Neuro-ophthalmic Mechanisms Of Disease

几种神经退行性疾病具有特征性的眼球运动异常，可用于诊断和分期疾病进展，并在治疗临床试验中作为生物替代品。通常情况下，眼球运动研究有助于深入了解大脑机制。 眼动记录可以用来研究短潜伏期、小幅度和对图案化目标的反射性眼动，这有助于理解运动视觉系统。 在与NeI的Boris Sheliga、Christian Quaia和Bruce Cumming的合作下，我们继续使用眼睛跟随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潜在机制。 在过去的一年里，我们研究了人类对白噪声刺激的短潜伏期视差集中反应(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。使用白噪声、带通白噪声和陷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幅度的增加。对于较大的差异，转变发生在较低的SFS。这些影响通过一个结合了两个因素的模型得到了很好的定量描述：(A)由刺激傅立叶分量的加权和确定的兴奋性驱动力，它由(B)对比度归一化机制来衡量。 这些研究有助于我们对视觉加工和运动视觉的理解。请参阅参考文献2。 在自然历史研究中，NIH对一批患有罕见或不寻常疾病的患者进行了跟踪调查，其中许多人接受了神经眼科检查。这些研究有助于研究基因-表型之间的相关性，并为今后的干预性研究提供基础。 隐球菌性脑膜脑炎 与Peter Williamson博士和他的NIAID团队一起，我们报告了跟踪观察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人死亡的主要原因。在后者中，感染后炎症反应综合征(PIIRS)与临床反应差有关，尽管抗真菌治疗和脑脊液培养阴性。 眼部表现在隐球菌性脑膜炎(CM)患者中很常见，但描述以前没有免疫抑制的健康个体的发现的数据很少。我们回顾了美国国立卫生研究院5年来对先前健康的CM患者的记录，包括人口统计学、脑脊液参数、眼科检查结果和MRI异常。纳入44例患者，中位数为CM诊断后12周。27人(61%)报告第一次看到时视力异常。71%的患者在首次眼睛检查时没有分流。最常见的眼部异常为视野缺陷21例(66%)，视力下降14例(38%)，乳头水肿8例(26%)。所有患者眼压均在正常范围内。脑神经损伤5例，视神经病变2例。有脑积水或没有接受脑室-腹膜分流术的患者没有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，最常见的眼部表现是视野缺陷、视力下降和乳头水肿。我们的结果强调了对CM患者进行全面眼科检查的必要性，这些患者可能并不总是报告出现视力变化。请参阅参考文献#1 我们继续研究和跟踪美国国立卫生研究院麦库恩-奥尔布赖特综合征/纤维发育不良、高谢病、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患者的神经眼科方面的研究。

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.