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In-Vivo Neuronal Retinal Cells Imaging

Editorial

The project management is responsible for the content of the information provided.

Cooperation

This project, funded by Gebert Rüf Stiftung, is supported by the following project partners: Laboratory of Applied Photonics Devices, Institute of Microengineering, École Polytechnique Fédérale de Lausanne, Switzerland; Hôpital Ophtalmique Jules Gonin, Fondation Asile des aveugles, Lausanne, Switzerland; Inserm, U1138, Team 17, From physiopathology of ocular diseases to clinical development, Paris Descartes University, Sorbonne Paris Cité, Centre de Recherche des Cordeliers, Paris, France

Project data

  • Project no: GRS-052/17 
  • Amount of funding: CHF 350'000 
  • Approved: 24.04.2018 
  • Duration: 07.2018 - 05.2020 
  • Area of activity:  Pilotprojekte, 1998 - 2018

Project management

Project description

Age related Macular Degeneration (AMD) and glaucoma, which affect approximately 150 million people worldwide, are retinal pathologies degenerating the retina, leading to vision loss or blindness.
The evaluation and monitoring of cells health in the human retina is then crucial for understanding such diseases and providing an early detection signal of the disease for a better treatment. Towards this goal, a major challenge is to image individual retinal cells in human eyes in a non-invasive manner within a time frame relevant for routine patient imaging (ten seconds maximum). Indeed, it would allow, on one hand, early detection of abnormalities well before pathological effects occur and, on another hand, the monitoring of therapeutic effects to develop new drugs.
Nowadays, in-vivo imaging of almost all of the retina cells with clinical devices is still elusive. It stems from the fact that the cells are transparent and therefore very difficult to observe. The invention at the heart of this project constitutes a major advance by using a novel method to visualize microscopic retinal cells with high contrast. The disruptive idea is to illuminate the retina by sending an infrared light beam (invisible) through the sclera of the eye (the white part around the iris). By passing through the sclera, the illumination beam arrives with a high oblique angle on the retina which in turn renders the transparent cell visible. Oblique illumination is often used to observe transparent structures in microscopy, but it is the first time that this technique is applied to an in-vivo human eye. Our technology is combining different oblique illumination directions to further increase the quality and visibility of the cells.
Thanks to the approval from the ethic committee of Canton de Vaud, we performed the first in-vivo tests in our research laboratory. The results showed the possibility of imaging retina pigment epithelium cells, an important class of retinal cells thought to be at the origin of the main retinal diseases. with high contrast and the obtained cell dimension and density analysis matches the literature. We aim at developing a more advanced in-vivo instrument for clinical use with funding help from the Gebert Rüf Stiftung.

What is special about the project?

For the first time, we have shown that the use of transscleral illumination contributed to visualize transparent retinal cells.
We demonstrated that this non-conventional illumination of the retina allows us to observe retinal cellular structures, while other transpupillary illumination-based commercial devices are unable to observe these features. The high-resolution images of several, yet unseen, human cell morphologies in vivo, such as retinal pigment epithelium and ganglions cells are obtained with a short acquisition time compatible for standard clinical examination. Indeed, our modality is, to our knowledge, the only technique fast enough to image the different retinal layers with cellular resolution over an area suitable for a meaningful diagnostic in patients having retinal diseases.
This innovative imaging method is complementary to Optical Coherence Tomography (OCT, the standard for retinal diseases diagnosis), and the combination of both may result in accelerating our understanding of retinal diseases but also the understanding of other neuronal diseases. Indeed, recent medical studies have shown that, due to the intricate connection of the retina to the brain, observing the retina can serve for detecting general neuronal diseases such as Parkinson or Alzheimer, which may largely extend the impact of a clinical use of our technology.

Status/Results

For the first time, we have shown that the use of transscleral illumination contributed to visualize transparent retinal cells.
We demonstrated that this non-conventional illumination of the retina allows us to observe retinal cellular structures, while other transpupillary illumination-based commercial devices are unable to observe these features. The high-resolution images of several, yet unseen, human cell morphologies in vivo, such as retinal pigment epithelium and ganglions cells are obtained with a short acquisition time compatible for standard clinical examination. Indeed, our modality is, to our knowledge, the only technique fast enough to image the different retinal layers with cellular resolution over an area suitable for a meaningful diagnostic in patients having retinal diseases.
The startup company EarlySight SA has been founded in February 2019 by Timothé Laforest, Mathieu Künzi, Christophe Moser and Francine Behar-Cohen. A clinical prototype for a study over approximately 100 patients and healthy people is currently under test.


Publications

Laforest T., Künzi M., Kowalczuk L., Carpentras D., Behar-Cohen F., Moser C., Transscleral Optical Phase Imaging of the Human Retina – TOPI, pre print, May 15th, 2019;
Carpentras D., Laforest T., Kunzi M., Moser C., Effect of backscattering in phase contrast imaging of the retina, Optics Express, Vol. 26, Issue 6, 2018

Links

Persons involved in the project

Prof. Christophe Moser, project leader
Dr. Timothé Laforest, postdoctoral researcher
Dr. Florentino dos Santos, postdoctoral researcher
Mathieu Künzi, scientist
Laura Kowalczuk, postdoctoral researcher

Last update to this project presentation  27.05.2021