TearLab monitors accuracy of its tear osmolarity test at every customer site, in an on-going Phase IV post-market surveillance study. Using an NIST traceable control solution with an exact osmolarity of 338 mOsm/L – indicative of a patient with moderately severe dry eye disease – TearLab measures accuracy and precision data on each of its instruments in the physician’s office. Each instrument is tested 10 times in a row with the high control solution. The results of 10-tests will provide (1) accuracy, or how close to the 338 mOsm/L target the instruments actual read, and (2) precision, or how variable the 10 measurements are from each other. Below are the current results of the survey:
|N =110||Number of instruments|
|Tests = 1067||Number of tests performed using high control solution|
|Mean = 338.0 mOsm/L||Average accuracy of all instruments combined|
|Bias = 0.0 mOsm/L||The error in measurement from the target value|
Median = 338.6 mOsm/L
Fifty % of the instruments tested above this value and 50% tested below this value
SD = 3.4 mOsm/L
Standard Deviation, or the maximum variation (+/-) from the target value that would be seen in 66 out of 100 tests (1SD)
|CV = 1.0%|
Coefficient of Variation, or variability as a percentage between consecutive measurements
So in conclusion, of 110 instruments tested, the average reading was 338 mOsm/L – a zero bias from the target value, with an expected deviation from this target within ±3.4 mOsm/L 66% of the time (1SD) and ±6.8 mOsm/L 95% of the time (2SD). Fifty percent of the tests read above 338.6 mOsm/L and 50% read below that mark indicating a tight Gaussian distribution centered around the mean - with no greater risk of a test being above than below the target value. The expected variability from measurement to measurement is 1.0%.
The take home message is that TearLab measures osmolarity with extreme accuracy and precision, with any variability between the left and right eye attributed to biological, not analytical, variability - a hallmark of dry eye disease. Normal patients with a healthy lacrimal system are capable of maintaining tear film homeostasis and have essentially no variability between left and right eye. From the data above, we know that a tear osmolarity difference between right and left eyes greater than 8 mOsm/L surpasses the analytical variation of 6.8 mOsm/L and must be attributed to biological variability – or instability of the tear film, an indication of failure of the lacrimal system to maintain proper homeostasis. The higher of the two eyes, not the average, is the proper indication of disease severity and should always be considered a bilateral indicator – regardless of which eye is higher. Using this methodology, published literature has established an 87% positive predictive value (PPV) when using tear osmolarity to diagnose dry eye disease, making tear osmolarity the most accurate and reliable measure of any dry eye test.