FEATURE Retinal prosthetics: science fiction or a vision for the future? BY ADAM YOUNG “Is it a fact – or have I dreamt it – that, by means of electricity, the world of matter has become a great nerve, vibrating thousands of miles in a breathless point of time?” – Nathaniel Hawthorne, The House of the Seven Gables (1851) n the 1987 film Predator, the formidable alien has the power of invisibility, to travel between stars and to hunt using Isuperhuman thermal vision. Visual prostheses – or bionic eyes – provide artificial electronic visual sensation to the brain. In most senses, this relates to simulating normal physiological capabilities. But it can also signify surpassing the ordinary function of eye, for example, by acquiring the performance- enhancing qualities of a fictional extraterrestrial species. Although a number of strategies have been trialled for restoring vision, for instance, stem cell transplantation and gene therapy, one of the contemporary approaches has been to artificially replace the dysfunctional neuronal components that generate the optic pathway from the eye to the brain. Surgically implanting electrode arrays into the retina enables the human eye to convert light into electrical Figure 1: The Argus® II Retinal Prosthesis System. © Second Sight. signals. These are then passed to retinal ganglion cells for processing [1]. – where no adequate therapies currently electrode is implanted between the retinal An intact functional visual pathway exist – are thus likely to benefit. Where pigment epithelium and malfunctioning from the retina to the brain is required for the structural integrity of the retina is photoreceptors; an epiretinal approach may traditional retinal prostheses. Patients compromised, however, or in abnormal early equally be used with an implant affixed onto with inherited retinal degenerative disease, visual development, a retinal prosthesis is the retinal surface, at the ganglion cell layer. such as retinitis pigmentosa (RP), and dry unlikely to be effective. Animal models of retinal prostheses have age-related macular degeneration (AMD) demonstrated promise in restoring vision. How do bionic eyes work? In a model of retinitis pigmentosa in rats, an Conceptually, a prosthesis could be organic semiconductor retinal prosthesis inserted at any given juncture in the visual successfully underwent implantation in pathway. In one prototype, a small camera vivo leading to a significant and persistent “Further research is is mounted on a pair of glasses to capture recovery of light-sensitivity and visual acuity needed to identify which images. These signals are transposed [3]. Likewise, in photoreceptor-degenerated initially from a microprocessor, which mouse models, subretinal implants have patients are likely to converts data into electrical signals, and demonstrated spatially and temporally benefit from prosthetics subsequently to a microelectrode array restricted retinal ganglion cell response implanted on the retina. After preliminary patterns [4]. and, importantly, at what processing, the signal is transmitted Alternative techniques depend on an stage the device should be along the optic nerve to the brain to implant which transmits images directly ultimately construct a retinotopic visual to the occipital cortex in patients with introduced” image [2]. In the subretinal method, an acquired visual impairment. Directly Eye News | DECEMBER/JANUARY | VOL 26 NO 4 | www.eyenews.uk.com FEATURE activating neurons, via a surgical implant in the brain, has the potential to bypass damaged retinal cells in the eye completely [5]. These cortical visual prostheses do not rely on a working optic nerve and could therefore open this technology up to patients with virtually all causes of acquired blindness, regardless of the ocular pathology. What’s currently available? Worldwide, there are a number of emerging systems. Most devices have focused on patients with degenerative retinopathy, such as RP and AMD. Although a wealth of technology is materialising, many models are at early stages of development and, so far, few have received commercial market approval. The Argus® II Retinal Prosthesis System, developed by Second Sight, is an epiretinal device consisting of a video camera mounted on glasses, a portable visual processing unit, and a wireless 60-electrode Figure 2: The PRIMA photovoltaic subretinal implant. © Pixium Vision. stimulating array [6]. It superseded the first- generation model, Argus I, a 16-electrode with a best measurement of 20/546 on – studied in animal experiments – which modified cochlear implant. In 2011, it was contrast-reversal Landolt-C testing [7], may offer superior biocompatibility [3]. the first retinal prosthesis in Europe to although the manufacturer Retina Implant Risks associated with both the device receive certification mark (CE) approval AG has since ceased trading. Of the 29 and implant surgery can be anticipated and for commercial use. It later received Food participants enrolled in the trial, with the safety profile of retinal prosthetics has & Drug Administration (FDA) regulatory advanced RP or cone-rod dystrophies, been monitored closely over the years. For approval in the US in 2013. Alpha IMS, 25 (86%) could perceive light and six the initial 30 patients in the Argus® II trial, created by Retina Implant AG in Germany, subjects could detect motion. In addition, approximately one third experienced a has also gained European CE marking [7]. 45% of patients reported useful daily serious adverse event in the first three years It is comprised of a wirelessly-powered, life experiences with the implant. There [10]. Complications included conjunctival subretinal microchip with 1500 photodiodes; remains nonetheless large variation in visual erosion (four), hypotony (four), culture- this photosensitive array stimulates the outcomes – including motion detection, negative presumed endophthalmitis (three) bipolar cell layer in the retina. target localisation, form discrimination and and retinal detachment (two). For one Two devices are being developed by orientation / mobility – between patients patient, requiring treatment for recurrent Pixium Vision but are yet to gain commercial with all devices. conjunctival erosion, the implant was approval. The Iris® II Bionic Vision System removed. Most events occurred during is an epiretinal device, incorporating 150 What are the risks and possible the first year and, encouragingly, at five electrodes, which is undergoing initial safety long-term effects? years post-implant, 60% of participants studies in a small number of subjects [8]. Constraints on the hardware and software of experienced no device-related adverse PRIMA is a photovoltaic subretinal implant devices may ultimately limit longevity. Likely events. In addition, 24 of the 30 devices which delivers images to the eye in bursts of as a result of stress on biological tissue, remained implanted and functioning at five near-infrared light. Researchers at Stanford compared to their epiretinal counterparts, years. Beyond this, the longer-term risks University are piloting the device in patients subretinal systems appear to have a shorter are unknown and it is recommended that with geographic atrophy from advanced dry lifespan. The current required for the patients with new devices are followed up at AMD [9]. complex arrangement of inductive coils is least annually. in the region of 50mA [12] and scientists What are the results? are cautious of destructive in vivo heat What obstacles have emerged? Argus® II has allowed patients with RP to see generation. Extrapolating the progress Outputs from artificial visual devices geometric shapes and high-contrast letters in restoring visual function, based on the may contrast significantly from normal in black and white after total loss of central number of electrodes, a higher density array vision. Electrical stimulation typically vision [6]. The best grating visual acuity with upwards of a thousand electrodes elicits discrete light sensations, called achieved with the device to date is logMAR could theoretically restore the patient’s phosphenes, which are described as images 1.8 (Snellen equivalent of 20/1262). At five ability to recognise faces and read large in a number of different shapes. Measuring years, the benefits of the system have been print. Difficulties arise in obtaining such the success of these devices has thus been a favourable [10] and feasibility trials have fine resolution with the existing hardware contentious issue and employing a battery now been extended to evaluate the device given the dangerous charge density of of tests, including psychophysical tests, in patients with severe dry AMD who are such sophisticated circuit architecture [2]. performance in day-to-day activities and considered legally blind [11]. Electrical engineers are exploring novel subjective patient evaluation, has been Alpha IMS has established the highest heat-resistant materials, such as liquid suggested [14]. These measures differ from single subject visual acuity of any device, crystal polymers [13] and organic conductors conventional visual acuity and field tests, Eye News | DECEMBER/JANUARY | VOL 26 NO 4 | www.eyenews.uk.com FEATURE in order to detect smaller tangible changes to a discernible reality. Although emulating TAKE HOME MESSAGE associated with ultra-low levels of vision, Predator’s aptitude for interstellar travel and better reflect quality of life. Further seems unlikely, the evolution of bionic eyes • Retinal prosthetics, or