INVESTIGATION AND TREATMENT OF OCULAR MOTOR DISORDERS

本研究的长期目标是：(1)更多地了解损害日常活动所需视力的人类眼运动障碍；(2)评估恢复清晰视力的治疗措施。研究策略是将眼球运动的可靠测量与患者自然行为的视觉抱怨联系起来；通过对正常和异常眼球运动的测量来测试生物学上合理的数学模型；并通过对照试验评价眼球运动障碍的新治疗方法。有五个具体的目标，这些目标是从先前的研究中产生的：第一个项目包括获得性钟摆性眼球震颤模型的测试。确定大的凝视位移和亮度变化的影响将用于测试控制系统和神经网络模型。第二个项目旨在确定头部旋转前的眼球运动是否能在头部突然转动时提高前庭眼反射的增益。这种“启动”效应可能发生在各种先前的眼球运动中，但不会发生在凝视机制（神经整合器）缺陷的患者中。第三个项目旨在测试赫林定律是否适用于析取凝视移动期间的跳眼脉冲（即等脉冲大小）。研究对象为正常人和核间性眼麻痹患者。第四个项目包括检验解释跳变振荡的模型。利用新的实验技术诱导正常人和患者的跳眼振荡，系统地研究小脑和脑干病变对跳眼振荡的影响。第五个项目是东莨菪碱和加巴喷丁治疗获得性眼球震颤的对照评价。研究表明，加巴喷丁可抑制钟摆性眼球震颤，但其副作用如共济失调限制了剂量的耐受性。东莨菪碱可能对眼腭震颤患者更有效。总之，这些项目将为一系列常见的眼球运动疾病的发病机制和治疗提供新的信息，这些疾病会破坏清晰的视力。

The long-term objectives of the proposed research are: (1) to learn more about human ocular motor disorders that impair the vision necessary for everyday activities, and (2) to appraise therapeutic measures to restore clear vision. The research strategies are to relate reliable measurements of eye movements to visual complaints of patients doing natural behaviors; and to use measurements of normal and abnormal eye movements to test mathematical models that are biologically plausible; and evaluate new treatments of disorders of ocular motility using controlled trials. There are five specific aims, which grow out of prior studies: The first project comprises tests of models for acquired pendular nystagmus. Determination of the effects of large gaze shifts and luminance changes will be used to test control systems and neural network models. The second project aims to determine whether eye movements prior to head rotation improve the gain of the vestibulo-ocular reflex, during sudden head turns. This "priming" effect may occur with a variety of prior eye movements but not in patients with a deficient gaze-holding mechanism (neural integrator). The third project aims to test whether Hering's law applies to saccadic pulses (i.e., equal pulse size) during disjunctive gaze shifts. Normal subjects and patients with internuclear ophthalmoplegia will be studied. The fourth project comprises tests of models that account for saccadic oscillations. Using a new experimental technique to induce saccadic oscillations in normal subjects and patients, the effects of cerebellar and brainstem lesions will be systematically investigated. The fifth project is a controlled evaluation of scopolamine and gabapentin as treatment for acquired forms of nystagmus. It has been shown that gabapentin suppresses pendular nystagmus, but side-effects such as ataxia limit the dosage tolerated. Scopolamine may prove more effective in patients with oculopalatel tremor. In sum, these projects will prove new information on the pathogenesis and treatment of a range of common disorders of eye movements that disrupt clear vision.