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