Investigation and Treatment of Ocular Motor Disorders

描述(申请人提供)：拟议研究的长期目标是：(1)更多地了解在日常活动中损害视力的人类眼球运动障碍；(2)应用基础科学的见解来更好地了解临床问题(翻译方法)；以及(3)评估针对异常眼球运动的治疗措施，从而恢复清晰的视力。根据以前的研究，有五个具体的目标：第一个项目解决眼阵挛等疾病的发病机制，以及将这些眼睛振荡归因于小脑或脑干机制的模型。第二个项目研究快速眼球运动(眼跳)的速度分布，由于这些运动过早终止，某些影响脑干和小脑的疾病会中断眼球运动。第三个项目涉及视点自然移动过程中眼跳和集中运动相互作用的方式。使用一种新的范式，有可能在时间上分离眼跳和会聚成分，从而系统地研究它们的相互作用。第四个项目解决了前庭眼球运动是如何在观看靠近头部固定的目标时被抑制的(就像在走路时阅读一样)。其目的是为了更好地了解前庭或视觉调节眼球运动障碍患者在此类任务中的残疾。第五个项目是对美金刚和加巴喷丁治疗获得性眼球震颤的交叉评估。加巴喷丁可抑制获得性眼球震颤，改善部分患者的视力，但共济失调等副作用限制了患者的耐受量。据报道，美金刚还可以抑制多发性硬化症(MS)的摆动性眼球震颤和改善视力，但尚未进行双掩蔽试验。研究策略是(1)将可靠的眼球运动测量与患者在自然行为期间的视觉抱怨联系起来；(2)使用正常和异常眼球运动的测量来测试生物学上可信的数学模型；以及(3)通过对照试验评估眼球运动障碍的新疗法。因此，这些项目将为一系列破坏清晰视力的常见眼球运动障碍的发病机制和治疗提供新的信息。

DESCRIPTION (provided by applicant): The long-term objectives of the proposed research are: (1) to learn more about human ocular motor disorders that impair vision during everyday activities; (2) to apply insights from basic science to better understand clinical problems (a translational approach); and (3) to appraise therapeutic measures for abnormal eye movements and so restore clear vision. There are five specific aims, which grow out of prior studies: The first project addresses the pathogenesis of disorders such as opsoclonus, and models that attribute these ocular oscillations to either cerebellar or brainstem mechanisms. The second project investigates the velocity profiles of rapid eye movements (saccades), which are disrupted in certain disorders affecting the brainstem and cerebellum due to premature termination of these movements. The third project concerns the way in which saccades and vergence movements interact during natural shifts of the fixation point. Using a novel paradigm, it is possible to dissociate in time the saccadic and vergence components, and thus systematically study their interaction. The fourth project addresses how vestibular eye movements are suppressed while viewing a near, head fixed target (as in reading while walking). The goal is to better understanding disability for such tasks in patients with disorders of vestibular or visually mediated eye movements. The fifth project is a crossover evaluation of memantine and gabapentin as treatment for acquired forms of nystagmus. Gabapentin suppresses acquired nystagmus and improves vision in some patients, but side-effects such as ataxia limit the dosage tolerated. Memantine is also reported to suppress pendular nystagmus and improve vision in multiple sclerosis (MS), but no double-masked trial has been performed. The research strategies are (1) to relate reliable measurements of eye movements to visual complaints of patients during natural behaviors; (2) to use measurements of normal and abnormal eye movements to test mathematical models that are biologically plausible; and (3) to evaluate new treatments of disorders of ocular motility using controlled trials. Thus, these projects will provide new information on the pathogenesis and treatment of a range of common disorders of eye movements that disrupt clear vision.