MICA: Antimicrobial bandage contact lenses

The cornea is the clear window at the front of the eye. Following surgery or various treatments to the cornea a bandage contact lens will frequently be used to protect the cornea and increase comfort for the patient. To reduce the risk of infection antibiotics will also normally be administered.
In this project we will create a new type of contact lens that will combine both these processes. We have developed a novel hydrogel with a high water content, excellent transparency and mechanical properties similar to those of existing hydrogel contact lenses. The specific advantage of this new hydrogel is that it is naturally antimicrobial, unlike any of the existing materials. The hydrogel is synthesised in water at room temperature, whereas existing contact lens materials require the use the toxic solvents during synthesis and then need extensive washing procedures to remove them. We have shown that the novel hydrogel can be cast into a contact lens using existing moulding processes. We hypothesise that use of an antimicrobial bandage contact lens post-surgery or after an intervention such as corneal crosslinking, would increase comfort and reduce infection. In this study we will optimise the composition of the new hydrogel, fully characterise its antimicrobial and biocompatibility properties and evaluate its safety in a human healthy volunteer trial.
A second strand of this study will develop a therapeutic contact lens. Corneal infection is one of the commonest conditions affecting the cornea, accounting for 5% of cases of blindness worldwide. Contact lenses worn for vision are associated with a six fold increase in corneal infection. Treatment of corneal infection relies on frequent application of antibiotic drops; routinely every 5-15 minutes for the first 48 hours, then 2-6 hourly over 1-2 weeks. Contact lenses delivering therapeutic doses of antimicrobial drugs in a sustained and controlled manner would provide a more effective treatment strategy and augment conventional treatments. Corneal infection can be caused by both bacteria and fungi with each particular species requiring a different anti-infection drug treatment. We have demonstrated that our novel hydrogel can be loaded with antibiotic and antifungal drugs that are released at therapeutic levels that can kill bacteria and fungi in culture. In this study we will optimise the composition of the hydrogel to develop bandage contact lenses containing specific antibiotic and antifungal drugs that are used to treat corneal infections. We will fully characterise their anti-infection and cell compatibility properties in laboratory experiments using bacteria, fungi and corneal cells in culture and in an organ culture model of the front of the eye. Furthermore we will investigate if the bacteria and fungi species are able to develop resistance to the hydrogel with and without the added drugs using methods that analyse the genetic basis of antimicrobial resistance.
During this project we will collaborate with two companies; one with experience in the hydrogel synthesis and the other with extensive experience of contact lens manufacture. At the end of the project we intend to have 1) a bandage contact lens that is safe and has the potential to increase comfort for patients post corneal surgery and to reduce the risk of infection and 2) a therapeutic bandage contact lens that delivers clinically relevant antibiotics and antifungal drugs at therapeutic levels that have been shown to be effective at killing clinically relevant bacteria and fungi in the laboratory.

Corneal infection is a significant clinical problem. Following corneal surgery a bandage contact lens (BCL) is frequently used to protect the cornea and increase comfort for the patient. To reduce the risk of infection antibiotics are also normally administered. Current BCLs comprise silicone-hydrogel, hydrogel or less commonly, collagen-based materials. None have antimicrobial activity. Our BCLs will be produced from high water content, transparent poly-e-lysine gels. We can cast these gels using existing contact lens moulds. We have shown that poly-e-lysine can be covalently attached to the gel surfaces and these were shown to be non-cytotoxic to human corneal epithelial cells in culture and did not inhibit healing in an in vitro corneal epithelial scratch assay model. We have demonstrated that these gels can significantly reduce the growth of Gram +ve (S. aureus) and Gram -ve (E. coli) cultures. We will develop these as prophylactic BCLs to reduce the risk of infection post-surgery and determine their safety in a human trial.
A second strand of this study will develop novel therapeutic BCLs. Treatment of corneal infection relies on frequent application of antibiotic drops; routinely every 5-15 minutes for the first 48 hours, then 2-6 hourly over 1-2 weeks. BCLs that deliver therapeutic doses of antimicrobial drugs in a sustained and controlled manner would provide a more effective treatment strategy and augment conventional treatments. We have demonstrated that Penicillin G (as a model antibiotic) and Amphotericin B (as a model antifungal) can be incorporated into the poly-e-lysine gels after synthesis through electrostatic attachment and have antimicrobial properties in vitro. We will optimise the properties of the poly-e-lysine gel lenses and their manufacture, incorporate clinically relevant antimicrobial agents to control major bacterial and fungal keratitis species using standard in vitro assays and an ex vivo corneal infection model.

This is a translational project with the aim of developing a new class of bandage contact lenses that have excellent mechanical and handling properties, transparency, water content and have antimicrobial properties. Thus they will have impact in healthcare, commercial exploitation and in the academic community.
Healthcare: Many ophthalmologists advocate using a bandage contact lens after corneal surgery or intervention, such as corneal cross-linking, to enhance patient comfort. Currently they often also administer prophylactic antibiotics. This project will develop a bandage contact lens that is naturally antimicrobial with the aim of reducing the risk of infection in these patients without the need to administer antibiotics. This will be easier for the patients and clinicians as well as reducing the unnecessary use of antibiotics. Patients with corneal infection at present receive antibiotics via eye drops that need to be administered multiple times an hour early in the treatment. This project will develop bandage contact lenses that can deliver therapeutic levels of antibiotics over several hours. These lenses could provide clinicians with an additional and more effective treatment strategy and augment conventional treatments. This will have an impact on patients, their clinicians and their carers by improving patient compliance leading to fewer hospital admissions and thus reducing healthcare costs. Our clinical applicant will facilitate engagement with the clinical community to enhance uptake of the new treatment options.
Commercial: The aim of this project is to bring a new product onto the market via our collaboration with two industrial partners. We will also develop opportunities via these partners and with other companies to exploit the outputs from this project into other product areas. This could include tissue engineering applications and other drug delivery options. We will work closely through our TTO to develop new links and also use our existing contact with the HealthTech and Medicine KTN and the Precision Medicine and Cell and Gene Therapy Catapults.
Society: An advantage of the new hydrogel lenses to be developed in this project is that they are manufactured in more environmentally friendly processes than existing contact lens materials. This could have an impact on the environment. By working with our industrial collaborators we will ensure that the manufacturing process is optimised to take this into account. Part of the project will build an ex vivo corneal infection model which could reduce the need to perform as many in vivo animal experiments. This will help to fulfil the NC3Rs agenda as well as reducing costs in the development of future treatment strategies for corneal disorders.
Academic: Alongside the translational outputs this project has the potential to lead to high impact publications and an impact case study which will have impact for the academic team. Furthermore the strengthening of the cross-disciplinary collaboration by this project will underpin future academic grant applications. Throughout the project we will keep these aspects under discussion to ensure realisation of these impacts. The project will provide excellent training for the two PDRAs to develop their careers in this multidisciplinary area including both clinical and industrial input. The PDRAs will be provided with mentors to help them build personal development career plans.