Osmolarity and Dry Eye

It has been theorized that osmolarity changes in the tears have a direct impact on ocular surface abnormalities and decreases in conjunctival goblet cell density.1 Researchers found that by reducing the osmolarity via an artificial tear formulation with a demulcent and a buffering system, rose Bengal staining and patient dry eye symptoms decreased. Research has also shown that, in contact lens wearers who suffer from dry eye, there is less tear exchange, which results in increased tear evaporation from the lens surface, resulting in osmolarity changes.2


A study in 1985 showed a change in proteins and enzymes, such as lactoferrin and lysozyme, thus altering the tear components and indirectly showing a change in osmolarity of the tears.3 In fact, patients with Sjgrens Syndrome have about half the concentration of lactoferrin in the tears compared to normal levels.4 Studies have further evidence to associate an altered ocular surface, decreased corneal epithelial integrity and increased staining in eyes with reduced lactoferrin.5 So, a change in the normal proteins of the team film, which is typically 6 to 10 g/l, would be observed as a change in tear osmolarity (overall solutes as a percentage of solution), which also then has a correlation to the presence of an inflammatory process.6 This could also explain why medications such as Restasis and Lotemax are effective in the management of dry eye.7,8


From a diagnostic perspective it is theorized that keratoconjunctivitis sicca (KCS) may represent a chronic wound-healing response to a poorly lubricated and inflamed ocular surface; thus, vital dye staining may elicit which areas of surface damage are an indicator for KCS and inflammation.9 Having a test that can determine early osmolarity changes, however, would be of immense value in the diagnosis of dry eye.

 

Tear Testing

In the near future, additional technology will offer a new way to help diagnose and monitor the treatment of dry eye. OcuSenses TearLab technology is a tear-testing platform that measures various biomarkers in the tear film. The TearLab is a two-part system that consists of a disposable, microfluidic lab card and an instrument that reads the lab card and displays the results.


Although technologies exist to analyze tears, they often require microliter volumes of tears, which may induce reflex tearing and cause diagnostic variability. TearLab requires less than 50 nanoliters of tear film and has been designed to be Clinical Laboratory Improvement Amendments (CLIA)-waived. Each test takes less than two minutes to perform.


The TearLab allows clinicians to measure biomarkers in the tear to assist in making a differential diagnosis or in choosing a specific therapeutic regime.


OcuSense has chosen to initially test for osmolarity. Literature has demonstrated the role of osmolarity in tear homeostasis and disease pathogenesis.10 Elevated tear osmolarity has been identified as a global characteristic of dry eye disease. An increase in tear osmolarity results from a more concentrated salt concentration in tears, which occurs in both aqueous tear deficiency and evaporative dry eye, such as is seen in meibomian gland dysfunction.


It is possible that many of the current studies underestimate the elevation of tear osmolarity due to the dilutional factor. Despite this, the studies still report substantial differences between normal subjects and dry eye patients. A statistical meta-analysis of the literature on tear osmolarity over the last twenty years revealed that tear osmolarity was one of the most accurate diagnostic tests for dry eye, with a 90% accuracy rate when compared with other standard diagnostic tests.
11


The osmolarity test could assist clinicians in making a rapid differential diagnosis and enable a quantitative measurement of disease severity. OcuSense envisions that its osmolarity test could also serve as a basis for disease management, facilitating a more personalized prescribing decision and a method of tracking treatment outcomes.


In addition, OcuSense is developing tests to measure other biomarkers in the tear film, such as immunoglobulin E (IgE) for the diagnosis and management of ocular allergy. Considering that symptoms of dry eye and ocular allergy present similarly to the clinician,12 IgE is a synergistic biomarker with osmolarity to further differentiate these disease states.


The company also plans to develop other tests that can further distinguish dry eye and allergy patients by disease type, offering clinicians even more information when making prescribing choices.


New technologies continue to emerge and join the existing arsenal of diagnostic tests that allow us to provide better patient care in the diagnosis and management of dry eye disease.


Dr. Karpecki is clinical and education conference advisor for Review of Optometry and a contributing editor.  He is also a consultant to Allergan and Bausch & Lomb and serves on the Advisory Board for OcuSense.  The author thanks Michael A. Lemp, M.D., chief medical officer of OcuSense Inc., and Eric Donsky, CEO of OcuSense, who contributed to this article. 

 

1. Gilbard JP, Rossi SR, Heyda KG.  Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation.  American Journal of Ophthalmology.  2989 Apr15;107(4)348-55 .

2. Lemp MA.  Is the dry eye contact lens wearer at risk? Yes.  Cornea.  2990;9 Suppl 1:S48-50.

3. Baum J.  Clinical manifestations of dry eye states.  Trans Ophthalmology Soc of UK.  1985;104(pt 4):415-23.

4. Fujihara T, Nagano T, Nakamura M. et al.  Lactoferrin suppresses loss of corneal epithelial integrity in a rabbit short-term dry eye model.  Journal of Ocular Pharmaceutical Therapeutics.  1998 Apr;14(2):99-107.

5. Fujihara T, Nagano T, Nakamura M. et al.  Lactoferrin suppresses loss of corneal epithelial integrity in a rabbit short-term dry eye model.  Journal of Ocular Pharmaceutical Therapeutics.  1998 Apr;14(2):99-107.

6. Batellier L, Rea A, Chaumeil C et al.  Protein evaluation of tears: different biological parameters and their respective value.  Journal of French Ophthalmology.  1996;19(8-9):520-6.

7. Perry HD, Donnenfeld ED.  Topical 0.05% cyclosporine in the treatment of dry eye.  Expert Opinion Pharmacotherapy.  2004 Oct;5(10):2099-107. 

8. Pflugfelder SC, Maskin SL, Anderson B et al.  A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.05% and placebo for treatment of KCS in patients with delayed tear clearance.  American Journal of Ophthalmology.  2004 Sep;138(3):444-57.

9. Pflugfelder SC.  Advances in the diagnosis and management of KCS.  Current Opinions in Ophthalmology.  1998 Aug;9(4):50-3.

10. Farris RL, Stuchell LRN, Mandel ID. Tear osmolarity variation in the dry eye. Trans Am Ophthalmol Soc 1986;84:250-68.

11. Bron AJ, Tiffany JM, Yokoi N, Gouveia SM. Using osmolarity to diagnose dry eye: a compartmental hypothesis and review of our assumptions. Adv Exp Med Biol 2002;506(Pt B):1087-95.

12. Albeitz JM.  Conjunctival histology findings of dry eye and non-dry eye contact lens wearing subjects.  CLAO Journal.  2001 Jan;27(1):35-40.

Vol. No: 144:02Issue: 2/15/2007