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      Minimizing Iridium Oxide Electrodes for High Visual Acuity Subretinal Stimulation

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          Abstract

          Vision loss from diseases of the outer retina, such as age-related macular degeneration, is among the leading causes of irreversible blindness in the world today. The goal of retinal prosthetics is to replace the photo-sensing function of photoreceptors lost in these diseases with optoelectronic hardware to electrically stimulate patterns of retinal activity corresponding to vision. To enable high-resolution retinal prosthetics, the scale of stimulating electrodes must be significantly decreased from current designs; however, this reduces the amount of stimulating current that can be delivered. The efficacy of subretinal stimulation at electrode sizes suitable for high visual acuity retinal prosthesis are not well understood, particularly within the safe charge injection limits of electrode materials. Here, we measure retinal ganglion cell (RGC) responses in a mouse model of blindness to evaluate the stimulation efficacy of 10, 20, and 30 μm diameter iridium oxide electrodes within the electrode charge injection limits, focusing on measures of charge threshold and dynamic range. Stimulation thresholds were lower for smaller electrodes, but larger electrodes could elicit a greater dynamic range of spikes and recruited more ganglion cells within charge injection limits. These findings suggest a practical lower limit for planar electrode size and indicate strategies for maximizing stimulation thresholds and dynamic range.

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          Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.

          Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Analysis of 129,664 individuals (aged 30-97 years), with 12,727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45-85 years) of early, late, and any age-related macular degeneration to be 8.01% (95% CrI 3.98-15.49), 0.37% (0.18-0.77), and 8.69% (4.26-17.40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11.2% vs 6.8%, Bayes factor 3.9; any: 12.3% vs 7.4%, Bayes factor 4.3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11.2% vs 7.1%, Bayes factor 12.2; late: 0.5% vs 0.3%, 3.7; any: 12.3% vs 7.5%, 31.3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1.11%, 95% CrI 0.53-2.08) than Africans (0.14%, 0.04-0.45), Asians (0.21%, 0.04-0.87), and Hispanics (0.16%, 0.05-0.46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6.3% vs 14.3% and 12.8% [Bayes factor 2.3 and 7.6]; any: 6.9% vs 18.3% and 14.3% [3.0 and 3.8]). No significant gender effect was noted in prevalence (Bayes factor <1.0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140-261), increasing to 288 million in 2040 (205-399). These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. National Medical Research Council, Singapore. Copyright © 2014 Wong et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.
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            Retinitis pigmentosa.

            Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.
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              Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis.

              Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment.
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                Author and article information

                Journal
                eNeuro
                eNeuro
                eneuro
                eNeuro
                eNeuro
                Society for Neuroscience
                2373-2822
                19 November 2021
                10 December 2021
                Nov-Dec 2021
                : 8
                : 6
                : ENEURO.0506-20.2021
                Affiliations
                [1 ]Department of Bioengineering, University of California San Diego , La Jolla, CA 92093
                [2 ]Department of Psychology, University of California San Diego , La Jolla, CA 92093
                [3 ]Department of Electrical and Computer Engineering, University of California San Diego , La Jolla, CA 92161
                [4 ]Jacobs Retina Center at Shiley Eye Institute, Department of Ophthalmology, University of California San Diego , La Jolla, CA 92093
                Author notes

                S.D., Y.-H.L., W.R.F., and N.W.O. have an equity interest in Nanovision Biosciences, Inc. Y.-H.L., W.R.F., and N.W.O. also serve on the Scientific Advisory Board. Although this grant (EY029259) has been identified for conflict of interest management based on the overall scope of the project and its potential benefit to Nanovision Biosciences, Inc., the research findings included in this particular publication may not necessarily relate to the interests of Nanovision Biosciences, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All other authors declare no competing financial interests.

                Author contributions: S.D. and N.W.O. designed research; S.D., M.C., and T.K., S.A., performed research; S.D., M.C., T.K., S.A., and N.W.O. analyzed data; S.D., W.R.F., Y.-H.L., and N.W.O. wrote the paper.

                This work was supported by the National Institutes of Health Grant EY029259 (to N.W.O.).

                Correspondence should be addressed to Nicholas W. Oesch at noesch@ 123456ucsd.edu .
                Author information
                https://orcid.org/0000-0001-6972-0741
                Article
                eN-NWR-0506-20
                10.1523/ENEURO.0506-20.2021
                8704424
                34799411
                d04fe819-41a3-451b-a56b-b6dd5756e8a6
                Copyright © 2021 Damle et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 23 November 2020
                : 28 October 2021
                : 15 November 2021
                Page count
                Figures: 10, Tables: 0, Equations: 3, References: 45, Pages: 13, Words: 00
                Funding
                Funded by: NIH
                Award ID: EY029259
                Categories
                3
                Research Article: New Research
                Disorders of the Nervous System
                Custom metadata
                November/December 2021

                blindness,electrical stimulation,neural stimulation,prosthetic,retina,retinal prosthetic

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