Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, each electrode acting as a pixel. Unintended stimulation of retinal ganglion cell axons causes patients to see large, oblong shapes of light, rather than focal spots, making it difficult for them to perceive forms. To address this problem, we performed calcium imaging in isolated retinas and mapped the patterns of cells activated by different electrical stimulation protocols. We found that pulse durations two orders of magnitude longer than those typically used in existing implants stimulate inner retinal neurons while avoiding activation of ganglion cell axons, thus confining retinal responses to the site of the electrode. We show that multielectrode stimulation with 25-ms pulses can pattern letters on the retina corresponding to a Snellen acuity of 20/312. We validated our findings in a patient with an implanted epiretinal prosthesis by demonstrating that 25-ms pulses evoke focal spots of light.

No abstract

Epiretinal prostheses are being developed to bypass a degenerated photoreceptor layer and excite surviving ganglion and inner retinal cells. We used custom microfabricated multielectrode arrays with 200-μm-diameter stimulating electrodes and 10-μm-diameter recording electrodes to stimulate and record neural responses in isolated tiger salamander retina. Pharmacological agents were used to isolate direct excitation of ganglion cells from excitation of other inner retinal cells. Strength-duration data suggest that, if amplitude will be used for the coding of brightness or gray level in retinal prostheses, shorter pulses (200 μs) will allow for a smaller region in the area of the electrode to be excited over a larger dynamic range compared with longer pulses (1 ms). Both electrophysiological results and electrostatic finite-element modeling show that electrodeelectrode interactions can lead to increased thresholds for sites half way between simultaneously stimulated electrodes (29.4 ± 6.6 nC) compared with monopolar stimulation (13.3 ± 1.7 nC, p < 0.02). Presynaptic stimulation of the same gan-glion cell with both 200-and 10-μm-diameter electrodes yielded threshold charge densities of 12 ± 6 and 7.66 1.30 nC/cm 2 , respectively, while the required charge was 12.5 ± 6.2 and 19 ± 3.3 nC.

Epiretinal prostheses for the blind bypass diseased photosensitive cells in the retina, directly stimulating retinal neurons electrically and evoking signals that are relayed to the brain. Current clinical implants have few electrodes and provide limited visual acuity. Acuity may be improved by identifying electrode array design features and operational details that enhance or interfere with visual percept formation. We labeled all retinal ganglion cells in whole mount retina with a calcium reporter and then measured the number and pattern of cells responding, over a range of electrode diameters and stimulus durations. Span of the response scaled with electrode diameter for electrodes 60 μm and larger. Short stimulation pulse widths selectively activated cells nearest the electrode. Our measurements in the salamander retina suggest that the spatial resolution is 150 μm, which on a human retina is equivalent to 0.55° of human visual field and corresponding Snellen acuity of 20/660. Reading large print could be possible with such a prosthesis.

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.