Delivery of Information and Power to the Implant, Integration of the Electrode Array with the Retina, and Safety of Chronic Stimulation

  • James LoudinEmail author
  • Alexander Butterwick
  • Philip Huie
  • Daniel Palanker


The fundamental function of a visual prosthesis is to deliver information about a patient’s surroundings to his/her neurons, usually via patterned electronic stimulation. In addition to transmitting visual information from the outside world to the implanted stimulating array, visual prostheses must also pass the electrical power necessary for such stimulation from the external world to the intraocular electrode array. The first section of this chapter reviews three common methods for achieving this data and power transfer: direct wireline connections (suitable for research studies), inductively coupled coils, and photodiode-based optical systems which utilize the natural optics of the eye.

Once the data and power has been received, retinal prostheses must effectively deliver stimulation currents to surviving retinal neurons. This necessitates an understanding of the electrode/retina interface. The second section of this chapter is a histological description of this interface for the case of subretinal implants, investigating the tissue response to flat implants coated with different materials. Several three-dimensional geometries are also described and evaluated to decrease the implant–neuron distance.

Finally, stimulation currents must not damage the stimulated neurons. The third section of this chapter describes measurements and scaling laws associated with tissue damage from electric currents. Damage thresholds are found to be approximately 50–100 times stimulation thresholds.


Cochlear Implant Damage Threshold Inner Nuclear Layer Subretinal Space Stimulation Threshold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Alternating current


Artificial silicon retina, a retinal prosthesis fabricated by Optobionics


Combined metal on silicon


Computational molecular phenotyping


Direct current


European Union


Intelligent medical implants, a company fabricating a retinal prosthesis


Inner nuclear layer




Liquid crystal display


Microphotodiode array, retinal prosthesis fabricated by retina implant AG


Outer nuclear layer


45 days after birth


Propidium iodide

RCS rat

Royal College of Surgeons rat, a common animal model of retinal degeneration


Radio frequency


Retinal pigmented epithelium


Sputtered iridium oxide film


A photo-curable epoxy


University of Southern California


  1. 1.
    (2004), Active Implantable Medical Devices, in Directive 90/285/EEC.Google Scholar
  2. 2.
    (2007), Second Sight Medical Retinal Prosthesis Receives FDA Approval for Clinical Trials, in medGadget.Google Scholar
  3. 3.
    [Anon], Radiati ICN (2000), ICNIRP statement on light-emitting diodes (LEDs) and laser diodes: Implications for hazard assessment. Health Phys, 78: p. 744–52.Google Scholar
  4. 4.
    Abrams LD, Hudson WA, Lightwood R (1960), A surgical approach to the management of heart-block using an inductive coupled artificial cardiac pacemaker. Lancet, 1: p. 1372–4.CrossRefGoogle Scholar
  5. 5.
    Berntson A, Taylor WR (2000), Response characteristics and receptive field widths of on-bipolar cells in the mouse retina. J Physiol, 524(  Pt  3): p. 879–89.CrossRefGoogle Scholar
  6. 6.
    Besch D, Sachs H, Szurman P, et al. (2008), Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients. Br J Ophthalmol, 92(10): p. 1361–8.CrossRefGoogle Scholar
  7. 7.
    Brindley G (1964), Transmission of electrical stimuli along many independent channels through a fairly small area of intact skin. J Physiol, 177: p. 44–6.Google Scholar
  8. 8.
    Brindley G, Lewin W (1968), The sensations produced by electrical stimulation of the visual cortex. J Physiol, 196: p. 479–93.Google Scholar
  9. 9.
    Butterwick A, Huie P, Jones BW, et al. (2009), Effect of shape and coating of a subretinal prosthesis on its integration with the retina. Exp Eye Res, 88: p. 22–9.CrossRefGoogle Scholar
  10. 10.
    Butterwick A, Vankov A, Huie P, et al. (2007), Tissue damage by pulsed electrical stimulation. IEEE Trans Biomed Eng, 54(12): p. 2261–7.CrossRefGoogle Scholar
  11. 11.
    Caspi A, Dorn JD, McClure KH, et al. (2009), Feasibility study of a retinal prosthesis: spatial vision with a 16-electrode implant. Arch Ophthalmol, 127(4): p. 398–401.CrossRefGoogle Scholar
  12. 12.
    Chow A (1993), Electrical stimulation of the rabbit retina with sub-retinal electrodes and high density microphotodiode array implants. ARVO abstracts. Invest Ophthalmol Vis Sci, 34: p. 835.Google Scholar
  13. 13.
    Chow A, Chow V, Packo K, et al. (2004), The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol, 122(4): p. 460–9.CrossRefGoogle Scholar
  14. 14.
    Cogan S, Troyk P, Ehrlich J, et al. (2006), Potential-biased, asymmetric waveforms for charge-injection with activated iridium oxide (AIROF) neural stimulation electrodes. IEEE Trans Biomed Eng, 53(2): p. 327–32.CrossRefGoogle Scholar
  15. 15.
    DeMarco P, Yarbrough G, Yee C, et al. (2007), Stimulation via a subretinally placed ­prosthetic elicits central activity and induces a trophic effect on visual responses. Invest Ophthalmol Vis Sci, 48(2): p. 916–26.CrossRefGoogle Scholar
  16. 16.
    Dobelle WH, Mladejovsky MG, Girvin JP (1974), Artifical vision for the blind: electrical stimulation of visual cortex offers hope for a functional prosthesis. Science, 183(123): p. 440–4.CrossRefGoogle Scholar
  17. 17.
    Fisher SK, Erickson PA, Lewis GP, Anderson DH (1991), Intraretinal proliferation induced by retinal detachment. Invest Ophthalmol Vis Sci, 32(6): p. 1739–48.Google Scholar
  18. 18.
    Ghovanloo M, Najafi K (2002). Fully integrated power supply design for wireless biomedical implants, in Microtechnologies in Medicine & Biology 2nd Annual International IEEE-EMB Special Topic Conference. Madison, WI.Google Scholar
  19. 19.
    Hamici Z, Itti R, Champier J (1996), A high-efficiency power and data transmission system for biomedical implanted electronic devices. Meas Sci Technol, 7: p. 192–201.CrossRefGoogle Scholar
  20. 20.
    Heetderks W (1988), RF powering of millimeter and submillimeter sized neural prosthetic implants. IEEE Trans Biomed Eng, 35: p. 323–6.CrossRefGoogle Scholar
  21. 21.
    Humayun M (2009), Preliminary results from Argus II feasibility study: a 60 electrode epiretinal prosthesis. Invest Ophthalmol Vis Sci, 50: E-Abstr# 4744.Google Scholar
  22. 22.
    Humayun MS, de Juan E, Jr., Weiland JD, et al. (1999), Pattern electrical stimulation of the human retina. Vision Res, 39(15): p. 2569–76.CrossRefGoogle Scholar
  23. 23.
    Humayun M, Weiland J, Fujii G, et al. (2003), Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res, 43: p. 2573–81.CrossRefGoogle Scholar
  24. 24.
    Jensen RJ, Rizzo JF, Ziv OR, et al. (2003), Thresholds for activation of rabbit retinal, ganglion cells with an ultrafine, extracellular microelectrode. Invest Ophthalmol Vis Sci, 44(8): p. 3533–43.CrossRefGoogle Scholar
  25. 25.
    Jones BW, Marc RE (2005), Retinal remodeling during retinal degeneration. Exp Eye Res, 81(2): p. 123–37.CrossRefGoogle Scholar
  26. 26.
    Jones BW, Watt CB, Frederick JM, et al. (2003), Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol, 464(1): p. 1–16.CrossRefGoogle Scholar
  27. 27.
    Kelly S (2003). A system for efficient neural stimulation with energy recovery. Thesis, Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge.Google Scholar
  28. 28.
    Kendir G, Liu W, Wang G, et al. (2005), An optimal design methodology for inductive power link with Class-E amplifier. IEEE Trans Circ Syst, 52(5): p. 857–65.CrossRefGoogle Scholar
  29. 29.
    Khanani AM, Brown SM, Xu KT (2004), Normal values for a clinical test of letter-recognition contrast thresholds. J Cataract Refract Surg, 30(11): p. 2377–82.CrossRefGoogle Scholar
  30. 30.
    Knutson J, Naples G, Peckham P, Keith M (2002), Electrode fracture rates and occurences of infection and granuloma associated with percutaneous intramuscular electrodes in upper-limb functional electrical stimulation applications. J Rehabil Res Dev, 39(6): p. 671–84.Google Scholar
  31. 31.
    Ko W, Liang S, Fung C (1977), Design of radio-frequency powered coils for implant instruments. Med Biol Eng Comput, 15(6): p. 634–40.CrossRefGoogle Scholar
  32. 32.
    Li L, Sheedlo HJ, Turner JE (1993), Muller cell expression of glial fibrillary acidic protein (GFAP) in RPE-cell transplanted retinas of RCS dystrophic rats. Curr Eye Res, 12(9): p. 841–9.CrossRefGoogle Scholar
  33. 33.
    Liu W, Vichienchom K, Clements M, et al. (2000), A neuro-stimulus chip with telemetry unit for retinal prosthesis device. IEEE Solid-State Circuits, 35: p. 1487–97.CrossRefGoogle Scholar
  34. 34.
    Loudin JD, Palanker D (2008), Photovoltaic retinal prosthesis. Invest Ophthalmol Vis Sci, 49: E-Abstr# 3014.Google Scholar
  35. 35.
    Loudin JD, Simanovskii DM, Vijayraghavan K, et al. (2007), Optoelectronic retinal prosthesis: system design and performance. J Neural Eng, 4(1): p. S72–84.CrossRefGoogle Scholar
  36. 36.
    Mahadevappa M, Weiland JD, Yanai D, et al. (2005), Perceptual thresholds and electrode impedance in three retinal prosthesis subjects. IEEE Trans Neural Syst Rehabil Eng, 13(2): p. 201–6.CrossRefGoogle Scholar
  37. 37.
    Margalit E, Maia M, Weiland J, et al. (2002), Retinal prothesis for the blind. Surv Ophthalmol, 47(4): p. 335–56.CrossRefGoogle Scholar
  38. 38.
    Margalit E, Weiland JD, Clatterbuck RE, et al. (2003), Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia. J Neurosci Methods, 123(2): p. 129–37.CrossRefGoogle Scholar
  39. 39.
    McCreery DB, Agnew WF, Yuen TG, Bullara L (1990), Charge density and charge per phase as cofactors in neural injury induced by electrical stimulation. IEEE Trans Biomed Eng, 37(10): p. 996–1001.CrossRefGoogle Scholar
  40. 40.
    Mokaw W (2004), MEMS technologies for epiretinal stimulation of the retina. J Micromech Microeng, 14: p. S12–6.CrossRefGoogle Scholar
  41. 41.
    Neumann E (1992), Membrane electroporation and direct gene-transfer. Bioelectrochem Bioenerg, 28: p. 247–67.CrossRefGoogle Scholar
  42. 42.
    Neumann E, Toensing K, Kakorin S, et al. (1998), Mechanism of electroporative dye uptake by mouse B cells. Biophys J, 74(1): p. 98–108.CrossRefGoogle Scholar
  43. 43.
    Osepchuck JM (1983), Biological Effects of Electromagnetic Radiation. IEEE Press Selected Reprint Series. New York: IEEE.Google Scholar
  44. 44.
    Palanker D, Huie P, Vankov A, et al. (2004), Migration of retinal cells through a perforated membrane: implications for a high-resolution prosthesis. Invest Ophthalmol Vis Sci, 45(9): p. 3266–70.CrossRefGoogle Scholar
  45. 45.
    Palanker D, Vankov A, Huie P, Baccus S (2005), Design of a high-resolution optoelectronic retinal prosthesis. J Neural Eng, 2(1): p. S105–20.CrossRefGoogle Scholar
  46. 46.
    Pardue M, Phillips M, Yin H, et al. (2005), Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats. J Neural Eng, 2: p. S39–47.CrossRefGoogle Scholar
  47. 47.
    Pardue MT, Stubbs EB, Jr., Perlman JI, et al. (2001), Immunohistochemical studies of the retina following long-term implantation with subretinal microphotodiode arrays. Exp Eye Res, 73(3): p. 333–43.CrossRefGoogle Scholar
  48. 48.
    Peachey N, Chow A (1999), Subretinal implantation of semiconductor-based photodiodes: progress and challenges. J Rehabil Res Dev, 36(4): p. 371–6.Google Scholar
  49. 49.
    Radovanovic S, Annema A, Nauta B (2004), Bandwidth of integrated photodiodes in standard CMOS for CD/DVD applications. Microelectron Reliab, 45: p. 705–10.CrossRefGoogle Scholar
  50. 50.
    Refinetti R, Menaker M (1992), The circadian rhythm of body temperature. Physiol Behav, 51: p. 613–37.CrossRefGoogle Scholar
  51. 51.
    Rizzo J, Wyatt J, Loewenstein J, et al. (2003), Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays. Invest Ophthalmol Vis Sci, 44: p. 5355–61.CrossRefGoogle Scholar
  52. 52.
    Rohsenow W, Hartnett J, Gani E (1985), Handbook of Heat Transfer Fundamentals. New York: McGraw-Hill, p. 164.Google Scholar
  53. 53.
    Sachs HG, Bartz-Schmidt U, Gekeler F, et al. (2009), The transchoroidal implantation of subretinal active micro-photodiode arrays in blind patients: long term surgical results in the first 11 implanted patients demonstrating the potential and safety of this new complex surgical procedure that allows restoration of useful visual percepts. Invest Ophthalmol Vis Sci, 50: E-Abstr# 4742.Google Scholar
  54. 54.
    Sachs HG, Gekeler F, Schwahn H, et al. (2005), Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development. Eur J Ophthalmol, 15(4): p. 493–9.Google Scholar
  55. 55.
    Sailer H, Shinoda K, Blatsios G, et al. (2007), Investigation of thermal effects of infrared lasers on the rabbit retina: a study in the course of development of an active subretinal prosthesis. Graefes Arch Clin Exp Ophthalmol, 245(8): p. 1169–78.CrossRefGoogle Scholar
  56. 56.
    Schule G, Huttmann G, Framme C, et al. (2004), Noninvasive optoacoustic temperature determination at the fundus of the eye during laser irradiation. J Biomed Opt, 9(1): p. 173–9.CrossRefGoogle Scholar
  57. 57.
    Scott J (1988), The computation of temperature rises in the human eye induced by infrared radiation. Phys Med Biol, 33(2): p. 243–57.CrossRefGoogle Scholar
  58. 58.
    Scribner D, Johnson L, Skeath P, et al. (2005), Microelectronic array for stimulation of retinal tissue, in NRL Review. Naval Research Lab, p. 53–61.Google Scholar
  59. 59.
    Shannon C (1998), Communication in the presence of noise. Proc IEEE, 86(2): p. 447–57.CrossRefGoogle Scholar
  60. 60.
    Sliney D, Aron-Rosa D, DeLori F, et al. (2005), Adjustment of guidelines for exposure of the eye to optical radiation from ocular instruments: statement from a task group of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Appl Opt, 44(11): p. 2162–76.CrossRefGoogle Scholar
  61. 61.
    Stett A, Barth W, Weiss S, et al. (2000), Electrical multisite stimulation of the isolated chicken retina. Vision Res, 40(13): p. 1785–95.CrossRefGoogle Scholar
  62. 62.
    Sullivan C (1999), Optimal choice for number of strands in a litz-wire transformer winding. IEEE Trans Power Electron, 14(2): p. 283–91.CrossRefGoogle Scholar
  63. 63.
    Theogarajan L, Wyatt J, Rizzo J, et al. (2006). Minimally invasive retinal prosthesis, in IEEE International Solid-State Circuits Conference.Google Scholar
  64. 64.
    Troyk P, Bradley D, Bak M, et al. (2005). Intracortical visual prosthesis research – approach and progress, in IEEE Engineering in Medicine and Biology 27th Annual Conference. Shanghai: IEEE.Google Scholar
  65. 65.
    Veraart C, Wanet-Defalque M, Gerard B, et al. (2003), Pattern recognition with the optic nerve visual prosthesis. Artif Organs, 27(11): p. 996–1004.CrossRefGoogle Scholar
  66. 66.
    Von Arx J (1998). A single chip, fully integrated, telemetry powered system for peripheral nerve stimulation. Thesis, Electrical Engineering, University of Michigan, Ann Arbor.Google Scholar
  67. 67.
    Von Arx J, Najafi K (1997). On-chip coils with integrated cores for remote inductive powering of integrated microsystems, in 1997 International Conference on Solid-State Sensors and Actuators. Chicago.Google Scholar
  68. 68.
    Wang G, Liu W, Sivaprakasam M, Kendir G (2005), Design and analysis of an adaptive transcutaneous power telemetry for biomedical implants. IEEE Trans Circ Syst, 52(10): p. 2109–17.CrossRefGoogle Scholar
  69. 69.
    Wickelgren I (2006), A vision for the blind. Science, 312: p. 1124–6.CrossRefGoogle Scholar
  70. 70.
    Wilde GJ, Sundstrom LE, Iannotti F (1994), Propidium iodide in vivo: an early marker of neuronal damage in rat hippocampus. Neurosci Lett, 180(2): p. 223–6.CrossRefGoogle Scholar
  71. 71.
    Yamauchi Y, Enzmann V, Franco M, et al. (2005). Subretinal placement of the microelectrode array is associated with a low threshold for electrical stimulation, in Annual Meeting of the Association for Research in Vision and Opthalmology. Fort Lauderdale, FL.Google Scholar
  72. 72.
    Yang Z, Liu W, Basham E (2007), Inductor modeling in wireless links for implantable electronics. IEEE Trans Magn, 43(10): p. 3851–60.CrossRefGoogle Scholar
  73. 73.
    Yang XL, Wu SM (1997), Response sensitivity and voltage gain of the rod- and cone-bipolar cell synapses in dark-adapted tiger salamander retina. J Neurophysiol, 78(5): p. 2662–73.Google Scholar
  74. 74.
    Zierhofer C, Hochmair-Desoyer I, Hochmair E (1995), Electronic design of a cochlear implant for multichannel high-rate pulsatile stimulation strategies. IEEE Trans Rehab Eng, 3(1): p. 112–6.CrossRefGoogle Scholar
  75. 75.
    Zrenner E (2002), The subretinal implant: can microphotodiode arrays replace degenerated retinal photoreceptors to restore vision? Ophthalmologica, 216(Suppl 1): p. 8–20; discussion 52–3.CrossRefGoogle Scholar
  76. 76.
    Zrenner E (2007), Restoring neuroretinal function: new potentials. Doc Ophthalmol, 115:p. 56–9.Google Scholar
  77. 77.
    Zrenner E, Gabel V, Gekeler F, et al. (2004). From passive to active subretinal implants, serving as adapting electronic substitution of degenerated photoreceptors, in IEEE International Joint Conference.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • James Loudin
    • 1
    Email author
  • Alexander Butterwick
  • Philip Huie
  • Daniel Palanker
  1. 1.Department of Applied PhysicsStanford UniversityStanfordUSA

Personalised recommendations