• Gerald J Chader, James Weiland, and Mark S Humayun.
• Doheny Retina Institute, USC School of Medicine, Los Angeles, CA, USA. gchader@doheny.org
• Prog. Brain Res. 2009 Jan 1; 175: 317-32.

AbstractHundreds of thousands around the world have poor vision or no vision at all due to inherited retinal degenerations (RDs) like retinitis pigmentosa (RP). Similarly, millions suffer from vision loss due to age-related macular degeneration (AMD). In both of these allied diseases, the primary target for pathology is the retinal photoreceptor cells that dysfunction and die. Secondary neurons though are relatively spared. To replace photoreceptor cell function, an electronic prosthetic device can be used such that retinal secondary neurons receive a signal that simulates an external visual image. The composite device has a miniature video camera mounted on the patient's eyeglasses, which captures images and passes them to a microprocessor that converts the data to an electronic signal. This signal, in turn, is transmitted to an array of electrodes placed on the retinal surface, which transmits the patterned signal to the remaining viable secondary neurons. These neurons (ganglion, bipolar cells, etc.) begin processing the signal and pass it down the optic nerve to the brain for final integration into a visual image. Many groups in different countries have different versions of the device, including brain implants and retinal implants, the latter having epiretinal or subretinal placement. The device furthest along in development is an epiretinal implant sponsored by Second Sight Medical Products (SSMP). Their first-generation device had 16 electrodes with human testing in a Phase 1 clinical trial beginning in 2002. The second-generation device has 60+ electrodes and is currently in Phase 2/3 clinical trial. Increased numbers of electrodes are planned for future versions of the device. Testing of the device's efficacy is a challenge since patients admitted into the trial have little or no vision. Thus, methods must be developed that accurately and reproducibly record small improvements in visual function after implantation. Standard tests such as visual acuity, visual field, electroretinography, or even contrast sensitivity may not adequately capture some aspects of improvement that relate to a better quality of life (QOL). Because of this, some tests are now relying more on "real-world functional capacity" that better assesses possible improvement in aspects of everyday living. Thus, a new battery of tests have been suggested that include (1) standard psychophysical testing, (2) performance in tasks that are used in real-life situations such as object discrimination, mobility, etc., and (3) well-crafted questionnaires that assess the patient's own feelings as to the usefulness of the device. In the Phase 1 trial of the SSMP 16-electrode device, six subjects with severe RP were implanted with ongoing, continuing testing since then. First, it was evident that even limited sight restoration is a slow, learning process that takes months for improvement to become evident. However, light perception was restored in all six patients. Moreover, all subjects ultimately saw discrete phosphenes and could perform simple visual spatial and motion tasks. As mentioned above, a Phase 2/3 trial is now ongoing with a 60+ device. A 250+ device is on the drawing board, and one with over 1000 electrodes is being planned. Each has the possibility of significantly improving a patient's vision and QOL, being smaller and safer in design and lasting for the lifetime of the patient. From theoretical modeling, it is estimated that a device with approximately 1000 electrodes could give good functional vision, i.e., face recognition and reading ability. This could be a reality within 5-10 years from now. In summary, no treatments are currently available for severely affected patients with RP and dry AMD. An electrical prosthetic device appears to offer hope in replacing the function of degenerating or dead photoreceptor neurons. Devices with new, sophisticated designs and increasing numbers of electrodes could allow for long-term restoration of functional sight in patients with improvement in object recognition, mobility, independent living, and general QOL.

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