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Tear Osmolarity in the Diagnosis and Management of Dry Eye Disease

Published:February 10, 2011DOI:https://doi.org/10.1016/j.ajo.2010.10.032

      Purpose

      To evaluate the use of tear osmolarity in the diagnosis of dry eye disease.

      Design

      A prospective, observational case series to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose dry eye disease.

      Methods

      A multicenter, 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age. Bilateral tear osmolarity, tear film break-up time (TBUT), corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal, mild or moderate, or severe dry eye. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic curve, and intereye variability.

      Results

      Of the 6 tests, tear osmolarity was found to have superior diagnostic performance. The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L, whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity. By contrast, the other common tests exhibited either poor sensitivity (corneal staining, 54%; conjunctival staining, 60%; meibomian gland grading, 61%) or poor specificity (tear film break-up time, 45%; Schirmer test, 51%). Tear osmolarity also had the highest area under the receiver operating characteristic curve (0.89). Intereye differences in osmolarity were found to correlate with increasing disease severity (r2 = 0.32).

      Conclusions

      Tear osmolarity is the best single metric both to diagnose and classify dry eye disease. Intereye variability is a characteristic of dry eye not seen in normal subjects.
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      References

        • Tomlinson A.
        Epidemiology of dry eye disease.
        in: Asbell P. Lemp M.A. Dry Eye Disease: The Clinician's Guide to Diagnosis and Treatment. Thieme, New York2006: 1-15
        • International Dry Eye Workshop
        Methodologies to diagnose and monitor dry eye disease.
        in: Report of the International Dry Eye Workshop (DEWS). 2007Ocul Surf. 2007; 5: 108-123
        • Begley C.G.
        • Chalmers R.L.
        • Abetz L.
        • et al.
        The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity.
        Invest Ophthalmol Vis Sci. 2003; 44: 4753-4761
        • International Dry Eye Workshop
        The definition and classification of dry eye disease.
        in: Report of the International Dry Eye Workshop (DEWS). 2007Ocul Surf. 2007; 5: 75-92
        • Sullivan B.D.
        • Whitmer D.
        • Nichols K.K.
        • et al.
        An objective approach to severity in dry eye disease.
        Invest Ophthalmol Vis Sci. 2010; 51: 6125-6130
        • Korb D.R.
        Survey of preferred tests for the diagnosis of the tear film and dry eye.
        Cornea. 2000; 19: 483-486
        • Foulks G.N.
        • Bron A.J.
        Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification and grading.
        Ocul Surf. 2003; 1: 107-126
        • Bell A.J.
        • Sejnowski T.J.
        An information-maximization approach to blind separation and blind deconvolution.
        Neural Comp. 1995; 7: 1129-1159
        • Tomlinson A.
        • Khanal S.
        • Ramaesh K.
        • Diaper C.
        • McFadyen A.
        Tear film osmolarity: determination of a referent for dry eye diagnosis.
        Invest Ophthalmol Vis Sci. 2006; 47: 4309-4315
        • Tomlinson A.
        • McCann L.C.
        • Pearce E.I.
        Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques.
        Cornea. 2010; 29: 1036-1041
        • Khanal S.
        • Tomlinson A.
        • McFadyen A.
        • et al.
        Dry eye diagnosis.
        Invest Ophthal Vis Sci. 2008; 49: 1407-1414
        • Mathers W.D.
        • Lane J.A.
        • Sutphin J.E.
        • Zimmerman M.B.
        Model for ocular tear film function.
        Cornea. 1996; 15: 110-119
        • Gilbard J.P.
        • Farris R.L.
        • Santamaria 2nd, J.
        Osmolarity of tear film microvolumes in keratoconjunctivitis sicca.
        Arch Ophthalmol. 1978; 96: 677-681
        • Rolando M.
        • Refojo M.F.
        • Kenyon K.R.
        Increased tear evaporation in eyes with keratoconjunctivitis sicca.
        Arch Ophthalmol. 1983; 101: 557-558
        • Versura P.
        • Profazio V.
        • Campos E.C.
        Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases.
        Curr Eye Res. 2010; 35: 553-564
        • Bron A.J.
        • Yokoi N.
        • Gafney E.
        • Tiffany J.M.
        Predicted phenotypes of dry eye: proposed consequences of its natural history.
        Ocul Surf. 2009; 7: 78-92
        • Farris R.L.
        • Stuchell R.N.
        • Mandel I.D.
        Tear osmolarity variation in the dry eye.
        Trans Am Ophthalmol Soc. 1986; 84: 250-268
        • Pflugfelder S.C.
        • diPavia C.S.
        • Tong L.
        • Luo L.
        • Stern M.E.
        • Li D.Q.
        Stress activated protein kinase signaling pathways in dry eye and ocular surface disease.
        Ocul Surf. 2005; 3: S154-S157
        • Li D.Q.
        • Chen Z.
        • Song X.J.
        • Luo L.
        • Pflugfelder S.C.
        Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells.
        Invest Ophthalmol Vis Sci. 2004; 45: 4302-4311
        • Luo L.
        • Li D.Q.
        • Corrales R.M.
        • Pflugfelder S.C.
        Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface.
        Eye Contact Lens. 2005; 31: 186-193
        • Lam H.
        • Bleiden L.
        • de Paiva C.S.
        • et al.
        Tear cytokine profiles in dysfunctional tear syndrome.
        Am J Ophthalmol. 2009; 147: 198-205
        • De Paiva C.S.
        • Corrales R.M.
        • Villarreal A.L.
        • et al.
        Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye.
        Exp Eye Res. 2006; 83: 526-535
        • Luo L.
        • Li D.Q.
        • Pflugfelder S.C.
        Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and MAPK pathways.
        Cornea. 2007; 26: 452-460
        • Liu H.
        • Begley C.
        • Chen M.
        • et al.
        A link between tear instability and hyperosmolarity in dry eye.
        Invest Ophthalmol Vis Sci. 2009; 50: 3671-3679

      Biography

      Michael A. Lemp, a corneal specialist, is clinical professor of ophthalmology at Georgetown and George Washington universities, former chair of ophthalmology at Georgetown, and the author of 210 scientific papers and five books. He is retired from clinical practice but is active in clinical research in ocular surface disease. He is founding editor of The Ocular Surface, recipient of the Castroviejo medal, reviewer for eight journals and consultant for companies developing drugs and devices.