Skip to main content Accessibility help
×
Home
  • Print publication year: 2015
  • Online publication date: September 2015

26 - Photovoltaic retinal prosthesis for restoring sight to the blind

from Part V - Bionics

Summary

Introduction

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world, with an incidence of 1:500 in patients aged 55–64, and 1:8 in patients over 85 [1]. Retinitis pigmentosa (RP) is an inherited disease blinding about 1 in every 4000 individuals much earlier in life [2]. In both of these conditions the photoreceptor layer degenerates, while the inner retinal neurons survive to a large extent [3–5]. Electrically activating these neurons provides an alternative route for visual information and raises hope for the restoration of sight to the blind.

In a normal retina, photoreceptors convert light into neural signals that are processed by inner retinal neurons, leading to generation of action potentials in the retinal ganglion cells (RGCs). These signals travel to the brain through the optic nerve and serve as the basis for visual perception. Electrical stimulation of the retina with microelectrodes can also produce action potentials in RGCs, creating spatially patterned percepts of light called phosphenes. Indeed, recent clinical trials with retinal prosthetic electrode arrays have restored visual acuity to subjects blinded by retinal degeneration up to 20/1200 using epiretinal placement (facing the ganglion cell side) [6], and up to 20/550 with subretinal implantation [7]. While this serves as an important proof of concept with clinically useful implications, existing retinal prosthesis designs have a number of shortcomings.

References
Smith, W., Assink, J., Klein, R. et al., Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology, 2001. 108(4): p. 697–704.
Haim, M., Epidemiology of retinitis pigmentosa in Denmark. Acta Ophthalmol Scand Suppl, 2002(233): p. 1–34.
Kim, S.Y., Sadda, S., Pearlman, J. et al., Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina, 2002. 22(4): p. 471–7.
Mazzoni, F., Novelli, E., and Strettoi, E., Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci, 2008. 28(52): p. 14282–92.
Stone, J.L., Barlow, W. E., Humayan, M. S. et al., Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol, 1992. 110(11): p. 1634–9.
Humayun, M.S., Dorn, J. D., da Cruz, L. et al., Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology, 2012. 119(4): p. 779–88.
Stingl, K., Bach, M., Bartz-Schmidt, K. U. et al., Safety and efficacy of subretinal visual implants in humans: methodological aspects. Clin Exp Optom, 2013. 96(1): p. 4–13.
Ahuja, A.K., Dorn, J. D., Caspi, A. et al., Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br J Ophthalmol, 2011. 95(4): p. 539–43.
Zrenner, E., Bartz-Schmidt, K. U., Benav, H. et al., Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci, 2011. 278(1711): p. 1489–97.
Mathieson, K., Loudin, J., Goetz, G. et al., Photovoltaic retinal prosthesis with high pixel density. Nature Photon, 2012. 6(6): p. 391–7.
DeMarco, P.J., Yarbrough, G. L., Yee, C. W. et al., Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Invest Ophthalmol Vis Sci, 2007. 48(2): p. 916–26.
Chow, A.Y., Chow, V.Y., Packo, K.H., et al., The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol, 2004. 122(4): p. 460–9.
Pardue, M.T., Phillips, M., Yin, H. et al., Neuroprotective effect of subretinal implants in the RCS rat. Invest Ophthalmol Vis Sci, 2005. 46(2): p. 674–82.
Zrenner, E., Bartz-Schmidt, K. U., Gekeler, F. et al., Seeing with subretinal electronic implants: study in ten patients with wireless implant Alpha-IMS. ARVO Meeting Abstr 2012. 53(6): p. 6948.
Bourne, M.C., Campbell, D.A., and Tansley, K., Hereditary degeneration of the rat retina. Br J Ophthalmol, 1938. 22(10): p. 613–23.
Wang, L., Mathieson, K., Kamins, T. et al., Photovoltaic retinal prosthesis: implant fabrication and performance. J Neural Eng, 2012. 9(4): p. 046014.
Nanduri, D., Fine, I., Horsager, A. et al., Frequency and amplitude modulation have different effects on the percepts elicited by retinal stimulation. Invest Ophthalmol Vis Sci, 2012. 53(1): p. 205–14.
Loudin, J.D., Simanovskii, D. M., Vijayraghavan, K. et al., Optoelectronic retinal prosthesis: system design and performance. J Neural Eng, 2007. 4(1): p. S72–S84.
Palanker, D., Vankov, A., Huie, P., and Baccus, S., Design of a high resolution optoelectronic retinal prosthesis. J Neural Eng, 2005. 2: p. S105–S120.
Loudin, J.D., Cogan, S. F., Mathieson, K. et al., Photodiode circuits for retinal prostheses. IEEE Trans Biomed Circuits Systems, 2011. 5(5): p. 468–80.
Beebe, X. and Rose, T.L., Charge injection limits of activated iridium oxide electrodes with 0.2 ms pulses in bicarbonate buffered saline. IEEE Trans Biomed Eng, 1988. 35(6): p. 494–5.
Cogan, S.F., Troyk, P. R., Ehrlich, J. et al., Potential-biased, asymmetric waveforms for charge-injection with activated iridium oxide (AIROF) neural stimulation electrodes. IEEE Trans Biomed Eng, 2006. 53(2): p. 327–32.
Negi, S., Bhandari, R., Rieth, L. et al., Neural electrode degradation from continuous electrical stimulation: comparison of sputtered and activated iridium oxide. J Neurosci Methods, 2010. 186(1): p. 8–17.
ANSI Z136.1: American National Standard for Safe Use of Lasers. The Laser Institute of America, 2007.
Delori, F.C., Webb, R.H., and Sliney, D.H., Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices. J Opt Soc Am A:Opt Image Sci Vision, 2007. 24(5): p. 1250–65.
Litke, A.M., Bezayiff, N., Chichinsky, E. J. 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, 2004. 51(4): p. 1434–40.
Field, G.D., Greschner, M., Gauthier, J. L. et al., High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina. Nature Neurosci, 2009. 12(9): p. 1159–64.
Jones, B.W. and Marc, R.E., Retinal remodeling during retinal degeneration. Exp Eye Res, 2005. 81(2): p. 123–37.
Derwent, J.J.K., Padnick-Silver, L., McRipley, M. et al., The electroretinogram components in Abyssinian cats with hereditary retinal degeneration. Invest Ophthalmol Vis Sci, 2006. 47(8): p. 3673–82.
Jacobs, G.H., Fenwick, J.A., and Williams, G.A., Cone-based vision of rats for ultraviolet and visible lights. J Exp Biol, 2001. 204(Pt 14): p. 2439–46.
Wells, E.F., Bernstein, G. M., Scott, B. W. et al., Critical flicker frequency responses in visual cortex. Exp Brain Res, 2001. 139(1): p. 106–10.
Chang, B., Heckenlively, J. R., Bayley, P. R. et al., The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses. Vis Neurosci, 2006. 23(1): p. 11–24.
Jensen, R.J. and Rizzo, III J.F., Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode. Exp Eye Res, 2006. 83(2): p. 367–73.
Wilke, R.G., Moghadam, G. K., Lovell, N. H. et al., Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants. J Neural Eng, 2011. 8(4): p. 046016.
Wilke, R., Gabel, V. P., Sachs, H. et al., Spatial resolution and perception of patterns mediated by a subretinal 16-electrode array in patients blinded by hereditary retinal dystrophies. Invest Ophthalmol Vis Sci, 2011. 52(8): p. 5995–6003.
Nadig, M.N., Development of a silicon retinal implant: cortical evoked potentials following focal stimulation of the rabbit retina with light and electricity. Clin Neurophysiol, 1999. 110(9): p. 1545–53.
Li, L., Cao, P., Sun, M. et al., Intraorbital optic nerve stimulation with penetrating electrodes: in vivo electrophysiology study in rabbits. Graefes Arch Clin Exp Ophthalmol, 2009. 247(3): p. 349–61.
Tsai, D., Morley, J. W., Suaning, G. J., and Lovell, N. H., Direct activation and temporal response properties of rabbit retinal ganglion cells following subretinal stimulation. J Neurophysiol, 2009. 102(5): p. 2982–93.
Jensen, R.J. and Rizzo, III J.F., Responses of ganglion cells to repetitive electrical stimulation of the retina. J Neural Eng, 2007. 4(1): p. S1–6.
Cai, C., Ren, Q., Desai, N. J. et al., Response variability to high rates of electric stimulation in retinal ganglion cells. J Neurophysiol, 2011. 106(1): p. 153–62.
Jones, B.W., Watt, C. B., Frederick, J. M. et al., Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol, 2003. 464(1): p. 1–16.
Marc, R., Jones, B. W., Anderson, J. R. et al., Neural reprogramming in retinal degeneration. Investig Ophthalmol Vis Sci, 2007. 48(7): p. 3364–71.
Sekirnjak, C., Hottowy, P., Sher, A. et al., High-resolution electrical stimulation of primate retina for epiretinal implant design. J Neurosci, 2008. 28(17): p. 4446–56.
Butterwick, A., Huie, P., Jones, B. W. et al., Effect of shape and coating of a subretinal prosthesis on its integration with the retina. Exp Eye Res, 2009. 88(1): p. 22–9.
Palanker, D., Huie, P., Vankov, A. et al., Migration of retinal cells through a perforated membrane: implications for a high-resolution prosthesis. Invest Ophthalmol Vis Sci, 2004. 45(9): p. 3266–70.
Lorach, H., Goetz, G., Mandel, Y. et al., Performance of photovoltaic array in-vivo and characteristics of prosthetic vision in animals with retinal degradation. Vis Res, in press. doi: .