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.

Despite recent advances in our understanding of corneal structure and the methods used to test corneal tissue in the lab, it is still impossible to measure corneal properties in-vivo. The inability to determine the basic biomechanical properties (such as hyperelasticity, hysteresis and viscoelasticity) in-vivo had a serious adverse effect on our ability to optimise treatments or predict their outcome, and made it necessary to rely on average properties obtained ex-vivo.This project aims to make in-vivo measurement of corneal biomechanical properties a reality. It seeks to cover the research needs underpinning the development of this technology and address two fundamental questions that have prevented progress in this field. The two questions revolve around the extraction of the material's stress-strain behaviour from the overall cornea's response to mechanical actions. Once these obstacles are removed, the path to establish in-vivo measurement technology becomes straightforward.There are significant potential benefits that can be achieved if corneal biomechanical properties could be measured in-vivo. The examples include better design of implants to restore clear vision in keratoconus patients, better planning of refractive surgery procedures that currently result in unexpected aberrations in 1:7 of patients, and the ability to eliminate effect of corneal stiffness on intraocular pressure measurements, which are required for glaucoma management. These potential developments will mean significant benefits to patients, healthcare services and medical device manufacturers.The research starts with an experimental study to determine the regional variation of corneal and scleral hyperelasticity, hysteresis and viscoelasticity. The study will use 3D digital imaging of human eye globes subjected to cycles of both intraocular pressure and external applanation forces and aim to address the key gaps in knowledge in ocular biomechanics.With maps of biomechanical properties established, numerical analysis tools will be built to embody these maps, in addition to existing knowledge on the biomechanical, topographic and micro-structural characteristics of the human eye. The tools, which will be custom built, will be validated against ocular behaviour data obtained experimentally before using them to develop conceptual techniques to measure corneal biomechanics in-vivo.Two types of property measurement techniques, based on contact and non-contact methods, will be assessed. In both cases, corneal response to a mechanical action is correlated to corneal stress-strain behaviour. This exercise will focus on the key research questions, and aim to formalise an analysis procedure to extract the cornea's stress-strain behaviour from its mechanical response, and to exclude the effects of intraocular pressure and cornea's geometric parameters on the results.The results of the numerical study will be assessed using proof-of-concept prototypes both experimentally on human eye globes and on volunteers within a clinical setting. The tests are intended to validate the numerical findings, cast light onto the characteristics of ocular deformation under mechanical actions, and provide initial results which will be important for the conduct of future clinical studies on fully operational device prototypes.Overall, the project addresses a challenging problem that is affecting progress in several areas of patient care in ophthalmology. It seeks to overcome the main barriers to making the in-vivo measurement of corneal properties a reality. The project follows a systematic approach where necessary knowledge about ocular behaviour is generated and a predictive tool of ocular mechanical response built before assessing the property measurement methods. With the knowledge and understanding to be generated in this project, research and development can progress to embody the new technology into medical devices suitable for clinical use.

Chronic eye diseases and trauma due to lacrimal gland disease, meibomian gland dysfunction, laser-assisted in situ keratomileusis (LASIK) and refractive eye surgeries result in a decrease in tear secretion and/or an increase in tear evaporation. This imbalance of ocular physiology alters the concentrations of electrolytes in the tear film. The associated dry eye syndrome (keratoconjunctivitis sicca) impairs the daily activities of 5.3 million patients in the UK and 60 million people globally. Early-stage and effective treatment of such ocular disorders is paramount to prevent corneal scarring that lead to impaired vision and blindness. Although efficacious ophthalmic instruments exist to test ocular physiology in clinical settings, no portable companion diagnostic is available in point-of-care settings to adjust eye drops and medication dose. Although hypotonic artificial tear formulations are commonly used to treat imbalances in ocular physiology with limited effectiveness, individualised electrolyte compositions and controlled drug dosing in artificial tears have been shown to be significantly more efficacious in re-establishing ocular homeostasis. Hence, the ability to monitor continually ocular physiology can enable personalised formulation and controlled administration of eye drops. This project aims to create multiplexed scleral lens sensors that colorimetrically display the concentrations of tear electrolytes for continually monitoring ocular physiology in point-of-care settings. Scleral lenses represent a polymeric platform to build biosensors for minimally-invasive continual measurements of tear electrolytes. This project will involve developing wearable multiplexed scleral lens sensors to sample and analyse tear electrolyte composition. The successful completion of this project will result in a companion diagnostic platform that will enable personalised eye treatments. In the first objective, acryloylated ion-selective chelators will be synthesised to bind to electrolytes reversibly. The second objective is to form a colorimetric transducer in the chelator-functionalised sensing regions of a scleral lens using holographic laser interference lithography. The tear fluid will be collected in physically-separated sensing regions to display the concentration of electrolytes based on colour changes. The third objective is to develop a portable spectrometer using a smartphone camera application to convert the colorimetric images of the scleral lens sensors into quantitative concentration values. The fourth objective is to test the scleral lens sensors in an ex vivo anterior porcine eye disease model. The selectivity and sensitivity of the scleral lens sensors will be evaluated by simulating the electrolyte concentrations imbalances in the ex vivo eye model to monitor ocular physiology disorders. In the last objective, human tear samples will be obtained from volunteer patients with dry eye syndrome and healthy patients. Selectivity, sensitivity and response time of the scleral lens sensors in monitoring human tear electrolytes will be compared to those of ion-selective electrodes (gold standard) to validate in vitro device performance. This project will result in a companion diagnostic platform assisted by smartphones to provide quantitative measurements of tear biomarkers in personalised medicine. The ability to monitor continually tears biomarkers with scleral lens sensors will enable the formulation of individualised eye medications and adjusting drug dosing in eye disorders. Broader applications of this ophthalmic sensing platform are in the diagnoses of chronic ocular diseases and metabolic deficiencies in point-of-care settings. The results of this project will be used to create a basis for a controlled clinical trial of the scleral lens sensors. The deployment of minimally-invasive companion diagnostics will decrease the work load and reduce hospitalisation costs in the NHS ophthalmology services.