Use of Penetrating Electrodes in the Boston Retinal Prosthesis

描述（由申请人提供）： 创新视力康复中心（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一个产物，该项目自20世纪80年代末以来一直是哈佛医学院/马萨诸塞州眼耳医院和马萨诸塞州理工学院之间的多学科合作。CIVR的目标是开发先进技术，创造新的疗法，以恢复因视网膜疾病失明的退伍军人的视力。更具体地说，CIVR的目标是创造一种微电子植入物，以恢复患有无法治疗的视网膜疾病的退伍军人的视力。这种类型的最重要的致盲条件是年龄相关性黄斑变性（AMD），这是退伍军人失明的主要原因。我们的设备也可能能够帮助大约8,000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更严重和更广泛的失明。我们的假体也可能适用于因战场受伤而造成视网膜损伤的退伍军人。CIVR已经成功构建并测试了一种无线视网膜假体，该假体在猪眼中的功能已达到设计的一年。我们的团队最近与FDA进行了沟通，以寻求研究器械豁免（IDE），以实现长期人体植入物的性能。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，使其适合人类使用。两个大问题阻碍了盲人退伍军人成功恢复视力：1）电刺激阈值的趋势非常高，这引起了人们对长期刺激安全性的担忧; 2）缺乏对进行慢性人类植入的群体的高质量视觉感知的证明。这两个问题都可以通过使用穿透电极而不是扁平电极来解决。全世界所有的研究小组，包括我们自己的，都在他们的视网膜修复装置中使用扁平电极。该提案的重点是设计，创建和手术植入的三维，穿透电极，将在一个灵活的基板。为了实现这些目标，该提案描述了使用先进的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这些装置植入尤卡坦小型猪视网膜下空间之前、期间和之后的电极的电气和物理完整性。将对植入电极阵列的生物相容性进行额外研究，主要通过植入后数月对眼睛进行组织学检查。这项提议的结果有可能产生一种改进的电极阵列，这将加强我们正在开发的人类质量假体的升级计划。一个新的电极阵列可以很容易地纳入我们的假体，因为我们已经开发了一个“模块化和可重构”的设计概念，使我们能够引入新的组件，而不需要在我们的系统的基本设计或制造的任何变化。

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.