Neuro-ophthalmic Mechanisms Of Disease

疾病的神经眼科机制

• 批准号: 10930504
• 负责人: Edmond J FitzGibbon
• 金额: $ 76.98万
• 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/10930504
• 关键词: Antifungal Therapy; Brain; CADASIL; Characteristics; Clinical; Collaborations; Cranial Nerves; Creation of ventriculo-peritoneal shunt; Cryptococcal Meningitis; Cryptococcus; Data; Defect; Diagnosis; Disease; Disease Progression; Disparity; Dyskinetic syndrome; Dysplasia; Etiology; Eye Movements; Frequencies; Future; Gaucher Disease; Genotype; Goals; Human; Hydrocephalus; Image; Immunocompromised Host; Individual; Inflammatory Response; Intervention Studies; Laboratories; Magnetic Resonance Imaging; McCune-Albright Syndrome; Meningoencephalitis; Metabolic; Modeling; Motion; National Institute of Allergy and Infectious Disease; Natural History; Nerve Degeneration; Neurodegenerative Disorders; Noise; Normal Range; Papilledema; Patients; Pattern; Phenotype; Physiologic Intraocular Pressure; Rare Diseases; Records; Reporting; Scotoma; Staging; Stimulus; Sum; Syndrome; System; Techniques; Testing; Therapeutic Clinical Trial; Time; United States National Institutes of Health; Vascular Diseases; Vision; Visual Acuity; Visual Motion; Visual System; cohort; demographics; detector; disease diagnosis; disparity reduction; experience; insight; mortality; neoplastic; notch protein; ophthalmic examination; optic nerve disorder; response; visual processing; visual stimulus

Several neurodegenerative diseases have characteristic eye movement abnormalities that can be used to diagnose and stage disease progression and as a bio-surrogate in therapeutic clinical trials. Often, eye movement studies help to gain insights into brain mechanisms. Eye movement recordings can be used to study short latency, small amplitude, and reflexive eye movements to patterned targets which can help in understanding the motion visual system. In collaboration with Boris Sheliga, Christian Quaia, and Bruce Cumming of the NEI, we continue to probe the visual motion system using ocular-following response techniques. These approaches use the machine-like eye movements subjects make in response to differing visual stimuli to help elucidate the mechanisms underlying motion and stereovision. In the past year, we studied short-latency disparity vergence response (DVR) to white noise stimuli in humans. While natural images are broadband, detectors in early visual processing are selective for narrow bands of spatial frequency (SF). White noise, along with band-passed and notch-filtered white noise, visual stimuli were used. Removing lower spatial frequency (SF) components reduced DVR amplitude, whereas removing higher SF components led to an increase in DVR amplitude. For larger disparities, the transition occurred at lower SFs. These effects were quantitatively well described by a model that combined two factors: (a) an excitatory drive determined by a weighted sum of stimulus Fourier components, which was scaled by (b) a contrast normalization mechanism. These studies contribute to our understanding of visual processing and motion vision. See Reference #2. Cohorts of patients with rare or unusual diseases are followed at NIH in natural history studies and many undergo neuro-ophthalmic exams. These studies help in genotype-phenotype correlations and provide a basis for future interventional studies. Cryptococcal meningoencephalitis Along with Dr. Peter Williamson and his NIAID team, we reported our experience in following patients with cryptococcal meningoencephalitis. Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with a poor clinical response despite antifungal therapy and negative CSF cultures. Ocular manifestations are common in cryptococcal meningitis (CM) patients but data describing findings in non-immunosuppressed previously healthy individuals is scant. We reviewed our records over a 5-year period at NIH of previously healthy CM patients, including demographics, CSF parameters, eye exam results, and MRI abnormalities. Forty-four patients with a median of 12 weeks after CM diagnosis were included. Twenty-seven (61%) reported abnormal vision when first seen. Seventy-one percent of patients were not shunted at the time of their initial eye examination. The most common ocular abnormalities were visual field defects in 21 (66%), decreased visual acuity in 14 (38%), and papilledema in 8 (26%) patients. Intraocular pressure was within normal range in all patients. Cranial nerve defects were identified in 5 patients and optic neuropathy in 2 patients. Patients who had hydrocephalus or did not receive a ventriculoperitoneal shunt were not noted to have worse ocular abnormalities. The most common ocular findings in our cohort of nontransplant, non-HIV cryptococcal meningitis patients were visual field defects, decreased visual acuity, and papilledema. Our results emphasize the need for a comprehensive eye examination in patients with CM who may not always report a change in vision on presentation. See Reference #1 We continue to study and follow the neuro-ophthalmic aspects of NIH study patients with McCune-Albright Syndrome/Fibrous Dysplasia, Gaucher disease, CADASIL and associated vascular diseases, and other metabolic, neurodegenerative and neoplastic disease cohorts.

几种神经退行性疾病具有特征性眼动异常，可用于诊断和分期疾病进展，并作为治疗性临床试验中的生物替代品。通常，眼动研究有助于深入了解大脑机制。 眼动记录可用于研究短延迟、小幅度和对图案目标的反射性眼动，这有助于理解运动视觉系统。 我们与 NEI 的 Boris Sheliga、Christian Quaia 和 Bruce Cumming 合作，继续使用眼部跟随反应技术来探索视觉运动系统。这些方法利用受试者响应不同视觉刺激而做出的类似机器的眼球运动，以帮助阐明运动和立体视觉的机制。 去年，我们研究了人类对白噪声刺激的短延迟视差聚散反应（DVR）。 虽然自然图像是宽带的，但早期视觉处理中的检测器对窄带空间频率 (SF) 具有选择性。 使用白噪声以及带通和陷波滤波白噪声以及视觉刺激。 去除较低的空间频率 (SF) 分量会降低 DVR 幅度，而去除较高的 SF 分量会导致 DVR 幅度增加。对于较大的差异，转变发生在较低的 SF 处。 这些效应通过结合两个因素的模型得到了很好的定量描述：（a）由刺激傅里叶分量的加权和确定的兴奋驱动，并通过（b）对比度归一化机制进行缩放。 这些研究有助于我们理解视觉处理和运动视觉。请参阅参考文献#2。 美国国立卫生研究院对患有罕见或不寻常疾病的患者进行自然史研究，其中许多患者接受了神经眼科检查。 这些研究有助于基因型-表型相关性，并为未来的干预研究提供基础。 隐球菌性脑膜脑炎 我们与 Peter Williamson 博士和他的 NIAID 团队一起报告了我们跟踪隐球菌性脑膜脑炎患者的经验。隐球菌性脑膜脑炎 (CM) 是免疫抑制患者和既往健康个体死亡的主要原因。在后者中，尽管进行了抗真菌治疗且脑脊液培养呈阴性，但感染后炎症反应综合征 (PIIRS) 仍与临床反应不佳相关。 眼部表现在隐球菌性脑膜炎 (CM) 患者中很常见，但描述非免疫抑制既往健康个体的发现的数据很少。 我们回顾了 NIH 5 年期间以前健康的 CM 患者的记录，包括人口统计、脑脊液参数、眼科检查结果和 MRI 异常。 纳入 CM 诊断后中位时间为 12 周的 44 名患者。二十七 (61%) 的人在第一次见到时报告视力异常。 71% 的患者在初次眼科​​检查时没有被分流。最常见的眼部异常包括 21 名患者 (66%) 的视野缺损、14 名患者 (38%) 的视力下降以及 8 名患者 (26%) 的视乳头水肿。所有患者的眼压均在正常范围内。 5 名患者出现颅神经缺损，2 名患者出现视神经病变。患有脑积水或未接受脑室腹腔分流术的患者并未发现有更严重的眼部异常。在我们的非移植、非 HIV 隐球菌性脑膜炎患者队列中，最常见的眼部症状是视野缺损、视力下降和视乳头水肿。我们的结果强调了对 CM 患者进行全面眼科检查的必要性，他们可能并不总是在就诊时报告视力变化。 请参阅参考文献#1 我们继续研究和跟踪 NIH 研究中患有 McCune-Albright 综合征/纤维发育不良、戈谢病、CADASIL 和相关血管疾病以及其他代谢、神经退行性和肿瘤疾病队列患者的神经眼科方面的情况。

项目成果

Clinical guidelines for the management of craniofacial fibrous dysplasia.

• DOI: 10.1186/1750-1172-7-s1-s2
• 发表时间: 2012-05-24
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Lee JS;FitzGibbon EJ;Chen YR;Kim HJ;Lustig LR;Akintoye SO;Collins MT;Kaban LB
• 通讯作者: Kaban LB

Reply.

回复。

• DOI: 10.1002/art.40923
• 发表时间: 2019
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Kim,AlfredHJ;Strand,Vibeke;Atkinson,JohnP
• 通讯作者: Atkinson,JohnP

Eye movement sequence generation in humans: Motor or goal updating?

• DOI: 10.1167/10.14.28
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF VISION
• 影响因子: 1.8
• 作者: Quaia, Christian;Joiner, Wilsaan M.;Smith, Maurice A.
• 通讯作者: Smith, Maurice A.

Absent optic chiasm presenting with horizontal nystagmus.

视交叉缺失并伴有水平眼球震颤。

• DOI: 10.3928/01913913-20090818-08
• 发表时间: 2010
• 期刊: Journal of pediatric ophthalmology and strabismus
• 影响因子: 1.2
• 作者: Salchow,DanielJ;Kohlhase,Jurgen;Miller,Marijean;Kadom,Nadja;FitzGibbon,EdmondJ;Caruso,RafaelC;Brooks,BrianP
• 通讯作者: Brooks,BrianP

Anisotropy in spatial summation properties of human Ocular-Following Response (OFR).

人类眼球跟随响应 (OFR) 空间总和特性的各向异性。

• DOI: 10.1016/j.visres.2015.02.015
• 发表时间: 2015
• 期刊: Vision research
• 影响因子: 1.8
• 作者: Sheliga,BM;Quaia,C;FitzGibbon,EJ;Cumming,BG
• 通讯作者: Cumming,BG