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C. G. Begley, H. Liu, M. Chen, M. Jansen, A. Bradley, J. Bonanno; A Link Between Tear Instability and Hyperosmolarity in Dry Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1543.
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Tear film instability and tear hyperosmolarity are considered core mechanisms in the development of dry eye. We hypothesize that evaporation and instability produce transient shifts in tear hyperosmolarity that lead to chronic epithelial stress. The purpose of this study was to (1) provide indirect evidence for short term hyperosmolar conditions during tear instability and to (2) test whether the corneal epithelium responds to transient hyperosmolar stress.
Exp#1: Five subjects kept one eye open as long as possible (using the method of tear break-up dynamics or TBUD). Overall discomfort and sensations associated with tear break-up were recorded. Later, the same subjects used the same scales after instillation of hyperosmolar drops from 300mOsm/Kg to 1000mOsm/Kg. A 2 alternative forced choice experiment was used to obtain the threshold. Exp#2: Primary cultured bovine corneal epithelial cells were transiently stressed with the same range of hyperosmolar culture media and pro-inflammatory Mitogen Activitied Protein Kinase (MAPK) was measured.
During TBUD, all subjects showed tear film breakup or thinning with an average discomfort rating of 6.13 and reported sensations of burning and stinging. These sensations also occurred with hyperosmolar solutions (threshold = 450mOsm/Kg) that required 816mOsm/Kg to generate the same level of discomfort as during TBUD. MAPK was activated at 600mOsm/Kg of transient hyperosmolar stress.
The Exp#1 symptoms of burning and stinging, the threshold, and the levels of discomfort suggest a link between transient spikes in hyperosmarity and tear instability, suggesting that hyperosmolar levels may reach approximately 800mOsm/Kg during tear instability. Exp#2 demonstrates that the corneal epithelium reacts to transient hyperosmolar stress at 600mOsm/Kg. These results suggest that dry eye symptoms may originate from an unstable tear film, which leads to fluctuating tear hyperosmolarity and results in an epithelial inflammatory response and nerve stimulation.
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