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Transscleral optical phase imaging of the human retina

Nature Photonics volume 14, pages 439–445 (2020)Cite this article

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Abstract

In vivo observation of the human retina at the cellular level is crucial to detect the first signs of retinal diseases and properly treat them. Despite the phenomenal advances in adaptive optics systems, clinical imaging of many retinal cells is still elusive due to the low signal-to-noise ratio induced by transpupillary illumination. We present a transscleral optical phase imaging method, which relies on high-angle oblique illumination of the retina, combined with adaptive optics, to enhance cell contrast. Examination of 11 healthy volunteer eyes, without pupil dilation, shows the ability of this method to produce in vivo images of retinal cells, from the retinal pigment epithelium to the nerve fibre layer. This method also allows the generation of high-resolution label-free ex vivo phase images of flat-mounted retinas. The in vivo images with 4.4° × 4.4° field of view are recorded in less than 10 s, opening new avenues in the exploration of healthy and diseased retinas.

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Fig. 1: Illumination of the retinal layers provided as transscleral illumination.
Fig. 2: Optical diagram of the in vivo TOPI system.
Fig. 3: In vivo full-field (4.4° × 4.4°) image of the RPE of a healthy volunteer.
Fig. 4: Microcapillaries and NFL TOPI images of subject S10, taken at different eccentricities.
Fig. 5: Comparison between in vivo images from a transpupil flood illumination commercial system and a transscleral illumination TOPI image on the same area.
Fig. 6: Image correlation analysis between oblique illumination OPI microscopy and fluorescence confocal microscopy of retinal vessels and their surrounding cells.

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Data availability

All data needed to evaluate the conclusions in this paper are present in the paper and/or the Supplementary Information. The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

Code availability

The code for performing the reconstruction process is available on request from the authors.

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Acknowledgements

We thank M. Nicolas from the eye bank of the Jules-Gonin Eye Hospital for providing a post-mortem human eye, I. Mantel and the team of the centre for clinical investigation for their time spent in performing the ophthalmologic checks for our study on healthy participants, and S. Roy, A. Matet and D. Sage for discussions. In addition to the research partners, this study was supported by the following programmes: the Enable programme of the Technology Transfer Office at EPFL (610263), EPFL Innogrant (INNO 17-15), Bridge Proof of Concept (InnoSuisse and SNSF, 20B1-1_178253), the Gebert Rüf Stiftung Foundation (GRS-052/17) and EIT Health Innovation by Idea (19323-ASSESS).

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Author notes

  1. These authors contributed equally: Timothé Laforest, Mathieu Künzi.

Authors and Affiliations

  1. Laboratory of Applied Photonic Devices (LAPD), School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Timothé Laforest, Mathieu Künzi, Dino Carpentras & Christophe Moser

  2. EarlySight SA, EPFL Innovation Park, Lausanne, Switzerland

    Timothé Laforest & Mathieu Künzi

  3. Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

    Laura Kowalczuk & Francine Behar-Cohen

  4. Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland

    Laura Kowalczuk

  5. Centre de Recherche des Cordeliers, Inserm, USPC, Université de Paris, Sorbonne Université, Paris, France

    Francine Behar-Cohen

  6. OphtalmoPôle, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France

    Francine Behar-Cohen

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  1. Timothé Laforest
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Contributions

T.L. designed and built the ex vivo microscope, obtained the ex vivo results, built the in vivo device, wrote the code for ex vivo and in vivo processing and wrote the paper. M.K. designed and built the in vivo device, wrote the code for in vivo processing and wrote the paper. D.C. developed the theoretical model and wrote the paper. L.K. provided and prepared the ex vivo samples, participated in the interpretation of the phase images and wrote the paper. F.B.-C. supervised the project and wrote the paper. C.M. designed the experiment, supervised the project and wrote the paper.

Corresponding author

Correspondence to Christophe Moser.

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Competing interests

T.L., M.K., F.B.-C. and C.M. are involved in a company (EarlySight SA, Switzerland) aiming to commercialize the technology. A patent application, no. WO2017195163A1, has been submitted.

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Supplementary Figs. 1–10, Table 1 and Notes 1–3.

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Laforest, T., Künzi, M., Kowalczuk, L. et al. Transscleral optical phase imaging of the human retina. Nat. Photonics 14, 439–445 (2020). https://doi.org/10.1038/s41566-020-0608-y

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