Retinal dystrophies and age-related macular degeneration related to photoreceptor degeneration can cause blindness. In blind patients, although the electrical activation of the residual retinal circuit can provide useful artificial visual perception, the resolutions of current retinal prostheses have been limited either by large electrodes or small numbers of pixels. Here we report the evaluation, in three awake non-human primates, of a previously reported near-infrared-light-sensitive photovoltaic subretinal prosthesis. We show that multipixel stimulation of the prosthesis within radiation safety limits enabled eye tracking in the animals, that they responded to stimulations directed at the implant with repeated saccades and that the implant-induced responses were present two years after device implantation. Our findings pave the way for the clinical evaluation of the prosthesis in patients affected by dry atrophic age-related macular degeneration.
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All data supporting the results in this study are available in the Article and Supplementary Information. The raw and analysed datasets generated during the study are available for research purposes from the corresponding author on reasonable request.
The custom codes used in this study are available from the corresponding author on request.
Brandli, A., Luu, C. D., Guymer, R. H. & Ayton, L. N. Progress in the clinical development and utilization of vision prostheses: an update. Eye Brain 8, 15–25 (2016).
Cha, K., Horch, K. & Normann, R. A. Simulation of a phosphene-based visual field: visual acuity in a pixelized vision system. Ann. Biomed. Eng. 20, 439–449 (1992).
Cha, K., Horch, K. W., Normann, R. A. & Boman, D. K. Reading speed with a pixelized vision system. J. Opt. Soc. Am. A 9, 673–677 (1992).
Fornos, A. P., Sommerhalder, J., Pittard, A., Safran, A. B. & Pelizzone, M. Simulation of artificial vision: IV. Visual information required to achieve simple pointing and manipulation tasks. Vis. Res. 48, 1705–1718 (2008).
Sommerhalder, J. et al. Simulation of artificial vision: I. Eccentric reading of isolated words, and perceptual learning. Vis. Res. 43, 269–283 (2003).
Sommerhalder, J. et al. Simulation of artificial vision: II. Eccentric reading of full-page text and the learning of this task. Vis. Res. 44, 1693–1706 (2004).
Jung, J.-H., Aloni, D., Yitzhaky, Y. & Peli, E. Active confocal imaging for visual prostheses. Vis. Res. 111, 182–196 (2015).
Stingl, K. et al. Interim results of a multicenter trial with the new electronic subretinal implant Alpha AMS in 15 patients blind from inherited retinal degenerations. Front. Neurosci. 11, 445 (2017).
Da Cruz, L. et al. The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br. J. Ophthalmol. 97, 632–636 (2013).
Joucla, S. & Yvert, B. Improved focalization of electrical microstimulation using microelectrode arrays: a modeling study. PLoS ONE 4, e4828 (2009).
Bendali, A. et al. Synthetic 3D diamond-based electrodes for flexible retinal neuroprostheses: model, production and in vivo biocompatibility. Biomaterials 67, 73–83 (2015).
Lorach, H. et al. Photovoltaic restoration of sight with high visual acuity. Nat. Med. 21, 476–482 (2015).
Picaud, S. et al. GABAA and GABAC receptors in adult porcine cones: evidence from a photoreceptor‐glia co‐culture model. J. Physiol. 513, 33–42 (1998).
Jones, B. W. et al. Retinal remodeling and metabolic alterations in human AMD. Front. Cell. Neurosci. 10, 103 (2016).
Jensen, R. J., Ziv, O. R. & Rizzo, J. F. Thresholds for activation of rabbit retinal ganglion cells with relatively large, extracellular microelectrodes. Invest. Ophthalmol. Vis. Sci. 46, 1486–1496 (2005).
Fried, S. I., Hsueh, H.-A. & Werblin, F. S. A method for generating precise temporal patterns of retinal spiking using prosthetic stimulation. J. Neurophysiol. 95, 970–978 (2006).
Freeman, D. K., Rizzo, J. F. III & Fried, S. I. Encoding visual information in retinal ganglion cells with prosthetic stimulation. J. Neural Eng. 8, 035005 (2011).
Boinagrov, D., Pangratz-Fuehrer, S., Goetz, G. & Palanker, D. Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes. J. Neural Eng. 11, 026008 (2014).
Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photonics 6, 391–397 (2012).
Lorach, H. et al. Retinal safety of near infrared radiation in photovoltaic restoration of sight. Biomed. Opt. Express 7, 13–21 (2016).
Li, P. H. et al. Anatomical identification of extracellularly recorded cells in large-scale multielectrode recordings. J. Neurosci. 35, 4663–4675 (2015).
Schiller, P. H. & Lee, K. The effects of lateral geniculate nucleus, area V4, and middle temporal (MT) lesions on visually guided eye movements. Vis. Neurosci. 11, 229–241 (1994).
Smith, R., Smith, G. & Wong, D. Refractive changes in silicone filled eyes. Eye 4, 230–234 (1990).
Lapuerta, P. & Schein, S. J. A four-surface schematic eye of macaque monkey obtained by an optical method. Vis. Res. 35, 2245–2254 (1995).
Silverman, M. & Hughes, S. Transplantation of photoreceptors to light-damaged retina. Invest. Ophthalmol. Vis. Sci. 30, 1684–1690 (1989).
This work was supported by BPIfrance (grant no. 2014-PRSP-15), the Foundation Fighting Blindness, the Fédération des Aveugles de France and LabEx LIFESENSES (grant no. ANR-10-LABX-65) and was managed by the French Agence National pour la Recherche as part of the first Investissements d’Avenir programme (grant no. ANR-11-IDEX-0004-02). This project also received funding from the European Union’s Horizon 2020 research and innovation programme for the European Graphene Flagship under grant agreement no. 785219. The content is solely the responsibility of the authors and does not necessarily represent the views of the funders. The authors had the final say over the data collection and analysis, decision to publish and preparation of the manuscript.
J.-A.S., R.B. and S.P. were consultants and founders of Pixium Vision. Y.L. is a consultant for Pixium Vision. E.Bo., M.D., R.H. and G.B. are employees at Pixium Vision.
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Prévot, P., Gehere, K., Arcizet, F. et al. Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates. Nat Biomed Eng (2019) doi:10.1038/s41551-019-0484-2