Although tear osmolarity has been reported to be the single best marker for dry eye disease, its measurement has been limited to laboratory instruments requiring large microliter volumes of tear fluid, unsuitable for use at most clinical study sites.
The new TearLab Osmolarity System changes all this. Now, for the first time, the dry eye researcher has a tool to accurately and objectively test tear osmolarity in a matter of seconds at the point of care. Recent studies have established osmolarity as the dry eye test that best correlates to disease severity. And in the most common forms of the disease – the mild to moderate category – osmolarity is essentially the only test that can correctly identify dry eye subjects. All other tests were no better than “random number generators” in this category of patients (Foulks, GN, TearLab Osmolarity as a Biomarker for Disease Severity in Mild to Moderate Dry Eye Disease – http://www.tearlab.com/products/doctors/articles.htm).
Critical to good study design, osmolarity can now be used to establish inclusion or exclusion criteria, accurately define and enroll normal or dry eye cohorts and establish objective and quantitative clinical end-points.
The following are ten tips on the use of the TearLab Osmolarity System in your research or clinical study for Dry Eye Disease. These recommendations address issues in study design that will give your trial the best chance of success.
1- Test Two Eyes
Although dry eye is a bilateral disease, it is not symmetrical. It is imperative to test both eyes and take the higher of the two numbers – which will more accurately reflect the disease process.
2- Testing Order
It is important that the least invasive tests be performed first to avoid destabilizing the tear film. Nanoliter volume tear collection used in TearLab osmolarity testing is the least invasive test and should always be performed first.
3- Eye Drops and Medications
If the subject is using eye drops or topical medication, either as part of the study or on their own, it is essential that the subject be instructed to stop using eye drops at least 2 hours prior to testing to allow time for the drop to clear from the eye. After all, it is the osmolarity of the basal tear that is of interest, not the osmolarity of the eye drop.
4- Contact Lens Studies
Contact lens wear will affect osmolarity differently in normal and dry eye subjects so correctly identify dry eye subjects prior to recruitment and without the effect of contact lens wear. Also, you must measure the effect of lens wear with the lens in the eye, as tear film may return to normal levels over time after removal of the lens.
5- Inclusion / Exclusion Criteria
Tests such as staining that do not correlate well with severity may mis-categorize study subjects if used for inclusion criteria. Incorrectly recruiting subjects into your normal or dry eye cohort can doom a study, even before it begins. Techniques have been developed using osmolarity as a selection criteria that can correctly identify dry eye subjects nearly 100% of the time. (Eldridge, DC, Longitudinal Variability of Tear Film Osmolarity in Normal and Dry Eye Patients – http://www.tearlab.com/products/doctors/articles.htm).
6- Symptom Questionnaire
If your study tracks symptoms, it is important to consider a symptom questionnaire that includes a measure of relative change in symptoms following the onset of therapy, e.g., visual analog scales or the “Symptom Assessment iN Dry Eye” (SANDE) questionnaire.
7-Treatment Logs
If your study requires use of eye drops, medications or nutritional supplements, a daily log documenting usage will encourage compliance, and allow you to identify non-compliance during data analysis.
8- Training
Although TearLab is extremely simple to operate, it is important that the operation of the device, including tear collection, follows manufacturer recommendations to ensure accurate results. TearLab offers a training video to assist in this effort - http://www.tearlab.com/products/doctors/videos.htm.
9-Daily Quality Control
Take the guesswork out of your data set. Running daily control solutions will provide confidence in your osmolarity data, even when the study is presenting unexpected or unusual results. TearLab offers a convenient Daily Quality Control Log and procedure to assist researchers in maintaining quality control during their study - http://www.tearlab.com/products/doctors/research.htm.
10- Data Analysis
The multifactorial nature of dry eye disease makes statistical analyses non-trivial. Analyzing data against a composite severity scale often clarifies the clinical end points. The TearLab Clinical team is available to assist study investigators in utilizing independent component analysis to implement a severity scale in your data assessment.
TearLab Corporation (www.tearlab.com) provides a “TearLab Research Guide” (http://www.tearlab.com/products/doctors/research.htm) that lists and discusses these points in greater detail and is available free of charge. In addition they will provide assistance in study design, protocol review and recommendation, as it pertains to the measurement of tear film osmolarity.
Dry eye clinical studies are time consuming, expensive and complex. Adding a simple, objective and quantitative tool such as TearLab to your study design may prove to be the one factor that makes the study a success, both in implementation and outcome.
