ReviewAn update on retinal prostheses
Introduction
Blindness and vision loss are among the most feared sensory disabilities (Chader et al., 2009). Unfortunately, despite the advances of modern medicine, millions of people around the world are experiencing the challenges that can come with severe vision loss. The field of vision restoration research is working to help these people, through the development of interventions specific to each indication, such as gene therapy, stem cells, optogenetics, vision restoration training, non-invasive stimulation, and vision prostheses. The latter is indicated for severe vision loss arising from degenerative retinal disease and is the subject of this review.
Over the past 30 years, technology has advanced to the point where it is now possible to implant electronic devices into the visual pathway to restore some version of sight. These devices, known as vision prostheses, can be implanted anywhere along the visual pathway; retina, optic nerve, lateral geniculate nucleus or visual cortex (Fig. 1). Whilst there are advantages and disadvantages of all locations, many devices to date have been implanted in or near the retina, or within the confines of the ocular globe. Devices in these positions may benefit from the geometric representation of the world at the retinal level and from residual retinal processing, although this is still to be proven conclusively. Retinal prostheses are also relatively easy to access surgically.
To date, retinal prostheses have been implanted in patients with either inherited retinal degenerations (such as retinitis pigmentosa, RP) or age-related degenerative disease (such as atrophic age-related macular degeneration, AMD). In these conditions, the photoreceptors in the outer layers of the retina are damaged or lost, but the inner retinal neurons (bipolar and ganglion cells) remain relatively intact (Santos et al., 1997). This means that the devices can stimulate residual elements of the visual pathway, to restore basic vision to participants.
From early crude experiments of electrical stimulation of the visual pathway (Foerster, 1929), we now are at a time in history when retinal prostheses have been approved by regulatory authorities for people with profound vision loss. However, many challenges of the field have not been surmounted. The aim of this review is to provide an overview of the relevant anatomy and physiology involved with retinal prostheses, and the retinal remodeling that occurs during retinal disease (and how that can complicate the visual outcomes of prostheses). We will provide a history of retinal prosthesis development since the 1920s, and report on the current technical capabilities and limitations. Finally, we will offer a glimpse of what the future for retinal prostheses may hold, and the manner in which multi-disciplinary groups around the world are working together to improve sight for millions of people with profound vision loss.
Section snippets
Basic retinal anatomy and physiology
Retinal prostheses aim to replace the function of photoreceptors in a degenerate eye, and hence restore vision. However, there are challenges in this aim. In part, this is due to the complexity of retinal processing which the devices aim to replicate.
Vision begins when the optics of the eye project spatio-temporal patterns of light into the deepest layer of a thin sheet of neural tissue called the retina, lining the back of the eye. There, light-sensitive molecules called photopigments, located
Retinal remodelling in degenerative disease
Another significant challenge in the development of retinal prostheses is the fact that the retina does not maintain its layered structure and clearly defined functions during disease processes. As such, it is important to have an understanding of the remodeling that can occur in retinal degeneration, and what that can mean for retinal prosthesis design.
The earliest clinical manifestations of retinal degenerative disease depend upon the initiating mechanism(s) and the retinal cell types
History of retinal prostheses
Before delving into the current state of play in this field, it is useful to have an understanding of the history. The first experiments using electricity to stimulate the visual pathway, and hence restore some degree of vision, were completed using direct cortical stimulation. In the 1700s, the French chemist and physician Charles Le Roy attempted to use crude transcranial electrical stimulation to cure a patient’s blindness (Uhlig et al., 2001). With repeated stimulation, the patient briefly
Basic mechanism of action of retinal prostheses
Retinal prostheses utilise engineered devices to replace the function of the damaged or missing photoreceptors in the retina. They can do this either via direct electrical stimulation, where a current is directed to electrodes implanted in or near the retina (Humayun et al., 2003, Ayton et al., 2014, Fujikado et al., 2016), or via photodiodes (Zrenner et al., 2011, Lorach et al., 2015), which utilise incident light to trigger the electrical stimulation.
In direct electrical stimulation, the
Image perception with a retinal prosthesis
Patients implanted with retinal prostheses can see light patterns of monochromatic dots, or “phosphenes”. The quality of the perceived image depends on a number of factors, including the number of electrodes/photodiodes on the implant, the stimulation strategies implemented, and the levels of greyscale that can be identified by the patient.
In short, if a patient looks at a cup with a camera-based (e.g., epiretinal) device, the camera first captures an image of the cup. The gain of the image is
Types of retinal prosthesis
Distinguished by surgical approach, there are four types of retinal prostheses; epiretinal prostheses (in which electrodes are placed on the retina), subretinal prostheses (in which electrodes are placed beneath the retina), suprachoroidal prostheses (in which electrodes are placed in the suprachoroidal space) and intrascleral prostheses (where the electrodes are placed within a pocket in the sclera); Fig. 2.
Engineering considerations in retinal prostheses
To achieve measurable vision outcomes from retinal prostheses, as described in the previous sections, there are a number of engineering, retinal stimulation and image processing aspects that need to be considered in device design and system implementation.
An electronic retinal prosthesis must perform several basic functions in order to replace the sense of vision. First, it must detect light in the nearby environment of the implant patient. Secondly, the light must be converted to an electrical
Retinal stimulation strategies
No matter the engineering design, all retinal prostheses need to activate retinal cells in order to generate phosphenes, the visual percepts that make up prosthetic vision.
It has been the historical custom to contrast epiretinal with subretinal electrodes as stimulating either retinal ganglion cells (RGCs) or bipolar cells (BCs), respectively. This oversimplification, however, has given rise to the mistaken impression that subretinal electrodes cannot stimulate RGCs directly and that epiretinal
Image processing
Use of an external camera, worn on glasses or goggles, and a processing unit makes possible the implementation of image processing algorithms that can enhance and/or simplify an image, to account for the low-resolution of retinal protheses. Image processing has been defined as hardware or software operations that transform visual data from the sensor to perceptual parameters that are coded as stimulation (Barnes et al., 2016).
Real-time image processing is necessary, since the subjects will be
Retinal implant surgery
This section will provide an overview of the surgical techniques required for retinal prostheses. Of course, different devices have specific surgical methods (which would be too lengthy to detail in full); instead, we will provide a high-level discussion of the surgical requirements.
To date, chronic clinical implantations have been completed on ten devices, as detailed in Table 1.
All retinal implants require a vitreoretinal surgeon to implant the device. An operation known as a “3-port pars
Clinical psychophysics
Following a period of recovery post-surgery, the electrical device parameters must be personalized to the recipient. Although retinal implants may specify tens or hundreds of electrodes, the proximity of the electrodes to the target neurons, as well as density and interconnectedness of remaining viable inner retinal neurons will greatly affect the efficacy of stimulation and the quality of the visual perception. Variation between recipients can include duration of blindness, retinal health,
Visual function and functional vision testing
Once the basic psychophysical tests have been completed with the retinal implant, and the optimal device parameters have been set, it is possible to measure visual function outcomes for the patient.
Visual function is a broad term, as natural human vision has many aspects and all of them contribute to the functionality of vision. The most important ones are visual acuity and visual field, but contrast discrimination, dark adaptation and color vision as well as movement perception are essential
Patient reported outcome (PRO) questionnaires
Clinical outcome measures, and even standardized functional performance measures (as described in the previous section) do not comprehensively capture the range of a person's activities of daily living (ADLs). The prosthesis wearer's subjective experience of benefit may not be captured by such measures, and is difficult to capture in a quantifiable way that allows comparison among wearers of a single retinal implant, let alone different prosthesis systems, or vision restoration attempts brought
Conclusion
The field of retinal prostheses has developed rapidly over the past three decades, and advances have been significant. Within this time frame, we have moved from theoretical musings to the commercial availability of three retinal prosthesis devices, albeit not without commercial challenges. The two manufacturers with the largest patient base, Retina Implant AG and Second Sight Medical Products, have recently withdrawn their current offerings from the market, with the latter now conducting
Funding and Declaration of Competing Interest
LA receives licensing royalties for purchase by commercial entities for the IVI-VLV tool and is supported by a NHMRC Next Generation Fellowship (1151055) and an NHMRC Project Grant (1082358). GD is a consultant to Second Sight Medical Products (USA), and receives licensing royalties for purchase by commercial entities for the ULV-VFQ tool. JW is a consultant to Second Sight Medical Products (USA). BJ is supported by NIH grants R01 EY015128, R01 EY028927, a P30 EY014800 Vision Core Grant and an
Acknowledgements
The authors would like to acknowledge Dr Alfred Stett, OkuVision GmBH (Germany) for his helpful review of this manuscript.
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