Activity and biocompatibility of antimicrobial contact lenses

Abstract

Contact lens related infection and inflammation are major problems for contact lens wearers and practitioners alike. Colonisation by a variety of microorganisms such as bacteria, fungi and Acanthamoeba on contact lenses is implicated in the development of these adverse events. A contact lens with high antimicrobial activity may inhibit the ability of microorganisms to grow on the surface and consequently reduce these adverse events. Antimicrobial peptides (AMPs) are small proteins which have been shown to have activity against a wide spectrum of microorganisms. This thesis investigated the spectrum of antimicrobial activity of an AMP covalently attached to contact lenses and its subsequent safety and biocompatibility in animal and human studies. The AMPs melimine and LL-37 were covalently attached onto contact lenses via EDC coupling, which was able to bind high concentrations of melimine but not LL-37. Further, melimine coated lenses demonstrated high antimicrobial activity including activity against multidrug-resistant bacteria, fungal and Acanthamoeba strains. However, the lenses were associated with apparently high levels of dead bacterial cells (evidenced by no differences in radio-labelled RNA or bacterial endotoxin from Gram negative bacteria on melimine-coated and uncoated lenses). The melimine coating was readily heat sterilisable, non-toxic to mammalian cells in vitro, did not change contact lens parameters, and formed a wettable lens surface. The melimine coating was compatible with the lens care disinfectants Biotrue™ and RevitaLens OcuTec®. In vivo investigation of the safety of the melimine coating in a rabbit model of contact lens wear following ISO guidelines revealed that these lenses were not associated with any toxic or hypersensitive responses. A one day clinical trial showed that melimine-coated lenses could be safely worn by humans without any major side effects and any delayed toxic reactions. However, melimine lenses were associated with higher corneal straining. This corneal staining was similar to solution induced corneal staining seen during contact lens wear. Following human wear, lenses retained more than 1.5 log inhibition against Pseudomonas aeruginosa and Staphylococcus aureus. Melimine coatings on contact lenses have excellent potential for further development of biocompatible and effective broad spectrum antimicrobial contact lenses.