Meibomian glands are holocrine glands embedded in the upper and lower eyelids that secrete lipid (meibum) onto the tear film to retard aqueous tear evaporation [1,2]. Importantly, clinical studies have linked obstruction of the meibomian glands to meibomian gland dysfunction (MGD) leading to signs and symptoms of dry eye disease; a common disorder characterized by burning of the eye and blurry vision related to tear film abnormalities, increased tear evaporation, and ocular surface inflammation [3]. Based on early studies of MGD in rabbits, mice, primates and humans [[4], [5], [6], [7]], a general mechanism associated with hyperkeratinization of the meibomian gland orifice causing ductal plugging, dilation, and a disuse acinar atrophy has been proposed as the most common cause of MGD [8].

Notably, recent studies suggest that altered meibum composition can produce similar obstructive changes within the meibomian gland. Specifically, knockout mice lacking expression of acyl-CoA wax alcohol acyltransferase 2 (AWAT2), which is responsible for the synthesis of meibum wax esters [9], and fatty acyl-CoA reductase 2 (FAR2), which affects meibum fatty alcohol synthesis and consequently wax ester synthesis [10], both show plugging and obstruction of the meibomian gland. Since meibum contains predominantly a mixture of wax and cholesterol esters that comprise from 80 to 90 % of the meibum lipid, loss of wax esters that have a lower melting point than cholesterol esters appear to lead to thickening and increased meibum viscosity [11,12]. Interestingly, Shrestha et al. have discovered increased cholesterol esters in meibum from patients with MGD compared to normal subjects and that cholesterol ester composition increases with age [13]. Similar age-related changes in meibum lipids have also been identified by Sullivan et al., concurrent with changes in meibum opacity [14]. Since aging is a major predictor of MGD, these findings together indicate that changes in meibum viscosity may play the major role in meibomian gland obstruction that leads to dry eye disease.

How changes in meibum viscosity affect meibum secretion is not clear. Recent studies by Rosenfeld et al., have shown that meibum is a non-Newtonian fluid, whose viscosity is modified by shear stress [15]. Since secretion of meibum is passive and a function of eyelid blink pressure [16], we tested the hypothesis that changes in meibum melting temperature and viscosity might decrease meibum flow sufficiently to obstruct the gland leading to the development of MGD and dry eye. To evaluate this hypothesis, we have developed a finite element model of meibum secretion based on previous reports describing meibum rheology, meibomian gland structure and eyelid pressure.