Intraocular retinal prosthesis.

Humayun MS

摘要

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.

机译：目的：提出了一种电子植入物，可以绕过受损的感光细胞并电刺激剩余的视网膜神经元，以恢复有用的视力。要使这种方法可行，还有许多关键问题。本文的目的是解决以下两个特定的零假设：（1）刺激参数在电诱发的视网膜反应中没有差异。（2）正如我们拥有数百万个感光器一样，它需要一种能够产生数百万个像素/光点的设备来创建有用的视觉。方法：对于电生理实验，使用了2种不同的设置。在第一种设置中，电荷平衡的脉冲通过在正常或盲态视网膜退化（rd）小鼠中通过露天途径插入的电极传递到视网膜表面。在第二种设置中，将兔子视网膜在红光条件下从摘下眼睛的眼睛中取出，然后将其保持在一个小室内，同时与充氧的加热的Ames培养基融合。在这两种设置中，将刺激电极和记录电极放置在视网膜表面上，以评估变化的刺激参数对正畸视网膜反应的影响（即，将记录电极放置在刺激电极和视神经头之间）。对于心理物理实验，视觉图像被分为可在多达8位视力良好的志愿者中以一定模式投射到视网膜上的光像素。要求受试者执行各种任务，从阅读和面部识别到日常生活的各种活动。结果：电生理实验：在正常小鼠中，1 kHz正弦波的单个周期比1 kHz方波的效率显着提高（P <.05），但是在8个鼠标中，没有一个发现这种差异。或16周龄的rd小鼠组（8周龄，P = 0.426; 16周龄，P = 0.078）。在每个刺激期间，16周龄rd小鼠的充电阈值均显着高于8周龄rd和正常小鼠（P <.05）。在所有组中，短时脉冲（40、80和120微秒）在总电荷（脉冲幅度和脉冲持续时间的乘积）方面比长时脉冲（500和1,000微秒）更有效（P <.05）。在所有组中，施加脉冲串都不会导致更有效的电荷使用（P <.05）。心理物理实验：在高对比度测试中，使用25 x 25的网格（间隙为4.5弧分），漏失率为30％，所有点大小最长为31.5分钟的受试者，面部识别率均达到75％以上。和6个灰度等级。即使使用4 x 4像素阵列，某些对象也能够准确地描述其中两个对象。能够读取4像素字母高的句子（在6 x 10和16 x 16阵列上）的对象似乎具有良好的扫描技术。以适当的速度扫描会在文字中带来更大的对比度。 72点字体的读取速度比下一个较小的字体要慢一些。这可能是由于在这种大字体的窗口中可见的字母（3）数量有限。结论：确定了刺激视网膜所需的特定参数。描绘出最佳参数将降低电流要求。心理物理测试表明，在有限的像素和图像处理的情况下，有用的视觉是可能的。这两个发现应大大简化电子视网膜假体的工程设计。

Intraocular retinal prosthesis.

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