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眼内视网膜假体。

Intraocular retinal prosthesis.

作者信息

Humayun M S

机构信息

Retina Institute, Doheny Eye Institute, Keck School of Medicine of USC, Los Angeles, California, USA.

出版信息

Trans Am Ophthalmol Soc. 2001;99:271-300.

Abstract

PURPOSE

An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision.

METHODS

For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living.

RESULTS

Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every stimulus duration (P < .05). In all groups, short duration pulses (40, 80, and 120 microseconds) were more efficient in terms of total charge (the product of pulse amplitude and pulse duration) than longer (500 and 1,000 microseconds) pulses (P < .05). In all groups, applying a pulse train did not lead to more efficient charge usage (P < .05). Psychophysical experiments: In high-contrast tests, facial recognition rates of over 75% were achieved for all subjects with dot sizes of up to 31.5 minutes of arc when using a 25 x 25 grid with 4.5 arc minute gaps, a 30% dropout rate, and 6 gray levels. Even with a 4 x 4 array of pixels, some subjects were able to accurately describe 2 of the objects. Subjects who were able to read the 4-pixel letter height sentences (on the 6 x 10 and 16 x 16 array) seemed to have a good scanning technique. Scanning at the proper velocity tends to bring out more contrast in the lettering. The reading speed for the 72-point font is a bit slower than for the next smaller font. This may be due to the limited number of letters (3) visible in the window with this large font.

CONCLUSIONS

Specific parameters needed to stimulate the retina were identified. Delineating the optimum parameters will decrease the current requirements. Psychophysical tests show that with limited pixels and image processing, useful vision is possible. Both these findings should greatly simplify the engineering of an electronic retinal prosthesis.

摘要

目的

已提出一种电子植入物,其可绕过受损的光感受器并电刺激剩余的视网膜神经元以恢复有用视力。要使这种方法可行,仍有许多关键问题有待解决。本论文的目标是解决以下两个特定的零假设:(1)刺激参数对电诱发的视网膜反应没有影响。(2)正如我们有数百万个光感受器一样,也需要一个能够产生数百万个像素/光点的设备来创造有用视力。

方法

对于电生理实验,使用了两种不同的设置。在第一种设置中,通过经开放视野方法插入电极,将电荷平衡脉冲传递到正常或失明视网膜退化(rd)小鼠的视网膜表面。在第二种设置中,在红光条件下从摘除的眼球中取出兔视网膜,然后将其置于腔室中,同时用含氧、加热的艾姆斯培养基进行灌流。在两种设置中,刺激电极和记录电极都置于视网膜表面,以评估不同刺激参数对顺行性视网膜反应的影响(即记录电极置于刺激电极和视神经乳头之间)。对于心理物理学实验,视觉图像被分成光点像素,这些像素可以以一种模式投射到多达8名有视力志愿者的视网膜上。受试者被要求执行各种任务,从阅读和人脸识别到各种日常生活活动。

结果

电生理实验:在正常小鼠中,1千赫兹正弦波的单个周期比1千赫兹方波效率显著更高(P <.05),但在8周龄或16周龄的rd小鼠组中均未观察到这种差异(8周龄,P =.426;16周龄,P =.078)。对于每个刺激持续时间,16周龄rd小鼠的电荷阈值显著高于8周龄rd小鼠和正常小鼠(P <.05)。在所有组中,短持续时间脉冲(40、80和120微秒)在总电荷(脉冲幅度与脉冲持续时间的乘积)方面比长脉冲(500和1000微秒)更有效(P <.05)。在所有组中,施加脉冲序列不会导致更有效的电荷使用(P <.05)。心理物理学实验:在高对比度测试中,当使用间距为4.5角分的25×25网格、30%的漏失率和6个灰度级时,对于点大小高达31.5角分的所有受试者,面部识别率超过75%。即使使用4×4像素阵列,一些受试者也能够准确描述其中2个物体。能够阅读4像素字母高度句子(在6×10和16×16阵列上)的受试者似乎有良好的扫描技术。以适当速度扫描往往会使字母中的对比度更明显。72点字体的阅读速度比下一个较小字体稍慢。这可能是由于使用这种大字体时窗口中可见的字母数量有限(3个)。

结论

确定了刺激视网膜所需的特定参数。确定最佳参数将降低电流需求。心理物理学测试表明,通过有限的像素和图像处理,可以实现有用视力。这两个发现都应极大地简化电子视网膜假体的工程设计。

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