Dry eye disease affects up to 20% of the population in North America.¹ Dry eye disease has a number of risk factors: aging, androgen deficiency, chronic environmental stress, changes in blink patterns, systemic autoimmune disease, systemic drugs, corneal nerve damage during surgery, contact lens wear, and preservative toxicity of topical medications.² Regardless of which of the risk factors initiate the process, the Dry Eye Workshop reports that the final common pathway leads to the core manifestations of tear film instability and tear hyperosmolarity.³ Tear osmolarity has been reported to be the single best marker for dry eye disease.³

Tear osmolarity is believed to be a global indicator of dry eye disease independent of its etiology.⁴ A recent multicenter study evaluating the clinical usefulness of tear osmolarity and commonly used objective tests (tear break up time, corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading) to diagnose dry eye disease found tear osmolarity to have superior diagnostic performance.² At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity in this study.² The authors concluded that tear osmolarity is the single best metric to both diagnose and classify dry eye disease.² In an earlier study⁵, compared with a panel of the most commonly used objective tests for dry eye disease, tear osmolarity was found to represent "the best single test for the diagnosis of dry eye" and is suitable for use in the clinical setting.^6,7

Consistent with its status as a global marker for dry eye disease, tear osmolarity was the only sign that exhibited meaningful correlation across normal, mild to moderate, and severe categories of dry eye disease in a ten site clinical study.⁸ Tear film hyperosmolarity has long been associated with an increase in dry eye disease severity.⁸ This makes inherent sense, as an increase in the concentration of the tear fluid has also been implicated as the central pathogenic mechanism that is common to all forms of dry eye disease.⁹ A recent study also demonstrated that osmolarity showed the lowest variability among the commonly used objective tests for dry eye disease.¹⁰ This study also demonstrated that osmolarity was the only sign sensitive enough to reveal changes in tear physiology, and the only sign to reduce its variation after treatment.¹⁰ Previous studies have shown that the therapeutic reduction of tear osmolarity is followed by an improvement in patient symptoms.¹¹

Conclusion
The lack of correlation between the signs and symptoms of dry eye disease seems to favor tear film osmolarity as the best current clue to the correct diagnosis.¹² Because of the dynamic and often transient nature of all dry eye disease markers, our assessment is required to piece together a complete portrait of the patient's dry eye status to form a basis for therapy. In this sense, the application of tear osmolarity is similar to how intraocular pressure and blood pressure are used clinically.^13,14

However, all the aforementioned studies indicate that effective dry eye therapy should achieve a stable, low tear film osmolarity. How do we measure that in our offices? We will discuss that in the next newsletter.

REFERENCES
1. Tomlinson A. Epidemiology of dry eye disease. In: Asbell P, Lemp MA, eds. Dry Eye Disease: The Clinician's Guide to Diagnosis and Treatment. New York: Thieme, 2006: 1-15.
2. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011; 1512: 792-798.
3. International Dry Eye Workshop. The definition and classification of dry eye disease. In: 2007 Report of the International Dry Eye Workshop (DEWS). Ocul Surf 2007; 5 (2): 75-92.
4. International Dry Eye Workshop. The definition and classification of dry eye disease. In: 2007 Report of the International Dry Eye Workshop (DEWS). Ocul Surf 2007; 5 (2): 65-204.
5. Korb DR. Survey of preferred tests for the diagnosis of the tear film and dry eye. Cornea 2000; 19 (4): 483-486.
6. International Dry Eye Workshop. Methodologies to diagnose and monitor dry eye disease. In: 2007 Report of the International Dry Eye Workshop (DEWS). Ocul Surf 2007; 5 (2): 108-123.
7. Tomlinson A, Khamil S, Ramaesh K, et al. Tear film osmolarity: determination of a reference for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006; 47 (10): 4309-4315.
8. Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010; 51 (12): 6125-6130.
9. Gilbard JP, Rossi SR. Changes in tear ion concentration in dry eye disorders. Adv Exp Med Biol 1994; 350: 529-533.
10. Sullivan BD, Crews LA, Sonmez B, et al. Clinical utility of objective tests for dry eye disease: Variability over time and implications for clinical trials and disease management. Cornea 2012; 31: 1000-1008.
11. Nelson JD, Farris RL. Sodium hyaluronate and polyvinyl alcohol artificial tear preparations. A comparison in patients with keratoconjunctivitis sicca. Arch Ophthalmol 1988; 106: 484-487.
12. McGinnigle S, Naroo SA, Eperjesi F. Evaluation of dry eye. Surv Ophthalmol 2012; 57 (4): 293-316.
13. Tatasciore A, Renda G, Zimarino M, et al. Awake systolic blood pressure variability correlates with target organ damage in hypertensive subjects. Hypertension 2007; 50: 325-332.
14. Fogagnolo P, Sangermans C, Oddone F, et al. Long-term perimetric fluctuation in patients with different stages of glaucoma. Br J Ophthalmol 2011; 95: 189-193.