Determination of Corneal Biomechanical Properties in vivo

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.

The project aims to address the research needs underpinning the development of technology to measure corneal biomechanical properties in-vivo. The technology to be developed in this research aims to provide essential information on corneal mechanical behaviour, without which progress in ophthalmic patient care had to rely on experimental tests involving ex-vivo tissue. The ability to measure corneal properties in-vivo promises huge benefits to patients, healthcare services and medical device manufacturers, and a step change in the effectiveness of patient care in several areas of ophthalmology including the following: The measurement of intraocular pressure (IOP) is an essential part of glaucoma management. All IOP measurement (tonometry) techniques are affected by corneal stiffness, and the resulting inaccuracies are potentially great and can lead to poor management outcomes. If corneal stiffness can be measured in-vivo, its effect on IOP measurement can be eliminated resulting in accurate estimates of IOP, better risk-profiling of patients and ultimately a reduction in the number of mismanaged cases with better targeting of treatment. Implementing the new technology therefore has the potential to benefit glaucoma patients, healthcare services and tonometer manufacturers. Stiff implants are commonly used to restore clear vision in keratoconus patients. The implants interact mechanically with the cornea to force it into a more natural shape and reduce the coning associated with keratoconus. With the accurate determination of corneal stiffness, the design of implants would improve, leading to better vision and less reliance on corrective glasses. This application requires the development of standalone devices for the measurement of corneal stiffness in-vivo and simple techniques to consider its effect on the design of corneal implants. In spite of the huge potential of refractive surgery to achieve ideal vision correction, unexpected aberrations commonly develop. Post-operative corneal response to the change in structure imposed by the surgical procedure could be predicted and used to guide the planning of the surgery and improve its outcome but only if corneal biomechanics could be measured in-vivo. With a standalone device to measure corneal biomechanical properties (stiffness, hysteresis and viscoelasticity), refractive surgeries could be simulated numerically to predict their outcome and optimised to ensure an ideal vision correction. The proposed research seeks to overcome the major obstacles preventing the development of in-vivo measurement technology and to assess a number of conceptual methods to make in-vivo measurement a reality. Once validated, the basic technology is expected to be taken up by industry to develop it into clinical devices. The involvement of UltraVision and the International Glaucoma Association in this project is designed to ensure the technology remains suitable for clinical application. UV and the IGA will form part of the Advisory Group overseeing the progress of the project and meeting twice a year. However, UV will have a more active involvement within the project, especially during the testing stages, due to its interest in the technology and realisation that if the research questions posed in this project are answered, the result would have a huge potential. The outcomes of the research will be made public as early as reasonably practicable. In part, this will be done through a dedicated website providing information in forms accessible to clinicians, academics and device development engineers. The site will contain general background information as well as the main results of laboratory and numerical experiments. Dissemination will also be achieved through presentations at academic and professional conferences and through the traditional academic channel of publications in peer-reviewed journals.