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Retinal diseases are one of the main reasons for vision loss where all available drug treatments are based on invasive drug administration such as intravitreal injections. Despite huge efforts and some promising results in animal models, almost all delivery technologies tested have failed in human trials. There are however examples of clinically effective topical delivery systems such as fast dissolving aqueous eye drop suspensions. Six obstacles to topical drug delivery to the eye have been identified and discussed in some details. These obstacles consist of static membrane barriers to drug permeation into the eye, dynamic barriers such as the lacrimal drainage and physiochemical barriers such as low thermodynamic activity. It is explained how and why these obstacles hamper drug permeation and how different technologies, both those that are applied in marketed drug products and those that are under investigation, have addressed these obstacles. The reason that most topical drug delivery systems have failed to deliver therapeutic drug concentrations to the retina is that they do not address physiochemical barriers such as the thermodynamic activity of the permeating drug molecules. Topical drug delivery to the retina has only been successful when the static, dynamic, and physiochemical barriers are addressed simultaneously.

Topical drug delivery to the retina: obstacles and routes to success