Science, medicine, and the future
1 Academic Department of Ophthalmology, University of Nottingham, Eye, Ear, Nose, and Throat Centre, Queen's Medical Centre, Nottingham NG7 2UH
Introduction
Degeneration of the retina occurs in age related macular degeneration and retinitis pigmentosa, resulting in loss of vision. Age related macular degeneration is a major cause of visual impairment among people over 65 in Western countries1; in the United Kingdom its incidence has increased by 30-40% over the past 40 years.2 Retinitis pigmentosa generally occurs in a younger age group (incidence 1 per 4000 live births) and affects 1.5 million people worldwide.3
, 百拇医药
In both conditions patients are visually impaired due to loss of photoreceptors. At present few treatments can remedy this and lead to recovery of vision.4 5 Photodynamic laser therapy has been beneficial in some patients with age related macular degeneration, but this therapy does not address photoreceptor loss. Different gene and drug therapies have been tried,4 5 but their ability to replace lost photosensitive tissue is limited. Researchers are therefore investigating the possibility of using prostheses to restore vision.
, 百拇医药
Advances in microtechnology have facilitated the development of a variety of prostheses that can be connected to the brain or implanted in the eye. Some of these approaches have improved the eyesight of patients with visual impairment. This article gives an overview of the methods that are being assessed to restore vision in patients with severe sight loss.
Methods
We carried out a comprehensive search through Medline and PubMed using the terms "age related maculopathy", "visual prosthesis", "retinitis pigmentosa", "retina", and "eye". We also searched for the latest developments in artificial vision through the website of the Association for Research in Vision and Ophthalmology.
, http://www.100md.com
A brief history of visual prostheses
Efforts to develop visual prostheses are not new. Attempts at artificial vision began in the 18th century with direct electrical stimulation of blind eyes.6 In the 1920s, the German neurosurgeon Otfrid Foerster developed this approach further by investigating direct electrical stimulation of the visual cortex.7 Several of his patients experienced limited subjective visual phenomena. By the '60s, investigations began on devices that could be implanted on the surface of the visual cortex.8 In 1977, electrodes were implanted in the eye to try to evoke a visual response.9 Since the '20s several types of visual prostheses have been examined.10 Most of these earlier devices were limited by a lack of visual resolution (pixels) or by their overall size and the electrical constraints this imposed. Early approaches were also prone to complications after implantation.8 With recent advances in microtechnology, however, progress has been made in the development of implants, some of which can be placed in the eye. These implants have greater potential for visual resolution and remain viable for several years.
, 百拇医药
Summary points
Artificial means of restoring vision include cortical implants, optic nerve stimulation, and retinal implants
These approaches are being assessed in clinical trials
Patients with implants have a crude level of visual perception
Problems with implants include availability of a power source, surgical complications, and long term viability
, 百拇医药
No visual prosthesis has yet restored vision
Three methods to restore vision are currently being developed: stimulation of the visual cortex using cortical implants, stimulation of the optic nerve, and retinal devices implanted either in the retina or on its surface.
Cortical implants
In the 1960s investigators implanted electrodes on the visual cortex (epicortical implants) of human patients through a burr hole.7 8 11 The patients reported seeing spots of light or "phosphenes."7 12 These early studies were limited by problems such as flickering phosphenes and interactions between phosphenes. The excessive electrode currents also irritated the meninges, causing pain around the implant.11 Later modifications to the implants enabled them to be embedded in the visual cortex (intracortical implants), and thus smaller electrodes and lower electrical currents could be used. These advances led to localised intracortical stimulation with less pain.7 12 13 Visual prostheses have the disadvantages of the surgical complications of any artificial implant, and complex mapping of the visual cortex is required to achieve visual perception.11 Despite these limitations, patients with implants can be trained to navigate around objects, perform simple tasks, and identify large letters.14
, http://www.100md.com
Intracortical implants have two main advantages over other methods for restoring vision. Firstly, the electrodes are protected by the skull. Secondly, the technique bypasses disease proximal to the primary visual cortex, making it potentially useful for treating diseases of the optic nerve and retina.
Optic nerve stimulation
The optic nerve can be directly stimulated to restore vision (fig 1). Stimulation of electrodes placed around the optic nerve of a patient with retinitis pigmentosa resulted in coloured phosphenes throughout the visual field.15 By changing the duration and amplitude of the electrical stimulus, the patient was able to perceive different levels of phosphene generation as brightness. Similar work has enabled a patient to localise objects and to discriminate between them.15 Direct stimulation of the optic nerve has several potential advantages over other methods for restoring vision. Firstly, it does not require the surgical penetration of sensitive intraocular or intracranial tissues. Secondly, the photosensitive component, for example, video device, can be placed outside the body, thus allowing the use of an external power source. The main disadvantages of this approach are that a normal functioning optic nerve is required (thus this method has limited use in diseases such as glaucoma) and that there is a risk of infection from the external wires.
, http://www.100md.com
Retinal prostheses
Prostheses can be implanted in the retina to act as a substitute for the host's photoreceptors. Retinal prostheses are only viable if the visual pathway distal to the retina is intact and functional. Two types of prostheses are under development according to the layer of retina receiving the device: epiretinal (on the surface of the retina) and subretinal (under the retina) implants.
Subretinal prostheses
, 百拇医药
Subretinal prostheses contain microphotodiodes attached to microelectrodes. These implants, such as the artificial silicon retina (5000 microelectrodes),16 are placed in the subretinal space between the outer retina and retinal pigment epithelium (figs 2 and 3). They are inserted either in the subretinal space through an incision in the sclera (extraocular approach) or by standard vitrectomy followed by retinotomy (intraocular approach).8 16 17
The photodiodes are stimulated by light passing through the retina, and the resulting electric current excites adjacent retinal sensory neurones.16 The specifications for subretinal implants vary—for example, one device measures 50-100 μm wide, has a diameter of 2 or 3 mm, and carries microphotodiodes constructed on a microelectrode array.16 These implants do not require an external electrical source as incident light is sufficient for stimulation.8 17
, http://www.100md.com
The viability of subretinal devices has been assessed in animal experiments. Several species have shown tolerance to the implants,18 some for up to 30 months.16 Histological evidence has shown no important changes to the retina's architecture.10 Visual perception was improved in six patients with retinitis pigmentosa who received an artificial silicon retina, including subjective improvements in appreciation of brightness, contrast, colour, movement, shape, and visual field.16 Some patients showed improvement in visual acuity.
, 百拇医药
Subretinal prostheses have two major advantages over other methods for restoring vision.7 Firstly, they utilise forces between the neurosensory retina and retinal pigment epithelium to maintain their position. Secondly, they have the potential to allow for greater spatial resolution as they are positioned closer to retinal nerve cells and can stimulate the nerves at lower electrical currents. The main disadvantages of subretinal implants include impaired nourishment of the inner retina due to the creation of a mechanical barrier between the outer retina and the choroid7 8 and trauma to the retina during implantation.7 These prostheses also show poor dissipation of heat and therefore could damage the retina.8
, http://www.100md.com
The mechanism of action of these implants may be by direct stimulation of retinal neurones or by probable neurotrophic effects on photoreceptors.16 A study of subretinal artificial silicon implants in rats showed a temporary neuroprotective effect on the retina, resulting in increased generation of photoreceptors.18
Epiretinal prostheses
Epiretinal prostheses comprise an array of electrodes implanted on the surface of the retina between the vitreous and internal limiting membrane. The implants receive electrical signals from a camera positioned outside the body (figs 3 and 4). In one such device—the second sight model—the camera transmits light signals to a microchip within the camera. This microchip deciphers the signal and relays it to a microchip in the epiretinal implant which in turn stimulates the retinal ganglion cells.19 20 A vitrectomy is required to implant the intraocular component of this prosthesis.7
, http://www.100md.com
Early studies in dogs22 23 and rabbits8 24 showed the feasibility of using epiretinal prostheses. A few clinical trials in humans have reported simple visual perception as phosphenes.20 Perception of light only was reported by three "completely blind" patients with retinitis pigmentosa who received the second sight model: these implants have survived for up to two years.7 21 25 26
One advantage of epiretinal implants over subretinal devices is that the camera can process signals before they reach the implant. This permits optimisation of the signal's quality, which may lead to improved visual perception. Epiretinal implants can also use the heat dissipating properties of the vitreous and are therefore less likely than subretinal implants to damage the retina. The superficial location of the implant reduces the risks of trauma during implantation and allows for the implant to be replaced.
, 百拇医药
Ongoing research
Transcleral, intrascleral, or suprachoroidal electrodes to generate electrical evoked potentials by transretinal stimulation31 32
Biocompatible carbon nanotubes as microelectrodes for retinal prostheses33
Implants with photosensitive dyes to generate impulses34
Neural prostheses that use neurotransmitters instead of direct electrical activity to stimulate retinal neurones35 36
, 百拇医药
Implantable miniature intraocular telescope in patients with stable age related macular degeneration37
The main disadvantages of epiretinal implants are the need for complicated microtechnology and surgical techniques that ensure secure fixation of the implant on the retina. The device also requires a higher electrical current than the subretinal implant.7 8 Implants are being developed to generate their own electrical currents on stimulation.
, 百拇医药
Conclusion
Advances in microtechnology have enabled major improvements in the design of different implants for restoring vision.27 The newer devices allow greater levels of visual perception than before, with the subretinal and epiretinal prostheses showing most promise. As yet, however, no patient has had an acceptable level of vision restored. Clinical results have been limited to small numbers of patients with severe visual impairment, so it is unclear to what degree vision could be restored in patients with less severe disease. Furthermore, no large controlled trials have compared the current approaches. The general and comparative costs of the implants are also not known (E Zrenner, personal communication, 2003).
, 百拇医药
Ongoing developments are increasing the sophistication of devices for resolving capability,28-30 and these advances are likely to further improve visual perception. From a historical perspective, the progress to restore vision using implants has been likened to the clinical success of cochlear implants in treating deafness.7 With this in mind, one day it may be possible for visual prostheses to restore vision in patients with retinitis pigmentosa or age related macular degeneration.
, http://www.100md.com
Competing interests: None declared.
References
VanNewkirk MR, Nanjan MB, Wang JJ, Mitchell P, Taylor HR, McCarty CA. The prevalence of age-related maculopathy: the visual impairment project. Ophthalmology 2000;107: 1593-600.
Evans J, Wormald R. Is the incidence of registrable age-related macular degeneration increasing Br J Ophthalmol 1996;80: 9-14.
Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet 1980;32: 223-35.
, 百拇医药
Klein ML, Francis PJ. Genetics of age-related macular degeneration. Ophthalmol Clin North Am 2003;16: 567-74.
Hunt DW, Margaron P. Status of therapies in development for the treatment of age-related macular degeneration. IDrugs 2003;6: 464-9.
Uhlig CE, Tanen S, Benner FP, Gerding H. Electrical stimulation of the visual system. From empirical approach to visual prostheses. Ophthalmologe 2001;98: 1089-96.
, 百拇医药
Lakhanpal RR, Yanai D, Weiland JD, Fujii GY, Caffey S, Greenberg R, et al. Advances in the development of visual prostheses. Curr Opin Ophthalmol 2003;14: 122-7.
Margalit E, Maia M, Weiland JD, Greenberg RJ, Fujii GY, Torres G, et al. Retinal prosthesis for the blind. Surv Ophthalmol 2002;47: 335-56.
Dawson WW, Radtke ND. The electrical stimulation of the retina by indwelling electrodes. Invest Ophthalmol Vis Sci 1977;16: 249-52.
, 百拇医药
Zrenner E, Stett A, Weiss S Aramant RB, Guenther E, Miliczek KD, et al. Can subretinal microphotodiodes successfully replace degenerated photoreceptors Vision Res 1999;39: 2555-67.
Humayun MS. Intraocular retinal prosthesis. Trans Am Ophthalmol Soc 2001;99: 271-300.
Gerding H. Development of microelectronic visual implants. In: Alberti WE, Richard G, Sagerman RH, eds. Age-related macular degeneration: current treatment concepts. New York: Springer-Verlag, 2001: 55.
, http://www.100md.com
Schmidt EM, Bak MJ, Hambrecht FT, Kufta CV, O'Rourke DK, Vallabhanath P. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex. Brain 1996;119: 507-22
Dobelle WH. Artificial vision for the blind by connecting a television camera to the visual cortex. ASAIO J 2000;46: 3-9.
Veraart C, Raftopoulos C, Mortimer JT, Delbeke J, Pins D, Michaux G, et al. Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode. Brain Res 1998;813: 181-6.
, 百拇医药
Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, Schuchard R. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol 2004;122: 460-9.
Zrenner E. Will retinal implants restore vision Science 2002;295: 1022.
Sippy BD, Yin H, Ball SL, Phillips MJ, Blum M, Chow AT, et al. Investigative Ophthalmology and Visual Science. www.arvo.org, 2003;e-abstract Nos 5062, 5063, 5075, 5071 (accessed May 2004).
, 百拇医药
Grossniklaus HE. Will retinal implants restore vision Am J Ophthalmol 2002;133: 865-6.
Humayun MS, de Juan E, Weiland JD, Dagnelie G, Katona S, Greenberg R, et al. Pattern electrical stimulation of the human retina. Vision Res 1999;39: 2569-76.
Humayun MS, Weiland JD, Fujii GY, Greenberg R, Williamson R, Little J, et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res 2003;43: 2573-81.
, http://www.100md.com
Majji AB, Humayun MS, Weiland JD, Suzuki S, D'Anna SA, de Juan E. Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. Invest Ophthalmol Vis Sci 1999;40: 2073-81.
Weiland JD, Fujii GY, Mech BV, Greenberg RJ, Guven D, Mahadevappa M, et al. Chronic electrical stimulation of the retina in RCD1 and normal dog. Invest Ophthalmol Vis Sci 2003;e-abstract 5081/B740 (accessed May 2004).
, 百拇医药
Ikuno Y, Choi JS, Nakauchi K, Sakaguchi H, Kamei M, Hirakata A, et al. Histologic analysis of a retinal prosthesis implant in an animal model. Invest Ophthalmol Vis Sci 2003;e-abstract 5050/B709 (accessed May 2004).
Humayun MS, de Juan E, Dagnelie G, Greenberg RJ, Propst RH, Phillips DH. Visual perception elicited by electrical stimulation of retina in blind humans. Arch Ophthalmol 1996;114: 40-6.
Humayun MS, Weiland JD, Fujii GY, Greenberg R, Williamson R, Little J, et al. Chronically implanted intraocular retinal prosthesis in three blind subjects. Invest Ophthalmol Vis Sci 2004;e-abstract 3397 (accessed May 2004).
, http://www.100md.com
Rizzo JF, Wyatt J, Humayun M, de Juan E, Liu W, Chow A, et al. Retinal prosthesis: an encouraging first decade with major challenges ahead. Ophthalmology 2001;108: 13-4.
Guven D, Fujii G, Maghribi MN, Okanden M, Krulevitch P, Wessendorf K, et al. High density electrode count retinal stimulating arrays. Invest Ophthalmol Vis Sci 2003;e-abstract 5060/B719 (accessed May 2004).
Palanker DV, Vankov A, Hui P, Fishman HA, Marmor MF, Blumenkranz MD, et al. Can a self-powered retinal prosthesis support 100,000 pixels in the macula Invest Ophthalmol Vis Sci 2003;e-abstract 5067/B726 (accessed May 2004).
, 百拇医药
Liu W, Singh P, Humayun M, Weiland J. New micro-stimulator for high resolution retinal prosthesis. Invest Ophthalmol Vis Sci 2003;e-abstract 5088/B747 (accessed May 2004).
Kanda H, Sawai H, Morimoto T, Fujikado T, Tano Y, Fukuda Y, et al. Suprachoroidal transretinal stimulation (STS) can elicit localised evoked responses from the superior colliculus in normal and RCS rats. Invest Ophthalmol Vis Sci 2003;e-abstract 5053/B712 (accessed May 2004).
, http://www.100md.com
Nakauchi K, Fujikado T, Kanda H, Ikuno Y, Sakaguchi H, Karnwei M, et al. Transretinal electrical stimulation by intrascleral multichannel electrode in rabbit eyes. Invest Ophthalmol Vis Sci 2003;e-abstract 5061/B720 (accessed May 2004).
Wang K, Loftus D, Leng T, Harris JS, Fishman H. Carbon nanotubes as microelectrodes for a retinal prosthesis. Invest Ophthalmol Vis Sci 2003;e-abstract 5054/B713 (accessed May 2004).
Matsuo T. A simple method for screening photoelectric dyes towards the use for retina prosthesis. Invest Ophthalmol Vis Sci 2003;e-abstract 5049/B708 (accessed May 2004).
, 百拇医药
Peterman MC, Bloom DM, Lee C, Bent SF, Marmor MF, Blumenkranz MS, et al. Localized neurotransmitter release for use in a prototype retinal interface. Invest Ophthalmol Vis Sci 2003;44: 3144-9.
Peterman MC, Noolandi J, Blumenkranz MS, Fishman HA. Localized chemical release from an artificial synapse chip. Proc Natl Acad Sci USA 2004;101: 9951-4.
Hamill MB, Kuppermann BD, Fine IH, Lane SS. The implantable miniature telescope: 12-month results of the US IMT 001. Clinical trial in patients with stable age-related macular degeneration. Invest Ophthalmol Vis Sci 2003;e-abstract 4209 (accessed May 2004)., 百拇医药(Parwez Hossain, Ian W See)
Introduction
Degeneration of the retina occurs in age related macular degeneration and retinitis pigmentosa, resulting in loss of vision. Age related macular degeneration is a major cause of visual impairment among people over 65 in Western countries1; in the United Kingdom its incidence has increased by 30-40% over the past 40 years.2 Retinitis pigmentosa generally occurs in a younger age group (incidence 1 per 4000 live births) and affects 1.5 million people worldwide.3
, 百拇医药
In both conditions patients are visually impaired due to loss of photoreceptors. At present few treatments can remedy this and lead to recovery of vision.4 5 Photodynamic laser therapy has been beneficial in some patients with age related macular degeneration, but this therapy does not address photoreceptor loss. Different gene and drug therapies have been tried,4 5 but their ability to replace lost photosensitive tissue is limited. Researchers are therefore investigating the possibility of using prostheses to restore vision.
, 百拇医药
Advances in microtechnology have facilitated the development of a variety of prostheses that can be connected to the brain or implanted in the eye. Some of these approaches have improved the eyesight of patients with visual impairment. This article gives an overview of the methods that are being assessed to restore vision in patients with severe sight loss.
Methods
We carried out a comprehensive search through Medline and PubMed using the terms "age related maculopathy", "visual prosthesis", "retinitis pigmentosa", "retina", and "eye". We also searched for the latest developments in artificial vision through the website of the Association for Research in Vision and Ophthalmology.
, http://www.100md.com
A brief history of visual prostheses
Efforts to develop visual prostheses are not new. Attempts at artificial vision began in the 18th century with direct electrical stimulation of blind eyes.6 In the 1920s, the German neurosurgeon Otfrid Foerster developed this approach further by investigating direct electrical stimulation of the visual cortex.7 Several of his patients experienced limited subjective visual phenomena. By the '60s, investigations began on devices that could be implanted on the surface of the visual cortex.8 In 1977, electrodes were implanted in the eye to try to evoke a visual response.9 Since the '20s several types of visual prostheses have been examined.10 Most of these earlier devices were limited by a lack of visual resolution (pixels) or by their overall size and the electrical constraints this imposed. Early approaches were also prone to complications after implantation.8 With recent advances in microtechnology, however, progress has been made in the development of implants, some of which can be placed in the eye. These implants have greater potential for visual resolution and remain viable for several years.
, 百拇医药
Summary points
Artificial means of restoring vision include cortical implants, optic nerve stimulation, and retinal implants
These approaches are being assessed in clinical trials
Patients with implants have a crude level of visual perception
Problems with implants include availability of a power source, surgical complications, and long term viability
, 百拇医药
No visual prosthesis has yet restored vision
Three methods to restore vision are currently being developed: stimulation of the visual cortex using cortical implants, stimulation of the optic nerve, and retinal devices implanted either in the retina or on its surface.
Cortical implants
In the 1960s investigators implanted electrodes on the visual cortex (epicortical implants) of human patients through a burr hole.7 8 11 The patients reported seeing spots of light or "phosphenes."7 12 These early studies were limited by problems such as flickering phosphenes and interactions between phosphenes. The excessive electrode currents also irritated the meninges, causing pain around the implant.11 Later modifications to the implants enabled them to be embedded in the visual cortex (intracortical implants), and thus smaller electrodes and lower electrical currents could be used. These advances led to localised intracortical stimulation with less pain.7 12 13 Visual prostheses have the disadvantages of the surgical complications of any artificial implant, and complex mapping of the visual cortex is required to achieve visual perception.11 Despite these limitations, patients with implants can be trained to navigate around objects, perform simple tasks, and identify large letters.14
, http://www.100md.com
Intracortical implants have two main advantages over other methods for restoring vision. Firstly, the electrodes are protected by the skull. Secondly, the technique bypasses disease proximal to the primary visual cortex, making it potentially useful for treating diseases of the optic nerve and retina.
Optic nerve stimulation
The optic nerve can be directly stimulated to restore vision (fig 1). Stimulation of electrodes placed around the optic nerve of a patient with retinitis pigmentosa resulted in coloured phosphenes throughout the visual field.15 By changing the duration and amplitude of the electrical stimulus, the patient was able to perceive different levels of phosphene generation as brightness. Similar work has enabled a patient to localise objects and to discriminate between them.15 Direct stimulation of the optic nerve has several potential advantages over other methods for restoring vision. Firstly, it does not require the surgical penetration of sensitive intraocular or intracranial tissues. Secondly, the photosensitive component, for example, video device, can be placed outside the body, thus allowing the use of an external power source. The main disadvantages of this approach are that a normal functioning optic nerve is required (thus this method has limited use in diseases such as glaucoma) and that there is a risk of infection from the external wires.
, http://www.100md.com
Retinal prostheses
Prostheses can be implanted in the retina to act as a substitute for the host's photoreceptors. Retinal prostheses are only viable if the visual pathway distal to the retina is intact and functional. Two types of prostheses are under development according to the layer of retina receiving the device: epiretinal (on the surface of the retina) and subretinal (under the retina) implants.
Subretinal prostheses
, 百拇医药
Subretinal prostheses contain microphotodiodes attached to microelectrodes. These implants, such as the artificial silicon retina (5000 microelectrodes),16 are placed in the subretinal space between the outer retina and retinal pigment epithelium (figs 2 and 3). They are inserted either in the subretinal space through an incision in the sclera (extraocular approach) or by standard vitrectomy followed by retinotomy (intraocular approach).8 16 17
The photodiodes are stimulated by light passing through the retina, and the resulting electric current excites adjacent retinal sensory neurones.16 The specifications for subretinal implants vary—for example, one device measures 50-100 μm wide, has a diameter of 2 or 3 mm, and carries microphotodiodes constructed on a microelectrode array.16 These implants do not require an external electrical source as incident light is sufficient for stimulation.8 17
, http://www.100md.com
The viability of subretinal devices has been assessed in animal experiments. Several species have shown tolerance to the implants,18 some for up to 30 months.16 Histological evidence has shown no important changes to the retina's architecture.10 Visual perception was improved in six patients with retinitis pigmentosa who received an artificial silicon retina, including subjective improvements in appreciation of brightness, contrast, colour, movement, shape, and visual field.16 Some patients showed improvement in visual acuity.
, 百拇医药
Subretinal prostheses have two major advantages over other methods for restoring vision.7 Firstly, they utilise forces between the neurosensory retina and retinal pigment epithelium to maintain their position. Secondly, they have the potential to allow for greater spatial resolution as they are positioned closer to retinal nerve cells and can stimulate the nerves at lower electrical currents. The main disadvantages of subretinal implants include impaired nourishment of the inner retina due to the creation of a mechanical barrier between the outer retina and the choroid7 8 and trauma to the retina during implantation.7 These prostheses also show poor dissipation of heat and therefore could damage the retina.8
, http://www.100md.com
The mechanism of action of these implants may be by direct stimulation of retinal neurones or by probable neurotrophic effects on photoreceptors.16 A study of subretinal artificial silicon implants in rats showed a temporary neuroprotective effect on the retina, resulting in increased generation of photoreceptors.18
Epiretinal prostheses
Epiretinal prostheses comprise an array of electrodes implanted on the surface of the retina between the vitreous and internal limiting membrane. The implants receive electrical signals from a camera positioned outside the body (figs 3 and 4). In one such device—the second sight model—the camera transmits light signals to a microchip within the camera. This microchip deciphers the signal and relays it to a microchip in the epiretinal implant which in turn stimulates the retinal ganglion cells.19 20 A vitrectomy is required to implant the intraocular component of this prosthesis.7
, http://www.100md.com
Early studies in dogs22 23 and rabbits8 24 showed the feasibility of using epiretinal prostheses. A few clinical trials in humans have reported simple visual perception as phosphenes.20 Perception of light only was reported by three "completely blind" patients with retinitis pigmentosa who received the second sight model: these implants have survived for up to two years.7 21 25 26
One advantage of epiretinal implants over subretinal devices is that the camera can process signals before they reach the implant. This permits optimisation of the signal's quality, which may lead to improved visual perception. Epiretinal implants can also use the heat dissipating properties of the vitreous and are therefore less likely than subretinal implants to damage the retina. The superficial location of the implant reduces the risks of trauma during implantation and allows for the implant to be replaced.
, 百拇医药
Ongoing research
Transcleral, intrascleral, or suprachoroidal electrodes to generate electrical evoked potentials by transretinal stimulation31 32
Biocompatible carbon nanotubes as microelectrodes for retinal prostheses33
Implants with photosensitive dyes to generate impulses34
Neural prostheses that use neurotransmitters instead of direct electrical activity to stimulate retinal neurones35 36
, 百拇医药
Implantable miniature intraocular telescope in patients with stable age related macular degeneration37
The main disadvantages of epiretinal implants are the need for complicated microtechnology and surgical techniques that ensure secure fixation of the implant on the retina. The device also requires a higher electrical current than the subretinal implant.7 8 Implants are being developed to generate their own electrical currents on stimulation.
, 百拇医药
Conclusion
Advances in microtechnology have enabled major improvements in the design of different implants for restoring vision.27 The newer devices allow greater levels of visual perception than before, with the subretinal and epiretinal prostheses showing most promise. As yet, however, no patient has had an acceptable level of vision restored. Clinical results have been limited to small numbers of patients with severe visual impairment, so it is unclear to what degree vision could be restored in patients with less severe disease. Furthermore, no large controlled trials have compared the current approaches. The general and comparative costs of the implants are also not known (E Zrenner, personal communication, 2003).
, 百拇医药
Ongoing developments are increasing the sophistication of devices for resolving capability,28-30 and these advances are likely to further improve visual perception. From a historical perspective, the progress to restore vision using implants has been likened to the clinical success of cochlear implants in treating deafness.7 With this in mind, one day it may be possible for visual prostheses to restore vision in patients with retinitis pigmentosa or age related macular degeneration.
, http://www.100md.com
Competing interests: None declared.
References
VanNewkirk MR, Nanjan MB, Wang JJ, Mitchell P, Taylor HR, McCarty CA. The prevalence of age-related maculopathy: the visual impairment project. Ophthalmology 2000;107: 1593-600.
Evans J, Wormald R. Is the incidence of registrable age-related macular degeneration increasing Br J Ophthalmol 1996;80: 9-14.
Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet 1980;32: 223-35.
, 百拇医药
Klein ML, Francis PJ. Genetics of age-related macular degeneration. Ophthalmol Clin North Am 2003;16: 567-74.
Hunt DW, Margaron P. Status of therapies in development for the treatment of age-related macular degeneration. IDrugs 2003;6: 464-9.
Uhlig CE, Tanen S, Benner FP, Gerding H. Electrical stimulation of the visual system. From empirical approach to visual prostheses. Ophthalmologe 2001;98: 1089-96.
, 百拇医药
Lakhanpal RR, Yanai D, Weiland JD, Fujii GY, Caffey S, Greenberg R, et al. Advances in the development of visual prostheses. Curr Opin Ophthalmol 2003;14: 122-7.
Margalit E, Maia M, Weiland JD, Greenberg RJ, Fujii GY, Torres G, et al. Retinal prosthesis for the blind. Surv Ophthalmol 2002;47: 335-56.
Dawson WW, Radtke ND. The electrical stimulation of the retina by indwelling electrodes. Invest Ophthalmol Vis Sci 1977;16: 249-52.
, 百拇医药
Zrenner E, Stett A, Weiss S Aramant RB, Guenther E, Miliczek KD, et al. Can subretinal microphotodiodes successfully replace degenerated photoreceptors Vision Res 1999;39: 2555-67.
Humayun MS. Intraocular retinal prosthesis. Trans Am Ophthalmol Soc 2001;99: 271-300.
Gerding H. Development of microelectronic visual implants. In: Alberti WE, Richard G, Sagerman RH, eds. Age-related macular degeneration: current treatment concepts. New York: Springer-Verlag, 2001: 55.
, http://www.100md.com
Schmidt EM, Bak MJ, Hambrecht FT, Kufta CV, O'Rourke DK, Vallabhanath P. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex. Brain 1996;119: 507-22
Dobelle WH. Artificial vision for the blind by connecting a television camera to the visual cortex. ASAIO J 2000;46: 3-9.
Veraart C, Raftopoulos C, Mortimer JT, Delbeke J, Pins D, Michaux G, et al. Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode. Brain Res 1998;813: 181-6.
, 百拇医药
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