In the last decade, retinal implants, or prostheses, have gone from futuristic research projects to reality. Devices have gained Food and Drug Administration approval in the United States and CE marking in Europe for the purpose of vision restoration in persons with advanced degenerative retinopathy. Several research groups have led the forefront of this field, as each approach to this elaborate engineering process encounters unique challenges.

The collective experience with retinal implant development has also shifted focus at different junctures to meet these challenges. From numerical, hardware-based, proof-of-principle experiments, emphasis is now moving towards optimizing the tissue-device interface of existing implants to improve patients’ quality of life. In particular, two devices with the most clinical availability, the Argus II (Second Sight Medical Products, Sylmar, Calif.) and Alpha IMS (Retina Implant AG, Reutlingen, Germany), demonstrate a modified trajectory in prosthetic research and serve as models for optimization of retinal implants.


Two retinopathies that have the greatest potential benefit from retinal implants are retinitis pigmentosa and age-related macular degeneration. Retinitis pigmentosa is a hereditary degenerative disease of the outer retina-retinal pigment epithelium complex, with relative sparing of the inner retina and upstream visual pathway. Visual impairment generally presents in early to mid-adulthood and can progress to hand-motion or light-perception visual acuity. Currently, there is no available disease-modifying treatment. Similarly, age-related macular degeneration, the most common cause of severe visual impairment in older adults, presently has no available cure. Typically, central vision is lost with sparing of peripheral vision, while visual processing is retained upstream.

Retinal implants have been primarily tested in patients with hand-motion or light-perception vision. They are placed in the worse eye, augmenting retinal tissue presumed minimally functional. Best attained visual acuity to date has been Snellen 20/546 by the Alpha IMS, though outcome emphasis is now shifting towards assessing functional improvement in daily life, using scores such as the Functional Low Vision Observer Rate Assessment (FLORA). Many research groups have developed distinct models of retinal implants, most of which are being studied in vitro or in animals. Only Argus II has received both FDA approval (2013) and CE marking (2011).1 Alpha IMS received CE marking in 2013.2

One means of classifying retinal implants is by insertion position—either epiretinal or subretinal. Epiretinal devices, such as the Argus II, are surgically more straightforward to place, but require stabilization by retinal tacks that increase rates of scarring and gliosis, or complicate implant removal. Functionally, these implants bypass the outer retina, interfacing directly with upstream neuronal cells. Subretinal devices, such as the Alpha IMS, are surgically more difficult to insert, but do not require tacks, as the natural forces within the eye tamponade the implant in position. Functionally, these devices aim to replace degenerated photoreceptor cells.

A second means of classifying retinal implants is by image-acquisition technology. External cameras are used in the Argus II, while intraocular photosensitive elements are used in the Alpha IMS. In both modalities, pixel number was initially thought to be a primary determinant of image quality. However, recent literature suggests that crosstalk between individual electrodes, distance from each electrode to interfacing tissue and frequency, rather than intensity of conduction, may play more important roles than previously believed. Further research should clarify the interaction among each of these factors. Currently, a multifactorial effect is assumed.

Argus II

The Argus II is the second-generation device by Second Sight, which has a collaborative affiliation with the University of Southern California. The system consists of an epiretinal implant, an episcleral image processor, an external camera and a battery pack. The Argus II was the first retinal implant to receive CE marking, and the only implant granted an FDA approval as a Humanitarian Use Device. Currently, it has been implanted in more than 70 patients. Research is ongoing, and has documented improvement in visual acuity (best achieved 20/1,262) and task completion with the 60-electrode array. Increased emphasis has been placed on functional improvements, using measurements such as the FLORA score.3,4

Common complications with the Argus II include conjunctival erosion and retinal tack gliosis (form of retinal scarring). Other complications include endophthalmitis, hypotony and retinal tears/detachment. Most of the complications occurred in patients involved in earlier studies; complication rates decreased with improved procedural protocols, clinical experience and device modification. The longest retention time for an implanted Argus II is 7.2 years, and for Argus I it is 10 years. Long-term biocompatibility is favorably reflected by these examples of visual improvement with stable safety profiles.5

Alpha IMS

The Alpha IMS has been developed by the Retina Implant AG group at the University of Tubingen, Germany, and has received CE marking. The device consists of a subretinal 1,500-photodiode array that interfaces with the bipolar cell layer of the inner retina, and a subdermal electronics case behind the ear. The current clinical trial consists of 29 patients, with increased success in visual tasks (best-achieved Snellen, 20/546) as the trial progressed.6 Although optimization of implant engineering and insertion was continued throughout the trial, researchers have theorized that a nontrivial portion of the functional restoration by subretinal implants may be from localized physical and electrical stimulation.7 Alterations in subretinal tissues through electrical stimulation (e.g., increased release of growth factors) may be a potential direction for further investigation.

The safety profile in the current Alpha IMS study showed the most common complications were conjunctival erosions and elevated intraocular pressure. Rarer complications were retinal tears/detachment, and one case of accidentally intraoperatively touching the optic nerve and perforation of the choroid. Similar to the Argus II, these complications decreased as the study progressed. Overall, more complications were associated with the initial implantation procedure, which is understandable given the higher complexity of subretinal compared to epiretinal insertion. The longest retention time for the Alpha IMS was 1.9 years.8

Better Outcomes, New Directions

With the recent clinical availability of retinal implants, translational research may be the ideal means by which to continue device development. Through the dynamic balance of updating research goals to match clinical needs, further optimization can continue to improve the utility of retinal implants. In many ways, this process has already begun: The objectives of research have moved from proof-of-principle and safety to achieving surgical finesse in maximizing implant benefit. Patient criteria have changed, as those with visual acuity below 20/800 may now be offered retinal implants in clinical trials in an effort to preserve more vision before it is lost.7 Methods of optimization of implants have additionally shifted from hardware to software, by focusing on reducing crosstalk between electrodes, increasing edge detection instead of brightness/contrast alone, and balancing conduction frequency to limit flickering without allowing image fading.2,7,9

Measurements of outcomes have moved from visual acuity, phosphene detection and detailed experimental tasks, to functional assays, such as the FLORA score in assessing the impact of retinal implants on patients’ daily life. Studies have also investigated Quality Adjusted Life Years with retinal implants, annual cost to care for patients disabled by retinitis pigmentosa (~$15,000), and estimated retinal implant cost (~$100,000 to $115,000). Given that the average age of disability in retinitis pigmentosa is in early to mid-adulthood, the cost-to-benefit ratio favors the devices. This trend should continue as outcomes improve and technical cost of production declines.10,11

To continue retinal implant development, researchers may find increased collaboration between research groups beneficial. Previously, this type of interaction was limited by the small number of clinical and pre-clinical devices. The proprietary nature of early product

development was another important concern. However, the opportunities to learn from shared experiences may now outweigh these obstacles. Research will tend to shift from physical parameters of designing and building devices to adjusting the electronic-tissue interface and maximizing the efficiency of systems already found to be biocompatible through prolonged clinical trials. This may include altering surgical techniques, which should be facilitated with each additional case performed, as demonstrated in decreasing complications over time in previous studies.

In summary, multiple devices have demonstrated significant benefit in controlled experimental settings, but these measures may be insufficient clinical surrogates as more advanced devices are developed. As research moves forward, greater emphasis on functional outcomes will be needed to fully appreciate the role and benefits of retinal implants.  REVIEW

Dr. Chuang is an internal medicine resident at the Santa Clara Valley Medical Center. Dr. Margo is a professor of ophthalmology, and pathology and cell biology at the Morsani College of Medicine, University of South Florida. Dr. Greenberg is a professor of surgery (ophthalmology) at the Warren Alpert Medical School of Brown University. Dr. Greenberg may be reached at:

Drs. Chuang, Margo and Greenberg all share a special interest in retinal prosthetic research and the processes by which new technologies become integrated into clinical practice. They declare no financial interest in any product discussed.

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