Osmokinetics: Defining the Characteristics of Osmotic Challenge to the Ocular Surface

Abstract

The association of severe dry eye disease with elevated osmolarity in the tear film is a subject of ongoing discussions. As the absolute value of osmolarity in tear film is highly variable, the daily variation in osmolarity (DVO) has recently been proposed to further identify the osmotic stress at the ocular surface. However, the DVO alone does not explain the variations in the available published data or allow their use in diagnostic testing or therapy. We therefore investigated and evaluated further details of osmokinetics and their importance for ocular surface disease on the basis of the available literature. Additionally, osmolarity was measured in the tear samples of volunteers in the morning hours between 8 – 10 a. m., midday noon–2 p. m., and afternoon between 3 – 5 p. m., i.e., during normal office hours. The results were compared with available published data which suggested that within the DVO, the daily maximal amplitude of osmotic variation (M-DVO) and the frequency of osmotic cycles (defined as daily osmolarity cycles, DOC) could be the main factors that further characterize osmokinetics. In addition, a decisive role could be the level of osmolarity at which the variation does occurs (L-DVO). The possible effects of these characteristics on ocular surface pathophysiology are discussed, along with their relationship to topical therapy with hypo-osmolar solutions, and the model of the osmotic roller coaster is introduced.

Zusammenfassung

Die Assoziation einer erhöhten Tränenosmolarität mit dem Vorliegen von schweren Erkrankungen des trockenen Auges ist ein aktuelles Thema derzeitiger Diskussionen. Wegen der großen Variabilität der gemessenen absoluten Osmolaritätswerte wurde die Tagesschwankung der Osmolarität (TSO = Daily Variation of Osmolarity, DVO) als Parameter zur Beurteilung des osmotischen Stresses auf der Augenoberfläche vorgeschlagen. Doch auch mit dem TSO lassen sich nicht alle vorliegenden Ergebnisse erklären oder therapeutisch nutzen. Daher wurde die vorliegende Literatur auf weitere Erkenntnisse zu den Eigenschaften der Osmokinetik und ihre mögliche Bedeutung für die Augenoberfläche untersucht. Außerdem wurde das Tagesprofil der Tränenosmolarität an Probandenaugen erstellt (Messungen zwischen 8 und 10 Uhr, 12 und 14 Uhr sowie 15 und 17 Uhr, also während eines normalen Arbeitstags). Beim Vergleich der Resultate mit den Erkenntnissen der Literatur erscheint es möglich, dass die Bedeutung der TSO (DVO) von der maximalen Amplitude der DVO (M-DVO) und der Anzahl von osmotischen Zyklen per Zeiteinheit, nämlich Tageszyklen (DOC), abhängig sein kann. Darüber hinaus ist das Osmolaritätsniveau (Level of DVO = L-DVO), auf dem diese Veränderungen stattfinden, von potenziell entscheidender Bedeutung. Die möglichen Auswirkungen dieser Charakteristika auf die Pathophysiologie der Augenoberfläche werden diskutiert, auch unter dem Aspekt der Topikaltherapie mit hypoosmolaren Augenpräparaten, wobei das Modell der osmolaren Achterbahn vorgestellt wird.

Key words

cornea - tear film - ocular surface - osmolarity - osmotic stress

Schlüsselwörter

Kornea - Biochemie - Tränen - Oberflächenstress - Osmolarität

• References

• 1 van Setten GB. Osmokinetics: A new dynamic concept in dry eye disease. J Fr Ophtalmol 2019; 42: 221-225
• 2 Ng A, Keech A, Jones L. Tear osmolarity changes after use of hydroxypropyl-guar-based lubricating eye drops. Clin Ophthalmol 2018; 12: 695-700
• 3 Lee JE, Kim NM, Yang JW. et al. A randomised controlled trial comparing a thermal massager with artificial teardrops for the treatment of dry eye. Br J Ophthalmol 2014; 98: 46-51
• 4 Suzuki M, Massingale ML, Ye F. et al. Tear osmolarity as a biomarker for dry eye disease severity. Invest Ophthalmol Vis Sci 2010; 51: 4557-4561
• 5 Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res 2010; 35: 553-564
• 6 Craig JP, Nelson JD, Azar DT. et al. TFOS DEWS II Report Executive Summary. Ocul Surf 2017; 15: 802-812
• 7 Khanal S, Tomlinson A, McFadyen A. et al. Dry eye diagnosis. Invest Ophthalmol Vis Sci 2008; 49: 1407-1414
• 8 Baenninger PB, Voegeli S, Bachmann LM. et al. Variability of Tear Osmolarity Measurements with a Point-of-Care System in Healthy Subjects – Systematic Review. Cornea 2018; 37: 938-945
• 9 Messmer EM, Bulgen M, Kampik A. Hyperosmolarity of the tear film in dry eye syndrome. Dev Ophthalmol 2010; 45: 129-138
• 10 Keech A, Senchyna M, Jones L. Impact of time between collection and collection method on human tear fluid osmolarity. Curr Eye Res 2013; 38: 428-436
• 11 Sullivan BD, Whitmer D, Nichols KK. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010; 51: 6125-6130
• 12 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
• 13 Bulgen M. Osmolarität des Tränenfilms bei Augengesunden und Patienten mit Trockenem Auge [Dissertation]. Munich, Bavaria, Germany: Ludwig-Maximilians-University; 2013: 1-66
• 14 Kang SS, Ha SJ, Kim ES. et al. Effect of nerve growth factor on the in vitro induction of apoptosis of human conjunctival epithelial cells by hyperosmolar stress. Invest Ophthalmol Vis Sci 2014; 55: 535-541
• 15 Kim YH, Oh TW, Park E. et al. Anti-Inflammatory and Anti-Apoptotic Effects of Acer Palmatum Thumb. Extract, KIOM-2015EW, in a Hyperosmolar-Stress-Induced In Vitro Dry Eye Model. Nutrients 2018; 28: 10
• 16 Warcoin E, Baudouin C, Gard C. et al. In Vitro Inhibition of NFAT5-Mediated Induction of CCL2 in Hyperosmotic Conditions by Cyclosporine and Dexamethasone on Human HeLa-Modified Conjunctiva-Derived Cells. PLoS One 2016; 11: e0159983
• 17 Pietuch A, Brückner BR, Janshoff A. Membrane tension homeostasis of epithelial cells through surface area regulation in response to osmotic stress. Biochim Biophys Acta 2013; 1833: 712-722
• 18 Versura P, Profazio V, Schiavi C. et al. Hyperosmolar stress upregulates HLA-DR expression in human conjunctival epithelium in dry eye patients and in vitro models. Invest Ophthalmol Vis Sci 2011; 52: 5488-5496
• 19 Dutescu RM, Panfil C, Schrage N. Osmolarity of prevalent eye drops, side effects, and therapeutic approaches. Cornea 2015; 34: 560-566
• 20 Mergler S, Garreis F, Sahlmueller M. et al. Thermosensitive transient receptor potential channels in human corneal epithelial cells. J Cell Physiol 2011; 226: 1828-1842
• 21 Wright P, Cooper M, Gilvarry AM. Effect of osmolarity of artificial tear drops on relief of dry eye symptoms: BJ6 and beyond. Br J Ophthalmol 1987; 71: 161-164
• 22 Chure G, Lee HJ, Rasmussen A. et al. Connecting the Dots between Mechanosensitive Channel Abundance, osmotic Shock, and Survival at Single-Cell Solution. J Bacteriol 2018; 200: 460-18
• 23 Pflugfelder SC, de Paiva CS, Tong L. et al. Stress-activated protein kinase signaling pathways in dry eye and ocular surface disease. Ocul Surf 2005; 3 (Suppl. 04) S154-S157
• 24 Chen Z, Tong L, Li Z. et al. Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK. Invest Ophthalmol Vis Sci 2008; 49: 539-549
• 25 Schwartz L, Guais A, Pooya M. et al. Is inflammation a consequence of extracellular hyperosmolarity?. J Inflamm (Lond) 2009; 6: 21-31
• 26 Abusharha AA, AlShehri TM, Hakami AY. et al. Analysis of basal and reflex human tear osmolarity in normal subjects: assessment of tear osmolarity. Ther Adv Ophthalmol 2018; 10: 1-6
• 27 van Setten GB. Osmolarity in Ocular Surface Disease and Dry Eye – The Concept of Osmokinetics. Symposium: Where Are We in Ocular Surface Disease? Reality – Our Responsibility – Our Future. Chair: van Setten GB, Seitz B, Deutsche Ophthalmologische Gesellschaft (DOG), Jahreskongress 28.09.2019.