 The past 15th and 16th of June took place Imcustomeye Annual Review Meeting. The event was hosted by VioBio Lab (CSIC) and the Institute of Physical Chemistry (Polish Academy of Sciences) and, due to this year exceptional circumstances, the meeting was virtual and took place via Zoom.
All partners, including the IPs, attended the two days meeting, gaving an update on the research, IP and outreach progress of the project during this past year. Professor Cynthia Roberts (Department of Biomedical Engineering, Ohio State University), member of the Advisory Board, was invited to the meeting where she gave a lecture on "The importance of corneal biomechanics as a diagnostic marker". The event also included bilateral discussions on specifics of the project between designated partners, a steering committee session and a debate on the impact of COVID-19 on market of medical devices and clinical studies.
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 Optical coherence tomography (OCT) is a non-invasive depth resolved optical imaging modality, that enables high resolution, cross-sectional imaging in biological tissues and materials at clinically relevant depths. Though OCT offers high resolution imaging, the best ultra-high-resolution OCT systems are limited to imaging structural changes with a resolution of one micron on a single B-scan within very limited depth. Nanosensitive OCT (nsOCT) is a recently developed technique that is capable of providing enhanced sensitivity of OCT to structural changes. Improving the sensitivity of OCT to detect structural changes at the nanoscale level, to a depth typical for conventional OCT, could potentially improve the diagnostic capability of OCT in medical applications. Researchers from the National University of Ireland Galway demonstrates in this paper, published by Biomedical Optics Express, the capability of nsOCT to detect structural changes deep in the rat cornea following superficial corneal injury. Full reference: C. Lal, S. Alexandrov, S. Rani, Y. Zhou, T. Ritter, M. Leahy, “Nanosensitive optical coherence tomography to assess wound healing within the cornea”. Biomed. Opt. Express 11 (7) 3407-3422 (2020) https://doi.org/10.1364/BOE.389342 Full article here  Corneal cross‐linking (CXL) using ultraviolet‐A (UVA) irradiation with a riboflavin photosensitizer has grown from an interesting concept to a practical clinical treatment for corneal ectatic diseases globally, such as keratoconus. This research led by NUI Galway reports the application of oversampling nanosensitive OCT for probing the corneal structural alterations. The results indicate that the spatial period increases slightly after 30 minutes riboflavin instillation but decreases significantly after 30 minutes UVA irradiation following the Dresden protocol. The proposed noninvasive method can be implemented using existing OCT systems, without any additional components, for detecting nanoscale changes with the potential to assist diagnostic assessment during CXL treatment, and possibly to be a real‐time monitoring tool in clinics.
Full reference: Y. Zhou, S. Alexandrov, A. Nolan, N. Das, R. Dey and M. Leahy, “Non‐invasive detection of nanoscale structural changes in cornea associated with corneal cross‐linking treatment”. Journal of Biophotonics 13 (6) e201960234 (2020) https://doi.org/10.1002/jbio.201960234 Full article here  First press release on Imcustomeye project was published by Consejo Superior de Investigaciones Científicas (CSIC) this May. The press release seeks to introduce the project to the general public, including a description of the consortium of academic experts, ophthalmic clinics and companies, the objectives of the project and an overview on corneal biomechanics. The article also includes quotes from interviews with PI Prof. Susana Marcos and postdoctoral researchers from VioBio Lab Judith Birkenfeld and Andrea Curatolo.
Link to the press release here  Most of the fundamental pathological processes in living tissues exhibit changes at the nanoscale. Noninvasive, label-free detection of structural changes in biological samples pose a significant challenge to both researchers and healthcare professionals. Modern nanoscopy largely requires labeling, is limited to superficial 2D imaging, and is generally not suitable for in vivo applications. In this article published in Applied Physics Letters, we presented a method, spatial frequency domain correlation mapping optical coherence tomography (sf-cmOCT), developed at NUI Galway, for detection of depth resolved nanoscale structural changes noninvasively. Our approach is based on detection and correlation of the depth resolved spectra of axial spatial frequencies of the object which are extremely sensitive to structural alterations. These experimental results demonstrate possibilities for the study of nanoscale structural changes, without the need for biomarkers or labels. Thus, sf-cmOCT offers exciting and far-reaching opportunities for early disease diagnosis and treatment response monitoring, as well as a myriad of applications for researchers. Full reference: Sergey Alexandrov, Paul M. McNamara, Nandan Das, Yi Zhou, Gillian Lynch, Josh Hogan, and Martin Leahy. Spatial frequency domain correlation mapping optical coherence tomography for nanoscale structural characterization. Applied Physics Letters 115:12 (2019). Full article here  One option for treating keratoconus, a degenerative disease that results in a weakened cornea and vision loss, is cross-linking. Cross-linking strengthens the overall structure of the cornea by promoting the creation of covalent bonds between neighboring collagen fibrils or between fibrils and the surrounding extracellular matrix. To measure how cross-linking affects the cornea at different depths inside the stroma, three different corneal treatments were performed on rabbit animal models: no treatment, Riboflavin instillation/Ultraviolet irradiation, and Rose Bengal instillation/Green light irradiation. Rabbits were sacrificed one and two months after treatment. Images of corneal lamellae were taken with a second harmonic generation laser scanning microscopic developed at VioBio Lab (CSIC) and were analyzed with a MATLAB script to measure the different directions of the collagen fibers. The collagen fibers in the cross-linked corneas had more uniform fiber orientations than in untreated corneas through a depth of 300 microns. The amount of second harmonic generation is also greater in cross-linked corneas than in control corneas. Both the organization and second harmonic generation signal increased between one month and two months after treatment. This research was a collaboration between CSIC, the University of Valladolid, and the Wellman Center for Photomedicine.
Full reference: James A. Germann, Eduardo Martínez-Enríquez, M. Carmen Martínez-García, Irene E. Kochevar, Susana Marcos; Corneal Collagen Ordering After In Vivo Rose Bengal and Riboflavin Cross-Linking. Invest. Ophthalmol. Vis. Sci. 61(3):28 (2020). Full article here  Imcustomeye partners were present at the SPIE Photonics West that took place in San Francisco this February 2020. SPIE Photonics West is the premier laser, photonics, biomedical optics event, organized by The International Society for Optics and Photonic (SPIE). The not-for-profit society promotes emerging technologies through interdisciplinary information exchange, continuing education, publications, patent precedent, and career and professional growth.
A progress meeting of the Imcustomeye project was held the past February 5 coinciding with the presence of CSIC, NUIG, PAN and 2EyesVision partners at the Conference. The meeting covered a wide range of topics including status of the technology, prospects for clinical measurements and project communications. Here are the Imcustomeye contributions at the SPIE Photonics West: Sunday 2 February - Ocular Biomechanics Session. 9:40 am Susana Marcos “Corneal dynamic imaging and second harmonic generation to evaluate in vivo corneal cross-linking” (Invited Paper). Consejo Superior de Investigaciones Científicas (Spain). - Ocular Biomechanics Session. 9:10am Andrea Curatolo “Customized swept-source optical coherence tomography system for air-puff induced corneal deformation imaging on multiple meridians” A. Curatolo, J. Birkenfeld, E. Martínez, J.A. Germann, D. Pascual, G. Muralidharan, Consejo Superior de Investigaciones Científicas (Spain); J. Palací, 2Eyes Vision SL (Spain); J. Solarski, K. Karnowski, M. Wojtkowski, Institute of Physical Chemistry (Poland); S. Marcos, Consejo Superior de Investigaciones Científicas (Spain). - Poster Session. Simultaneous optical coherence tomography measurements at two arbitrary meridians, Karol Karnowski, J. Solarski, A. Consejo, M. Wojtkowski, Institute of Physical Chemistry (Poland). - Poster Session. Light intensity distribution from corneal Scheimpflug images as a predictor of eye diseases, Alejandra Consejo, Polish Academy of Sciences (Poland); K. Karnowski, J. Solarski, Institute of Physical Chemistry PAS (Poland); D.R. Iskander, Wroclaw Univ. of Science and Technology (Poland); M. Wojtkowski, Institute of Physical Chemistry PAS (Poland). - Poster Session. Use of optical coherence yomography to access corneal vibrational resonance. Ryan McAuley, A. Nolan, S.A. Alexandrov, M.J. Leahy. National Univ. of Ireland, Galway (Ireland).  The first Review Meeting of the IMCUSTOMEYE project took place in Brussels on June 12 2019 at the European Commission - DG Connect. The goal of the meeting organized by the European Comission was to cover and assess all the project activities carried out during the first reporting period.
The Review Meeting was attended by the IPs and other staff members of all partners from the consortium and the presentations were reviewed by the Project Officer and two external independent experts, Ms. Ieva Sliesoraityte from the private for profit research organisation “Institut Arthur Vernes” and Mr. Thomas Klein, CEO of the company OPTORES. The following topics were presented during the meeting by the different partners: Project highlights and workplan review; Dissemination and exploitation; WP2 achievements: “Air-puff OCT 3D corneal deformation imaging device”; WP3 achievements: “Phase sensitive/nano sensitive OCT vibrography device”; WP4 achievements: “Compact dynamic OCT prototype”; WP5 achievements: “Corneal biomechanical parameters from dynamicimaging based FEM models”; WP6-WP7 prospects: “Diagnostic paramenters & treatment predictions” and “Impact on customized treatments”.  A progress meeting of the Imcustomeye project was held the past May 1st in Vancouver (Canada), coinciding with the presence of some of the consortium partners at the ARVO 2019 Annual Meeting. The ARVO congress takes place every year and plays a key role for research in vision and ophthalmology since it is the largest gathering of researchers in the field.
The meeting was focused on the clinical area of the project and the following aspects were covered: status of the technology, ethical issues, prospects for clinical measurements and project communications. The meeting attendees were CSIC, Instituto Oftalmológico Fernández-Vega, Oculus Gmbh and Moorfields Eye Hospital. The partners also had the opportunity to meet with Prof. Cynthia Roberts, advisor of the Imcustomeye project. Judith Birkenfeld, postdoctoral researcher in VioBio Lab (CSIC), presented the poster "Assessment of asymmetries in biomechanical properties from corneal deformation imaging" on Thursday May 2nd. Dr. Birkenfeld discussed the new contributions on air-puff corneal deformation imaging and crosslinking (CXL), a common treatment in eye diseases like keratoconus by allowing the weakened cornea to strengthen using light.  The past 7th and 8th of March took place in Warsaw the Annual Meeting of the Imcustomeye project. The event was hosted by one of the partners of the consortium: the Institute of Physical Chemistry of the Polish Academy of Sciences.
The IMCUSTOMEYE partners, academic, clinical and industrial, attending the meeting gave an update on the research and technology progress during this past year. The meeting concluded with a discussion about the product commercialization perspective.  The commercialization meeting of the IMCUSTOMEYE project took place in Madrid (Instituto de Óptica, CSIC) on November 2018 led by the partner IROC Science.
The IMCUSTOMEYE project will develop a new optical imaging system that will allow to obtain biomarkers to improve the diagnosis of a certain range of vision-threatening conditions. The main objective of the two day meeting was to establish new strategies for the development and commercialization of the Imcustomeye technologies defining their market perspective and potential applications. Each of the attending partners also gave an update on R&D status, which led to a product development roadmap. The IMCUSTOMEYE consortium consists of 10 partners, from 6 different countries and different fields, academic, clinical and industrial. The attendees to the meeting were: IROC Science, CSIC, National University of Ireland, Polish Academy of Science, University of Liverpool, University College London, Oculus Gmbh, 2EyesVision SL and Optimo Medical AG.  Application of the air‐puff swept source optical coherence tomography (SS‐OCT) instrument to determine the influence of viscoelasticity on the relation between overall the air‐puff force and corneal apex displacement of porcine corneas ex vivo has been demonstrated. Micrometer resolution, fast acquisition and noncontact character of the air‐puff SS‐OCT measurements have potential to improve the in vivo assessment of mechanical properties of the human corneas. This work was successfully published in Journal of Biophotonics.
Full reference: Maczynska E, Karnowski K, Szulzycki K, Malinowska M, Dolezyczek H, Cichanski A, Wojtkowski M et al. Assessment of the influence of viscoelasticity of cornea in animal ex vivo model using air‐puff optical coherence tomography and corneal hysteresis. J. Biophotonics. 2018; e201800154. Full article here  Dr. Andrea Curatolo received Young Investigator Award for his presentation entitled "Customised optical coherence tomography system for corneal deformation imaging on multiple meridians" at Reunion Nacional de Optica, the Congress of the Optical Society of Spain, Sedoptica, which celebrated its 50th Anniversary. The award is co-sponsored by the Optical Society of America, and presented by Prof. Chris Dainty, past OSA President.
Dr. Curatolo presented the first swept source OCT system for air-puff-induced corneal deformation imaging on two meridians, an flagship milestone of the IMCUSTOMEYE H2020 Innovation Action.  An informal progress meeting of the project was held in Honolulu (Hawaii) the past 30th of April, coinciding with the presence of many of the IMCUSTOMEYE partners at the ARVO 2018 Annual Meeting, the largest gathering of eye and vision researchers in the world.
The partners present at the meeting were Instituto Oftalmológico Fernández-Vega, Polish Academy of Science, Oculus Gmbh, IROC Science and CSIC. The meeting started with the presentation of Judith Birkenfeld's poster (“Assessment of ocular mechanical resonances using phase-sensitive OCT and frequency-domain air puff stimulation”), followed by a team discussion to follow up on the different action items, technical advances and administrative and logistical aspects of the IMCUSTOMEYE project for the following months.  The kick-off meeting of the H2020 Innovation Action IMCUSTOMEYE has taken place this week at CSIC led by Prof. Susana Marcos, researcher of the Institute of Optics (CSIC). The IMCUSTOMEYE project will develop a new optical imaging system that will allow to obtain biomarkers to improve diagnosis of certain ocular pathologies such as glaucoma and keratoconus, and the development of customize treatments such as refractive surgery, cataract surgery and corneal treatments. Nowadays the diagnosis of corneal conditions and the selection of patients for refractive surgery are performed based on purely morphological effects (asymmetries in the cornea, corneal thickness). The new instrument will provide biomechanical parameters, which will allow to plan treatments based on the prediction of the corneal response (for example, to incisions or corneal implants). IMCUSTOMEYE will develop new diagnostic paradigms for these vision-threatening conditions. The IMCUSTOMEYE consortium consists of 10 partners, from 6 different countries and different fields, academic, clinical and industrial: National University of Ireland, Polish Academy of Science, University of Liverpool, University College London-Moorfields Eye Hospital, Instituto Oftalmológio Fernandez Vega, Oculus Gmbh, 2EyesVision SL, IROC Science, Optimo Medical AG. During the kick-off meeting the partners presented their research activities and expected contributions to the project, and hold 10 round table discussions on technical aspects of the project, IP handling, and commercialization, among others.  The IMCUSTOMEYE project, a competitive H2020 Innovation Action of the Photonics KET Program, has just been launched under the leadership of the Visual Optics and Biophotonics Laboratory (Institute of Optics, CSIC; Principal Investigator: Susana Marcos). IMCUSTOMEYE will develop a novel non-invasive label-free imaging-based in-depth diagnostic tool to create a step change in the paradigm for diagnostics of vision-threatening conditions including keratoconus, myopia, glaucoma, cataract and presbyopia, some of which potentially lead to loss of independence and productivity, with an impact on their treatment. The prevalence of these conditions ranges between 0.05% (keratoconus) to 100% (presbyopia in population >50 yr), and increase with age. Current standards for diagnosis and therefore treatment rely on limited quantitative information preventing treatments to be customised for individual patient’s needs. The proposed in-depth diagnostic paradigm will make use of morphological, biomechanical and optical biomarkers acquired from a new imaging device, based on Optical Coherence Tomography. These will allow creating predictive customised eye models that can guide diagnosis and treatment of individual patients. The optimisation and customisation of diagnosis, which has not been possible before, are expected to lead to significant improvement in both the provision and cost of eye healthcare. The consortium is formed by leading institutions and companies in optical imaging, ocular biomechanics and ophthalmology. Partners include Academic Institutions: University of Liverpool (UK), Institute of Physical Chemistry of the Polish Academy of Sciences (Poland), National University of Ireland, Galway (Ireland); Eye Hospitals: Instituto Oftalmológio Fernandez Vega (Spain), and University College London Institute of Ophthalmology and Moorfields Eye Hospital (UK) and companies: IROC Science to Innovation AG (Switzerland), 2EyesVision SL (Spain), Oculus Optikgeräte GmbH (Germany), Optimo Medical AG (Switzerland) More information and updates of the project will be found at www.imcustomeye.eu and @IMCUSTOMEYE |
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