity level itself, the range of osmolarity values measured over time in any one subject may be clinically important. While patients with a healthy ocular surface maintain a consistent tear film osmolarity, dry eye disease patients show much greater variability in values measured at different times. Interestingly, patients in the earlier stages of dry eye disease seem to show the greatest variability—more so than normal individuals or patients with severe dry eye disease—perhaps because early-stage patients maintain some ability to compensate for the environmental challenges that can elevate osmolarity.
   
Gary N. Foulks, MD, FACS, is the Arthur and Virginia Keeney professor of ophthalmology, University of Louisville, Louisville, KY, and is editor-in-chief of The Ocular Surface. He is a consultant to TearLab, Inc., serves on the company’s clinical advisors board, and has received research contracts to conduct trials in the use of this instrument.

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REFERENCE
1.    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 Oct;47(10):4309-15.