Stellenwert neuer Untersuchungsmethoden des Tränenfilms in der Diagnostik des trockenen Auges: Tränenfilmosmolarität und Matrixmetalloproteinasen (MMP-9)

Zusammenfassung

Die Keratoconjunctivitis sicca ist eine der häufigsten Diagnosen in der Augenheilkunde. Eine Vielzahl von subjektiven und objektiven Testverfahren mit ungenauen Grenzbereichen und unterschiedlich hohen Sensitivitäten und Spezifitäten erschwert die Diagnostik. Gerade geringe bis moderate pathologische Befunde können so fehldiagnostiziert werden. In den letzten Jahren haben sich durch die Entwicklung neuer, klinisch einfach einsetzbarer Diagnostikgeräte bspw. für die Analyse der Tränenfilmosmolarität oder der Matrixmetalloproteinasen (MMP-9) neue Optionen ergeben. Der Stellenwert der Tränenfilmosmolarität und der Bestimmung der MMP-9-Werte in der Diagnostik des trockenen Auges und seiner Subformen wird diskutiert und anhand publizierter Studienergebnisse objektiv zu bewerten versucht.

Abstract

Dry eye disease is one of the most common diagnoses in ophthalmology. A variety of subjective and objective test methods with imprecise limits and highly different sensitivities and specificities complicate the diagnosis. Especially mild to moderate pathological findings can be misdiagnosed. In recent years, new options have opened, through the development of new, clinical practicable diagnostic equipment, for example, for the analysis of tear film osmolarity or matrix metalloproteinases (MMP-9). The value of tear film osmolarity and determination of MMP-9 levels in the diagnosis of dry eye and its subtypes will be discussed and evaluated objectively, on the basis of published study results.

Schlüsselwörter

trockenes Auge - Diagnostik - Osmolarität

Key words

dry eye - diagnostics - osmolarity - MMP-9

• Literatur

• 1 Schargus M, Geerling G. [The “wet” dry eye]. Ophthalmologe 2009; 106: 235-238 240, 241
• 2 [Anonymous] 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; 5: 75-92
• 3 [Anonymous] The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 93-107
• 4 [Anonymous] Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 108-152
• 5 [Anonymous] Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 163-178
• 6 Nichols KK, Foulks GN, Bron AJ. et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 2011; 52: 1922-1929
• 7 Lemp MA, Crews LA, Bron AJ. et al. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea 2012; 31: 472-478
• 8 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
• 9 Luo L, Li DQ, Corrales RM. et al. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye Contact Lens 2005; 31: 186-193
• 10 Li DQ, Chen Z, Song XJ. et al. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2004; 45: 4302-4311
• 11 Korb DR. Survey of preferred tests for diagnosis of the tear film and dry eye. Cornea 2000; 19: 483-486
• 12 Khanal S, Tomlinson A, McFadyen A. et al. Dry eye diagnosis. Invest Ophthalmol Vis Sci 2008; 49: 1407-1414
• 13 Tomlinson A, Khanal S, Ramaesh K. et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006; 47: 4309-4315
• 14 Lemp MA, Bron AJ, Baudouin C. et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011; 151: 792-798.e1
• 15 [Anonymous] Section VI 510(k) summary. San Diego, CA, USA: Ocusense Inc; 2009
• 16 Tomlinson A, McCann LC, Pearce EI. Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques. Cornea 2010; 29: 1036-1041
• 17 Bunya VY, Fuerst NM, Pistilli M. et al. Variability of tear osmolarity in patients with dry eye. JAMA Ophthalmol 2015; 133: 662-667
• 18 Szczesna-Iskander DH. Measurement variability of the TearLab Osmolarity System. Cont Lens Anterior Eye 2016; 39: 353-358
• 19 Sullivan BD, Whitmer D, Nichols KK. et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010; 51: 6125-6130
• 20 Schargus M, Meyer-ter-Vehn T, Menrath J. et al. Correlation between tear film osmolarity and the disease score of the International Chronic Ocular Graft-Versus-Host-Disease Consensus Group in hematopoietic stem cell transplantation patients. Cornea 2015; 34: 911-916
• 21 Schargus M, Wolf F, Tony HP. et al. Correlation between tear film osmolarity, dry eye disease, and rheumatoid arthritis. Cornea 2014; 33: 1257-1261
• 22 De Paiva CS, Corrales RM, Villarreal AL. 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
• 23 Zimmermann N, Erb C. [Immunoassay for matrix metalloproteinase-9 in the tear film of patients with pseudoexfoliation syndrome – a pilot study]. Klin Monatsbl Augenheilkd 2013; 230: 804-807
• 24 Acera A, Rocha G, Vecino E. et al. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res 2008; 40: 315-321
• 25 Chotikavanich S, de Paiva CS, Li DQ. et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci 2009; 50: 3203-3209
• 26 Geerling G, Joussen AM, Daniels JT. et al. Matrix metalloproteinases in sterile corneal melts. Ann N Y Acad Sci 1999; 878: 571-574
• 27 VanDerMeid KR, Su SP, Ward KW. et al. Correlation of tear inflammatory cytokines and matrix metalloproteinases with four dry eye diagnostic tests. Invest Ophthalmol Vis Sci 2012; 53: 1512-1518
• 28 Aragona P, Aguennouz M, Rania L. et al. Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease. Ophthalmology 2015; 122: 62-71
• 29 Gurdal C, Genc I, Sarac O. et al. Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings, conjunctival epithelial apoptosis, and MMP-9 expression. Curr Eye Res 2010; 35: 771-777
• 30 Kaufman HE. The practical detection of mmp-9 diagnoses ocular surface disease and may help prevent its complications. Cornea 2013; 32: 211-216
• 31 Sambursky R, Davitt 3rd WF, Latkany R. et al. Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. JAMA Ophthalmol 2013; 131: 24-28
• 32 Sambursky R, Davitt 3rd WF, Friedberg M. et al. Prospective, multicenter, clinical evaluation of point-of-care matrix metalloproteinase-9 test for confirming dry eye disease. Cornea 2014; 33: 812-818
• 33 Schargus M, Ivanova S, Kakkassery V. et al. Correlation of tear film osmolarity and 2 different MMP-9 tests with common dry eye tests in a cohort of non-dry eye patients. Cornea 2015; 34: 739-744
• 34 Kramann C, Boehm N, Lorenz K. et al. Effect of contact lenses on the protein composition in tear film: a ProteinChip study. Graefes Arch Clin Exp Ophthalmol 2011; 249: 233-243
• 35 Lemp MA, Eldrige DC. Prognosis. In: Norihiko Y. ed. Dry Eye Syndrome: basic and clinical Perspectives. London: Future Medicine Ltd; 2013: 110-120
• 36 Lanza NL, McClellan AL, Batawi H. et al. Dry eye profiles in patients with a positive elevated surface matrix metalloproteinase 9 point-of-care test versus negative patients. Ocul Surf 2016; 14: 216-223
• 37 Epitropoulos AT, Donnenfeld ED, Shah ZA. et al. Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes. Cornea 2016; 35: 1185-1191
• 38 Sullivan BD, Crews LA, Messmer EM. et al. Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications. Acta Ophthalmol 2014; 92: 161-166