tisdag 6 augusti 2013

Retina Implant


What are visual implants?

"...Generally speaking, an implant or prosthesis in the field of medicine designates a device which takes over the functions of organs or their parts. In this sense, many types of implants and prostheses have already been introduced in the field of ophthalmology - artificial lenses, corneal implants, iris implants, filtration implants in glaucoma surgery and - in the narrower sense of the word - silicone oil. To be understood under "visual implants", however, are technical devices which seek to take over the neuronal functions of vision. We speak here of "artificial sight".
Various approaches exist for the use of visual implants. Corresponding to the visual pathway itself, there are subretinal, epiretinal, optic nerve and cortical visual implants.
In principle, the subretinal implant [1 - 3] replaces the photoreceptors in retinitis pigmentosa or other forms of retinal degeneration in which the inner retina and the rest of the visual pathway remain intact. Such a neurological implant converts incident light into an electrical signal which is then transmitted on to the bipolar cells.
 An epiretinal prosthesis [4 - 7] directly stimulates ganglion cells and is positioned on the nerve fibre layer. Epiretinal implants work with an external camera mounted on a spectacles frame and require an "encoder" whose function is to take over the role of the neurons of the inner retina, which carry out preliminary processing of visual information. A problem encountered in stimulation of the ganglion cells with this method is that there is usually no stimulation of fibres in the vicinity of the original cell when the stimulus is transmitted from the original retinal cell to the papilla of the eye. For its part, the brain invariably interprets excitement of such a fibre as a specific point of light within the visual field.
This point of light corresponds to the location of the original cell in the retina, but not to the location of the electrode. For that reason, an image generated with this method must first be assembled with "spatial accuracy" before it is transmitted to the fibre side of the retina. This task can, for example, be taken over by a 'learning' software, that is, by an "encoder" which shifts the stimulus location in each case within the image field to match the actual visual sensation within the visual field - a complex assignment for which the required hardware cannot presently be located within the eye.
The subretinal implant, on the other hand, is positioned at the level of the photoreceptor layer and can thus make full, correct use of the retinotopy of bipolar cells linked to it. This is a major difference from the epiretinal approach, in which a camera is mounted on a spectacles frame and the patient must regularly move his head – that is, the camera - back and forth; to prevent the image from disappearing, as in the case of stabilized retinal images. With the subretinal approach, in which light receivers are located beneath the retina, assistance is provided by natural microsaccades which constantly refresh the image. In addition, the eye's direction of gaze can be used to find the object viewed without need of resorting to movement of the head. On the other hand, no overall change in image processing can take place after implantation of the active subretinal implant, since its image-processing electronics are completely within the body. It has been found, however, that due to the very good retinotopy the adjustment of sensitivity and maximum brightness provide adequate possibilities for varying adjustment.
Like epiretinal prostheses, optic nerve implants [8] stimulate the axons of the optic nerve and likewise function with an external camera. Even though retinotopy within the optic nerve is demonstrably preserved, the high density of the axons makes it impossible to achieve a high level of resolution. Cortical implants [9] directly stimulate the neurons of the primary visual cortex and require a very elaborate surgical procedure.
Currently, the visual implants developed farthest are the epiretinal and subretinal implants. Although both have advantages and disadvantages the best three-dimensional resolution, visual acuity, and stability of visual perception to date have been attained with the subretinal approach[10, 17].
In a collaborative effort with the University of Tübingen's Ophthalmological Clinic, a subretinal chip has been undergoing development since 1995 [18]; following successful animal trials [1, 11 - 15], implantation in blind patients began in 2005. A pilot study from 2005 to 2009 showed that such implants represent no major risk for the human retina and that it is possible to mediate meaningful visual perceptions by means of this subretinal chip. Currently, we have been using a technologically improved implant, the Alpha IMS, since May 2010 in a multicentre study with blind retinitis pigmentosa patients.
Picture of the subretinal implant in detail
Figure 1) Detailed view of the subretinal implant on the microchip, which for its part has 1,500 pixels on a surface area of 3×3 mm. The chip consists of 1,500 microphotodiodes, each of which is connected to an amplifier and an electrode. Each microphotodiode collects the incident light signal, and an amplified electrical signal is sent by the electrode to the bipolar cells. The entire implant consists of the subretinal chip, a power supply cable (polyimide film and a thin silicone cable with gold wires), and the secondary coil, which is affixed to bone in the retroauricular region.

How does the subretinal chip function?

In a healthy retina, light is converted by the photoreceptors into nerve signals through a change in cell membrane polarization. The subretinal implant takes over this function. For its part, the 70 µm-thick microchip consists of 1,500 elements ("pixels") on a surface area of 3 × 3 mm (● see Figure 1). Each of these elements contains a silicon photodiode, a differential amplifier, and an electrode. Incident light is collected point for point by the photodiodes and converted into electrical signals. An amplifier downline from each photodiode passes on an adequately strong electrical charge to the bipolar cells of the retina via electrodes. Since this process takes place in each pixel independently, the natural retinotopy of the visual signal is preserved with geometrical correctness.

In contrast to the natural photoreceptors, however, the energy of incident light does not suffice to directly stimulate the cells of the inner retina. For that reason, subretinal visual implants require an external power supply. The entire implant therefore consists not only of the microchip but also of a subdermal power supply behind the ear with a connecting cable (● see Figures 1, 2, 4).
The chip is connected to its power supply unit via a 20 µm-thick sheet of polyimide film and a thin silicone cable with gold wire (● see Figure 1). The energy transfer to this power supply takes place via electromagnetic induction through a subdermal secondary coil and an epidermal primary coil which is held magnetically in place (● see Figure 2).
Picture of the external power supply


Figure 2a) The external power supply with the external primary coil.

This picture shows the position of the primary coil on the patient's head

Figure 2b) The primary coil is magnetically held in position in the retroauricular region at the position of the secondary coil and is always positioned there for the purpose of activation of the implants. Energy transfer between the two coils takes place via electromagnetic induction.

Picture of the control device which is used by the patient

Figure 2c) Adjustment of the perceptual parameters (depending on the brightness and contrast of the objects to be viewed) is carried out manually by the patient himself by means of the external power supply.
An external power supply unit delivers pulsed energy to the primary coil. The chip as a whole uses its 1,500 microphotodiodes to record an electrical image several times a second for 1 ms and send it on to the bipolar cells.
The chip is surgically implanted [16] and positioned subretinally - if possible directly beneath the macula (● see Figure 3). 
The picture shows the retina implant as it gets implanted

Abbildung 3) The subretinal microchip is implanted at the posterior pole of the eye, if possible beneath the macular area. The surface area of the active implant is 3×3 mm. The strip with the cable connections leads to the retinal periphery.

The polyimide film is also positioned subretinally and exits from the eye at the equator through the choroid and the sclera. This part of the implant is held in place through intraocular pressure alone. The transition to the silicone cable is mounted episclerally. The cable then runs intraorbitally to the  bony edge of the orbit of the eye, to which it is likewise affixed. From there, the cable runs below the temporal muscle to the secondary coil, which is mounted on bone in the retroauricular region (● see Figure 4). The cable is adequately secured by being laid under the periosteum. The power supply too is below the periosteum, if necessary in a precisely shaped hollow which is milled out of the bone. .
Scheme of the subretinal implant's position in the eye


Figure 4a) Intraocular position of the subretinal implant. The microchip itself is positioned subretinally below the macula. The tiny band which connects the microchip with the power supply cable runs subretinally into the retinal periphery and exits transchodioidally and transsclerally out of the globe.

This computer generated image shows the positioning of the coils

Figure 4b) The power supply cable exits from the orbit at the lateral bony edge of the orbit of the eye and passes under the masseter muscle into the retroauricular region, where it is attached to the secondary coil. Taking a leaf from cochlear implants, the latter is surgically attached to the bone and is supplied with power for activation of the implant via electromagnetic induction by the externally positioned primary coil...."


(From: Stingl K et al., Klin Monatsbl Augenheilkd, 2010; 227: 940-945)


[1] Zrenner E. Will retinal implants restore vision? Science 2002; 295:1022–1025
[2] Zrenner E, Gekeler F, Gabel PV et al. Subretinal microphotodiode array as replacement for degenerated photoreceptors? Ophthalmologe 2001; 98: 357–363

[3] Gekeler F, Zrenner E. Status of the subretinal implant project. An overview. Ophthalmologe 2005; 102: 941–949

[4] Yanai D et al. Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am J Ophthalmol 2001; 143: 820–827

[5] Horsager A, Greenberg RJ, Fine I. Spatiotemporal interactions in retinal prosthesis subjects. Invest Ophthalmol Vis Sci 2010; 51: 1223–1233

[6] Chader GJ, Weiland J, Humayun MS. Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis. Prog Brain Res 2009; 175: 317–332

[7] Hornig R, Laube T,Walter P et al. Amethod and technical equipment for an acute human trial to evaluate retinal implant technology. J Neural Eng 2005; 2: S129–S134

[8] Brelen ME, Vince V, Gérard B et al. Measurement of evoked potentials following electrical stimulation of the human optic nerve. Invest Ophthalmol Vis Sci 2010 10.1167/iovs.09-4346

[9] Normann RA, Greger B, Greger BA et al. Toward the development of a cortically based visual neuroprosthesis. J Neural Eng 2009; 6: 035001

[10] Humayun MS, Dorn JD, Ahuja AK et al. Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study. Conf Proc IEEE Eng Med Biol Soc 2009; 2009: 4566–4568

[11] Zrenner E, Stett A, Weiss S et al. Can subretinal microphotodiodes successfully replace degenerated photoreceptors? Vision Res 1999; 39:2555–2567

[12] Schwahn H, Gekeler F, Kohler K et al. Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan micropig and rabbit. Graefe’s Archive for Clinical and Experimental Ophthalmology 2001; 239:961–967

[13] Kohler K, Hartmann JA, Werts D et al. Histological studies of retinal degeneration and biocompatibility of subretinal implants. Ophthalmologe 2001; 98: 364–368

[14] Guenther E, Tröger B, Schlosshauer B et al. Long-term survival of retinal cell cultures on retinal implant materials. Vision Res 1999; 39: 3988–3994

[15] Zrenner E, Miliczek KD, Gabel VP et al. The development of subretinal microphotodiodes for replacement of degenerated photoreceptors. Ophthalmic Res 1997; 29: 269–280

[16] Besch D et al. Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients. British Journal of Ophthalmology 2008; 92:1361–1368

[17] Zrenner E, Wilke R, Bartz-Schmidt KU. et al. Subretinal Microelectrode Arrays Allow Blind Retinitis Pigmentosa Patients to Recognize Letters and Combine them toWords. Biomedical Engineering and Informatics 2009. BMEI ’09. 2nd International Conference, Tianjin, 17 – 19 Oct 2009: 1–4 10.1109/BMEI.2009.5305315

[18] Zrenner E. Restoring neuroretinal function: new potentials. Doc Ophthalmol 2007; 115: 56–59

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