Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Photovoltaic retinal prosthesis with high pixel density

A Corrigendum to this article was published on 23 November 2012

This article has been updated

Abstract

Retinal degenerative diseases lead to blindness due to loss of the ‘image capturing’ photoreceptors, while neurons in the ‘image-processing’ inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating the surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems that deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation is produced in normal and degenerate rat retinas, with pulse durations of 0.5–4 ms, and threshold peak irradiances of 0.2–10 mW mm−2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 µm bipolar pixel, demonstrating the possibility of a fully integrated photovoltaic retinal prosthesis with high pixel density.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Simplified system diagram.
Figure 2: Subretinal photodiode arrays.
Figure 3: In vitro electrophysiology.
Figure 4: Stimulation of healthy retina.
Figure 5: Stimulation of degenerate retina and strength-duration data.
Figure 6: Pillar arrays for improved proximity.

Change history

  • 16 November 2012

    A relevant publication on the topic of the flexible substrate concept applied to a retinal implant should have been cited in this Article. The publication is by Dinyari, R., Loudin, J. D., Huie, P., Palanker, D. & Peumans, P. and is entitled "A Curvable silicon retinal implant" published in International Electron Devices Meeting (IEDM) (IEEE International, 2009). It is now cited as reference 39 in the Article. Additionally, Fig. S4a in the Supplementary Information of the Article is reproduced from the same new reference, with permission from IEEE. These revisions have been made in HTML and PDF versions of the Article, and PDF version of the Supplementary Information.

References

  1. Smith, W. et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology 108, 697–704 (2001).

    Article  Google Scholar 

  2. Haim, M. Epidemiology of retinitis pigmentosa in Denmark. Acta Ophthalmol. Scand. (Suppl) 233, 1–34 (2002).

    Article  Google Scholar 

  3. Kim, S. Y. et al. Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina 22, 471–477 (2002).

    Article  Google Scholar 

  4. Mazzoni, F., Novelli, E. & Strettoi, E. Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J. Neurosci. 28, 14282–14292 (2008).

    Article  Google Scholar 

  5. Stone, J. L., Barlow, W. E., Humayun, M. S., de Juan, E. Jr & Milam, A. H. Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch. Ophthalmol. 110, 1634–1639 (1992).

    Article  Google Scholar 

  6. Ahuja, A. K. et al. Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br. J. Ophthalmol. 95, 539–543 (2010).

    Article  Google Scholar 

  7. Zrenner, E. et al. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc. R. Soc. B 278, 1489–1497 (2010).

    Article  Google Scholar 

  8. Besch, D. et al. Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients. Br. J. Ophthalmol. 92, 1361–1368 (2008).

    Article  Google Scholar 

  9. DeMarco, P. et al. Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Invest. Ophthalmol. Vis. Sci. 48, 916–926 (2007).

    Article  Google Scholar 

  10. Pardue, M. et al. Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats. J. Neural Eng. 2, S39–S47 (2005).

    Article  Google Scholar 

  11. Bourne, M. C., Campbell, D. A. & Tansley, K. Hereditary degeneration of the rat retina. Br. J. Ophthalmol. 22, 613–623 (1938).

    Article  Google Scholar 

  12. Loudin, J. D. et al. Optoelectronic retinal prosthesis: system design and performance. J. Neural Eng. 4, S72–S84 (2007).

    Article  Google Scholar 

  13. Palanker, D. V. et al. Design of a high-resolution optoelectronic retinal prosthesis. J. Neural Eng. 2, S105–S120 (2005).

    Article  Google Scholar 

  14. Stelzle, M., Stett, A., Brunner, B., Graf, M. & Nisch, W. Electrical properties of micro-photodiode arrays for use as artificial retina implant. Biomed. Microdev. 3, 133–142 (2001).

    Article  Google Scholar 

  15. Brummer, S. B. & Turner, M. J. Electrical-stimulation of nervous-system—principle of safe charge injection with noble-metal electrodes. Bioelectrochem. Bioenerg. 2, 13–25 (1975).

    Article  Google Scholar 

  16. Cogan, S. F., Guzelian, A. A., Agnew, W. F., Yuen, T. G. & McCreery, D. B. Over-pulsing degrades activated iridium oxide films used for intracortical neural stimulation. J. Neurosci. Methods 137, 141–150 (2004).

    Article  Google Scholar 

  17. Active Implantable Medical Devices, in Directive 90/385/EEC; available at http://ec.europa.eu/enterprise/policies/european-standards/harmonised-standards/implantable-medical-devices/ (2004).

  18. Loudin, J., Cogan, S., Mathieson, K., Sher, A. & Palanker, D. Photodiode circuits for retinal prostheses. IEEE Trans. Biomed. Circ. Syst. 5, 468–480 (2011).

    Article  Google Scholar 

  19. Chow, A. et al. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch. Ophthalmol. 122, 460–469 (2004).

    ADS  Article  Google Scholar 

  20. Beebe, X. & Rose, T. Charge injection limits of activated iridium oxide electrodes with 0.2 ms pulses in bicarbonate buffered saline (neurological stimulation application). IEEE Trans. Biomed. Eng. 35, 494–495 (1988).

    Article  Google Scholar 

  21. Cogan, S., Troyk, P., Ehrlich, J., Plante, T. & Detlefsen, D. Potential-biased, asymmetric waveforms for charge-injection with activated iridium oxide (AIROF) neural stimulation electrodes. IEEE Trans. Biomed. Eng. 53, 327–332 (2006).

    Article  Google Scholar 

  22. Negi, S., Bhandari, R., Rieth, L., Van Wagenen, R. & Solzbacher, F. Neural electrode degradation from continuous electrical stimulation: comparison of sputtered and activated iridium oxide. J. Neurosci. Methods 186, 8–17 (2010).

    Article  Google Scholar 

  23. Green, M. A. & Keevers, M. J. Optical properties of intrinsic silicon at 300 K. Prog. Photovoltaics 3, 189–192 (1995).

    Article  Google Scholar 

  24. Litke, A. M. et al. What does the eye tell the brain?: development of a system for the large-scale recording of retinal output activity. IEEE Trans. Nucl. Sci. 51, 1434–1440 (2004).

    ADS  Article  Google Scholar 

  25. Field, G. D. et al. High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina. Nature Neurosci. 12, 1159–1164 (2009).

    Article  Google Scholar 

  26. Field, G. D. et al. Spatial properties and functional organization of small bistratified ganglion cells in primate retina. J. Neurosci. 27, 13261–13272 (2007).

    Article  Google Scholar 

  27. Petrusca, D. et al. Identification and characterization of a Y-like primate retinal ganglion cell type. J. Neurosci. 27, 11019–11027 (2007).

    Article  Google Scholar 

  28. Jones, B. W. & Marc, R. E. Retinal remodeling during retinal degeneration. Exp. Eye Res. 81, 123–137 (2005).

    Article  Google Scholar 

  29. Jones, B. W. et al. Retinal remodeling triggered by photoreceptor degenerations. J. Comp. Neurol. 464, 1–16 (2003).

    Article  Google Scholar 

  30. Pu, M., Xu, L. & Zhang, H. Visual response properties of retinal ganglion cells in the Royal College of Surgeons dystrophic rat. Invest. Ophthalmol. Vis. Sci. 47, 3579–3585 (2006).

    Article  Google Scholar 

  31. Hornbeck, L. J. Digital light processing for high-brightness, high-resolution applications (invited paper). Proc. SPIE Projection Disp. III 3013, 27–40 (1997).

    ADS  Google Scholar 

  32. Jensen, R. J. & Rizzo, J. F. Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode. Exp. Eye Res. 83, 367–373 (2006).

    Article  Google Scholar 

  33. Sekirnjak, C. et al. High-resolution electrical stimulation of primate retina for epiretinal implant design. J. Neurosci. 28, 4446–4456 (2008).

    Article  Google Scholar 

  34. Butterwick, A. et al. Effect of shape and coating of a subretinal prosthesis on its integration with the retina. Exp. Eye Res. 88, 22–29 (2009).

    Article  Google Scholar 

  35. Palanker, D. et al. Migration of retinal cells through a perforated membrane: implications for a high-resolution prosthesis. Invest. Ophthalmol. Vis. Sci. 45, 3266–3270 (2004).

    Article  Google Scholar 

  36. Dinyari, R., Rim, S.-B., Huang, K., Catrysse, P. B. & Peumans, P. Curving monolithic silicon for nonplanar focal plane array applications. Appl. Phys. Lett. 92, 091114 (2008).

    ADS  Article  Google Scholar 

  37. American National Standard for Safe Use of Lasers (ANSI 136.1). ANSI. Vol. ANSI 136.1-2000 (The Laser Institute of America, 2000).

  38. DeLori, F., Webb, R. & Sliney, D. Maximum permissable exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices. J. Opt. Soc. Am. A 24, 1250–1265 (2007).

    ADS  Article  Google Scholar 

  39. Dinyari, R., Loudin, J. D., Huie, P., Palanker, D. & Peumans, P. A Curvable silicon retinal implant. International Electron Devices Meeting (IEDM) (IEEE International, 2009).

Download references

Acknowledgements

The authors thank Optobionics, especially G. McLean, for providing the ASR samples, and P. Peumans and R. Dinyari from the Electrical Engineering Department at Stanford University for providing a sample of the flexible silicon grid36 for tests of its flexibility in a porcine eye. We also thank A.M. Litke, S. Kachiguine, A. Grillo and W. Dabrowski for the development of the 512-electrode recording system, and M. Krause for his help with retinal preparations. The authors thank M.F. Marmor, M.S. Blumenkranz, R. Gariano and S. Sanislo from the Department of Ophthalmology at Stanford for productive discussions regarding implant design and surgical procedures. Thanks also go to S. Cogan at EIC Labs for fabrication advice and for iridium oxide electrode deposition, M. McCall at the University of Louisville for critical manuscript reading, and M. Pardue at Emory University for advice on subretinal implantations into RCS rats. Funding was provided by the National Institutes of Health (grant no. R01-EY-018608), the Air Force Office of Scientific Research (grant FA9550-04) and a Stanford Bio-X IIP grant. K.M. was supported by an SU2P fellowship as part of an RCUK Science Bridges award. J.L. was supported in part by the National Science Foundation Graduate Research Fellowship programme. A.S. was supported in part by a Burroughs Welcome Fund Career Award at the Scientific Interface.

Author information

Authors and Affiliations

Authors

Contributions

J.L. and D.P. jointly conceived and designed the pulsed-NIR photovoltaic retinal prosthesis system, and the three-diode pixel devices. K.M., T.K. and J.H. led the fabrication team of L.W. and L.G., with L.W. performing most of the fabrication steps that produced the implant device. A.S. and D.P. conceived the electrophysiology experiments, which were carried out by K.M., J.L., G.G. and R.S. under the guidance of A.S. Data analysis was performed by K.M. and G.G. with direction from A.S. The subretinal implantations and histological analysis was performed by P.H. J.L. wrote the first draft of the paper, with K.M., A.S. and D.P. contributing several sections and extensive edits. The project was organized and coordinated by D.P.

Corresponding author

Correspondence to James Loudin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mathieson, K., Loudin, J., Goetz, G. et al. Photovoltaic retinal prosthesis with high pixel density. Nature Photon 6, 391–397 (2012). https://doi.org/10.1038/nphoton.2012.104

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphoton.2012.104

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing