Neuro-ophthalmic Mechanisms Of Disease

在这份报告中，我将集中在各种神经退行性疾病的研究，这些疾病具有特征性的眼部异常，也对影响视力或有神经眼科后果的疾病，如纤维结构不良和神经纤维瘤病。 眼动控制分布在整个大脑中，不同影响大脑部分的疾病可以以不同且通常特定的方式影响眼球运动。我们记录了患有神经退行性疾病和遗传性疾病的患者的眼球运动，以表征他们的眼球运动障碍，以帮助做出具体的诊断，将表型与基因型相关联，分期疾病进展，并深入了解眼球运动产生的过程。我们目前正在分析一个尼曼匹克C病队列的纵向记录眼球运动。 纤维性发育不良（FD）是一种疾病，其中正常骨被纤维骨组织取代。多骨型常累及前颅底，包括蝶骨。视神经穿过蝶骨翼，在CT成像上经常被FD包裹。视神经纤维异常增殖症的治疗是有争议的，因为导致视力丧失的视神经病变是最常见的神经系统并发症。与牙科研究所的Michael柯林斯博士合作，对90多名纤维性结构不良患者进行了神经眼科检查，以追踪这种疾病的自然史。在过去的一年中，一份出版物介绍了在NIH举行的纤维结构不良会议的结果沿着推荐的临床指南。此外，还发表了一篇论文，比较了两组受控制和不受控制的高生长激素水平。数据显示，从小控制过量的生长激素可以降低视神经病变的风险。 1型神经纤维瘤病（NF1）是一种常见的常染色体显性遗传病。丛状神经纤维瘤发生在约25%的患者中，这些是NF1最令人衰弱的并发症。中枢神经系统胶质瘤和其他神经眼科表现的发病率也较高。与NCI的Brigitte Wideman合作，参加自然疾病研究的NF1患者继续在眼科诊所接受检查。几个参数，包括Lisch结节，视力，眼球运动和眼睑功能。进行完整的神经眼科检查和成像。 与乔治敦大学的同事合作，发表了一篇关于儿童眼眶丛状神经纤维瘤自然史的论文。 另一个正在进行的自然病史方案遵循2型神经纤维瘤病（NF 2）患者。这些患者患有听神经瘤，这些肿瘤（或前庭神经鞘瘤的手术矫正）的压迫可导致面瘫伴眼睑闭合不良、角膜麻醉和干眼。这些并发症使他们的眼睛面临视力丧失的风险，这对这些经常失聪的人来说可能是毁灭性的。NF2患者也可能出现白内障和视网膜错构瘤。 在与NEI的Boris Sheliga和Christian Kristia的合作中，我们继续使用NEI的Fred Miles开创的视觉跟随响应技术来探索视觉运动系统。这些方法使用类似机器的眼球运动来响应不同的刺激，以帮助理解运动视觉的机制。 在过去的一年中，发表了两篇论文，研究人类眼随动反应的空间特性。

In this report I will concentrate on studies of various neuro-degenerative diseases which have characteristic oculomotor abnormalities, and also on diseases that affect vision or have neuro-ophthalmic consequences such as fibrous dysplasia and neurofibromatosis. Oculomotor control is distributed throughout the brain, and diseases differentially affecting parts of the brain can affect eye movements in different, and often specific ways. We have recorded eye movements in patients with neurodegenerative and genetic diseases to characterize their ocular motility disorder, to help make a specific diagnosis, to correlate phenotype to genotype, to stage disease progression, and to give insight into the processes underlying eye movement generation. We are currently analyzing the longitudinally recorded eye movmement of a cohort with Niemann Pick C disease. Fibrous dysplasia (FD) is a disease where normal bone is replaced with fibro-osseous tissue. In the polyostotic form, the anterior cranial base is frequently involved, including the sphenoid bones. The optic nerve passes through the sphenoid wing and is often found to be encased by FD on CT imaging. The management of fibrous dysplasia encased optic nerves is controversial, as optic neuropathy resulting in vision loss is the most frequently reported neurological complication. In collaboration with Dr. Michael Collins of the Dental Institute, a cohort of more than 90 patients with fibrous dysplasia continue to be followed longitudinally with neuro-ophthalmologic exams to track the natural history of this disease. In the past year a publication presented the outcome of a meeting held at NIH on fibrous dysplasia along with recommended clinical guidelines. In addition a paper was published comparing two groups with controlled and uncontrolled high growth hormone levels. The data showed that controlling excess growth hormone from a young age reduces the risk of optic neuropathy. Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder. Plexiform neurofibromas develop in about 25% of patients and these are among the most debilitating complication of NF1. There is also a higher incidence of central nervous system gliomas and other neuro-ophthalmic manifestations. In collaboration with Brigitte Wideman of NCI, NF1 patients enrolled in a natural disease study continue to be examined in the eye clinic. Several parameters are followed including Lisch nodules, vision, ocular motility and lid function. Complete neuro-ophthalmic exams and imaging are performed. In collaboration with colleagues at Georgetown University a paper was published on the natural history of orbital plexiform neurofibromas in children. Another ongoing natural history protocol follows patients with neurofibromatosis type 2 (NF2). These patients have acoustic neuromas and compression from these (or from surgical correction of vestibular schwannomas) can lead to facial palsy with poor lid closure, corneal anesthesia, and dry eyes. These complications put their eyes at risk for vision loss which can be devastating in these often deaf individuals. NF2 patients may also present with cataracts and retinal hamartomas. In collaboration with Boris Sheliga and Christian Quaia of the NEI, we continue to probe the visual motion system using ocular following response techniques pioneered by Fred Miles of the NEI. These approaches use the machine like eye movements made in response to differing stimuli to help understand the mechanisms underlying motion vision. In the past year two papers were published examining the spatial properties of the ocular following response in humans.