The Analysis of Tear Biomarkers in the Diagnosis of Dry Eye Disease
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Published:
Aug 22, 2020
Keywords:
biomarker, dry eye disease, tear
Main Article Content
Abstract
Introduction: The diagnosis of dry eye disease (DED) especially in the early stages is important, but difficult. This is due to the lack of a gold standard and a poor correlation between the biochemical changes in tears and clinical signs. Tear biomarkers can be used in diagnosing and monitoring DED because they are non-invasive, and have a good correlation with biochemical changes in tears and disease progression.
Purpose: This article will describe some of the most important tear biomarkers for DED, namely markers for lacrimal gland dysfunction, inflammation, oxidative stress, and contact lens intolerance, and its correlation with subtypes and disease severity.
Method: The method used is literature study using the last 10 years journals obtained from search engines such as Sciencedirect, PubMed, Google Scholar and ClinicalKey.
Discussion: Biomarkers for lacrimal gland dysfunction are characterized by changes in protein levels (lactoferrin, lysozyme, etc.), neuromediators (NGF, CGRP, NPY, Serotonin), and mucin ((MUC)5AC); while the inflammatory response is characterized by changes in the expression of cytokines, chemokines, MMP-9, and albumin. Oxidative stress is characterized by changes in lipid levels (HNE, MDA). Meanwhile contact lens intolerance is associated with changes in 1D1-secretoglobin, β2-microglobulin, lacritin, secretoglobin 1A2, albumin, LPRR4, LCN-1, and PIP.
Conclusion: MMP-9 and a combination of Mammaglobin-B, lipophilin-A, and B2MG are biomarkers with the highest sensitivity and specificity of other biomarkers. Some of these biomarkers can be used to diagnose DED, differentiate between Sjögren DED syndrome and non-Sjögren DED syndrome, ADDE from EDE, and determine the severity of the disease.
Article Details
How to Cite
Furqan, M., Sidhi, S., & Amsari, L. (2020). The Analysis of Tear Biomarkers in the Diagnosis of Dry Eye Disease. JIMKI: Jurnal Ilmiah Mahasiswa Kedokteran Indonesia, 8(2), 146-158. https://doi.org/10.53366/jimki.v8i2.123
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References
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26. Versura P, Bavelloni A, Grillini M, Fresina M, Campos EC. Diagnostic performance of a tear protein panel in early dry eye. Mol Vis. 2013;19:1247–57.
27. Guo Q, Huang H, Pi Y, Zhang H. Evaluation of tear malate dehydrogenase 2 in mild dry eye disease. Eye Sci. 2014;29(4):204–8.
28. Schicht M, Rausch F, Beron M, Jacobi C, Garreis F, Hartjen N, Beileke S, Kruse F, Bräuer L, Paulsen F. Palate lung nasal clone (PLUNC), a novel protein of the tear film: three-dimensional structure, immune activation, and involvement in dry eye disease (DED). Invest Ophthalmol Vis Sci. 2015; 56(12):7312–23.
29. Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S. Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol. 2011;129:981–6.
30. Chhadva P, Lee T, Sarantopoulos CD, Hackam AS, McClellan AL, Felix ER, Levitt RC, Galor A. Human tear serotonin levels correlate with symptoms and signs of dry eye. Ophthalmology. 2015;122(8):1675–80.
31. Wei Y, Asbell PA. The core mechanism of dry eye disease (DED) is inflammation. Eye Contact Lens. 2014;40:248–56.
32. Seens S, Tong L. Dry eye disease and oxidative stress Acta Ophthalmol. 2018;96:e412–20.
33. Choi W, Lian C, Ying L, et al. Expression of lipid peroxidation markers in tear film and ocular surface of patients with non-Sjogren syndrome: potential biomarkers for dry eye disease. Curr Eye Res. 2016;41:1143–9.
34. Labbe A, Brignole-Baudouin F, Baudouin C. Ocular surface investigation in dry eye. J Fr Ophthalmol. 2007;30:76–97.
35. Chiva A. Electrophoresis of tear proteins as a new diagnostic tool for two high risk groups for dry eye: computer users and contact lens wearers. J Med Life. 2011;4:228–33.
36. Kramann N,Boehm N, Lorenz K, et al. Effects of contact lenses on the protein composition in tear film: a ProteinChip study. Graefes Arch Clin Exp Ophthalmol. 2011;249:233–43.
37. Glasson MJ, Stapleton F, Keay L, et al. Differences in clinical parameters and tear film of tolerant and intolerant contact lens wearers. Invest Opt Vis Sci. 2003;44:5116–24.
38. Wilcox MD. Is there a role for inflammation in contact lens discomfort? Eye Contact Lens. 2017;43:5–16.
39. Still KM, Soyars CL, Velez F, et al. Development of quantitative sandwich ELISAs for lacritin and the lacritin-c splice variant in human tears. Invest Ophthalmol Vis Sci. 2012;53:4233.
40. Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA. Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea. 2009; 28(9):1023–7.
41. Yoon KC, Park CS, You IC, Choi HJ, Lee KH, Im SK, Park HY, Pflugfelder SC. Expression of CXCL9, −10, −11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Invest Ophthalmol Vis Sci. 2010;51(2):643–50.
42. Sambursky R, Davitt WF, Latkany R, Tauber S, Starr C, Friedberg M, et al. Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. Arch Ophthalmol. 2013;131(1):24–8.
2. Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, et al. TFOS DEWS II Epidemiology Report. Ocul Surf [Internet]. 2017;15(3):334–65. Available from: http://dx.doi.org/10.1016/j.jtos.2017.05.003
3. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017;182:90–8.
4. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009;3(1):405–12.
5. Chiva A. Tear Biomarkers in Dry Eye Disease. Eur Ophthalmic Rev. 2019;13(1):21.
6. Chiva A. Dry Eye and Clinical Disease of Tear Film – Diagnosis and Management. Eur Ophthalmic Rev. 2014;08(01):8.
7. Bron AJ, Tomlinson A, Foulks GN, Pepose JS, Baudouin C, Geerling G, et al. Erratum: Erratum to: Rethinking dry eye disease: A perspective on clinical implications (Ocul Surf (2014) 12:2S (S1-S32)). Ocul Surf. 2014;12(3):231.
8. Willcox MDP, Argueso P, Georgiev GA, et al. TFOS DEWS II tearfilm report. Ocul Surf. 2017;15:366–403.
9. Versura P, Campos EC. Update on human tear proteome. European Ophthalmic Review. 2013;7:36–41.
10. Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II report executive summary. Ocul Surf. 2017;15:802–12.
11. Nichols JJ, Wilcox MD, Bron AJ, et al. The TFOS international workshop on contact lens discomfort: executive summary. Invest Ophthalmol Vis Sci. 2013;54:TFOS7–13.
12. Alipour F, Khaheshi S, Soleimanzadeh M, et al. Contact lens-related complications: a review. J Ophthalmic Vis Res. 2017;12:193–204.
13. Stephens DN, McNamara NA. Altered mucin and glycoprotein expression in dry eye disease. Ophtom Vis Sci. 2015;92:931–8.
14. Chiva A. Dry eye and clinical disease of tear film, diagnosis and management. European Ophthalmic Review. 2014;8:8–12.
15. González-Chávez SA, Arévalo-Gallegos S, Rascón-Cruz Q. Lactoferrin: structure, function and applications. Int J Antimicrob Agents. 2009;33(4):301.e1-301.e8.
16. D’Souza S, Tong L. Practical issues concerning tear protein assays in dry eye. Eye Vis. 2014;1(1):1–12.
17. Versura P, Nanni P, Bavelloni A, Blalock WL, Piazzi M, Roda A, et al. Tear proteomics in evaporative dry eye disease. Eye [Internet]. 2010;24(8):1396–402. Available from: http://dx.doi.org/10.1038/eye.2010.7
18. Callewaert L, Michiels CW. Lysozymes in the animal kingdom. J Biosci. 2010;35(1):127–60.
19. Sun Z, Hong J, Liu Z, Jin X, Gu C. Coal dust contiguity-induced changes in the concentration of TNF- and NF- B p65 on the ocular surface. Ocul Immunol Inflamm. 2009;17(2):76–82.
20. Hagan S, Martin E, Enríquez-de-Salamanca A. Tear fluid biomarkers in ocular and systemic disease: Potential use for predictive, preventive and personalised medicine. EPMA J [Internet]. 2016;7(1):1–20. Available from: http://dx.doi.org/10.1186/s13167-016-0065-3
21. Aluru SV, Agarwal S, Srinivasan B, Iyer GK, Rajappa SM, Tatu U, et al. Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome. PLoS One. 2012;7(12):1–9.
22. Zhou L, Beuerman RW, Chan CM, Zhao SZ, Li XR, Yang H, Tong L, Liu S, Stern ME, Tan D. Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics. J Proteome Res. 2009;8:4889–905.
23. Tong L, Zhou L, Beuerman RW, Zhao SZ, Li XR. Association of tear proteins with Meibomian gland disease and dry eye symptoms. Br J Ophthalmol. 2011;95:848–52.
24. Boehm N, Funke S, Wiegand M, Wehrwein N, Pfeiffer N, Grus FH. Alterations in the tear proteome of dry eye patients—a matter of the clinical phenotype. Invest Ophthalmol Vis Sci. 2013;54:2385–92.
25. Soria J, Durán JA, Etxebarria J, Merayo J, González N, Reigada R, García I, Acera A, Suárez T. Tear proteome and protein network analyses reveal a novel pentamarker panel for tear film characterization in dry eye and meibomian gland dysfunction. J Proteomics. 2013;78:94–112.
26. Versura P, Bavelloni A, Grillini M, Fresina M, Campos EC. Diagnostic performance of a tear protein panel in early dry eye. Mol Vis. 2013;19:1247–57.
27. Guo Q, Huang H, Pi Y, Zhang H. Evaluation of tear malate dehydrogenase 2 in mild dry eye disease. Eye Sci. 2014;29(4):204–8.
28. Schicht M, Rausch F, Beron M, Jacobi C, Garreis F, Hartjen N, Beileke S, Kruse F, Bräuer L, Paulsen F. Palate lung nasal clone (PLUNC), a novel protein of the tear film: three-dimensional structure, immune activation, and involvement in dry eye disease (DED). Invest Ophthalmol Vis Sci. 2015; 56(12):7312–23.
29. Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S. Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol. 2011;129:981–6.
30. Chhadva P, Lee T, Sarantopoulos CD, Hackam AS, McClellan AL, Felix ER, Levitt RC, Galor A. Human tear serotonin levels correlate with symptoms and signs of dry eye. Ophthalmology. 2015;122(8):1675–80.
31. Wei Y, Asbell PA. The core mechanism of dry eye disease (DED) is inflammation. Eye Contact Lens. 2014;40:248–56.
32. Seens S, Tong L. Dry eye disease and oxidative stress Acta Ophthalmol. 2018;96:e412–20.
33. Choi W, Lian C, Ying L, et al. Expression of lipid peroxidation markers in tear film and ocular surface of patients with non-Sjogren syndrome: potential biomarkers for dry eye disease. Curr Eye Res. 2016;41:1143–9.
34. Labbe A, Brignole-Baudouin F, Baudouin C. Ocular surface investigation in dry eye. J Fr Ophthalmol. 2007;30:76–97.
35. Chiva A. Electrophoresis of tear proteins as a new diagnostic tool for two high risk groups for dry eye: computer users and contact lens wearers. J Med Life. 2011;4:228–33.
36. Kramann N,Boehm N, Lorenz K, et al. Effects of contact lenses on the protein composition in tear film: a ProteinChip study. Graefes Arch Clin Exp Ophthalmol. 2011;249:233–43.
37. Glasson MJ, Stapleton F, Keay L, et al. Differences in clinical parameters and tear film of tolerant and intolerant contact lens wearers. Invest Opt Vis Sci. 2003;44:5116–24.
38. Wilcox MD. Is there a role for inflammation in contact lens discomfort? Eye Contact Lens. 2017;43:5–16.
39. Still KM, Soyars CL, Velez F, et al. Development of quantitative sandwich ELISAs for lacritin and the lacritin-c splice variant in human tears. Invest Ophthalmol Vis Sci. 2012;53:4233.
40. Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA. Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea. 2009; 28(9):1023–7.
41. Yoon KC, Park CS, You IC, Choi HJ, Lee KH, Im SK, Park HY, Pflugfelder SC. Expression of CXCL9, −10, −11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Invest Ophthalmol Vis Sci. 2010;51(2):643–50.
42. Sambursky R, Davitt WF, Latkany R, Tauber S, Starr C, Friedberg M, et al. Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. Arch Ophthalmol. 2013;131(1):24–8.