Gislin Dagnelie

Visual perception in a blind subject with a chronic microelectronic retinal prosthesis

A retinal prosthesis was permanently implanted in the eye of a completely blind test subject. This report details the results from the first 10 weeks of testing with the implant subject. The implanted device included an extraocular case to hold electronics, an intraocular electrode array (platinum disks, 4 x 4 arrangement) designed to interface with the retina, and a cable to connect the electronics case to the electrode array. The subject was able to see perceptions of light (spots) on all 16 electrodes of the array. In addition, the subject was able to use a camera to detect the presence or absence of ambient light, to detect motion, and to recognize simple shapes.

Retinal prosthesis for the blind

Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task

Background/aims To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. Methods High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19″ (48.3 cm) touch screen monitor located 12″ (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. Results Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. Conclusion In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss

Background Retinal prosthesis systems (RPS) are a novel treatment for profound vision loss in outer retinal dystrophies. Ideal prostheses would offer stable, long-term retinal stimulation and reproducible spatial resolution in a portable form appropriate for daily life. Methods We report a prospective, internally controlled, multicentre trial of the Argus II system. Twenty-eight subjects with light perception vision received a retinal implant. Controlled, closed-group, forced-choice letter identification, and, open-choice two-, three- and four-letter word identification tests were carried out. Results The mean±SD percentage correct letter identification for 21 subjects tested were: letters L, T, E, J, F, H, I, U, 72.3±24.6% system on and 17.7±12.9% system off; letters A, Z, Q, V, N, W, O, C, D, M, 55.0±27.4% system on and 11.8%±10.7% system off, and letters K, R, G, X, B, Y, S, P, 51.7±28.9% system on and 15.3±7.4% system off. (p<0.001 for all groups). A subgroup of six subjects was able to consistently read letters of reduced size, the smallest measuring 0.9 cm (1.7°) at 30 cm, and four subjects correctly identify unrehearsed two-, three- and four-letter words. Average implant duration was 19.9 months. Conclusions Multiple blind subjects fitted with the Argus II system consistently identified letters and words using the device, indicating reproducible spatial resolution. This, in combination with stable, long-term function, represents significant progress in the evolution of artificial sight.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind

PURPOSE Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.

PURPOSE To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS The patients vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

Understanding the origin of visual percepts elicited by electrical stimulation of the human retina

Abstract · Background: The success of a retinal prosthesis for patients with outer retinal degeneration (ORD) depends on the ability to electrically stimulate retinal cells other than photoreceptors. Experiments were undertaken in human volunteers to ascertain whether electrical stimulation of cells other than photoreceptors will result in the perception of light. · Methods: In two subjects, two areas of laser damage (argon green and krypton red) were created in an eye scheduled for exenteration due to recurrent cancer near the eye. In the operating room prior to exenteration, under local anesthesia, a hand-held stimulating device was inserted via the pars plana and positioned over the damaged areas and normal retina. Subjects’ psychophysical responses to electrical stimulation were recorded. · Results: In both subjects, electrical stimulation produced the following perceptions. Normal retina: dark oval (subject 1), dark half-moon (subject 2); krypton red laser-treated retina: small, white light (both subjects); argon green laser-treated retina: thin thread (subject 1), thin hook (subject 2). Histologic evaluation of the krypton red-treated retina showed damage confined to the outer retinal layers, while the argon green-treated area evinced damage to both the outer and the inner nuclear layers · Conclusion: The perception produced by electrical stimulation was dependent on the retinal cells present. Electrical stimulation of the krypton red-ablated area best simulated the electrically elicited visual perceptions of our blind, ORD patients, suggesting that the site of stimulation in blind patients is the inner retinal neurons.

Preliminary 6 month results from the argus tm ii epiretinal prosthesis feasibility study

The Argus™ II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.

Are lutein and zeaxanthin conditionally essential nutrients for eye health

The carotenoids lutein and zeaxanthin are found in the macula in high concentrations and may play a role in the pathogenesis of age-related macular degeneration (ARMD). Lutein and zeaxanthin may protect the macula and photoreceptor outer segments throughout the retina from oxidative stress and play a role in an antioxidant cascade that safely disarms the energy of reactive oxygen species. Although lutein and zeaxanthin are not essential nutrients, studies are beginning to suggest that they fit the criteria for conditionally essential nutrients. Low plasma lutein and zeaxanthin concentrations or dietary intake are associated with low macular pigment density and increased risk of ARMD. Dietary deprivation of lutein and zeaxanthin in primates causes pathological changes in the macula. Should controlled clinical trials show lutein and/or zeaxanthin supplementation protects against the development or progression of ARMD and other eye diseases, then lutein and zeaxanthin could be considered as conditionally essential nutrients for humans.

The functional performance of the Argus II retinal prosthesis.

Visual prostheses are devices to treat profound vision loss by stimulating nerve cells anywhere along the visual pathway, typically with electrical pulses. The Argus® II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA, USA), targets the retina and features 60 electrodes that electrically stimulate the surviving retinal neurons. Of the approximately 20 research groups that are actively developing visual prostheses, SSMP has the longest track record. The Argus II was the first visual prosthesis to become commercially available: it received the European conformity mark in 2011 and FDA approval was granted in early 2013 for humanitarian use in the USA. Meanwhile, the Argus II safety/benefit study has been extended for research purposes, and is still ongoing. In this review, we will discuss the performance of the Argus II in restoring sight to the blind, and we will shed light on its expected developments in the coming years.