Purpose: The aim of this review is to clarify the role of cross-linked Hyaluronic acid (HA) molecule as a tear supplement and to define its possible applications in dry eye disease. Methods: Current Literature about HA and its cross-linked derivatives has been examined. Results: HA is superior in increasing the viscosity and stability of the tear film compared with other tear supplements such as polyvinyl alcohol, hydroxypropyl methylcellulose, carboximethyl cellulose and polyethylene glycol. Moreover, HA can be modified in different ways to improve its properties such as molecular weight, viscosity, and hydrophobicity to adapt the new artificial molecule to different aims. Conclusions: The current pharmacological trend is to improve the properties of HA by cross-linking parts of the molecule to achieve better bioavailability and resistence to degradation. In dry eye disease, cross-linked HA as tear supplement seems to provide better ocular comfort than linear HA and is therefore subjected to growing interest and diffusion.
Keywords: cross-linked hyaluronic acid; dry eye disease; hyaluronic acid.