Neuro-ophthalmic Mechanisms Of Disease

一些神经退行性疾病具有特征性的眼动异常，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品。通常，眼动研究有助于深入了解大脑机制。

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.