A retinal implant is a visual prosthesis for restoration of sight to patients blinded by retinal degeneration. The system is meant to partially restore useful vision to those who have lost their photoreceptors due to retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Retinal implants are being developed by a number of private companies and research institutions, and three types are in clinical trials: epiretinal (on the retina), subretinal (behind the retina), and suprachoroidal (between the choroid and the sclera). The implants introduce visual information into the retina by electrically stimulating the surviving retinal neurons. So far, elicited percepts had rather low resolution, and may be suitable for light perception and recognition of simple objects.
History Foerster was the first to discover that electrical stimulation of the occipital cortex could be used to create visual percepts, phosphenes. The first application of an implantable stimulator for vision restoration was developed by Drs. Brindley and Lewin in 1968. This experiment demonstrated the viability of creating visual percepts using direct electrical stimulation, and it motivated the development of several other implantable devices for stimulation of the visual pathway, including retinal implants. Retinal stimulation devices, in particular, have become a focus of research as approximately half of all cases of blindness are caused by retinal damage. The development of retinal implants has also been motivated in part by the advancement and success of cochlear implants, which has demonstrated that humans can regain significant sensory function with limited input.
The Argus II retinal implant, manufactured by Second Sight Medical Products received market approval in the US in Feb 2013 and in Europe in Feb 2011, becoming the first approved implant. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities. The epiretinal device is known as the Retina Implant and was originally developed in Germany by Retina Implant AG. It completed a multi-centre clinical trial in Europe and was awarded a CE Mark in 2013, making it the first wireless epiretinal electronic device to gain approval.
Candidates Optimal candidates for retinal implants have retinal diseases, such as retinitis pigmentosa or age-related macular degeneration. These diseases cause blindness by affecting the photoreceptor cells in the outer layer of the retina, while leaving the inner and middle retinal layers intact. Minimally, a patient must have an intact ganglion cell layer in order to be a candidate for a retinal implant. This can be assessed non-invasively using optical coherence tomography (OCT) imaging. Other factors, including the amount of residual vision, overall health, and family commitment to rehabilitation, are also considered when determining candidates for retinal implants. In subjects with age-related macular degeneration, who may have intact peripheral vision, retinal implants could result in a hybrid form of vision. In this case the implant would supplement the remaining peripheral vision with central vision information.
Types There are two main types of retinal implants by placement. Epiretinal implants are placed in the internal surface of the retina, while subretinal implants are placed between the outer retinal layer and the retinal pigment epithelium.
Epiretinal implants
Design principles Epiretinal implants are placed on top of the retinal surface, above the nerve fiber layer, directly stimulating ganglion cells and bypassing all other retinal layers. Array of electrodes is stabilized on the retina using micro tacks which penetrate into the sclera. Typically, external video camera on eyeglasses acquires images and transmits processed video information to the stimulating electrodes via wireless telemetry. An external transmitter is also required to provide power to the implant via radio-frequency induction coils or infrared lasers. The real-time image processing involves reducing the resolution, enhancing contrast, detecting the edges in the image and converting it into a spatio-temporal pattern of stimulation delivered to the electrode array on the retina. The majority of electronics can be incorporated into the associated external components, allowing for a smaller implant and simpler upgrades without additional surgery. The external electronics provides full control over the image processing for each patient.
Advantages Epiretinal implants directly stimulate the retinal ganglion cells, thereby bypassing all other retinal layers. Therefore, in principle, epiretinal implants could provide visual perception to individuals even if all other retinal layers have been damaged.
Disadvantages Since the nerve fiber layer has similar stimulation threshold to that of the retinal ganglion cells, axons passing under the epiretinal electrodes are stimulated, creating arcuate percepts, and thereby distorting the retinotopic map. So far, none of the epiretinal implants had light-sensitive pixels, and hence they rely on external camera for capturing the visual information. Therefore, unlike natural vision, eye movements do not shift the transmitted image on the retina, which creates a perception of the moving object when person with such an implant changes the direction of gaze. Therefore, patients with such implants are asked to not move their eyes, but rather scan the visual field with their head. Additionally, encoding visual information at the ganglion cell layer requires very sophisticated image processing techniques in order to account for various types of the retinal ganglion cells encoding different features of the image.
Clinical study The first epiretinal implant, the ARGUS device, included a silicon platinum array with 16 electrodes. The Phase I clinical trial of ARGUS began in 2002 by implanting six participants with the device. All patients reported gaining a perception of light and discrete phosphenes, with the visual function of some patients improving significantly over time. Future versions of the ARGUS device are being developed with increasingly dense electrode arrays, allowing for improved spatial resolution. The most recent ARGUS II device contains 60 electrodes, and a 200 electrode device is under development by ophthalmologists and engineers at the USC Eye Institute. The ARGUS II device received marketing approval in February 2011 (CE Mark demonstrating safety and performance), and it is available in Germany, France, Italy, and UK. Interim results on 30 patients long term trials were published in Ophthalmology in 2012. Argus II received approval from the US FDA on April 14, 2013 . Another epiretinal device, the Learning Retinal Implant, has been developed by IIP technologies GmbH, and has begun to be evaluated in clinical trials. A third epiretinal device, EPI-RET, has been developed and progressed to clinical testing in six patients. The EPI-RET device contains 25 electrodes and requires the crystalline lens to be replaced with a receiver chip. All subjects have demonstrated the ability to discriminate between different spatial and temporal patterns of stimulation.
Subretinal implants
Design principles
Subretinal implants sit on the outer surface of the retina, between the photoreceptor layer and the retinal pigment epithelium, directly stimulating retinal cells and relying on the normal processing of the inner and middle retinal layers. Adhering a subretinal implant in place is relatively simple, as the implant is mechanically constrained by the minimal distance between the outer retina and the retinal pigment epithelium. A subretinal implant consists of a silicon wafer containing light sensitive microphotodiodes, which generate signals directly from the incoming light. Incident light passing through the retina generates currents within the microphotodiodes, which directly inject the resultant current into the underlying retinal cells via arrays of microelectrodes. The pattern of microphotodiodes activated by incident light therefore stimulates a pattern of bipolar, horizontal, amacrine, and ganglion cells, leading to a visual perception representative of the original incident image. In principle, subretinal implants do not require any external hardware beyond the implanted microphotodiodes array. However, some subretinal implants require power from external circuitry to enhance the image signal.
Advantages A subretinal implant is advantageous over an epiretinal implant in part because of its simpler design. The light acquisition, processing, and stimulation are all carried out by microphotodiodes mounted onto a single chip, as opposed to the external camera, processing chip, and implanted electrode array associated with an epiretinal implant. The subretinal placement is also more straightforward, as it places the stimulating array directly adjacent to the damaged photoreceptors. By relying on the function of the remaining retinal layers, subretinal implants allow for normal inner retinal processing, including amplification, thus resulting in an overall lower threshold for a visual response. Additionally, subretinal implants enable subjects to use normal eye movements to shift their gaze. The retinotopic stimulation from subretinal implants is inherently more accurate, as the pattern of incident light on the microphotodiodes is a direct reflection of the desired image. Subretinal implants require minimal fixation, as the subretinal space is mechanically constrained and the retinal pigment epithelium creates negative pressure within the subretinal space.
Disadvantages The main disadvantage of subretinal implants is the lack of sufficient incident light to enable the microphotodiodes to generate adequate current. Thus, subretinal implants often incorporate an external power source to amplify the effect of incident light. The compact nature of the subretinal space imposes significant size constraints on the implant. The close proximity between the implant and the retina also increases the possibility of thermal damage to the retina from heat generated by the implant. Subretinal implants require intact inner and middle retinal layers, and therefore are not beneficial for retinal diseases extending beyond the outer photoreceptor layer. Additionally, photoreceptor loss can result in the formation of a membrane at the boundary of the damaged photoreceptors, which can impede stimulation and increase the stimulation threshold.
Clinical studies