Determination of Corneal Biomechanical Properties in vivo

Lead Research Organisation: University of Liverpool
Department Name: School of Engineering

Abstract

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.

Planned Impact

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.
 
Description Experimental findings:

Based on experimental evidence, obtained for the first time, the regional variation of mechanical stiffness across the surface of the human eye has been determined.

The area separating the cornea and sclera has been found to have the highest stiffness in the eye.

Central cornea is stiffer than peripheral cornea, supporting earlier evidence obtained experimentally.

Posterior sclera has the lowest in all the sclera.

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Technology development:

A simple contact-based methodology has been developed to enable measurement of corneal mechanical stiffness in vivo.

The stiffness estimates are dependent on corneal geometeric parameters (thickness and curvature) and material parameters (age), but not the intraocular pressure. This findings satisfies a major objective of the study.
Exploitation Route A device prototype is being built based on the contact technology developed in this project. The prototype will be tested experimentally before trialling it in clinical studies. If successful, the device could be developed into a medical tool and exploited commercially.
Research publications will be prepared once we have sufficient experimental data.
Sectors Healthcare

URL http://www.ocular-biomechanics.liv.ac.uk
 
Description Study and associated publications showed importance of, and the ability to measure, corneal biomechanical properties in vivo. This work has been behind industrial interest in creating devices that can measure the properties using technology based on our work (Oculus) and in the start of research to consider the in vivo properties in the planning of surgeries and the measurement of intraocular pressure needed for glaucoma management.
First Year Of Impact 2013
Sector Healthcare
Impact Types Societal,Economic

 
Description Improved management of Meibomian gland dysfunction
Amount £73,120 (GBP)
Organisation University of Liverpool 
Department Knowledge Exploitation Laboratory Project
Sector Academic/University
Country United Kingdom
Start 05/2012 
End 09/2012
 
Description Improved management of Meibomian gland dysfunction
Amount £73,120 (GBP)
Organisation University of Liverpool 
Department Knowledge Exploitation Laboratory Project
Sector Academic/University
Country United Kingdom
Start 03/2012 
End 04/2013
 
Description Industrial funding (Cristalens)
Amount £50,000 (GBP)
Organisation Cristalens 
Sector Private
Country France
Start 01/2015 
End 06/2015
 
Description Beihang 
Organisation Beihang University
Country China 
Sector Academic/University 
PI Contribution Introduction of biomechanics skills into the biomedical research carried out at Beihang
Collaborator Contribution Funding and applications of biomedical research
Impact we are collaborating on a number of papers, none of them have been published yet.
Start Year 2018
 
Description Project with Cristalens 
Organisation Cristalens
Country France 
Sector Private 
PI Contribution Optimisation of circular corneal implants using numerical simulation
Collaborator Contribution Provision of clinical and manufacturing data
Impact Estimates of the refractive outcomes of using circular corneal implants with different shapes and sizes
Start Year 2014
 
Description Project with Oculus 
Organisation Oculus
Country Germany 
Sector Private 
PI Contribution Plan of a project to further develop a non contact tonometer (Corvis ST) produced by Oculus
Collaborator Contribution Full funding in addition to provision of technical and clinical data
Impact Fully funded industrial project - initial results are very promising - this is a high profile project that can make a significant impact on our standing in the ocular biomechanics community
Start Year 2013
 
Description Wenzhou 
Organisation Wenzhou Medical University
Country China 
Sector Academic/University 
PI Contribution Topography analysis based on techniques developed in EPSRC project
Collaborator Contribution Collection and analysis of a huge set of topography maps
Impact A number of papers linked to this projects have been produced as a result of this collaboration.
Start Year 2015
 
Title Medical device to estimate corneal biomechanical properties in vivo 
Description A contact device that indents the central cornea, monitors the resistance of the cornea to indentation and uses the resistance to estimate the main material properties of the cornea, and in particular the hyperepasticity, hysteresis and viscoelasticity. 
Type Of Technology Physical Model/Kit 
Year Produced 2014 
Impact We are still waiting for conduct of clinical study 
 
Description Invited seminar at Moorfields Eye Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Encouraged collaboration with researchers at Moorfields Eye Hspital and UCL in technologies that build on knowledge of the cornea's mechanical properties.

A new H2020 project is being prepared, partly based on knowledge created in this project.
Year(s) Of Engagement Activity 2014
 
Description Wenzhou 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Encouraged collaboration in studies that require knowledge of corneal mechanical properties

A number of papers being prepared on joint studies with Wenzhou on use of corneal mechanical properties in improving accuracy of techniques to measure intraocular pressure.
Year(s) Of Engagement Activity 2014