Use of Penetrating Electrodes in the Boston Retinal Prosthesis

描述(由申请人提供)： 项目概述/摘要创新视觉康复中心(CIVR)于2001年在波士顿VA医院成立，是波士顿视网膜植入项目的产物，该项目自20世纪80年代末以来一直是哈佛医学院/麻省眼耳医院和麻省理工学院之间的多学科合作。CIVR的目标是开发先进的技术，创造新的疗法，为因视网膜疾病而失明的退伍军人恢复视力。更具体地说，CIVR的目标是创造一种微电子植入物，为患有不可治疗的视网膜疾病的退伍军人恢复视力。这种类型的最严重的致盲情况是年龄相关性黄斑变性(AMD)，这是退伍军人失明的主要原因。我们的设备还可能帮助大约8000名患有视网膜色素变性的退伍军人中的一些人，视网膜色素变性比AMD导致更严重和更广泛的失明。我们的假体也可能与因战场伤势而出现视网膜损伤的退伍军人有关。CIVR已经成功地制造并测试了一种无线视网膜假体，该假体在猪眼上按设计工作了长达一年。我们的团队最近开始与FDA沟通，寻求调查设备豁免(IDE)，以实现长期人类植入物的性能。我们目前正在升级我们的实验室设备，该设备已用于动物实验，以使其适合人类使用。两大问题阻碍了盲人退伍军人成功恢复视力：1)电刺激阈值往往非常高，这引发了人们对长期刺激安全性的担忧；2)进行过长期人体植入手术的患者缺乏高质量的视觉感知。这两个问题都可能通过使用穿透电极而不是平坦的电极来解决。世界各地的所有组织，包括我们自己的组织，一直在为他们的视网膜假体设备使用平板电极。这项提案的重点是设计、创造和外科植入三维穿透电极，这种电极将在柔性基板上制造。为了实现这些目标，该提案描述了使用先进和定制的微制造技术来创建阵列，以及各种体外和体内方法来研究电极在将这些设备植入尤卡坦小型猪视网膜下空间之前、期间和之后的电和物理完整性。将对植入的电极阵列的生物相容性进行进一步的研究，主要是在植入几个月后对眼睛进行组织学检查。这项提议的结果有可能产生一个改进的电极阵列，这将加强我们正在开发的人类质量假体的升级计划。新的电极阵列可以很容易地集成到我们的假体中，因为我们已经开发了一种“模块化和可重新配置”的设计概念，允许我们在不需要对系统的基本设计或制造进行任何更改的情况下引入新的组件。 公共卫生相关性： 研究与退伍军人的相关性创新视觉康复中心(CIVR)的使命是为患有视网膜退行性疾病，特别是老年性黄斑变性(AMD)和视网膜色素变性(RP)的失明退伍军人恢复视力。AMD是导致退伍军人失明的主要原因，大约有7800名退伍军人患有RP。根据退伍军人管理局自己的估计，到2011年，患有严重视力障碍的退伍军人人数将达到43万人。对于因视网膜外部疾病而严重失明的患者，目前还没有恢复视力的治疗方法。这项拟议研究的潜在好处是开发了一种新型的电极阵列，它有可能改善电刺激的安全性，并可能提高假体产生的视觉质量。

DESCRIPTION (provided by applicant): Project Summary/Abstract The Center for Innovative Visual Rehabilitation (CIVR) was founded at the Boston VA hospital in 2001 as an outgrowth of the Boston Retinal Implant Project, which had been a multi-disciplinary collaboration between the Harvard Medical School/ Massachusetts Eye and Ear Infirmary and the Massachusetts Institute of Technology since the late 1980s. The goal of the CIVR is to develop advanced technologies to create new therapies to restore vision to veterans who are blind from retinal disease. More specifically, the goal of the CIVR is the creation of a micro-electronic implant to restore vision to veterans who have retinal disease that is not treatable. The most significant blinding condition of this type is age-related macular degeneration (AMD), which is the leading cause of blindness among veterans. Our device might also be able to help some of the roughly 8,000 veterans who have retinitis pigmentosa, which causes more severe and diffuse blindness than AMD. Our prosthesis could also potentially be relevant to veterans who develop retinal damage from battlefield injuries. The CIVR has successfully built and testing a wireless retinal prosthesis that has functioned as designed for up to one year in pig eye. Our group has recently initiated communication with the FDA to seek an Investigational Device Exemption (IDE) to enable performance of long-term human implants. We are currently in the process of upgrading our laboratory device that has been used in animal experiments to make it suitable for human use. Two large problems stand in the way of successfully restoring vision to blind veterans: 1) the tendency for electrical stimulation thresholds to be very high, which raises a concern about the safety of long-term stimulation; and 2) the lack of demonstration of high-quality visual percepts from the groups that have performed chronic human implants. Both problems can likely be solved by use of penetrating, rather than flat, electrodes. All groups worldwide, including our own, have been using flat electrodes for their retinal prosthetic devices. This proposal focuses on the design, creation and surgical implantation of three dimensional, penetrating electrodes that will be made on a flexible substrate. To accomplish these aims, the proposal describes use of advanced and customized microfabrication techniques to create the arrays, and a variety of in vitro and in vivo methods to study the electrical and physical integrity of the electrodes before, during and after implantation of these devices into the sub-retinal space of Yucatan mini-pigs. Additional studies will be made of the biocompatibility of the implanted electrode arrays, primary by histological examination of the eyes months after implantation. The results of this proposal have the potential to yield an improved electrode array that will enhance our plans for upgrading our human-quality prosthesis that is under development. A new electrode array could be easily incorporated into our prosthesis because we have developed a "modular and reconfigurable" design concept that allows us to introduce new components without requiring any change in the basic design or manufacture of our system. PUBLIC HEALTH RELEVANCE: Relevance of Research to VA The mission of the Center for Innovative Visual Rehabilitation (CIVR) is the restoration of vision to blind veterans who have degenerative retinal diseases, particularly age- related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is the leading cause of blindness among veterans, and roughly 7800 veterans have RP. According to the VA's own estimates, the number of veterans with significant visual impairment will reach 430,000 by the year 2011. There is no treatment to restore vision to patients who have become severely blind because of disease of the outer retina. The potential benefit of the proposed research is the development of a novel type of electrode array, which has the potential improve the safety of the electrical stimulation and possibly the quality of vision that is produced by our prosthesis.