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.
Organisations
- University of Liverpool (Lead Research Organisation)
- Beihang University (Collaboration)
- Cristalens (Collaboration)
- Oculus (Collaboration)
- Wenzhou Medical University (Collaboration)
- Implandata Ophthalmic Products GmbH (Collaboration)
- UltraVision CLPL (Project Partner)
- Ninewells Hospital (Project Partner)
- Aberdeen Royal Infirmary (Project Partner)
- International Glaucoma Association (Project Partner)
Publications
Joda AA
(2016)
Development and validation of a correction equation for Corvis tonometry.
in Computer methods in biomechanics and biomedical engineering
Lee H
(2017)
Effect of accelerated corneal crosslinking combined with transepithelial photorefractive keratectomy on dynamic corneal response parameters and biomechanically corrected intraocular pressure measured with a dynamic Scheimpflug analyzer in healthy myopic patients.
in Journal of cataract and refractive surgery
Maklad O
(2019)
Simulation of Air Puff Tonometry Test Using Arbitrary Lagrangian-Eulerian (ALE) Deforming Mesh for Corneal Material Characterisation.
in International journal of environmental research and public health
Vinciguerra R
(2016)
Influence of Pachymetry and Intraocular Pressure on Dynamic Corneal Response Parameters in Healthy Patients.
in Journal of refractive surgery (Thorofare, N.J. : 1995)
Vinciguerra R
(2016)
Detection of Keratoconus With a New Biomechanical Index.
in Journal of refractive surgery (Thorofare, N.J. : 1995)
Whitford C
(2016)
Ex vivo testing of intact eye globes under inflation conditions to determine regional variation of mechanical stiffness.
in Eye and vision (London, England)
Whitford C
(2015)
Biomechanical model of the human cornea: considering shear stiffness and regional variation of collagen anisotropy and density.
in Journal of the mechanical behavior of biomedical materials
Williams D
(2013)
Automatic segmentation of anterior segment optical coherence tomography images.
in Journal of biomedical optics
Wu Y
(2019)
Efficacy and Safety of Transglutaminase-Induced Corneal Stiffening in Rabbits.
in Translational vision science & technology
Yu JG
(2013)
Assessment of corneal biomechanical behavior under posterior and anterior pressure.
in Journal of refractive surgery (Thorofare, N.J. : 1995)
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. . 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. More recently, a method for estimating corneal biomechanical properties has been developed and implemented in a non-contact device (Corvis ST). |
Exploitation Route | The non-contact device (Corvis) that enables the estimation of the corneal biomechanical properties based on this project has been quite successful. Research is being carried out around the world to assess the estimated properties and clinical practice is starting to use the properties to assess progress of disease (keratoconus) and efficacy of treatment (collagen cross-linking). |
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. Over the 2017-2020 period, I have worked with Oculus to introduce a material parameter that can be obtained using their Corvis ST device. the parameter (Stress Strain Index or SSI) has been made available in the Corvis software from 2019. Another development was the biomechanically-corrected intraocular pressure (bIOP) measurement that is now also available with the Corvis ST. Work to optimise planning of surgeries will be starting soon. |
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 | 03/2012 |
End | 04/2013 |
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 | 04/2012 |
End | 09/2012 |
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 | Implandata |
Organisation | Implandata Ophthalmic Products GmbH |
Country | Germany |
Sector | Private |
PI Contribution | This is a collaboration in the development of an intraocular pressure measurement device developed by Implandata, which is to be tested and validated by our group. |
Collaborator Contribution | The partner will cover the cost of the testing and validation study. |
Impact | Not yet. After the validation work is completed, publications will be produced. There may also be further collaboration in device refinement. |
Start Year | 2019 |
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 |