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George Scarlatis
Northwestern University Medical School, Chicago, Ill

JAMA. 2000;283:2297.

Since antiquity, people have dreamed of restoring vision to the blind. Only recently, however, with the development of optical prostheses, has this prospect become a foreseeable reality. Early studies have demonstrated that direct electrical stimulation to neurons of the visual system will cause a subject to perceive points of light (phosphenes).¹ This observation spurred investigation into the use of electrical stimulation to overcome visual loss. Current approaches to optical prosthesis involve stimulation of nerves at either the retina or the visual cortex.² While both approaches are theoretically feasible, retinal prostheses have the advantage of being far less invasive and are the focus of this essay.

Visual impairment can result from lesions anywhere along the visual pathway. In the normal eye, light passes through the cornea, anterior chamber, lens, and vitreous and then stimulates the photoreceptors. The photoreceptors, which comprise the outer layer of the retina, transduce light energy into an electrical signal and propagate this signal through the layers of the retina to the retinal ganglion cells. From there, the electrical signal travels along the optic nerve, through the visual pathways, and eventually reaches the visual cortex, where sight perceptions are formed.

Retinal approaches to prosthetic vision are most readily applicable to those causes of blindness that involve injury to the outer retinal layer, where the photoreceptors are located. In age-related macular degeneration and retinitis pigmentosa, the photoreceptors of the outer retinal layer are destroyed and the inner retinal layer is preserved. These diseases thus disrupt the normal visual pathway at the point where light energy is transduced into neuroelectrical signals. Retinal prosthetics exploit the selective survival of the inner retinal layer neurons by bypassing the defective photoreceptors and directly stimulating the still-viable inner neuroretina.

To emulate the functions of the photoreceptors, optical prostheses must collect and deliver visual information efficiently. One approach to collecting visual information involves capturing images with a camera located outside the eye. These images are then translated by an image processor and sent via transmitter to the implanted device.³ Another approach uses light-activated microphotodiodes⁴ that are implanted within the eye and aligned geometrically to the information delivery apparatus. The camera method has the advantage of allowing multiple levels of image processing; the microphotodiode method obviates the need for external equipment and, due to its location, records fewer extraneous stimuli.

After the visual information has been collected, it is delivered to the surviving cells of the neuroretina by way of a microelectrode array. This array may be placed either just behind the retina (subretinal) or immediately anterior to it (epiretinal). Subretinal placement of semiconductor microphotodiodes is the more invasive method, but it is also technically simpler, allows for prolonged function in the absence of an external power supply, and does not significantly alter inner retinal function or architecture.^5-6 Epiretinal placement has the advantage of involving only very minimal surgical damage to the underlying retina.^7-8 Unlike the subretinal devices, however, the epiretinal devices have not yet been shown to be capable of generating in vivo a current in response to light stimulation over an extended period of time.

The available data indicate that visual prostheses have considerable potential for restoring rudimentary vision.³ Clinical studies have shown that when electrical signals are applied to a small area of the retina with a microelectrode, otherwise blind patients will perceive a small spot of light (phosphene). When multiple electrodes are activated by light in a 2-dimensional array, the patient perceives a series of small spots of light. Subretinal devices currently under study contain over 1000 pixels per square millimeter.⁴ The vision mediated by optical prostheses is analogous to the image formed on a scoreboard or on a dot-matrix printer, and it could allow blind patients to regain vision of basic geometric forms sufficient for restoration of ambulatory mobility and reading typed text.

While many issues relating to the biocompatibility, efficacy, and safety of visual prostheses need to be resolved, preliminary results are promising. Future research efforts will attempt to address current concerns and define stimulus patterns that will enable subjects to perceive complex images.³ The development of optical prosthetics is an important advance that may eventually make possible the restoration of vision for patients with outer retinal disorders.

REFERENCES
1. Brindley GS, Lewin WS. The sensations produced by electrical stimulation of the visual cortex. J Physiol. 1968;196:479-493. FREE FULL TEXT 2. Normann RA, Maynard EM, Rousche PJ, Warren DJ. A neural interface for a cortical vision prosthesis. Vision Res. 1999;39:2577-2587. FULL TEXT | ISI | PUBMED 3. De Juan E, Cooney MJ, Humayun MS, Jensen PS. Ocular surgery for the new millennium: treatment of retinal disease in the new millennium. Ophthalmology Clin North Am. 1999;12:539-562. 4. Peyman G, Chow AY, Liang C, Chow VY, Perlman JI, Peachey NS. Subretinal semiconductor microphotodiode array. Ophthalmic Surg Lasers. 1998;29:234-241. ISI | PUBMED 5. Zrenner E, Stett A, Weiss S, et al. Can subretinal microphotodiodes successfully replace degenerated photoreceptors? Vision Res. 1999;39:2555-2567. FULL TEXT | ISI | PUBMED 6. Peachey NS, Chow AY. Subretinal implantation of semiconductor-based photodiodes: progress and challenges. J Rehabil Res Dev. 1999;36:371-376. ISI | PUBMED 7. Majji AB, Humayun MS, Weiland JD, Suzuki S, D'Anna SA, de Juan E Jr. Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. Invest Ophthalmol Vis Sci. 1999;40:2073-2081. FREE FULL TEXT 8. Walter P, Szurman P, Vobig M, et al. Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits. Retina. 1999;19:546-552. FULL TEXT | PUBMED

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