Stability and Compressibility of Tear Film Lipid Layer: Impact of Benzalkonium Chloride Presence

Benzalkonium chloride (BAK), a common preservative in eye drops, has a major side effect of dry eye. The mechanisms are typically attributed to BAK cytotoxicity. However, due to its surfactant properties, BAK can disrupt the tear film lipid layer (TFLL), leading to dry eye. This study examined the stability and compressibility of the TFLL and the impact of the presence of BAK.

Meibomian gland secretion (meibum, source of the TFLL) was collected from sacrificed cows' eyelids. Lipids were extracted by dissolving meibum in chloroform to a final concentration of 1 mg/mL, with one solution additionally containing 0.1 mg/mL BAK. Each solution was overlaid on a water subphase in a Langmuir Trough-Blodgett trough. The changes of surface pressure (π) with area (A) for the lipid film upon compression were monitored, and the corresponding compression modulus (C_s ^-1) at each data point was determined.

The π-A isotherms for meibum lipid monolayers exhibited near-reversible behavior with a smooth profile with a maximum π of approximately 32 mN/m. The C_s ^-1-π isotherms of the meibum lipid monolayer show that the films are gel-like with a constant compressive modulus of 24-32 mN/m within the surface pressure range of 8-30 mN/m. In contrast, adding BAK dramatically decreased the maximum surface pressure to only 10 mN/m and the compressive modulus to only 2-10 mN/m.

This study demonstrated that BAK disrupts the meibum lipid layer by forming a monolayer with decreased stability and reduced compressive resistance, a mechanism that may underlie its dry-eye side effect yet has largely been neglected.