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，以及影响视神经或具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。 我们最近发表了对15例3型戈谢病患者进行随访的结果。重要的发现包括垂直扫视减慢，向下扫视更严重地受到影响，以及如扫视记录所指出的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下表型的可预测性较差。 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成像中经常发现被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80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，发表了一项荟萃分析，比较了颅面纤维结构不良患者的观察等待与视神经减压手术。研究证实，观察等待是推荐的过程。另一篇出版物介绍了在NIH举行的关于纤维结构不良的会议的结果以及推荐的临床指南。最后，一份初步报告比较了两组受控制和不受控制的高生长激素水平，表明从年轻时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，NF1患者正在参加自然疾病研究，并继续在眼科诊所接受检查。纵向上，几个参数，包括Lisch结节，视力，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，以比较他们的Lisch结节与其他疾病的措施。 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。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。 在过去的一年中，两个出版物审查的相互作用的大小和空间频率的移动垂直正弦波光栅和他们的空间安排。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。