Neuro-ophthalmic Mechanisms Of Disease

几种神经退行性疾病具有特征性眼球运动异常，可用于诊断和分期疾病进展，并在治疗性临床试验中作为生物替代物。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潜伏期、小幅度和反射性眼动，从而有助于理解运动视觉系统。 我们与NEI的Boris Sheliga、Christian Rupia和布鲁斯·卡明合作，继续使用眼跟踪反应技术来探索视觉运动系统。这些方法使用受试者对不同视觉刺激做出的类似机器的眼球运动来帮助阐明运动和立体视觉的机制。 在过去的一年中，我们研究了人类对白色噪声刺激的短潜伏期视差聚散反应（DVR）。 虽然自然图像是宽带的，但早期视觉处理中的检测器对空间频率（SF）的窄带具有选择性。 使用白色噪声沿着带通和陷波滤波的白色噪声、视觉刺激。 去除较低的空间频率（SF）分量降低了DVR幅度，而去除较高的SF分量导致DVR幅度的增加。对于较大的差距，过渡发生在较低的SF。 这些效应通过结合两个因素的模型进行了定量描述：（a）由刺激傅立叶分量的加权和确定的兴奋性驱动，其通过（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加工和运动视觉。参见参考文献#2。 NIH在自然史研究中对罕见或不常见疾病患者进行了队列研究，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，并为未来的干预性研究提供基础。 隐球菌性脑膜脑炎 沿着Peter威廉姆森博士和他的NIAID小组，我们报告了我们随访隐球菌脑膜脑炎患者的经验。隐球菌脑膜脑炎（CM）是免疫抑制患者和先前健康个体死亡的主要原因。在后者中，感染后炎症反应综合征（PIIRS）与尽管进行了抗真菌治疗和CSF培养阴性但临床反应较差相关。 隐球菌性脑膜炎（CM）患者的眼部表现很常见，但描述非免疫抑制既往健康个体的数据很少。 我们回顾了我们在NIH的5年期间以前健康的CM患者的记录，包括人口统计学，CSF参数，眼科检查结果和MRI异常。 纳入了44例CM诊断后中位数为12周的患者。27例（61%）报告第一次见到时视力异常。71%的患者在初次眼部检查时没有分流。最常见的眼部异常为21例（66%）患者的视野缺损，14例（38%）患者的视力下降和8例（26%）患者的视乳头水肿。所有患者的眼压均在正常范围内。颅神经缺损5例，视神经病变2例。患有脑积水或未接受脑室腹腔分流术的患者未发现有更严重的眼部异常。在我们的非移植、非HIV隐球菌脑膜炎患者队列中，最常见的眼部表现是视野缺损、视力下降和视乳头水肿。我们的研究结果强调，需要一个全面的眼科检查的患者与CM谁可能并不总是报告视力的变化介绍。 参见参考文献1 我们继续研究和随访NIH研究患者的神经眼科方面，包括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、神经退行性和肿瘤性疾病队列。

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.