In this report I will concentrate on studies of various neuro-degenerative 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. In the polyostotic form, 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. In the past year a publication presented the outcome of a meeting held at NIH on fibrous dysplasia along with recommended clinical guidelines. In addition a paper was published comparing two groups with controlled and uncontrolled high growth hormone levels. The data showed that controlling excess growth hormone from a young age reduces the risk of optic neuropathy. 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. 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 two papers were published examining the spatial properties of the ocular following response in humans.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat et al. (2014) Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11. Ann Clin Transl Neurol 1:379-389
Avery, Robert A; Dombi, Eva; Hutcheson, Kelly A et al. (2013) Visual outcomes in children with neurofibromatosis type 1 and orbitotemporal plexiform neurofibromas. Am J Ophthalmol 155:1089-1094.e1
Boyce, Alison M; Glover, McKinley; Kelly, Marilyn H et al. (2013) Optic neuropathy in McCune-Albright syndrome: effects of early diagnosis and treatment of growth hormone excess. J Clin Endocrinol Metab 98:E126-34
Schiffmann, Raphael; Fitzgibbon, Edmond J; Harris, Chris et al. (2008) Randomized, controlled trial of miglustat in Gaucher's disease type 3. Ann Neurol 64:514-22