Visual prosthesis

A visual prosthesis, often referred to as a bionic eye, is an experimental visual device intended to restore functional vision in those suffering from partial or total blindness. In 1983 Joao Lobo Antunes, a Portuguese doctor, implanted a bionic eye in a person born blind. Many devices have been developed, usually modeled on the cochlear implant or bionic ear devices, a type of neural prosthesis in use since the mid-1980s. The idea of using electrical current (e.g., electrically stimulating the retina or the visual cortex) to provide sight dates back to the 18th century, discussed by Benjamin Franklin,^[1] Tiberius Cavallo,^[2] and Charles LeRoy.^[3]

Biological considerations

The ability to give sight to a blind person via a bionic eye depends on the circumstances surrounding the loss of sight. For retinal prostheses, which are the most prevalent visual prosthetic under development (due to ease of access to the retina among other considerations), patients with vision loss due to degeneration of photoreceptors (retinitis pigmentosa, choroideremia, geographic atrophy macular degeneration) are the best candidate for treatment. Candidates for visual prosthetic implants find the procedure most successful if the optic nerve was developed prior to the onset of blindness. Persons born with blindness may lack a fully developed optical nerve, which typically develops prior to birth, though neuroplasticity makes it possible for the nerve, and sight, to develop after implantation.

Technological considerations

Visual prosthetics are being developed as a potentially valuable aid for individuals with visual degradation. Argus II, co-developed at the University of Southern California (USC) Eye Institute^[4] and manufactured by Second Sight Medical Products Inc., is not the only such device to have received marketing approval (CE Mark in Europe in 2011). Most other efforts remain investigational; the Retina Implant AG's Alpha IMS won a CE Mark July 2013 and is a significant improvement in resolution. It is not, however, FDA-approved in the US.^[5]

Ongoing projects

Argus retinal prosthesis

Mark Humayun, who joined the faculty of the Keck School of Medicine of USC Department of Ophthalmology in 2001;^[6] Eugene Dejuan, now at the University of California San Francisco; engineer Howard D. Phillips; bio-electronics engineer Wentai Liu, now at University of California Los Angeles; and Robert Greenberg, now of Second Sight, were the original inventors of the active epi-retinal prosthesis^[7] and demonstrated proof of principle in acute patient investigations at Johns Hopkins University in the early 1990s. In the late 1990s the company Second Sight^[8] was formed by Greenberg along with medical device entrepreneur, Alfred E. Mann,^[9]:35 Their first-generation implant had 16 electrodes and was implanted in six subjects by Humayun at University of Southern California between 2002 and 2004.^[9]:35[10] In 2007, the company began a trial of its second-generation, 60-electrode implant, dubbed the Argus II, in the US and in Europe.^[11][12] In total 30 subjects participated in the studies spanning 10 sites in four countries. In the spring of 2011, based on the results of the clinical study which were published in 2012,^[13] Argus II was approved for commercial use in Europe, and Second Sight launched the product later that same year. The Argus II was approved by the United States FDA on 14 February 2013. Three US government funding agencies (National Eye Institute, Department of Energy, and National Science Foundation) have supported the work at Second Sight, USC, UCSC, Caltech, and other research labs.^[14]

Microsystem-based visual prosthesis (MIVP)

Designed by Claude Veraart at the University of Louvain, this is a spiral cuff electrode around the optic nerve at the back of the eye. It is connected to a stimulator implanted in a small depression in the skull. The stimulator receives signals from an externally worn camera, which are translated into electrical signals that stimulate the optic nerve directly.^[15]

Implantable miniature telescope

Although not truly an active prosthesis, an Implantable Miniature Telescope is one type of visual implant that has met with some success in the treatment of end-stage age-related macular degeneration.^[16][17][18] This type of device is implanted in the eye's posterior chamber and works by increasing (by about three times) the size of the image projected onto the retina in order to overcome a centrally located scotoma or blind spot.^[17][18]

Created by VisionCare Ophthalmic Technologies in conjunction with the CentraSight Treatment Program, the telescope is about the size of a pea and is implanted behind the iris of one eye. Images are projected onto healthy areas of the central retina, outside the degenerated macula, and is enlarged to reduce the effect the blind spot has on central vision. 2.2x or 2.7x magnification strengths make it possible to see or discern the central vision object of interest while the other eye is used for peripheral vision because the eye that has the implant will have limited peripheral vision as a side effect. Unlike a telescope which would be hand-held, the implant moves with the eye which is the main advantage. Patients using the device may however still need glasses for optimal vision and for close work. Before surgery, patients should first try out a hand-held telescope to see if they would benefit from image enlargement. One of the main drawbacks is that it cannot be used for patients who have had cataract surgery as the intraocular lens would obstruct insertion of the telescope. It also requires a large incision in the cornea to insert.^[19]

Tübingen MPDA Project Alpha IMS

A Southern German team led by the University Eye Hospital in Tübingen, was formed in 1995 by Eberhart Zrenner to develop a subretinal prosthesis. The chip is located behind the retina and utilizes microphotodiode arrays (MPDA) which collect incident light and transform it into electrical current stimulating the retinal ganglion cells. As natural photoreceptors are far more efficient than photodiodes, visible light is not powerful enough to stimulate the MPDA. Therefore, an external power supply is used to enhance the stimulation current. The German team commenced in vivo experiments in 2000, when evoked cortical potentials were measured from Yucatán micropigs and rabbits. At 14 months post implantation, the implant and retina surrounding it were examined and there were no noticeable changes to anatomical integrity. The implants were successful in producing evoked cortical potentials in half of the animals tested. The thresholds identified in this study were similar to those required in epiretinal stimulation. The latest reports from this group concern the results of a clinical pilot study on 11 participants suffering from RP. Some blind patients were able to read letters, recognize unknown objects, localize a plate, a cup and cutlery. The results were to be presented in detail in 2011 in the Proceedings of the Royal Society B.^[20] In 2010 a new multicenter Study has been started using a fully implantable device with 1500 Electrodes Alpha IMS (produced by Retina Implant AG, Reutlingen, Germany), 10 patients included so far; first results have been presented at ARVO 2011. The first UK implantations took place in March 2012 and were led by Robert MacLaren at the University of Oxford and Tim Jackson at King's College Hospital in London.^[21][22] David Wong also implanted the Tübingen device in a patient in Hong Kong.^[23] In all cases previously blind patients had some degree of sight restored, confirming that despite the complexity of surgery, the device can be implanted successfully at other specialist centers around the World.

Harvard/MIT Retinal Implant

Joseph Rizzo and John Wyatt at the Massachusetts Eye and Ear Infirmary and MIT began researching the feasibility of a retinal prosthesis in 1989, and performed a number of proof-of-concept epiretinal stimulation trials on blind volunteers between 1998 and 2000. They have since developed a subretinal stimulator, an array of electrodes, that is placed beneath the retina in the subretinal space and receives image signals beamed from a camera mounted on a pair of glasses. The stimulator chip decodes the picture information beamed from the camera and stimulates retinal ganglion cells accordingly. Their second generation prosthesis collects data and sends it to the implant through RF fields from transmitter coils that are mounted on the glasses. A secondary receiver coil is sutured around the iris.^[24]

Artificial silicon retina (ASR)

The brothers Alan Chow and Vincent Chow have developed a microchip containing 3500 photodiodes, which detect light and convert it into electrical impulses, which stimulate healthy retinal ganglion cells. The ASR requires no externally worn devices.^[15]

The original Optobionics Corp. stopped operations, but Chow acquired the Optobionics name, the ASR implants and will be reorganizing a new company under the same name. The ASR microchip is a 2mm in diameter silicon chip (same concept as computer chips) containing ~5,000 microscopic solar cells called "microphotodiodes" that each have their own stimulating electrode.^[25]

Photovoltaic retinal prosthesis

Daniel Palanker and his group at Stanford University have developed a photovoltaic system for visual prosthesis^[26] that includes a subretinal photodiode array and an infrared image projection system mounted on video goggles. Information from the video camera is processed in a pocket PC and displayed on pulsed near-infrared (IR, 850–915 nm) video goggles. IR image is projected onto the retina via natural eye optics, and activates photodiodes in the subretinal implant that convert light into pulsed bi-phasic electric current in each pixel.^[27] Charge injection can be further increased using a common bias voltage provided by a radiofrequency-driven implantable power supply^[28] Proximity between electrodes and neural cells necessary for high resolution stimulation can be achieved utilizing the effect of retinal migration.

Bionic Vision Australia

An Australian team led by Professor Anthony Burkitt is developing two retinal prostheses. The Wide-View device combines novel technologies with materials that have been successfully used in other clinical implants. This approach incorporates a microchip with 98 stimulating electrodes and aims to provide increased mobility for patients to help them move safely in their environment. This implant will be placed in the suprachoroidal space. Researchers expect the first patient tests to begin with this device in 2013.

The Bionic Vision Australia consortium is concurrently developing the High-Acuity device, which incorporates a number of new technologies to bring together a microchip and an implant with 1024 electrodes. The device aims to provide functional central vision to assist with tasks such as face recognition and reading large print. This high-acuity implant will be inserted epiretinally. Patient tests are planned for this device in 2014 once preclinical testing has been completed.

Patients with retinitis pigmentosa will be the first to participate in the studies, followed by age-related macular degeneration. Each prototype consists of a camera, attached to a pair of glasses which sends the signal to the implanted microchip, where it is converted into electrical impulses to stimulate the remaining healthy neurons in the retina. This information is then passed on to the optic nerve and the vision processing centres of the brain.

The Australian Research Council awarded Bionic Vision Australia a $42 million grant in December 2009 and the consortium was officially launched in March 2010. Bionic Vision Australia brings together a multidisciplinary team, many of whom have extensive experience developing medical devices such as the cochlear implant (or 'bionic ear').^[29]

Dobelle Eye

Similar in function to the Harvard/MIT device, except the stimulator chip sits in the primary visual cortex, rather than on the retina. Many subjects have been implanted with a high success rate and limited negative effects. Still in the developmental phase, upon the death of Dobelle, selling the eye for profit was ruled against in favor of donating it to a publicly funded research team.^[15][30]

Intracortical visual prosthesis

The Laboratory of Neural Prosthetics at Illinois Institute Of Technology (IIT), Chicago, is developing a visual prosthetic using intracortical electrode arrays. While similar in principle to the Dobelle system, the use of intracortical electrodes allow for greatly increased spatial resolution in the stimulation signals (more electrodes per unit area). In addition, a wireless telemetry system is being developed^[31] to eliminate the need for transcranial wires. Arrays of activated iridium oxide film (AIROF)-coated electrodes will be implanted in the visual cortex, located on the occipital lobe of the brain. External hardware will capture images, process them, and generate instructions which will then be transmitted to implanted circuitry via a telemetry link. The circuitry will decode the instructions and stimulate the electrodes, in turn stimulating the visual cortex. The group is developing a wearable external image capture and processing system to accompany the implanted circuitry. Studies on animals and psyphophysical studies on humans are being conducted^[32] to test the feasibility of a human volunteer implant.

See also

• Bionic contact lens
• Human echolocation

References

1. Dobelle WH (2000). "Artificial vision for the blind by connecting a television camera to the visual cortex" (PDF). ASAIO J. 46 (1): 3–9. doi:10.1097/00002480-200001000-00002. Retrieved 21 July 2013.
2. Fodstad, H.; Hariz, M. (2007). "Electricity in the treatment of nervous system disease". In Sakas, Damianos E.; Krames, Elliot S.; Simpson, Brian A. Operative Neuromodulation. Springer. p. 11. ISBN 9783211330791. Retrieved 21 July 2013.
3. Sekirnjak C; Hottowy P; Sher A; Dabrowski W; et al. (2008). "High-resolution electrical stimulation of primate retina for epiretinal implant design". J Neurosci. 28 (17): 4446–56. doi:10.1523/jneurosci.5138-07.2008. Retrieved 21 July 2013.
4. "USC Eye Institute ophthalmologists implant first FDA-approved Argus II retinal prosthesis in western United States". Reuters. 27 August 2014. Retrieved 5 January 2015.
5. "Retinal implants: a systematic review.". Br J Ophthalmol. 98: 852–6. Jul 2014. doi:10.1136/bjophthalmol-2013-303708. PMID 24403565.
6. "Humayun faculty page at USC Keck". Retrieved February 15, 2015.
7. U.S. Department of Energy Office of Science. "Overview of the Artificial Retina Project".
8. Second Sight official website
9. Second Sight. November 14, 2014 Second Sight Amendment No. 3 to Form S-1: Registration Statement
10. Miriam Karmel (March 2012). "Clinical Update: Retina. Retinal Prostheses: Progress and Problems". Eyenet Magazine.
11. Second Sight (9 January 2007). "Press Release: Ending the Journey through Darkness: Innovative Technology Offers New Hope for Treating Blindness due to Retinitis Pigmentosa" (PDF).
12. Jonathan Fildes (16 February 2007). "Trials for bionic eye implants". BBC.
13. Humayun (April 2012). "Interim Results from the International Trial of Second Sight's Visual Prosthesis". Ophthalmology.
14. Sifferlin, Alexandra (19 February 2013). "FDA approves first bionic eye". CNN. TIME. Retrieved 22 February 2013.
15. James Geary (2002). The Body Electric. Phoenix.
16. Chun DW; Heier JS; Raizman MB (2005). "Visual prosthetic device for bilateral end-stage macular degeneration". Expert Rev Med Devices. 2 (6): 657–65. doi:10.1586/17434440.2.6.657. PMID 16293092.
17. Lane SS; Kuppermann BD; Fine IH; Hamill MB; et al. (2004). "A prospective multicenter clinical trial to evaluate the safety and effectiveness of the implantable miniature telescope". Am J Ophthalmol. 137 (6): 993–1001. doi:10.1016/j.ajo.2004.01.030. PMID 15183782.
18. Lane SS; Kuppermann BD (2006). "The Implantable Miniature Telescope for macular degeneration". Current Opinion in Ophthalmology. 17 (1): 94–8. doi:10.1097/01.icu.0000193067.86627.a1. PMID 16436930.
19. Lipshitz, Isaac. "Implantable Telescope Technology". VisionCare Ophthalmic Technologies, Inc. Retrieved 20 March 2011.
20. Eberhart Zrenner; et al. (2010). "Subretinal electronic chips allow blind patients to read letters and combine them to words". Proceedings of the Royal Society B. doi:10.1098/rspb.2010.1747.
21. "Blind man 'excited' at retina implant". BBC News. 3 May 2012. Retrieved May 23, 2016.
22. Fergus Walsh (3 May 2012). "Two blind British men have electronic retinas fitted". BBC News. Retrieved May 23, 2016.
23. "HKU performed the first subretinal microchip implantation in Asia Patient regained eyesight after the surgery". HKU.hk (Press release). The University of Hong Kong. 3 May 2012. Retrieved May 23, 2016.
24. Wyatt, Jr., J.L. "The Retinal Implant Project" (PDF). Research Laboratory of Electronics (RLE) at the Massachusetts Institute of Technology (MIT). Retrieved 20 March 2011.
25. "ASR® Device". Optobionics. Retrieved 20 March 2011.
26. Palanker Group. "Photovoltaic Retinal Prosthesis".
27. K. Mathieson, J. Loudin, G. Goetz, P. Huie, L. Wang, T. Kamins, L. Galambos, R. Smith, J.S. Harris, A. Sher and D. Palanker (2012). "Photovoltaic retinal prosthesis with high pixel density". Nature Photonics. 6 (6): 391–397. doi:10.1038/nphoton.2012.104.
28. J.D. Loudin; D.M. Simanovskii; K. Vijayraghavan; C.K. Sramek; et al. (2007). "Optoelectronic retinal prosthesis: system design and performance" (PDF). J Neural Engineering. 4 (1): S72–S84. doi:10.1088/1741-2560/4/1/S09. PMID 17325419.
29. "Bionic Vision Australia's progress of the bionic eye". Retrieved 23 July 2012. (subscription required (help)).
30. Simon Ings (2007). "Chapter 10(3): Making eyes to see". The Eye: a natural history. London: Bloomsbury. pp. 276–283.
31. Rush, Alexander; PR Troyk (November 2012). "A Power and Data Link for a Wireless-Implanted Neural Recording System". Transactions on Biomedical Engineering. 59 (11): 3255–3262. doi:10.1109/tbme.2012.2214385. PMID 22922687. Retrieved 26 September 2013.
32. Srivastava, Nishant; PR Troyk; G Dagnelie (June 2009). "Detection, eye-hand coordination and virtual mobility performance in simulated vision for a cortical visual prosthesis device". Journal of Neural Engineering. 6 (3): 035008. doi:10.1088/1741-2560/6/3/035008. PMID 19458397.

External links

• Research Fact Sheet ~ Retinal Prostheses