Why carry out this study?

Since preserved and unpreserved latanoprost-containing ophthalmic drugs, belonging to first-line therapy of glaucoma treatment, are often administered over many years, questions naturally arise about the associated problems of tolerability and ocular surface toxicity.

The toxic effect of preservatives on the ocular surface has been recognized for several years and demonstrated through several studies, but little attention has been paid to the other excipients and their interactions.

In vivo tolerability is time-dependent; therefore, either long-term studies or mimicking toxicity models are needed. The ex vivo bioreactor (EVEIT) model has been assessed in further studies and is relevant for our investigation.

The purpose of our study was to investigate the overall effect of preserved and unpreserved 0.005% latanoprost antiglaucoma drugs with different macrogolglycerol hydroxystearate 40 (MGHS 40) concentrations (0%, 2.5%, and 5%) on the corneal healing rate as well as on tissue integrity after mimicking chronic administration.

What was learned from the study?

Our first study over 3 days showed clear toxic effects of preservatives such as benzalkonium chloride (BAC) as well as evidence of slight changes in epithelial healing between the different unpreserved latanoprost formulations.

The toxic effect could need a longer time period of testing to become apparent and significant.

Our second study over 5 days confirmed that the toxic effect of MGHS 40 on the cornea is concentration-dependent and also enhanced by interactions with other excipients.

The association of MGHS in high concentration (5%) with viscosity agents such as macrogol 4000 or carbomer appears to be of great concern for ocular surface health in long-term glaucoma treatment.