Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa.

PURPOSE: Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. DESIGN: Case series. PARTICIPANTS: Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. METHODS: Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. MAIN OUTCOME MEASURES: Brightness and color of the electrically elicited visual perception reported by the subjects. RESULTS: Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. CONCLUSIONS: These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

Blockade of Retinal Oscillations by Benzodiazepines Improves Efficiency of Electrical Stimulation in the Mouse Model of RP, rd10.

Purpose: In RP, photoreceptors degenerate. Retinal prostheses are considered a suitable strategy to restore vision. In animal models of RP, a pathologic rhythmic activity seems to compromise the efficiency of retinal ganglion cell stimulation by an electrical prosthesis. We, therefore, strove to eliminate this pathologic activity. Methods: Electrophysiologic recordings of local field potentials and spike activity of retinal ganglion cells were obtained in vitro from retinae of wild-type and rd10 mice using multielectrode arrays. Retinae were stimulated electrically. Results: The efficiency of electrical stimulation was lower in rd10 retina than in wild-type retina and this was highly correlated with the presence of oscillations in retinal activity. Glycine and GABA, as well as the benzodiazepines diazepam, lorazepam, and flunitrazepam, abolished retinal oscillations and, most important, increased the efficiency of electrical stimulation to values similar to those in wild-type retina. Conclusions: Treatment of patients with these benzodiazepines may offer a way to improve the performance of retinal implants in cases with poor implant proficiency. This study may open the way to a therapy that supports electrical stimulation by prostheses with pharmacologic treatment.

Filtration of Short-Wavelength Light Provides Therapeutic Benefit in Retinitis Pigmentosa Caused by a Common Rhodopsin Mutation.

Purpose: The role of light exposure in accelerating retinitis pigmentosa (RP) remains controversial. Faster degeneration has however been observed in the inferior than superior retina in several forms ("sector" RP), including those caused by the rhodopsin P23H mutation, suggesting a modifying role of incident light exposure in such cases. Rearing of equivalent animal models in complete darkness has been shown to slow the degeneration. Here we investigate the use of red filters as a potential treatment strategy, with the hypothesis that minimizing retinal exposure to light <600 nm to which rods are maximally sensitive may provide therapeutic benefit. Methods: Knockin mice heterozygous for the P23H dominant rhodopsin mutation (RhoP23H/+) housed in red-tinted plastic cages were divided at weaning into either untinted or red-tinted cages. Subsequently, photoreceptor layer (PRL) thickness was measured by spectral-domain ocular coherence tomography, retinal function quantified by ERG, and cone morphology determined by immunohistochemical analysis (IHC) of retinal flatmounts. Results: Mice remaining in red-tinted cages had a significantly greater PRL thickness than those housed in untinted cages at all time points. Red housing also led to a highly significant rescue of retinal function as determined by both dark- and light-adapted ERG responses. IHC further revealed a dramatic benefit on cone morphology and number in the red- as compared with the clear-housed group. Conclusions: Limitation of short-wavelength light exposure significantly slows degeneration in the RhoP23H/+ mouse model. Red filters may represent a cost-effective and low-risk treatment for patients with rod-cone dystrophy in whom a sectoral phenotype is noted.

Association of Vitamin A Supplementation With Disease Course in Children With Retinitis Pigmentosa.

Importance: While oral vitamin A supplementation is considered to potentially slow loss of retinal function in adults with retinitis pigmentosa and normal liver function, little data from children with this disease are available. Objective: To compare disease courses in children with retinitis pigmentosa taking or not taking vitamin A supplementation. Design, Setting, and Participants: Retrospective, nonrandomized comparison of vitamin A and control cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service of the Massachusetts Eye and Ear Infirmary. The study included children with different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and 25 not taking vitamin A. The dates for patient evaluations ranged from June 1976 to July 2016, and the data analysis occurred in October 2016. Interventions: Age-adjusted dose of oral vitamin A palmitate (≤15 000 IU/d). Main Outcomes and Measures: Mean exponential rates of change of full-field cone electroretinogram amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression without and with adjusting for potential confounders. Results: Of the 55 children in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9] years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the 25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2 [1.7] years; and 25 (100%) were white. The estimated mean rates of change with the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263 loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to ocular safety, the mean exponential rates of change of visual field area and visual acuity and the incidences of falling to a visual field diameter of 20° or less or a visual acuity of 20/200 or less in at least 1 eye did not differ by cohort. Conclusions and Relevance: A vitamin A palmitate supplement was associated with a slower loss of cone electroretinogram amplitude in children with retinitis pigmentosa. Although the relatively small-sample, retrospective, nonrandomized design does not allow a test of causation and is subject to possible biases, these findings support consideration of an age-adjusted dose of vitamin A in the management of most children with the common forms of retinitis pigmentosa.

Lycium Barbarum Polysaccharides Protect Retina in rd1 Mice During Photoreceptor Degeneration.

Purpose: As an active component in wolfberry, lycium barbarum polysaccharides (LBP) are capable of protecting retinal neurons in several animal disease models. Here, we asked whether LBP rescues the retinal morphology and function in rd1 mouse, a photoreceptor fast-degenerating animal model of retinitis pigmentosa, and in particular focused on LBP's effects on the function of retinal ganglion cells (RGCs) during photoreceptor degeneration. Methods: An equal volume of LBP or control vehicle was daily intraperitoneal (i.p.) injected in rd1 mice from postnatal day 4 (P4) to P14, P20, or P24 when photoreceptors completely degenerate. Immunostaining, electroretinogram (ERG), visual behavior tests and multielectrode array (MEA) recordings were assessed to determine the structure and function of the treated retina. Results: LBP treatment greatly promoted photoreceptor survival, enhanced ERG responses, and improved visual behaviors in rd1 mice. MEA data showed that LBP treatment in general decreased the abnormally high spontaneous spiking that occurs in rd1 mice, and increased the percentage of light-responsive RGCs as well as their light-evoked response, light sensitivity, signal-to-noise ratio, and response speed. Interestingly, LBP treatment affected ON and OFF responses differently. Conclusions: LBP improves retinal morphology and function in rd1 mice, and delays the functional decay of RGCs during photoreceptor degeneration. This is the first study that has examined in detail the effects of LBP on RGC responses. Our data suggest that LBP may help extend the effective time window before more invasive RP therapeutic approaches such as retinoprosthesis are applied.

Randomized controlled trial of electro-stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa.

PURPOSE: We examined changes in visual function and ocular and retinal blood flow (RBF) among retinitis pigmentosa (RP) participants in a randomized controlled trial of electro-stimulation therapies. METHODS: Twenty-one RP participants were randomized (1:1:1) to transcorneal electrical stimulation (TES) at 6 weekly half-hour sessions, electro-acupuncture or inactive laser acupuncture (sham control) at 10 half-hour sessions over 2 weeks. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA), quick contrast sensitivity function, Goldmann visual fields, AdaptDx scotopic sensitivity, spectral flow and colour Doppler imaging of the central retinal artery (CRA), and RBF in macular capillaries were measured twice pre-treatment, after 2 TES sessions, within a week and a month after intervention completion. RESULTS: We measured a significant improvement in retrobulbar CRA mean flow velocity for both the TES (p = 0.038) and electro-acupuncture groups (p = 0.001) on average after 2 weeks of treatment when compared to sham controls. Transcorneal electrical simulation (TES) and electro-acupuncture subjects had significant 55% and 34% greater increases, respectively, in RBF in the macular vessels when compared to sham controls (p < 0.001; p = 0.008) within a week of completing six TES sessions or a month after electro-acupuncture. There was a significant difference in the proportion of eyes that had improved visual function when comparing the three intervention groups (p = 0.038): four of seven TES subjects (57%), two of seven electro-acupuncture subjects (29%) and none of the seven control subjects (0%) had a significant visual improvement outside of typical test-retest variability at two consecutive post-treatment visits. CONCLUSION: Increased blood flow following electro-stimulation therapies is an objective, physiological change that occurred in addition to visual function improvements in some RP patients.

Optimal voltage stimulation parameters for network-mediated responses in wild type and rd10 mouse retinal ganglion cells.

To further improve the quality of visual percepts elicited by microelectronic retinal prosthetics, substantial efforts have been made to understand how retinal neurons respond to electrical stimulation. It is generally assumed that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli (a non-monotonic response function). Therefore, it is necessary to identify stimuli that can be used to activate the majority of retinal neurons even when such non-monotonic cells are part of the neuronal population. Taking these non-monotonic responses into consideration, we establish the optimal voltage stimulation parameters (amplitude, duration, and polarity) for epiretinal stimulation of network-mediated (indirect) ganglion cell responses. We recorded responses from 3958 mouse retinal ganglion cells (RGCs) in both healthy (wild type, WT) and a degenerating (rd10) mouse model of retinitis pigmentosa-using flat-mounted retina on a microelectrode array. Rectangular monophasic voltage-controlled pulses were presented with varying voltage, duration, and polarity. We found that in 4-5 weeks old rd10 mice the RGC thresholds were comparable to those of WT. There was a marked response variability among mouse RGCs. To account for this variability, we interpolated the percentage of RGCs activated at each point in the voltage-polarity-duration stimulus space, thus identifying the optimal voltage-controlled pulse (-2.4 V, 0.88 ms). The identified optimal voltage pulse can activate at least 65% of potentially responsive RGCs in both mouse strains. Furthermore, this pulse is well within the range of stimuli demonstrated to be safe and effective for retinal implant patients. Such optimized stimuli and the underlying method used to identify them support a high yield of responsive RGCs and will serve as an effective guideline for future in vitro investigations of retinal electrostimulation by establishing standard stimuli for each unique experimental condition.

(2R, 3S)-Pinobanksin-3-cinnamate ameliorates photoreceptor degeneration in Pde6rd10 mice.

As an inherited disorder caused by initial death of rod photoreceptors, retinitis pigmentosa is currently untreatable and usually leads to partial or complete blindness. (2R, 3S)-Pinobanksin-3-cinnamate (PC) is a new flavonone isolated from the seed of Alpinia galanga Willd, and has been reported to exert neuroprotective effects by upregulating endogenous antioxidant enzymes. In this study, the anti-oxidative and neuroprotective activity of PC against photoreceptor apoptosis in rd10 mouse model of retinitis pigmentosa was explored. PC showed to produce significant improvement in histology and function in rd10 mice through reducing oxidative stress. For the first time, the protective effects of PC were demonstrated against retina degeneration in rd10 mice and our study provides scientific rationale on using PC as the supplementary treatment to the outer retina diseases, including retinitis pigmentosa, in which oxidative stress is thought to contribute to disease progression.

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds.

PURPOSE: To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. METHODS: Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity < 0.02 or visual field ≤5°, non-recordable ERGs) and 40 age-matched healthy subjects. Pupil responses to full-field red (605 nm) and blue (420 nm) stimuli of 28 lx corneal illumination were recorded and analysed for two stimulus durations (1 and 4 seconds). The perception threshold of phosphenes to transcorneal electrostimulation was ascertained and correlated to the pupil responses and visual acuity. RESULTS: Patients with RP showed significantly reduced pupil responses to red and blue stimuli compared with the controls. With red stimuli, pupillary escape could be observed; blue stimuli resulted in a well-preserved postillumination pupil response. Phosphene thresholds were significantly increased in patients with RP and correlated with the parameters of the pupil response if all subjects were considered. Within the RP group alone, this relationship was less pronounced and statistically not significant. CONCLUSIONS: Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant.

Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach?

BACKGROUND: Stargardt's disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. METHODS: Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25%) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3%) reported a high daily intake and 4/24 (16.7%) showed a low daily intake. With regard to RP, 4/56 (7.1%) reported to be within the recommended range, 37/56 (66.1%) reported high daily intake and 15/56 (26.8%) showed low daily intake of vitamin A. RESULTS: Interestingly, STGD patients with low vitamin A intake (<600 µg RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. CONCLUSION: The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients.

[Clinical observation of Erlong Xizhu acupuncture for retinitis pigmentosa].

OBJECTIVE: To explore the clinical effect of Erlong Xizhu acupuncture for retinitis pigmentosa. Methods Sixty patients with retinitis pigmentosa were randomly divided into an Erlong Xizhu acupuncture group and a conventional acupuncture group, 30 cases in each one. In the conventional acupuncture group, Tongziliao (GB 1), Sizhukong (TE 23), Taiyang (EX-HN 5) were acupunctured as the main acupoints by uniform reinforcing-reducing manipulation; acupoints based on syndrome differentiation were coordinated by acupuncture manipulation of reinforcing deficiency and reducing excess. The treatment in the Erlong Xizhu acupuncture group was the same as that in the conventional group, except acupuncture manipulation at the main acupoints replaced by Erlong Xizhu acupuncture. In the two groups, treatment was given once a day, 10 days as one session and there were 2 days at the interval between sessions. The change of the vision and visual field and the efficacy were observed after 3 sessions in the two groups. RESULTS: The total effective rate on enhancing the vision of patients in the Erlong Xizhu acupuncture group was 93. 10% (54/58), which was superior to 81. 36% (48/59) in the conventional acupuncture group (P<0. 01). And the effective rate on improving the visual field was 91. 38% (53/58) in the Erlong Xizhu acupuncture group, which was better than 83. 05% (49/59) in the conventional acupuncture group (P<0. 01). On the comprehensive effect, the effective rate was 90. 00% (27/30) in the Erlong Xizhu acupuncture group, which was better than 63. 34% (19/30) in the conventional acupuncture group (P<0. 05). CONCLUSION: The clinical effect of Erlong Xizhu acupuncture is superior to that of conventional acupuncture for retinitis pigmentosa and it is worthy of promoting.

[Effects of acupuncture on morphological changes of photoreceptor cells in rats with retinitis pigmentosa].

OBJECTIVE: To observe the morphological changes of photoreceptor cells in rats with retinitis pigmentosa (RP) induced by N-methyl-N-Nitrosourea (MNU) and the effects of acupuncture against it. METHODS: A total of 16 SD rats were treated with one-time intraperitoneal injection of MNU (50 mg/kg) to induce RP, and randomly divided into an acupuncture group and a model group, 8 rats in each one. In addition, 4 rats were selected as a control group. After model establishment, rats in the acupuncture group were treated with acupuncture at "Xinming-1" (Extra) and "Jingming" (BL 1) for 30 min, once a day for 7 days; rats in the model group and control group received no treatment, and the feeding conditions and fixation were identical as the acupuncture group. 2 h after the end of intervention, rats were sacrificed by cervical dislocation to observe the morphological changes of rhodopsin, rod terminals and rod bipolar cells. RESULTS: Due to the loss of retina photoreceptor cells induced by MNU in rats, in the model group the rhodopsin was stained in residual cell bodies, and there were sporadic rod terminals and little rod bipolar cells; outer segments, inter segments, cell bodies and cell terminals were all affected at different levels. The distribution of rhodopsin was also changed in the acupuncture group, showing more bodies of photoreceptor cells, and the residual rod terminals and rod bipolar cells were more than those in the model group; the injury of retina was less than that in the model group. CONCLUSION: MNU could lead to a comprehensive injury to the morphology of photoreceptor cells, however, acupuncture is capable of inhibiting morphological changes of photoreceptor cells induced by MNU.

Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial.

IMPORTANCE: X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE: To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS: A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non-X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS: All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS: Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse events were found. CONCLUSIONS AND RELEVANCE: Long-term DHA supplementation was not effective in slowing the loss of cone or rod ERG function associated with X-linked retinitis pigmentosa. Participant dropout and lower-than-expected disease event rate limited power to detect statistical significance. A larger sample size, longer trial, and attainment of a target blood DHA level (13%) would be desirable. While DHA supplementation at 30 mg/kg/d does not present serious adverse effects, routine monitoring of gastrointestinal tolerance is prudent. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00100230.

A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients.

BACKGROUND: Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. METHODS: A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. RESULTS: Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3-3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated by all, without adverse events or visual loss. CONCLUSIONS: Acupuncture entails minimal risk, if administered by a well-trained acupuncturist and may have significant, measurable benefits on residual visual function in patients with retinitis pigmentosa, in particular scotopic sensitivity, which had not previously been studied. These preliminary findings support the need for future controlled studies of potential mechanisms.

The Detection of Motion by Blind Subjects With the Epiretinal 60-Electrode (Argus II) Retinal Prosthesis.

OBJECTIVE: To investigate the ability of 28 blind subjects implanted with a 60-electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system to detect the direction of a moving object. METHODS: Blind subjects (bare light perception or worse in both eyes) with retinitis pigmentosa were implanted with the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple clinical sites worldwide. The experiment measured their ability to detect the direction of motion of a high-contrast moving bar on a flatscreen monitor in 3 conditions: with the prosthesis system on and a 1-to-1 mapping of spatial information, with the system off, and with the system on but with randomly scrambled spatial information. RESULTS: Fifteen subjects (54%) were able to perform the task significantly better with their prosthesis system than they were with their residual vision, 2 subjects had significantly better performance with their residual vision, and no difference was found for 11 subjects. Of the 15 better-performing subjects, 11 were available for follow-up testing, and 10 of them had significantly better performance with normal rather than with scrambled spatial information. CONCLUSIONS: This work demonstrates that blind subjects implanted with the Argus II retinal prosthesis were able to perform a motion detection task they could not do with their native vision, confirming that electrical stimulation of the retina provides spatial information from synchronized activation of multiple electrodes. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00407602

The Argus™ II retinal prosthesis: factors affecting patient selection for implantation.

The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date, the device has been implanted in multiple subjects with profound retinitis pigmentosa as part of a worldwide clinical feasibility study (clinicaltrials.gov ID: NCT00407602). The Argus II is intended to provide partial restoration of functional vision. Most subjects showed an improvement in tasks assessing orientation & mobility, spatial-motor localization, and ability of discerning the direction of motion of moving stimuli. Roughly one third of subjects experienced measurable improvement in visual acuity with the implant. Some subjects identified words with high accuracy, a result that has also been reported by the leading subretinal implant group. Perceptual threshold was correlated with electrode-retina distance, electrode-fovea distance, and light sensitivity, either as single variables or in bivariate linear regression. Taken together these three variables may be used to inform patient selection and develop algorithms for the fitting of higher-electrode count systems. Visual acuity for future generations of the Argus implant may not hit theoretical limitations until arrays hold an excess of several hundreds of electrodes. Nevertheless, preliminary safety and efficacy data are supportive of the development of higher-resolution systems that target macular placement from implant design and surgical perspectives.