Retinal Implants: A Systematic Review
Table 1 summarises characteristics of the five devices selected for significant development in clinical availability, vision restoration potential or long-term biocompatibility.
Clinical Availability. Of the analysed retinal implants, Argus II was the first approved device in clinical trials in both the US (FDA phase 4 postmarket surveillance) and Europe (phase IV, European CE marking). The first-generation model, Argus I, consisted of a 16-electrode array and was implanted in six subjects. Argus II consists of a 60-electrode array and has been implanted in 30 subjects for up to 38.3 months, with 94.4% of electrodes retaining function throughout their study. Twenty-nine patients continued home use of the device.
Vision Restoration. Testing included locating objects, identifying motion direction, reading letters and orientation and mobility tasks. Of 28 patients, 16–28 performed better with the implant on versus off with an estimated visual field of 20°. The highest achieved visual acuity ranged from logMAR 1.6 to 2.9, with letter reading measured at 20/1262. Furthermore, tracing paths on touchscreens with auditory feedback had higher accuracy but longer times with the implant on; this demonstrates potential learning and reactivating of the visual pathway.
Long-term Biocompatibility. The Argus II design incorporates transcleral cables, which may increase risk of infection. Image processing is as follows: data from the external camera are transferred to a processor and transmitter coil, then wirelessly to an electronics case. The electronics case is connected by a transcleral cable to the epiretinal implant, which is held in place with retinal tacks. While external electronics allow simpler technical updates and troubleshooting, long-term infectious complications may be more frequent with transcleral cables. In 30 subjects, there were 9 SAE, including conjunctival erosion, endophthalmitis and hypotony. All were successfully treated without permanent complications, and only one patient did not continue in the trial. SAE rate was decreased in later surgeries.
Vision Restoration. While not yet in humans trials, the Boston Retinal Implant may have the highest pixel resolution among devices using external cameras. This 100-electrode array prosthesis has been implanted in two minipigs for 3 and 5 months, respectively. Subretinal insertion is surgically more difficult, but this allows smoother integration with existing neuronal pathways. Power and data delivery successfully elicited electric current response in the electrodes at the eye surface, with reference electrodes at the ear.
In future research, glasses frames with an external camera will wirelessly provide image data and power to an electronics case. Transcleral cables connect this electronic case to the subretinal implant, similar to the epiretinal Argus II. In this model, special attention has been paid to developing a hermetic casing for the extrascleral electronics, as well as a ceramic feedthrough for the transcleral cables. Together with the higher electrode number, this implant may be considered more advanced from an engineering perspective. However, during animal trials the prosthesis wore through the conjunctiva, exposing the electronics and necessitating explantation. Improving biocompatibility will require additional development.
Clinical Availability. The Epi-Ret 3 is under clinical trials in Europe, with six subjects implanted for 28 days each. Electronic stimulation produced visual perceptions in patients, who were encouraged to describe the experiences and identify unknown objects. At device explantation, some tacks were loose and growth of epiretinal membranes was observed. At 2-year follow-up, gliosis appeared near tacked sites, but no change in quality of life was noted.
Long-term Biocompatibility. Future development encompasses glasses with an external camera for wireless data and power transfer to a receiver module. However, this receiver module is part of a completely intraocular device, unlike other implants. The receiver module is positioned in place of the lens and connects to the epiretinally tacked 25-electrode array. With no transcleral cable, long-term risks of complication may be lower; no SAE were reported. However, visual testing and higher resolution will be needed before implant success can be determined.
Clinical Availability. The intelligent medical implants (IMI) retinal implant is in clinical trials in Europe. The most recent study consisted of temporarily implanting 20 subjects each for 45 min, during which the device was handheld in place for electronic stimulation and patients were able to identify and describe phosphenes, or light perception. Previous studies used arrays with 49 electrodes, in which three subjects retained the prosthesis for 30 months.
Long-term Biocompatibility. IMI uses an external camera for image capture with wireless data and power transfer. Similar to Argus II (epiretinal) and the Boston Retinal Implant (subretinal), receiver electronics connect via a scleral tunnel to this epiretinal implant. Uniquely, the IMI device includes a retina encoder that allows individual calibration, attained through a series of repetitive adjustments upon device implantation to optimise each patient's visual perception. This may help overcome neural remodelling after decades of disuse, as visual perceptions can be shaped to match physical reality. Fewer than 100 iterations have been necessary in testing, presenting a practical approach to improving implant success rates. One case of retinal detachment was reported; no SAE have been reported.
Clinical Availability. Alpha-IMS has received the European CE marking, with additional clinical trials in Europe and Hong Kong. Early models incorporated a transdermal power supply, which limited the study to 126 days. In later trials, wireless battery power removed the time constraint, allowing patients to retain the device indefinitely. An algorithm that calculates optimal implant position has also been developed, improving the device–tissue interface.
Vision Restoration. In the most recent clinical trial, 19 patients were implanted. Visual testing was performed on eight over 3–9 months. Tests included letter recognition, identifying and localising household objects, and light/motion detection. Over a visual field of 15°, the highest achieved visual acuity was logMAR 1.43, Snellen 20/546 as measured using Landolt Cs. As image acquisition is achieved intraocularly, the working frequency of the implant, ranging 5 to 7 Hz, was individually optimised to avoid object fading in visual perception. Microsaccades were additionally observed to help prevent visual fading.
Long-term Biocompatibility. Unlike all other discussed devices, Alpha-IMS does not depend on an external camera. Instead, the subretinal implant is a 1500-pixel multiphotodiode array. Each of the 1500 pixels consists of a light-sensing photodiode that responds to ambient light entering the eye. Signals are amplified and transferred to local electrodes, stimulating the geographic region corresponding to phosphene detection. While image acquisition is solely intraocular, a cable connects the implant to a subdermal power control unit, which charges wirelessly through a handheld control unit that enables light-sensitivity adjustment. This wireless intraocular model closely mimics natural vision but also requires more advanced design. The most recent trial showed corrosion of the hermetic seal and one SAE of subretinal bleeding that increased intraocular pressure (IOP), indicating need for further biocompatibility modification.
Results
Table 1 summarises characteristics of the five devices selected for significant development in clinical availability, vision restoration potential or long-term biocompatibility.
Argus II
Clinical Availability. Of the analysed retinal implants, Argus II was the first approved device in clinical trials in both the US (FDA phase 4 postmarket surveillance) and Europe (phase IV, European CE marking). The first-generation model, Argus I, consisted of a 16-electrode array and was implanted in six subjects. Argus II consists of a 60-electrode array and has been implanted in 30 subjects for up to 38.3 months, with 94.4% of electrodes retaining function throughout their study. Twenty-nine patients continued home use of the device.
Vision Restoration. Testing included locating objects, identifying motion direction, reading letters and orientation and mobility tasks. Of 28 patients, 16–28 performed better with the implant on versus off with an estimated visual field of 20°. The highest achieved visual acuity ranged from logMAR 1.6 to 2.9, with letter reading measured at 20/1262. Furthermore, tracing paths on touchscreens with auditory feedback had higher accuracy but longer times with the implant on; this demonstrates potential learning and reactivating of the visual pathway.
Long-term Biocompatibility. The Argus II design incorporates transcleral cables, which may increase risk of infection. Image processing is as follows: data from the external camera are transferred to a processor and transmitter coil, then wirelessly to an electronics case. The electronics case is connected by a transcleral cable to the epiretinal implant, which is held in place with retinal tacks. While external electronics allow simpler technical updates and troubleshooting, long-term infectious complications may be more frequent with transcleral cables. In 30 subjects, there were 9 SAE, including conjunctival erosion, endophthalmitis and hypotony. All were successfully treated without permanent complications, and only one patient did not continue in the trial. SAE rate was decreased in later surgeries.
Boston Retinal Implant
Vision Restoration. While not yet in humans trials, the Boston Retinal Implant may have the highest pixel resolution among devices using external cameras. This 100-electrode array prosthesis has been implanted in two minipigs for 3 and 5 months, respectively. Subretinal insertion is surgically more difficult, but this allows smoother integration with existing neuronal pathways. Power and data delivery successfully elicited electric current response in the electrodes at the eye surface, with reference electrodes at the ear.
Long-term Biocompatibility
In future research, glasses frames with an external camera will wirelessly provide image data and power to an electronics case. Transcleral cables connect this electronic case to the subretinal implant, similar to the epiretinal Argus II. In this model, special attention has been paid to developing a hermetic casing for the extrascleral electronics, as well as a ceramic feedthrough for the transcleral cables. Together with the higher electrode number, this implant may be considered more advanced from an engineering perspective. However, during animal trials the prosthesis wore through the conjunctiva, exposing the electronics and necessitating explantation. Improving biocompatibility will require additional development.
Epi-Ret 3
Clinical Availability. The Epi-Ret 3 is under clinical trials in Europe, with six subjects implanted for 28 days each. Electronic stimulation produced visual perceptions in patients, who were encouraged to describe the experiences and identify unknown objects. At device explantation, some tacks were loose and growth of epiretinal membranes was observed. At 2-year follow-up, gliosis appeared near tacked sites, but no change in quality of life was noted.
Long-term Biocompatibility. Future development encompasses glasses with an external camera for wireless data and power transfer to a receiver module. However, this receiver module is part of a completely intraocular device, unlike other implants. The receiver module is positioned in place of the lens and connects to the epiretinally tacked 25-electrode array. With no transcleral cable, long-term risks of complication may be lower; no SAE were reported. However, visual testing and higher resolution will be needed before implant success can be determined.
Intelligent Medical Implants
Clinical Availability. The intelligent medical implants (IMI) retinal implant is in clinical trials in Europe. The most recent study consisted of temporarily implanting 20 subjects each for 45 min, during which the device was handheld in place for electronic stimulation and patients were able to identify and describe phosphenes, or light perception. Previous studies used arrays with 49 electrodes, in which three subjects retained the prosthesis for 30 months.
Long-term Biocompatibility. IMI uses an external camera for image capture with wireless data and power transfer. Similar to Argus II (epiretinal) and the Boston Retinal Implant (subretinal), receiver electronics connect via a scleral tunnel to this epiretinal implant. Uniquely, the IMI device includes a retina encoder that allows individual calibration, attained through a series of repetitive adjustments upon device implantation to optimise each patient's visual perception. This may help overcome neural remodelling after decades of disuse, as visual perceptions can be shaped to match physical reality. Fewer than 100 iterations have been necessary in testing, presenting a practical approach to improving implant success rates. One case of retinal detachment was reported; no SAE have been reported.
Alpha-IMS
Clinical Availability. Alpha-IMS has received the European CE marking, with additional clinical trials in Europe and Hong Kong. Early models incorporated a transdermal power supply, which limited the study to 126 days. In later trials, wireless battery power removed the time constraint, allowing patients to retain the device indefinitely. An algorithm that calculates optimal implant position has also been developed, improving the device–tissue interface.
Vision Restoration. In the most recent clinical trial, 19 patients were implanted. Visual testing was performed on eight over 3–9 months. Tests included letter recognition, identifying and localising household objects, and light/motion detection. Over a visual field of 15°, the highest achieved visual acuity was logMAR 1.43, Snellen 20/546 as measured using Landolt Cs. As image acquisition is achieved intraocularly, the working frequency of the implant, ranging 5 to 7 Hz, was individually optimised to avoid object fading in visual perception. Microsaccades were additionally observed to help prevent visual fading.
Long-term Biocompatibility. Unlike all other discussed devices, Alpha-IMS does not depend on an external camera. Instead, the subretinal implant is a 1500-pixel multiphotodiode array. Each of the 1500 pixels consists of a light-sensing photodiode that responds to ambient light entering the eye. Signals are amplified and transferred to local electrodes, stimulating the geographic region corresponding to phosphene detection. While image acquisition is solely intraocular, a cable connects the implant to a subdermal power control unit, which charges wirelessly through a handheld control unit that enables light-sensitivity adjustment. This wireless intraocular model closely mimics natural vision but also requires more advanced design. The most recent trial showed corrosion of the hermetic seal and one SAE of subretinal bleeding that increased intraocular pressure (IOP), indicating need for further biocompatibility modification.