Neuro-ophthalmic Mechanisms Of Disease

疾病的神经眼科机制

• 批准号: 8556824
• 负责人: Edmond J FitzGibbon
• 金额: $ 21.92万
• 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/8556824
• 关键词: Acoustic Neuroma; Affect; Age; Anesthesia procedures; Anterior; Blindness; Brain Diseases; Brain Part; Cataract; Characteristics; Clinic; Clinical; Collaborations; Complication; Cornea; Degenerative Disorder; Dental; Diagnosis; Disease; Disease Progression; Dysplasia; Enrollment; Etiology; Exhibits; Eye; Eye Movements; Facial paralysis; Frequencies; Gaucher Disease; Generations; Genotype; Glioma; Goals; Guidelines; Hamartoma; Hereditary Disease; Image; Incidence; Institutes; Iris; Laboratories; Lead; Lisch nodules; Measures; Meta-Analysis; Motion; Natural History; Neuraxis; Neurodegenerative Disorders; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis 2; Neurologic; Ocular Motility Disorders; Operative Surgical Procedures; Optic Nerve; Outcome; Patient observation; Patients; Phenotype; Plexiform Neurofibroma; Process; Protocols documentation; Publications; Publishing; Reporting; Retinal; Risk; Saccades; Somatotrophin increased; Somatotropin; Sphenoid bone structure; Staging; Stimulus; Subacute Neuronopathic Gaucher Disease; System; Techniques; Testing; Time; Tissues; Twin Multiple Birth; United States National Institutes of Health; Vision; Visual Motion; Wing; bone; cell motility; cohort; craniofacial; disease natural history; eye dryness; insight; meetings; nerve decompression; oculomotor; optic nerve disorder; response; skull base

In this report I will concentrate on studies of various neuro-degenerative diseases which have characteristic oculomotor abnormalities, and also in diseases that affect the optic nerve 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 recently published the results of following a cohort of 15 patients with Gaucher type 3 disease. Significant findings include vertical saccade slowing with downward saccades more severely affected and evidence of slow progression of the disease with time as noted by saccadic recordings. Another publication examined twins with Gaucher disease exhibiting highly discordant Gaucher phenotypes demonstrating the poor predictability of phenotype given a specific genotypic diagnosis. 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 80 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 meta-analysis was published comparing watchful waiting versus optic nerve decompression surgery in craniofacial fibrous dysplasia. The study confirmed that watchful waiting is the recommended course. Another publication presented the outcome of a meeting held at NIH on fibrous dysplasia along with recommended clinical guidelines. Lastly, a preliminary report comparing two groups with controlled and uncontrolled high growth hormone levels suggested 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 are being enrolled in a natural disease study and continue to be examined in the eye clinic. Longitudinally,several parameters are followed including Lisch nodules, vision, and ocular motility. Complete neuro-ophthalmic exams and imaging are performed. Currently we are examining the irides of these patients for comparison of their Lisch nodules with other disease measures. 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. 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. In the past year two publications examined the interactions of size and sppatial frequency of moving vertical sine wave gratings and on their spatial arrangement. These approaches use the machine like eye movements made in response to differing stimuli to help understand the mechanisms underlying motion vision.

在本报告中，我将集中研究具有特征性动眼神经异常的各种神经退行性疾病，以及影响视神经或具有神经眼科后果的疾病，例如纤维发育不良和神经纤维瘤病。 动眼神经控制分布在整个大脑中，对大脑各部分有不同影响的疾病可以以不同且通常是特定的方式影响眼球运动。我们记录了神经退行性疾病和遗传性疾病患者的眼球运动，以表征他们的眼球运动障碍，帮助做出具体诊断，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。 我们最近发表了对 15 名戈谢 3 型病患者进行随访的结果。重要的发现包括垂直扫视减慢，向下扫视受到更严重的影响，以及扫视记录表明疾病随时间缓慢进展的证据。另一篇出版物检查了患有戈谢病的双胞胎，表现出高度不一致的戈谢表型，表明在特定基因型诊断的情况下，表型的可预测性很差。 纤维性发育不良（FD）是一种正常骨被纤维骨组织取代的疾病。在多骨症中，前颅底经常受累，包括蝶骨。视神经穿过蝶骨翼，在 CT 成像上经常发现被 FD 包裹。视神经纤维异常增生的治疗存在争议，因为导致视力丧失的视神经病变是最常报告的神经系统并发症。与牙科研究所的 Michael Collins 博士合作，继续对 80 多名纤维性发育不良患者进行纵向随访，进行神经眼科检查，以追踪这种疾病的自然史。去年发表的一项荟萃​​分析比较了颅面纤维发育不良的观察等待与视神经减压手术。研究证实，观察等待是推荐的做法。另一份出版物介绍了美国国立卫生研究院 (NIH) 举行的关于纤维异常增生的会议的结果以及推荐的临床指南。最后，一份初步报告对两组受控和不受控的高生长激素水平进行了比较，结果表明，从小就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。大约 25% 的患者会出现丛状神经纤维瘤，这是 NF1 最严重的并发症之一。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，NF1 患者正在参加一项自然疾病研究，并继续在眼科诊所接受检查。纵向观察几个参数，包括 Lisch 结节、视力和眼球运动。进行完整的神经眼科检查和成像。 目前，我们正在检查这些患者的虹膜，以将他们的 Lisch 结节与其他疾病指标进行比较。 另一项正在进行的自然史方案是针对 2 型神经纤维瘤病 (NF2) 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）造成的压迫可导致面神经麻痹、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。 NF2 患者还可能出现白内障和视网膜错构瘤。 我们与 NEI 的 Boris Sheliga 和 Christian Quaia 合作，继续使用 NEI 的 Fred Miles 首创的眼部跟随反应技术来探索视觉运动系统。 去年，两篇出版物研究了移动垂直正弦波光栅的尺寸和空间频率的相互作用及其空间排列。这些方法使用类似眼球运动的机器来响应不同的刺激，以帮助理解运动视觉的机制。