Periodic Reporting for period 4 - IMCUSTOMEYE (IMaging-based CUSTOMised EYE diagnostics)
Periodo di rendicontazione: 2022-01-01 al 2022-12-31
The project’s main objective is to develop novel, non-invasive, label-free, imaging-based and in-depth diagnostic tool(s) meaning a change in the paradigm for diagnosis and treatment of vision-threatening conditions such as keratoconus, myopia, glaucoma, cataract and presbyopia. The prevalence of these conditions ranges between 0.05% (keratoconus) to 100% (presbyopia, in the >50 yr old population), and can often lead to loss of independence and productivity. Current standards for diagnosis and treatment rely on limited quantitative information, which limits the ability for treatment to be customised in line with individual patient needs. The novel imaging device delivers morphological, biomechanical and optical biomarkers for improved diagnosis, as well as inputs to customised numerical eye models for treatment guidance. This customised approach will lead to significant improvement in both the provision and cost of eye healthcare.
Within the 2nd reporting period, the partners have finished technical development of an OCT-based 3-D multimeridian air-puff swept source OCT system (hardware and software) (objective a) which is currently being used in clinic studies. The system allows un-obstructed view of corneal deformation in multiple meridians, automatic release of trigger and capture and is patient and operator friendly. Additional strategies to increase the data acquisition throughput include polarization based, depth-enconding and spatial multiplexing, which were tested to benchmark potential ways to reduce the footprint of the system towards a compact device. Besides corneal deformation imaging, the system also allows capture of 3-dimensional OCT-based corneal topography, therefore combining in one single instrument tomographic and biomechanical measurements in a dense collection of points. An European patent office has been filed to protect this technology.
In addition to corneal macro-deformation, the ssOCT (in phase sensitive mode) has been coupled with an acoustic stimulation (speaker) module system that produces modulated micro-deformations in the cornea, envisioned as a more suitable for screening and miniaturization, folliwing predictive simulations of its prospective performance of an acoustic-stimulation system. Pre-compensation methods of the sound excitation wave and signal processing algorithms have been developed to obtain resonance frequencies, and deformation amplitudes as corneal biomarkers. An European patent office has been filed to protect this technology.
The numerical eye models developed in the 1st period have been used in the 2nd period to predict performance of different technical specifications of the imaging techniques (both macro-deformation and micro-modulated pressure), to simulate corneal response in porcine and human eyes under different pressures, to model corneal biomarkers for disease, and to retrieve corneal mechanical properties from inverse modelling. The developed software and numerical simulation studies have allowed deploying methods for: 1) estimation of IOP from corneal deformation under different recitations; 2) Methods for identification of a healthy cornea from a keratoconic cornea; 3) Automatic identification of of cone location in keratoconus; 4) Corneal material stiffness estimation.
The imaging modalities of objective a) are developed into large footprint devices. Market research suggests that there is market potential for a high-end device that combines multimeridian corneal deformation and corneal topography leading to reliable corneal material property reconstruction and predictive surgical planning, as well as for a low-cost device to be successful for disease screening and IOP measurement, we took various steps towards reduction of cost of final designs. In order to minimize risks, two strategies are ongoing. The first one (medium cost, medium size) device entails downsizing of the macro-deformation device with dedicated developments: 1) custom swept laser; 2) foot-print reduction; 3) optomechanical module 9-spot illumination module; 4) custom driving electronics; 5) low-cost digitizers. The second one (low cost, low size) device uses acoustic stimulation and replaces the OCT engine by a multiplexed high-coherence interferometry technique.
During this period, efforts have concentrated in the development of the imaging technologies, biomarkers, corneal material property reconstructions, validations and collection of the first clinical data. Clinical and model data will serve as inputs for testing custom surgical planning software. Ongoing clinical studies have included patients with normal corneas, keratoconus and forme fruste keratoconus. Preparation for clinical studies on patients B&A LASIK surgery, keratoconic patients B&A ICRS and glaucoma and keratoconic patients B&A cross-linking are ongoing.
In addition to corneal macro-deformation, the ssOCT (in phase sensitive mode) has been coupled with an acoustic stimulation (speaker) module system that produces modulated micro-deformations in the cornea, envisioned as a more suitable for screening and miniaturization, folliwing predictive simulations of its prospective performance of an acoustic-stimulation system. Pre-compensation methods of the sound excitation wave and signal processing algorithms have been developed to obtain resonance frequencies, and deformation amplitudes as corneal biomarkers. An European patent office has been filed to protect this technology.
The numerical eye models developed in the 1st period have been used in the 2nd period to predict performance of different technical specifications of the imaging techniques (both macro-deformation and micro-modulated pressure), to simulate corneal response in porcine and human eyes under different pressures, to model corneal biomarkers for disease, and to retrieve corneal mechanical properties from inverse modelling. The developed software and numerical simulation studies have allowed deploying methods for: 1) estimation of IOP from corneal deformation under different recitations; 2) Methods for identification of a healthy cornea from a keratoconic cornea; 3) Automatic identification of of cone location in keratoconus; 4) Corneal material stiffness estimation.
The imaging modalities of objective a) are developed into large footprint devices. Market research suggests that there is market potential for a high-end device that combines multimeridian corneal deformation and corneal topography leading to reliable corneal material property reconstruction and predictive surgical planning, as well as for a low-cost device to be successful for disease screening and IOP measurement, we took various steps towards reduction of cost of final designs. In order to minimize risks, two strategies are ongoing. The first one (medium cost, medium size) device entails downsizing of the macro-deformation device with dedicated developments: 1) custom swept laser; 2) foot-print reduction; 3) optomechanical module 9-spot illumination module; 4) custom driving electronics; 5) low-cost digitizers. The second one (low cost, low size) device uses acoustic stimulation and replaces the OCT engine by a multiplexed high-coherence interferometry technique.
During this period, efforts have concentrated in the development of the imaging technologies, biomarkers, corneal material property reconstructions, validations and collection of the first clinical data. Clinical and model data will serve as inputs for testing custom surgical planning software. Ongoing clinical studies have included patients with normal corneas, keratoconus and forme fruste keratoconus. Preparation for clinical studies on patients B&A LASIK surgery, keratoconic patients B&A ICRS and glaucoma and keratoconic patients B&A cross-linking are ongoing.
PROGRESS BEYOND THE STATE OF THE ART
The project will deliver innovative optical imaging-based technologies and quantitative analysis that will have an impact on substantially improving in-depth diagnosis and more effective treatment of age and life-style eye diseases.
1. Screening of keratoconus will surpass current methods based only on corneal topography, through a biomarker probing mechanical properties.
2. Improved Introacular pressure measurement, taking into account mechanical properties, impacting glaucoma diagnostic and monintoring
3. Patient-specific distribution of mechanical elastic, viscoelastic and anisotropic parameters which will allow to construct patient-specific methods of mechanical response and planning of surgery.
EXPECTED RESULTS
Compact dynamic imaging device delivering corneal mechanical biomarker, corrected Intraocular Pressure (IOP) and corneal thickness.
Multi-meridian corneal deformation imaging system coupled with inverse modeling techniques to estimate corneal mechanical properties
Patient-specific eye opto-mechanical models for surgical planning
Clinical demonstrations on keratoconus and glaucoma patients
Clinical demonstrations in refractive surgery, ICRS and cataract patients, and predicted optimized surgery in those patients
POTENTIAL IMPACTS
Diagnosis of keratoconus will surpass current screening methods based only on corneal topography, including patient-specific distribution of mechanical elastic, viscoelastic and anisotropic parameters affecting visual degradation.
Management of glaucoma will also improve by accurate measurements of intraocular pressure, corrected by the individual's corneal biomechanical response.
Candidates for refractive surgery will be screened not only using corneal thickness and topographical observations, but also on the predicted mechanical response to surgery.
Predictive eye models will allow prescribing and customising corneal implants, and placement for the treatment of keratoconus, myopia or presbyopia, based on the simulated biomechanical and optical response.
The technology will be used as a benchmark for optimisation and customisation of treatment and serve to validate current treatment options, by comparing clinical outcomes with the predictions of the customised models.
The project will have an impact on securing and reinforcing industrial leadership in the biophotonics-related market for analysis and diagnostic imaging systems.
The project will deliver innovative optical imaging-based technologies and quantitative analysis that will have an impact on substantially improving in-depth diagnosis and more effective treatment of age and life-style eye diseases.
1. Screening of keratoconus will surpass current methods based only on corneal topography, through a biomarker probing mechanical properties.
2. Improved Introacular pressure measurement, taking into account mechanical properties, impacting glaucoma diagnostic and monintoring
3. Patient-specific distribution of mechanical elastic, viscoelastic and anisotropic parameters which will allow to construct patient-specific methods of mechanical response and planning of surgery.
EXPECTED RESULTS
Compact dynamic imaging device delivering corneal mechanical biomarker, corrected Intraocular Pressure (IOP) and corneal thickness.
Multi-meridian corneal deformation imaging system coupled with inverse modeling techniques to estimate corneal mechanical properties
Patient-specific eye opto-mechanical models for surgical planning
Clinical demonstrations on keratoconus and glaucoma patients
Clinical demonstrations in refractive surgery, ICRS and cataract patients, and predicted optimized surgery in those patients
POTENTIAL IMPACTS
Diagnosis of keratoconus will surpass current screening methods based only on corneal topography, including patient-specific distribution of mechanical elastic, viscoelastic and anisotropic parameters affecting visual degradation.
Management of glaucoma will also improve by accurate measurements of intraocular pressure, corrected by the individual's corneal biomechanical response.
Candidates for refractive surgery will be screened not only using corneal thickness and topographical observations, but also on the predicted mechanical response to surgery.
Predictive eye models will allow prescribing and customising corneal implants, and placement for the treatment of keratoconus, myopia or presbyopia, based on the simulated biomechanical and optical response.
The technology will be used as a benchmark for optimisation and customisation of treatment and serve to validate current treatment options, by comparing clinical outcomes with the predictions of the customised models.
The project will have an impact on securing and reinforcing industrial leadership in the biophotonics-related market for analysis and diagnostic imaging systems.