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How to use tear osmolarity to help treat dry eye disease


For the patient, perhaps the most significant symptom of DED is fluctuating or reduced vision.

Even in our era of modern health care, it is often challenging to identify and manage dry eye disease (DED)-at least in part because it is often difficult to diagnose.1 This disparity may be due to the fact that in many instances, the signs, symptoms, and severity of the condition correlate poorly or not at all.2 For the patient, perhaps the most significant symptom of DED is fluctuating or reduced vision.

Dry eye and osmolarity

According to the Dry Eye WorkShop (DEWS) definition, dry eye is “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.”3

Related: Combating dry eye with punctal plugs

Stern et al identified the disparate components that function together to protect and nourish the ocular surface:4



Accessory lacrimal glands

Meibomian glands

Main lacrimal gland

Interconnecting innervation system

This cumulative system eventually came to be known as the lacrimal functional unit (LFU).4 The concept of a multi-component unit that protects the ocular surface is vital; it reinforces the theory that failure of one or more segments of the unit can lead to DED. We must consider dry eye as a chronic, bilateral, asymmetric, progressive disease.

In 2014, Bron and colleagues sought to dispel several misconceptions that hamper clinical diagnosis and management of DED. They concluded that “osmolarity appears to be the best marker across all levels of disease severity as well as in different subtypes of DED.”5

Related: How to know when it’s not dry eye

Tear osmolarity

The concept of an association between increased tear osmolarity (TO) and DED is not new. In 1981, Farris published the first report showing a positive correlation among female gender, increasing age, contact lens wear, and elevated TO. Large-scale studies have reinforced the value of TO as a consistent marker in DED.6

In 2006, Tomlinson’s meta-analysis of TO in normal eyes and diverse subtypes of dry eye showed a predictive accuracy of 89 percent for the diagnosis of DED.7


Early research directed at the relationship between elevated TO and DED used the freezing point method of osmometry.8 This method has largely been confined to research facilities because it requires significant expertise, takes considerable time, and necessitates large volume samples of tears.7

In 2009, OcuSense, Inc. received FDA clearance for the TearLab Osmolarity System, a tear osmometer that determines osmolarity values via electrical impedance of tears.9 This ‘‘lab-on-a-chip’’ technology requires a tear sample of approximately 50 nanoliters (nL) to measure osmolarity, and I have found the instrument to be effective and easy use.

To put the required sample size into perspective, a nanoliter is one billionth of a liter. The older freezing point technique required nearly 500 to 1,000 times the volume used by the TearLab system.10

Homeostasis and dry eye

Homeostasis is the process by which biological systems maintain stability in order to survive. Diabetes is good systemic example of failure to maintain homeostasis. When the endocrine system fails to maintain blood glucose levels with a normal range of values, disease and damage result.11

DED can be thought of as a failure of the LFU to maintain homeostasis.5

Failure to maintain normal TO is a common and diagnostic feature of evaporative dry eye disease (EDED), aqueous deficiency dry eye (ADDE), or most commonly a combination of the two.3 In dry eye states, regardless of the type, TO is frequently elevated or asymmetric between the eyes, and the disparity increases with severity of the DED.5,12

Related: First-class dry eye treatment

Incorporating osmolarity

Before I used TearLab in my practice, I was confident in my ability to diagnose DED. As I gained experience in DED management, I realized that in relying on biomicroscopic evaluation, Schirmer strips (now over 100 years old), vital dye staining, and other tests, I missed many patients who had DED. TearLab provided a true biomarker utilizing a lab test in my own office. It changed the way I diagnose and manage DED.

Older techniques still have value, but they are much less consistent and accurate than obtaining osmolarity values.13 We now realize that corneal and conjunctival staining, which are often used as markers to initiate treatment, occur late in the DED process.12 Using staining alone as an indication for initiating dry eye therapy may result in delayed treatment for the majority of dry eye patients.

Because TearLab is a lab test, your office will be considered as such and a Clinical Laboratory Improvement Act (CLIA)-waived category license is required. The process is straightforward. Plus, once you obtain a license, it is typically good for two years and allows other CLIA-waived tests to be performed at your point-of-care clinic.

You will be required to perform several steps to ensure quality control. They are able to be conducted by office staff, and they are essential to ensure your that patients are getting precise readings. This is a small price to pay for having the access to lab tests performed and read in our clinics with quick results in less than eight seconds per eye and available while the patient is in the office.

I recommended implementing two steps in your patient flow protocols to be efficient and effective in determining which patients receive the test and how it will be administered.

First, ask your patients to complete a dry eye-specific questionnaire prior to their exam.

Second, empower technicians to review the questionnaire based on a protocol that you establish, then advise patients who fail the questionnaire that the doctor will want osmolarity test results available for the exam.

This process allows me to review patients’ TO values and discuss results with them during my exam. It also promotes office efficiency and better patient care.

Related: Reduce dropout in patients with dry eye

Patients should refrain from using any eyedrops, including over-the-counter and prescription drops for at least two hours prior to osmolarity testing. If not, we may obtain false low readings. The only two exceptions are topical anesthetic drops and/or dilating drops, which may be used less than two hours prior to osmolarity testing. Ideally, TO is the first test administered, even prior to tonometry or any bright lights, that could cause significant reflex tearing.


Retest and follow

Patient education is the foundation of good care. You may describe dry eye to your patients as simply having too much salt (solutes) in the tear layer and explain that it causes some patients to have any number of symptoms. I explain that our goal is to reduce that level of abnormal osmolarity.

Remember we are evaluating patients’ risk in the management process. There is no “magic” number. Patients like to know their findings and understand their significance. A good example is our colleagues in internal medicine and their long-term model for cholesterol management. They educate patients about the risks of hypercholesterolemia and benefits of preventive care.

Using the higher of a patient’s two eyes’ values as a starting point allows me to assign a severity range. Typically, mild patients range 300 to 320; moderate 320 to 340; and the severe category (only about eight percent of all dry eye) fall above 340.14

Because the TearLab device ranges from 275 to 400 mOsml/L, I can show each patient where he falls along a severity scale and avoid obsessing on an absolute number. Keep in mind the CV with TearLab is <1.5 percent, which is the equivalent to about ± 4 mOsm/L.

Going back to our cholesterol example, internists are not concerned about whether a patient’s total cholesterol is 201 or 198 mg/dL-rather, they want to know if the patient is in a mild, moderate, or high risk category for cardiovascular disease. Once they review the lab results, they establish a specific goal of therapy for each patient.

The same holds true for our management of patients with dry eye disease.

In some cases, patients may present very early in the process with intereye differences >8 mOsm/L but still have bilateral TO readings less than 300 mOsml/L; this is the classic sign of an unstable tear film.

Related: Complementary and alternative medicine help dry eye patients

If I have a high suspicion of DED, especially with significant intereye difference, retesting TO on subsequent visits may reveal higher values. Knowing that lab tests are not about an exact number but rather a range of values, I do not hesitate to repeat tests.

The caveat is that an intereye difference >8 mOsm/L is considered to be abnormal. If patients show normal values on a subsequent visit, I follow them over time to ensure they do not convert to elevated levels of hyperosmolarity that are potentially harmful.

Monitoring treatment

Once you have determined the underlying etiology of the DED, explained the results to the patient, and developed a treatment plan, the next step is monitoring the process. One additional benefit to tear testing is improved compliance because patients understand that you will be repeating this test when they return. Remind the patient not to use any drops on the day of the next visit to prevent unreliable test results.

Avoid the error of bringing the patient back too soon. A 10 mOsml/L decrease is considered clinically significant, but some therapies require at least four to six weeks before this goal is reached.

In some cases, a patient may return and despite good compliance have TO values higher than those obtained on the initial evaluation. The patient should be advised this is valuable information because it tells you her DED is more severe than initially thought and you will prescribe more aggressive therapy.

In my experience, the patient-doctor education made possible by lab tests facilitates a very high level of patient management.

Dry eye care is one of the most rewarding but challenging facets of my practice. Osmolarity testing has changed my treatment philosophy by providing additional information to help me diagnose and manage DED more effectively. In my opinion, many unsuccessful dry eye treatment plans result from failing to recognize the true severity of a patient’s condition and prescribe appropriate therapeutic measures.

Related: How TFOS brought dry eye to the forefront of optometry



1. Bartlett JD, Keith MS, Sudharshan L, Snedecor SJ. Associations between signs and symptoms of dry eye disease: a systematic review. Clin Ophthalmol. 2015 Sep 16;9:1719-1730.

2. Barabino S, et al. Understanding symptoms and quality of life in patients with dry eye syndrome. Ocul Surf. 2016 Jul;14(3):365-376.

3. The Definition and Classification of Dry Eye Disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):75-92.

4. Stern ME, et al. The role of the lacrimal functional unit in the pathophysiology of dry eye. Exp Eye Res. 2004 Mar;78(3):409-416.

5. Bron AJ, Tomlinson A, Foulks GN, Pepose JS, Baudouin C, Geerling G, Nichols KK, Lemp MA. Rethinking dry eye disease: a perspective on clinical implications. Ocul Surf. 2014 Apr;12(2 Suppl):S1-31.

6. Farris RL, Stuchell RN, Mandel ID. Basal and reflex human tear analysis. I. Physical measurements: osmolarity, basal volumes, and reflex flow rate. Ophthalmology. 1981 Aug;88(8):852-857.

7. Tomlinson A, McCann LC, Pearce EI. Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques. Cornea. 2010 Sep;29(9):1036-1041.

8. Gilbard JP, Farris RL. Ocular surface drying and tear film osmolarity in thyroid eye disease. Acta Ophthalmol (Copenh). 1983 Feb;61(1):108-116.

9. Jacobi C, Jacobi A, Kruse FE, Cursiefen C. Tear film osmolarity measurements in dry eye disease using electrical impedance technology. Cornea. 2011 Dec;30(12):1289-1292.

10. Zarbin MA, Montemagno C, Leary JF, Ritch R. Nanotechnology in ophthalmology. Can J Ophthalmol. 2010 Oct;45(5):457-476.

11. Holst JJ, Gribble F, Horowitz M, Rayner CK. Roles of the Gut in Glucose Homeostasis. Diabetes Care. 2016 Jun;39(6):884-892.

12. Lemp MA, Bron AJ, Baudouin C, Benítez Del Castillo JM, Geffen D, Tauber J, Foulks GN, Pepose JS, Sullivan BD. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011 May;151(5):792-798.e1.

13. Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res. 2010 Jul;35(7):553-564.

14. Potvin R, Makari S, Rapuano CJ. Tear film osmolarity and dry eye disease: a review of the literature. Clin Ophthalmol. 2015 Nov 2;9:2039-3047.

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