Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays
Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays
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DOI：
10.1167/iovs.02-0819
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发表时间：
2003-12-01
影响因子：
4.4
通讯作者：
Shire, D
中科院分区：
文献类型：
--
作者：
Rizzo, JF;Wyatt, J;Shire, D
目的.目的报道在急性手术试验中使用微制造电极阵列进行视网膜前电刺激并确定清醒人类志愿者感知阈值的方法。测试了四个假设：（1）视网膜前刺激可以在急性实验期间进行，而不会明显损害视网膜或降低视力或眼睛的健康;（2）在电荷密度低于公布的安全限度的盲人患者中，可以在50%的时间内获得感知;（3）在具有更严重视网膜变性的患者中，诱导感知所需的最小电荷将更高;以及（4）在较短的刺激持续时间下，阈值电荷将较低。研究对象包括5名因视网膜色素变性而严重失明的受试者和1名视力正常的受试者（因眼眶癌而接受眼球摘除术）。通过在清醒的志愿者的视网膜上放置单个250 μ m直径的手持针电极或10 μ m厚的氧化铱电极（400 μ m、100 μ m或50 μ m直径）的微制造阵列，对视网膜进行电刺激。眼睛外部的电流源将电荷输送到电极。通过观察眼睛的临床表现，比较术前和术后视力，获得一例视网膜组织学检查，并将感知阈值与已公布的安全限值进行比较，对损伤进行评估。未发生临床可见的眼睛损伤或视力丧失。即使在从刺激中移除的部位，组织学也显示感光细胞内节和外节肿胀，这被认为是非特异性发现。知觉不能可靠地引起与50微米直径的电极使用安全的费用在一个盲人患者。对于两个较大的电极，只有视力正常的患者在400 μ m和100 μ m直径电极的电荷密度分别低于0.25和1.0毫库仑（mC）/cm（2）时具有阈值，这是从每相电荷和每相电荷密度的乘积得出的一个看似合理的安全估计。在盲患者中，阈值总是超过这些水平，尽管在患者6中大多数接近这些限值。盲人患者使用400 μ m电极的电荷密度阈值范围为0.28至2.8 mC/cm（2）。视力正常的患者在400 μ m电极上的阈值为0.08 mC/cm（2），大约是盲人患者最低阈值的四分之一。在两个盲患者中获得的强度-持续时间曲线显示在0.25-或1.0-ms刺激持续时间处的最低阈值电荷。严重失明患者的阈值电荷密度明显高于正常视力患者。盲人患者的电荷密度总是超过一个看似合理的安全刺激估计。人工视网膜长期刺激的潜在不利因素尚未确定。
PURPOSE. To report methods for performing epiretinal electrical stimulation with microfabricated electrode arrays and determining perceptual thresholds on awake human volunteers during acute surgical trials.METHODS. Four hypotheses were tested: (1) epiretinal stimulation can be performed during acute experiments without obviously damaging the retina or degrading vision or the health of the eye; (2) perception can be obtained 50% of the time in blind patients with charge densities below published safety limits; (3) the minimal charge needed to induce perception would be higher in patients with more severe retinal degeneration; and (4) threshold charge would be lower at shorter stimulus durations. Five subjects with severe blindness from retinitis pigmentosa and one with normal vision (who underwent enucleation of the eye because of orbital cancer) were studied. Electrical stimulation of the retina was performed on awake volunteers by placing a single 250-mum diameter hand-held needle electrode or a 10-mum thick microfabricated array of iridium oxide electrodes (400-, 100-, or 50-mum diameter) on the retina. Current sources outside the eye delivered charge to the electrodes. Assessment of damage was made by observing the clinical appearance of the eyes, comparing pre- and postoperative Visual acuity, obtaining retinal histology in one case, and comparing perceptual thresholds with published safety limits.RESULTS. No clinically visible damage to the eye or loss of vision occurred. Even at sites removed from stimulation, histology revealed swollen photoreceptor inner and outer segments, which were believed to be nonspecific findings. Percepts could not be reliably elicited with 50-mum diameter electrodes using safe charges in one blind patient. With the two larger electrodes, only the normal-sighted patient had thresholds at charge densities below 0.25 and 1.0 millicoulombs (mC)/cm(2) for 400- and 100-mum diameter electrodes, respectively, which is one seemingly reasonable estimate of safety derived from the product of charge per phase and charge density per phase. In blind patients, thresholds always exceeded these levels, although most were close to these limits in patient 6. The range of charge density thresholds with the 400-mum electrode in blind patients was 0.28 to 2.8 mC/cm(2). The normal-sighted patient had a threshold of 0.08 mC/cm(2) with a 400-mum electrode, roughly one quarter of the lowest threshold in the blind patients. Strength- duration curves obtained in two blind patients revealed the lowest threshold charge at the 0.25- or 1.0-ms stimulus duration.CONCLUSIONS. Threshold charge densities in severely blind patients were substantially higher than that in a normal-sighted patient. Charge densities in blind patients always exceeded one seemingly reasonable estimate of safe stimulation. The potential adversity of long-term stimulation of the retina by a prosthesis has yet to be determined.