Direct Correlation of Levels of Meibum Cholesteryl Esters, Hydrocarbon Chain Saturation, and Protein With Lipid Structure, in Relation to Age and Dry Eye

Purpose: Meibum compositional, structural, and functional relationships have been inferred indirectly. The current study measured the relationships among cholesteryl esters (CEs), lipid hydrocarbon chain unsaturation (HCunsat), meibum protein, and meibum structure, directly on the same samples as correlation does not necessitate cause. Methods: Exactly 367 meibum samples were collected from a diverse group of donors, categorized by race, sex, and age including cohorts with individuals with (with CDED) and without (Cn) dry eye disease (DED) where "C" refers to cohort and "n" refers to normal. Meibum composition was measured using 1H-NMR. Meibum phase transition characteristics were measure using infrared spectroscopy. Results: A decrease in HCunsat and CEs with DED results in stiffer, more tightly packed, and less mobile lipids. Meibum proteins have an opposite effect on CDED lipids than CE and HCunsat, moderating structural changes due to compositional variation. Lipid hydrocarbon chain order and phase transition temperature were higher in DED than in healthy eyes, regardless of age, but both decreased with age in DED, indicating reduced order in older donors. In meibum without protein, DED samples showed greater stiffness and higher phase transition temperatures, even at similar unsaturation levels, whereas protein presence minimized these differences. Conclusions: A decrease in HCunsat and CEs with DED would likely inhibit the flow of meibum from the meibomian glands and cause a discontinuous patchy tear film lipid layer, resulting in deteriorated spreading, decreased surface elasticity, and an unstable tear film. Therapies to increase HCunsat and CEs could be successful in treating DED.