In contrast to BAC, the novel compounds SofZia and Polyquad, and the formulations preserved with them, did not impair the meibum/SIRC lipid extract surface properties. This can be explained by the fact that the new preservatives are designed to specifically interact with the membranes of bacteria,
5,6 and their mechanism is not based on a nonspecific, strong, detergent action.
The rest of the TravatanZ/DuoTrav components displayed good miscibility with meibum as even after their penetration in the film, the lipid-layer integrity and isotherm reversibility were maintained. The result is to be expected because the active ingredients (travoprost and timolol maleate, respectively) and the emulsifiers in TravatanZ/DuoTrav are of lipophilic character and thus are compatible with the lipid layer, whereas the remaining eyedrop ingredients are readily water soluble and with limited surface activity. Also as the pharmaceutical compounds were squeezed out of the surface film at subphysiologic surface pressures, it can be expected that the TravatanZ/DuoTrav impact on tear film lipid layer performance at the ocular surface will be short term if any.
After small instantaneous compression of the film is performed to establish a new equilibrium some molecular reorientation, adsorption/desorption, respreading, and structural rearrangement processes are necessary, which are not completed instantaneously. All processes on the scale of the short relaxation time, τ
1, can be described mainly by elasticity, whereas the slower processes, on the scale of the long relaxation time τ
2, by viscosity.
7,8,11 The analysis of the stress–relaxation results revealed that SofZia and Polyquad did not alter the viscoelasticity of meibum and that the fast processes remain dominant for the rheology performance of meibum. In contrast, BAC solution changed the balance and the slow “viscous” processes became determinant for the viscoelasticity of the surface layer. The possible reason is that once BAC molecules (added in the subphase as pure BAC solution
21 or as compound of pharmaceutical formulation) penetrated the film, due to their polar nature they were chemically incompatible with meibomian secretion. Thus instead of mixing uniformly, BAC and lipid molecules separated at the interface in BAC- and lipid-enriched regions (
Fig. 6,
top panel), which led to the disruption of the continuous multilayer structure of the film. The latter, as discussed earlier, might be a key prerequisite for meibomian film functionality and its obstruction could result in impaired viscoelasticity of tear lipids. It was already reported that the penetration of hydrophilic surfactants, such as BAC, in films of lipophilic molecules leads to slower relaxation of the resultant mixed layers.
52 The decreased contribution of elasticity to the rheologic properties of meibum well explains the BAC-induced decrease of isotherm reversibility in Langmuir trough experiments and impaired spread of TFLL in vivo.
4