New technology may objectively confirm patients’ subjective dry eye symptoms

Tear osmolarity measurements may provide a biomarker of dry eye severity.

Optometrists are finding that a new in-office diagnostic technology from TearLab Corp. helps guide their dry eye treatment regimen and improves patient compliance.

William Townsend, OD, FAAO, told Primary Care Optometry News that he conducts the TearLab Osmolarity Test on any patient whose complaints or physical findings suggest dry eye disease.

Chuck Aldridge, OD, said in an interview, “We know about 90% of dry eye patients are in level 1 and 2 (according to International Task Force guidelines), so they have symptoms, but little or no signs. Therefore, if a patient’s symptoms lead you to suspect they have dry eye, you can test them to not only confirm your diagnosis, but to gain an understanding of the severity.”

Clinical study results

Figure 1. Approximately 50 nL of tear is collected from the inferior lateral tear meniscus using electrical impedance. Clinical testing has shown the sampling to be performed in as few as 5 to 6 seconds. Image: Eldridge DC

Clinical testing of the TearLab device in more than 300 patients showed a strong correlation with a diagnosis of dry eye based upon composite clinical signs and symptoms of dry eye disease, particularly in mild to moderate disease. According to research performed by Gary N. Foulks, MD, FACS, and colleagues, the TearLab Osmolarity System more accurately predicted the severity of a patient’s dry eye disease compared with tests traditionally used to make a diagnosis.

According to the study, the TearLab is designed to measure osmolarity of a tear sample, approximately 50 nL collected from the inferior lateral tear meniscus of the ocular surface, using electrical impedance. In clinical testing, tear sampling has been performed in as few as 5 to 6 seconds, with calculation of osmolarity taking less than 20 seconds, Dr. Foulks said.

In patients with severe dry eye, tear film breakup time showed the strongest correlation with the severity score, with 98.7% sensitivity, while osmolarity had 94.7% sensitivity in this category of patients. However, osmolarity outperformed each diagnostic test in normal eyes and in eyes with mild or moderate dry eye.

In clinical practice, Dr. Townsend said he has “seen very good correlation between patient symptoms, objective findings and tear film osmolarity. It is interesting to note that some patients with significant ocular surface disease may have widely varying tear film osmolarity values. My impression is that it is often caused by hypersecretory tearing as part of the reflexive mechanism.

“This does not reflect badly on the technology, but rather gives us some insight as to what is going on in the eyes of patients with ocular surface disease,” he added.

Osmolarity mirrors, predicts severity of symptoms

Dr. Aldridge also said he is finding that the osmolarity “closely mirrors symptoms (inflammation), and changes in osmolarity precede symptoms, which helps us adjust treatment.

“For example, a patient may have osmolarity of 390 mOsms/L, which is high, and he or she is obviously experiencing symptoms,” he said. “We start treatment, and at their follow-up they are still complaining, so we are tempted to ramp up their treatment. But when we repeat the TearLab, we find their osmolarity is 320 mOsms/L, still in the inflammatory range, but improving. We share the number with the patient and convince them to stay the course and, sure enough, shortly thereafter the symptoms improve.”

Seeing their TearLab numbers improve, in turn, improves patient compliance, Dr. Aldridge added.

Improved patient care

“A literature review would show a lack of correspondence between subjective symptoms reported by patients and the objective signs we observe and the test results from biomicroscopy, staining, Schirmer’s testing, etc.,” Dr. Townsend said. “So far, we are impressed by the positive correlation we observe between patients’ complaints, evaluation of the ocular surface and tear film osmolarity values obtained with the TearLab instrument.”

“Patients love technology and are all about numbers,” Dr. Aldridge said. “Diabetics have numbers, hypertensives have numbers and if you’re watching your weight or cholesterol you have a number. Even my glaucoma patients remember their IOP from the last visit. They love having feedback on their treatment, and it helps them understand that there is a reason why they’re suffering.”

“In most instances, patients go to the lab, have blood drawn and leave,” Dr. Townsend said. “Days or weeks later, they may get a sheet with the results. In this instance, they see the test taking place before their eyes. In only a few seconds, they can see the values on the instrument. And once we explain what the numbers mean, they understand that hyperosmolarity is part of the overall disease process we call ‘ocular surface disease.’”

Patient selection, flow

Dr. Townsend is conducting a dry eye study using this new technology. Patients in his practice who meet certain criteria will be administered the TearLab test. “The criteria are really pretty simple: we identify patients who have signs and symptoms suggesting dry eye,” he said. “We instruct them not to use any drops at least 2 hours prior to the evaluation. We want to avoid a situation where the patient lives at a considerable distance from our practice; using drops can invalidate our readings and would necessitate an extra trip to the clinic.”

Dr. Aldridge said that if a patient has already experienced drops for dilation or tonometry, he may begin treatment and then schedule a follow-up visit for TearLab testing.

What the numbers mean

According to David C. Eldridge, OD, FAAO, vice president of professional development for TearLab Corp., a patient without dry eye disease will typically measure less than 308 mOsms/L and will be consistent between eyes. “Our research shows that levels of osmolarity in ‘normals’ vary by only 5 mOsms/L to 7 mOsms/L during the day, both intra-eye and inter-eye,” Dr. Eldridge told PCON. “Be suspicious if a patient has a difference between eyes of more than 8 mOsms/L to 10 mOsms/L. Dry eye disease is similar to glaucoma, where patients may have variable IOPs, and normals typically have less of a diurnal swing.”

Dr. Eldridge said “compensatory mechanisms” may result in a normal measurement in the first eye while the second eye measures above normal. “As we learn more about dry eye disease, we find that high osmolarity causes an unstable tear film to form, which is why it is critical to take the higher measurement of the two eyes when making a diagnosis,” he said. “The more unstable the tear film, the higher the osmolarity. Does the osmolarity cause the instability or vice versa?”

When patients are treated properly, Dr. Eldridge said, their osmolarity becomes lower and more stable over time, much the same way clinicians observe changes in blood pressure or IOP during treatment, he said.

According to Dr. Foulks’ study, patients with normal or severe disease severity scores were more likely to have a repeatable value on their osmolarity test, but patients with mild or moderate dry eye typically had greater variability on retest. That variability, he said, is the hallmark of disease and may be due to the decreased ability of the eye with mild or moderate dry eye to respond to environmental stimuli or insult, such that “a stress that would disturb the tear osmolarity in a mild to moderate patient would be compensated for in a normal patient with adequate reflex tearing.”

Making the diagnosis

“Some patients present with dry eye-like symptoms, but show consistently low osmolarity readings,” Dr. Eldridge said. “We have found that because dry eye disease is multifactorial, many clinicians attribute nonspecific ocular surface disease, by default, to dry eye. However, if a patient’s osmolarity is consistently low in both eyes, their symptoms are most likely not caused by dry eye disease, but by an undetected allergy, infection or inflammation around the nerve. With consistently low osmolarity, you can be confident that the lacrimal and meibomian glands are doing their job.

“TearLab is extremely accurate, but it shouldn’t replace the clinician’s skills in differential diagnosis,” Dr. Eldridge added. “It may be necessary to take a few readings over time to get a clear picture. This is not unlike our glaucoma patients when we repeat tonometry or visual fields to confirm our clinical suspicions.”

Dr. Foulks agreed, saying his study results indicate the need to evaluate values from one eye vs. the other. “In those patients suspected of having mild dry eye, it may take more than one measurement to prove your point,” he said.

Future directions

If tear osmolarity can function as a surrogate biomarker of disease severity, and if it can give clinicians an accurate portrayal of response to therapy over time, the testing modality may also be important for clinical trials involving new therapies for dry eye. Currently, the U.S. Food and Drug Administration does not recognize surrogate biomarkers as an endpoint upon which to base approval of new drugs or therapies.

In October, TearLab Corp. announced that according to the recommended payment determination for new codes issued by the Committee for Medicare and Medicaid Services, a new Current Procedural Terminology (CPT) code will apply to the TearLab Osmolarity Test as of January 2011 for reimbursement of $24.01 per eye.

According to a company press release, “reimbursement by CMS will only be available for offices with a moderate complex Clinical Laboratory Improvement Amendments (CLIA) certificate until TearLab receives a CLIA waiver categorization from the FDA. – by Nancy Hemphill, ELS, and Bryan Bechtel

• Chuck Aldridge, OD, is available at Aldridge Eye Institute, PO Box 218, Burnsville, NC 28714; (828) 682-2104; ccaldridge@yahoo.com. Dr. Aldridge is on the Clinical Advisory Board for TearLab.
• David C. Eldridge, OD, FAAO, vice president of professional development for TearLab Corp., can be reached at (918) 299-7443; dceldridge@gmail.com.
• Gary N. Foulks, MD, FACS, can be reached at University of Louisville Department of Ophthalmology and Visual Science, 301 E. Muhammad Ali Blvd., Louisville, KY 40202; (502) 852-7665; gnfoul01@gwise.louisville.edu. Dr. Foulks is a paid consultant to TearLab.
• William Townsend, OD, is available at Advanced Eye Care, 1801 4th Ave., Canyon, TX 79015; (806) 655-7748; drbilltownsend@gmail.com. Dr. Townsend is conducting gratis research using a TearLab instrument. He is on the Clinical Advisory Board for TearLab.