Matthew J. McMahon

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.

Off-axis Optical Quality and Retinal Sampling in the Human Eye

Using the double pass procedure, Navarro et al. (1993; Journal of the Optical Society of America A, 10, 201-212) measured the monochromatic modulation transfer function (MTF) of the human eye as a function of retinal eccentricity. They chose conditions as similar as possible to those encountered in natural viewing. We report new measurements obtained with conditions chosen instead to optimize retinal image quality: we paralyzed accommodation, used a 3 mm pupil, and corrected defocus and oblique astigmatism at each retinal location. MTFs were estimated at the tangential focus, circle of least confusion, and sagittal focus produced by oblique astigmatism. Though optical blur is well-known to have little effect on peripheral visual acuity, it can nonetheless substantially reduce aliasing by receptoral and post-receptoral spatial sampling.

Factors Affecting Perceptual Thresholds in Epiretinal Prostheses

PURPOSE The goal was to evaluate how perceptual thresholds are related to electrode impedance, electrode size, the distance of electrodes from the retinal surface, and retinal thickness in six subjects blind as a result of retinitis pigmentosa, who received epiretinal prostheses implanted monocularly as part of a U.S. Food and Drug Administration (FDA)-approved clinical trial. METHODS The implant consisted of an extraocular unit containing electronics for wireless data, power recovery, and generation of stimulus current, and an intraocular unit containing 16 platinum stimulating electrodes (260- or 520-microm diameter) arranged in a 4 x 4 pattern. The electrode array was held onto the retina by a small tack. Stimulation was controlled by a computer-based external system that allowed independent control over each electrode. Perceptual thresholds (the current necessary to see a percept on 79% of trials) and impedance were measured for each electrode on a biweekly basis. The distance of electrodes from the retinal surface and retinal thickness were measured by optical coherence tomography on a less regular basis. RESULTS Stimulation thresholds for detecting phosphenes correlated with the distance of the electrodes from the retinal surface, but not with electrode size, electrode impedance, or retinal thickness. CONCLUSIONS Maintaining close proximity between the electrode array and the retinal surface is critical in developing a successful retinal implant. With the development of chronic electrode arrays that are stable and flush on the retinal surface, it is likely that the influence of other factors such as electrode size, retinal degeneration, and subject age will become more apparent. (ClinicalTrials.gov number, NCT00279500.).

Feasibility Study of a Retinal Prosthesis Spatial Vision With a 16-Electrode Implant

OBJECTIVE To demonstrate that an epiretinal prosthesis can produce patterned visual perception in patients blinded by photoreceptor degeneration who have no other treatment options. METHODS A totally blind subject with retinitis pigmentosa had a 16-electrode epiretinal prosthesis implanted. The implant is controlled wirelessly by an external computer or a head-mounted video camera. Spatial vision was assessed by measuring the subjects response to direct stimulation of patterns and by comparing the ability of the subject to identify the orientation of gratings with the system on and off. RESULTS In response to stimulation of 2 orthogonal rows of electrodes, the subject drew 2 lines with a mean (SEM) angle of 87.4 degrees (1.8 degrees) between them. With the system on, the subject identified the orientation of the grating target up to a spatial resolution that matches the spacing between the adjacent electrodes. In contrast, with the system off, the subject could not detect or identify the targets orientation. CONCLUSION Synchronized stimulation of different retinal locations with an epiretinal prosthesis implanted long-term can produce spatial vision with an acuity level determined by the distance between the electrodes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00279500.

The Classical Receptive Field Surround of Primate Parasol Ganglion Cells Is Mediated Primarily by a Non-GABAergic Pathway

Although the center-surround receptive field is a fundamental property of retinal ganglion cells, the circuitry that mediates surround inhibition remains controversial. We examined the contribution of horizontal cells and amacrine cells to the surround of parasol ganglion cells of macaque and baboon retina by measuring receptive field structure before and during the application of drugs that have been shown previously to affect surrounds in a range of mammalian and nonmammalian species. Carbenoxolone and cobalt, thought to attenuate feedback from horizontal cells to cones, severely reduced the surround. Tetrodotoxin, which blocks sodium spiking in amacrine cells, and picrotoxin, which blocks the inhibitory action of GABA, only slightly reduced the surround. These data are consistent with the hypothesis that the surrounds of light-adapted parasol ganglion cells are generated primarily by non-GABAergic horizontal cell feedback in the outer retina, with a small contribution from GABAergic amacrine cells of the inner retina.

L and M cone contributions to the midget and parasol ganglion cell receptive fields of macaque monkey retina.

Analysis of cone inputs to primate parvocellular ganglion cells suggests that red–green spectral opponency results when connections segregate input from long wavelength (L) or middle wavelength (M) sensitive cones to receptive field centers and surrounds. However, selective circuitry is not an obvious retinal feature. Rather, cone receptive field surrounds and H1 horizontal cells get mixed L and M cone input, likely indiscriminately sampled from the randomly arranged cones of the photoreceptor mosaic. Red–green spectral opponency is consistent with random connections in central retina where the mixed cone ganglion cell surround is opposed by a single cone input to the receptive field center, but not in peripheral retina where centers get multiple cone inputs. The selective and random connection hypotheses might be reconciled if cone type selective circuitry existed in inner retina. If so, the segregation of L and M cone inputs to receptive field centers and surrounds would increase from horizontal to ganglion cell, and opponency would remain strong in peripheral retina. We measured the relative strengths of L and M cone inputs to H1 horizontal cells and parasol and midget ganglion cells by recording intracellular physiological responses from morphologically identified neurons in an in vitro preparation of the macaque monkey retina. The relative strength of L and M cone inputs to H1 and ganglion cells at the same locations matched closely. Peripheral midget cells were nonopponent. These results suggest that peripheral H1 and ganglion cells inherit their L and M cone inputs from the photoreceptor mosaic unmodified by selective circuitry.

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.

Brightness as a function of current amplitude in human retinal electrical stimulation.

PURPOSE With the goal of eventually restoring functional vision in patients with retinal degenerative diseases, USC/Second Sight Medical Products, Inc. chronically implanted blind human subjects with a prototype epiretinal prosthesis consisting of a 4 x 4 array of 16 stimulating electrodes. To accurately represent a visual scene, a visual prosthesis must convey luminance information across a range of brightness levels. To achieve this, the brightness of phosphenes produced by an individual electrode should scale appropriately with luminance, and the same luminance should produce equivalently bright phosphenes across the entire electrode array. The goal was to examine how apparent brightness changes as a function of stimulation intensity across electrodes. METHODS As described in previous studies, electrical stimulation of intact cells of the neural retina using this prosthetic device reliably elicits visual percepts in human subjects blinded by retinitis pigmentosa. Here, apparent brightness for a range of electrical amplitudes was measured using both subjective magnitude rating and brightness-matching procedures in chronically implanted human subjects. RESULTS It was found that apparent brightness can be described as a power function of stimulation intensity. The same model can also predict brightness matching across electrodes. CONCLUSIONS These results suggest that a relatively simple model for scaling current across electrodes may be capable of producing equivalently bright phosphenes across an entire array. (ClinicalTrials.gov number, NCT00279500.).

Predicting Visual Sensitivity in Retinal Prosthesis Patients

PURPOSE With the long-term goal of restoring functional vision in patients with retinal degenerative diseases, the eyes of blind human subjects were implanted chronically with epiretinal prostheses consisting of two-dimensional electrode arrays that directly stimulated cells of the neural retina. METHODS Psychophysical techniques were used to measure the brightness of electrically generated percepts on single electrodes using a variety of electrical stimulation patterns. RESULTS It was possible to predict the sensitivity of the human visual system to a wide variety of retinal electrical stimulation patterns using a simple and biologically plausible model. CONCLUSIONS This is the first study to demonstrate that, on the single-electrode level, retinal electrical stimulation in humans can produce visual qualia that are predictable using a quantitative model, a prerequisite for a successful retinal prosthesis. (ClinicalTrials.gov number, NCT00279500.).

Retinal prosthesis phosphene shape analysis

A retinal prosthesis system to restore sight for the blind is under development. The system is analogous to cochlear implants, in which photoreceptor input is bypassed and replaced by direct electrical stimulation of the retinal ganglion cells. Currently, six test subjects have been implanted with a 4×4 electrode array and stimulator. We report here psychophysical clinical data examining how stimulation amplitude affects phosphene shape and repeatability on a single electrode. Phosphene shape data was quantified by a set of numerical descriptors calculated from image moments. Comparison of phosphene descriptors for a single electrode across repeated trials and amplitude levels measured the repeatability within an amplitude group. Our experimental findings show that stimulation of the retina creates repeatable percept shapes and that an increase in stimulation amplitude causes a significant change in size and shape of phosphenes.