The Focal Electro-Oculogram in Macular Disease

黄斑疾病的局灶眼电图

• 批准号: 9362431
• 负责人: Brett Jeffrey
• 金额: $ 5.51万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9362431
• 关键词: Age related macular degeneration; Area; Atrophic; Biological Preservation; Caliber; Cells; Cessation of life; Characteristics; Clinical; Clinical Trials; Coloboma; Complex; Dark Adaptation; Dependence; Development; Disease; Electrophysiology (science); Enrollment; Environment; Eye; Functional disorder; Generations; Genes; Light; Measures; Metabolic; Methods; Natural History; Normal Range; Outcome Measure; Participant; Pathogenesis; Patients; Peripheral; Photoreceptors; Retina; Retinal Diseases; Stargardt' s disease; Stimulus; Structure of retinal pigment epithelium; Test Result; Testing; Variant; Visit; Vitelliform macular dystrophy; base; disorder of macula of retina; extracellular; fovea centralis; healthy volunteer; human subject; interest; light scattering; luminance; macula; research study; response; small molecule; volunteer

Specific Aim 1: Develop a method for recording the focal EOG in response to a centrally presented light stimulus. A total of 15 healthy volunteers over the course of 1-3 study visits have participated in the study. Initial experiments to induce a dark trough before generating the light peak were shown to be highly variable. We shifted towards elimination of the dark trough in favor of generating a baseline dark amplitude during a long dark adaptation period of 40 minutes. For the light peak, we tested various stimulus sized and found that a 20o central stimulus was insufficient to generate a response from the target area, but a 40o central stimulus could produce the target response. Therefore, our current method is dark adaptation for 25 minutes, recording in the dark (to establish the baseline amplitude) for 20 minutes, then presentation of the light stimulus for 15 minutes. This method produces a recording lasting 35 minutes, which has been well-tolerated by all subjects. In order to test the response to centrally presented 40o light stimuli, volunteers were presented various central stimuli ranging from 10 to 150 cd/m2 in intensity. While 5/9 (56%) of eyes showed a light rise to 10 cd/m2, all 36 eyes tested showed light rises in response to intensities 40 cd/m2. Light peak:baseline averaged 1.370.19. Therefore, 40 cd/m2 appears to be the minimum 40 stimulus necessary and sufficient to generate a light rise. In order to test the variation in response to scattered light from central stimuli, various background intensities ranging from 0.4 cd/m2 to 1.1 cd/m2 were presented to volunteers. At the lowest background tested, participants had no or minimal light rise. The results above indicate that our method is able to measure an EOG light rise using a centrally presented 40 deg stimulus. Specific Aim 2: Testing in healthy volunteers to determine intra- and inter-session variability. We have not yet attempted to measure variability in the focal EOG response. Specific Aim 3: Examine the focal EOG in participants with macular disease. Our results from testing healthy volunteers suggests that method provides the capability to measure an EOG light rise from a centrally presented 40 deg stimulus. We then conducted proof-of-principle experiments in 6 patients with ABCA4 retinopathy who had foveal preservation with good acuity and whom had contiguous atrophy across the macular but a normal peripheral retina. We hypothesized that these patients would have a normal full-field EOG but no focal EOG, if indeed there is no light scatter from the 40 deg stimulus. Two subjects did have normal full-field EOG with no focal EOG as predicted which supports our hypothesis. However, three other patients with ABCA4 patients had a light rise with both full-field and focal EOGs. There are two possible explanations of these results: First, the level of atrophy across the macula was not sufficient to reduce the focal EOG. Second, that the apparent focal EOG light rise was caused by scattered light. Therefore, these experiments did not provide conclusive evidence that the focal EOG is being driven by the central retina without a contribution from scattered light. Therefore, we are now enrolling patients with uveal colobomas larger than 40 deg in diameter and which do not involve the fovea. These patients have a clear cut loss of retina/RPE complex with surrounding normal retina and therefore, should provide a better test of whether scattered light confounds recording of the focal EOG.

具体目标1：开发一种方法，用于记录响应于中央呈现的光刺激的局灶性EOG。 在1-3次研究访视期间，共有15名健康志愿者参与了本研究。在产生光峰之前诱导暗槽的初始实验显示出高度可变性。我们转向消除暗槽，有利于在40分钟的长暗适应期间产生基线暗振幅。对于光峰，我们测试了各种大小的刺激，发现20 o的中枢刺激不足以产生来自目标区域的响应，但40 o的中枢刺激可以产生目标响应。 因此，我们目前的方法是暗适应25分钟，在黑暗中记录（以建立基线振幅）20分钟，然后呈现光刺激15分钟。这种方法产生持续35分钟的记录，所有受试者都能很好地耐受。 为了测试对中央呈现的40 °光刺激的反应，向志愿者呈现强度范围从10到150 cd/m2的各种中央刺激。虽然5/9（56%）的眼睛显示光升高至10 cd/m2，但所有36只受试眼睛均显示响应强度40 cd/m2的光升高。光峰：基线平均值为1.370.19。因此，40 cd/m2似乎是产生光升高所需的最小40刺激。 为了测试响应于来自中枢刺激的散射光的变化，向志愿者呈现范围从0.4 cd/m2至1.1 cd/m2的各种背景强度。在测试的最低背景下，参与者没有或只有最小的光上升。 上述结果表明，我们的方法能够使用中心呈现的40度刺激来测量EOG光上升。 具体目标2：在健康志愿者中进行测试，以确定阶段内和阶段间的变异性。 我们尚未尝试测量局灶性眼电图反应的变异性。 具体目标3：检查黄斑疾病参与者的局灶性EOG。 我们对健康志愿者的测试结果表明，该方法能够测量来自中心呈现的40度刺激的EOG光上升。 然后，我们在6例ABCA 4型视网膜病变患者中进行了原理验证实验，这些患者具有良好的视敏度和黄斑连续萎缩，但周边视网膜正常。 我们假设这些患者将有正常的全视野EOG，但没有局灶性EOG，如果确实没有来自40度刺激的光散射。 两名受试者的全视野EOG正常，但没有预测的局灶性EOG，这支持了我们的假设。 然而，其他三名ABCA 4患者的全视野和局灶性EOG均轻微上升。 这些结果有两种可能的解释：第一，黄斑萎缩的程度不足以降低局灶性EOG。 第二，表观焦点EOG光上升是由散射光引起的。 因此，这些实验没有提供结论性的证据表明，焦点EOG是由中央视网膜驱动的，而没有散射光的贡献。 因此，我们现在招募葡萄膜缺损直径大于40度且不累及中央凹的患者。 这些患者的视网膜/RPE复合体与周围正常视网膜明显缺失，因此，应提供更好的测试，以确定散射光是否会混淆局灶性EOG的记录。