Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. Conventional intensity-based OCT provides depth-resolved imaging with a typical resolution and sensitivity to structural alterations of about 5–10 microns. It would be desirable for functional biological imaging to detect smaller features in tissues due to the nature of pathological processes. In this article, researchers from the National University of Ireland Galway, perform the analysis of the spatial frequency content of the OCT signal based on scattering theory. We demonstrate that the OCT signal, even at limited spectral bandwidth, contains information about high spatial frequencies present in the object which relates to the small, sub-wavelength size structures.  Presented results provide a theoretical and experimental basis to substantially improve the sensitivity of OCT to structural alterations at clinically relevant depths.

Full reference: Alexandrov, S., Arangath, A., Zhou, Y. et al. "Accessing depth-resolved high spatial frequency content from the optical coherence tomography signal". Sci Rep 11, 17123 (2021). https://doi.org/10.1038/s41598-021-96619-7

Full article here

​In the past months, Imcustomeye partners have presented multiple results of the project on corneal biomechanics at several international congresses including ARVO 2021 Annual Meeting, OSA Biophotonics Congress 2021, SPIE Conference "Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine" and European Conferences on Biomedical Optics. 

ARVO is the largest and most respected eye research organization in the world, with 11,000 members worldwide, and its congress takes place every year playing a key role for research in vision and ophthalmology. This year Judith Birkenfeld's poster on first results with the newest device ImTOPScanner was designated Hot Topic by the organization.  Here are the Imcustomeye contributions: 

- Judith S. Birkenfeld; Andrea Curatolo; Ashkan Eliasy et al. “Improved detection of corneal deformation asymmetries in keratoconus patients using multi-meridian deformation imaging" Investigative Ophthalmology & Visual Science Vol.62, 2031 (2021)

- Lupe Villegas; James Germann; Susana Marcos. "Biomechanical effects of Scleral crosslinking using Rose Bengal/Green-light and Rivoflavin/UVA". Investigative Ophthalmology & Visual Science Vol.62, 2281 (2021)

- Ashkan Eliasy; Bernardo Teixeira Lopes; Ahmed Abass et al. "Evaluation of Stress-Strain Index (SSI2) in Healthy and Keratoconic corneas". Investigative Ophthalmology & Visual Science Vol.62, 777 (2021)

- Bernardo T Lopes; Ahmed Abass; Ashkan Eliasy; Haixia Zhang; Ahmed Elsheikh. "A New Method to Describe Cone Shape in Keratoconic Corneas". Investigative Ophthalmology & Visual Science Vol.62, 2025 (2021)

OPTICA, formerly OSA, and SPIE are international professional societies working to advance optics and photonics. Imcustomeye has contributed with the following talks at conferences organized by these societies: 

- Andrea Curatolo, Angela Pachacz, Jedrzej Solarski et al. "Corrections of motion artifacts in dynamic low-cost, swept-source optical coherence tomography" in Biophotonics Congress 2021. OSA Technical Digest (Optical Society of America), paper DTh1A.4 (2021)

- Karol Karnowski, Jedrzej Solarski, Andrea Curatolo et al. "Corrections of axial shift artifact in dynamic swept-source optical coherence tomography" in SPIE BiOS 2021. Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXV, Proceedings Vol. 11630 (2021). 

- Judith S. Birkenfeld, David Bronte-Ciriza, Andrés de la Hoz et al. "Proof-of-concept method to estimate scleral mechanical properties from air-puff Optical Coherence Tomography". European Conferences on Biomedical Optics 2021. 

Moorfields Eye Hospital, clinical partner of the IMCUSTOMEYE consortium, has published a post about the IMCUSTOMEYE project on their intranet and newsletter. The post introduce the project and talks about the Moorfields’ role testing patients with keratoconus, cataract and glaucoma to validate the new devices’ ability to identify corneal disease and measure eye pressure accurately.

Moorfields Eye Hospital is the leading provider of eye health services in the UK and a world-class centre of excellence for ophthalmic research and education. The main focus of their 2300 staff members is the treatment and care of NHS patients with a wide range of eye problems. The volume and variety of conditions treated by Moorfields clinicians means that they have a unique range of skills and knowledge.

The next step in the project for Moorfields will be to set up the study mentioned before and then begin recruiting patients from clinics to take part in the testing. 

You can read the post here

The University of Liverpool, member of the IMCUSTOMEYE consortium, has published a press release on the project in its research section. The article highlights the role of the University’s Biomechanical Engineering Group in the development of new imaging techniques to diagnose and treat corneal diseases and glaucoma in a personalised manner. 

Professor Ahmed Elsheikh, head of the research group, explains that “despite the fact that these treatments, and the conditions they help with, interact or interfere mechanically with the cornea, there is currently no method to accurately measure corneal biomechanical properties in vivo. Such a method would be essential for customising these treatments for individual patients’ needs and ultimately improving their clinical outcomes. The IMCUSTOMEYE project is intended to address this need,” 

Check out the full press release here

An EU Horizon 2020 IMCUSTOMEYE project landmark paper has just been published in Biomedical Optics Express. It is the result of a collaboration between CSIC, University of Liverpool, and the Polish Academy of Science. It presents the first multi-meridian corneal imaging device, based on a swept-source optical coherence tomography system with high transverse scanning frame rates, to measure a promising early keratoconus biomarker based on air-puff-induced deformation asymmetry. The system will serve both as the basis for determining the minimum viable specifications for a keratoconus screening device based on a deformation asymmetry biomarker, and as a platform to estimate patient-specific corneal biomechanical properties, that can be fed in corneal surgery planning simulators. Currently the system is employed in a pilot clinical study with Keratoconus and Lasik-candidate subjects in collaboration with Fernandez Vega Ophthalmological Institute.

Full reference: Andrea Curatolo, Judith S. Birkenfeld, Eduardo Martinez-Enriquez, James A. Germann, Geethika Muralidharan, Jesús Palací, Daniel Pascual, Ashkan Eliasy, Ahmed Abass, Jędrzej Solarski, Karol Karnowski, Maciej Wojtkowski, Ahmed Elsheikh, and Susana Marcos, "Multi-meridian corneal imaging of air-puff induced deformation for improved detection of biomechanical abnormalities," Biomed. Opt. Express 11, 6337-6355 (2020)

Full article here

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 PIs, 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. 

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).

​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
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