In this report I will concentrate on studies of various diseases which have characteristic oculomotor abnormalities, and also on diseases that affect vision 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 are currently analyzing the longitudinally recorded eye movmement of a cohort with Niemann Pick C disease. Fibrous dysplasia (FD) is a disease where normal bone is replaced with fibro-osseous tissue. Patients with McCune Albright syndrome have polyostotic fibrous dysplasia, endocrine abnormalities, and caf au lait spots. In McCune Albright syndrome, 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 90 patients with fibrous dysplasia continue to be followed longitudinally with neuro-ophthalmologic exams to track the natural history of this disease. Our experience in this cohort is that optic neuropathy is unusual and the recommendation is that surgical decompression not be done. Patients with high growth hormone are at risk for optic neuropathy but not if the growth hormone excess can be controlled. We continue to longitudinally follow these patients and recruit new patients with McCune Albright syndrome. 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 enrolled in a natural disease study continue to be examined in the eye clinic. Several parameters are followed including Lisch nodules, vision, ocular motility and lid function. Complete neuro-ophthalmic exams and imaging are performed. In collaboration with colleagues at Georgetown University a paper was published on the natural history of orbital plexiform neurofibromas in children. 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 which can be devastating in these often deaf individuals. NF2 patients may also present with cataracts and retinal hamartomas. These patients are followed longitudinally for new tumor development. Erdheim Chester disease is a rare histiocytosis typically developing in patient in their 5th decade of life. Collections of histiocytes may be found in the long bones, retroperitoneal space, in the kidneys, lungs and the orbits among other spaces. Presentation in the orbit can lead to proptosis, diplopia, and optic neuropathy. We are longitudinally following a cohort of Erdheim Chester patients with Dr. Juvianee Estrada Veras for neuro-ophthalmic findingss. Orbital involvement is uncommon with less than 20% of our cohort demonstrating orbital masses. 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. These approaches use the machine like eye movements made in response to differing stimuli to help understand the mechanisms underlying motion vision. In the past year experiments demonstrated how ocular following responses are constrained by early stages of the human visual system.
Showing the most recent 10 out of 23 publications
