Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort. Lipid mediators, often termed oxylipins, can be produced enzymatically or non-enzymatically, and may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of lipid mediators after various eyelid treatments (eyelid warming and thermopulsation) over 12 weeks. Secondly, we aimed to assess the chirality of mono-hydroxyl lipid mediators from tears of MGD and healthy participants. Tears lipid mediators were extracted from Schirmer's strips and levels were quantified by liquid chromatography mass spectrometry (LC-MS) techniques. We quantified 33 lipid mediators in the tear, 18 of which (including 11-HETE, 20-OH-LTB, and 15-oxoETE) were reduced significantly after treatment. Changes in concentrations of 10-HDoHE (r = 0.54) and 15-oxoETE (r = 0.54) were correlated to the number of meibomian gland plugs at baseline, so increased severity of MGD was associated with treatment-induced change in lipid mediators. The chiral analysis demonstrated that 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 14(S)-HDoHE, 17(S)-HDoHE and 11(R)-HETE were produced with significant enantiomeric excess (ee %) in controls compared to patients, due to enantiomer selective enzymatic action, whereas most lipid mediators were racemates in patients, due to dominance of oxidative effects which have no enantiomeric preference. Treatment of MGD restored the concentrations of 15(S)-HETE, 14(S)-HDoHE and 17(S)-HDoHE with significant ee values, suggesting reduction in oxidative action. Overall, MGD therapy reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress.