Changes of eicosanoids after eyelid warming or thermopulsation treatment for Meibomian gland dysfunction (MGD)

Abstract

Purpose : Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort characterized by an unstable tear film. Eicosanoids produce enzymatically and non-enzymatically (through oxidative stress) may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of eicosanoids after various eyelid treatment over 12 weeks. Secondly, we aimed to assess the chirality of monohydroxyl eicosanoids from tears of control and dry eye patients and consequently the proportion of enzymatic and non-enzymatic eicosanoids.

Methods : Thirty-seven participants with MGD involved in interventional trials (eyelid warming and thermopulsation) and 12 healthy participants were used in this study. Tear samples were collected from healthy and patients using Schirmer’s strip. Eicosanoids were analyzed using liquid chromatography mass spectrometry (LC-MS) techniques. The changes in eicosanoids were evaluated before and 12 weeks after start of treatment. We also measured chirality of monohydroxyl eicosanoids from the tear samples.

Results : We were able to quantify 38 tear eicosanoids in the tear of dry eye patients. Eighteen of the tested eicosanoids were reduced significantly in patients 12-weeks after treatment compared to baseline, including mono-hydroxyl eicosanoids hydroxyeicosatetraenoic acids (HETEs) and hdroxydocosahexaenoic acids (HDoHEs). Changes in tear concentrations of 10-HDoHE (r=0.54) and 15-oxoETE (r=0.54) were correlated to number of Meibomian gland plugs at baseline.
The targeted chiral analysis shows that 5(S)-(HETE), 14(S)-HDoHE, 17(S)-HDoHE and 18(S)-HEPE were produced enantioselectively in healthy human tear whereas 11-HETE, 12-HETE and 15-HETE produce with no stereo-selectivity between R and S enantiomers. The levels of S and R enantiomers for all targeted 7 eicosanoids were not significantly different in the dry eye patients before treatment, whereas the proportion of chiral enantiomers were significantly altered after treatment in 5-HETE, 12-HETE, 17-HDoHE and 18-HEPE.

Conclusions : The eyelid/thermopulsation therapy reduced many eicosanoids in the tear, especially pro-inflammatory molecules generated by lipoxygenase and oxidative stress markers. In MGD, some eicosanoids may be generated by non-enzymatic oxidative stress. If severity of MGD increased, more alteration of eicosanoids (10-HDoHE, 15-oxoETE) may be expected after treatment.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.