This application proposes expanded programs of patient-oriented research and mentoring by Laura J. Balcer, M.D., M.S.C.E., an established clinical investigator whose work has focused on the development of visual outcomes for clinical trials in multiple sclerosis (MS). Dr. Balcer's research has demonstrated validity for low-contrast letter acuity and for retinal nerve fiber layer (RNFL) thickness and macular volume by optical coherence tomography (OCT) in MS, but has not established roles for these parameters in outcomes assessment for acute optic neuritis (ON), a model for acute demyelization and axonal/neuronal loss in MS and an ideal target for examining neuroprotective therapies. The research plan will accomplish the following aims:
Specific Aim 1 : Refine and validate low-contrast letter acuity and OCT as new visual outcomes for clinical trials in MS, and in acute ON as a model system for future testing of neuroprotective agents.
Specific Aim 2 : Determine how new visual outcomes, low-contrast letter acuity and OCT, reflect vision-specific and overall health-related quality of life in longitudinal studies of MS and ON, and examine the validity and usefulness of a new 10-ltem Neuro-Ophthalmic Supplement to the 25-ltem NEI Visual Functioning Questionnaire (NEI-VFQ-25) in these patient populations. These investigations will further define potential roles for new measures of low-contrast letter acuity and OCT in MS clinical trials, and will apply paradigms from MS vision research to the study of acute ON as a more specific model system for assessment of natural history and neuroprotective treatment trial outcomes. Participation by mentees in refinement of study design, performance of hands-on testing, data analysis, and manuscript preparation will be a central focus of the candidate's mentoring plan. These proposed new projects have been designed and selected to facilitate trainee involvement, and are sufficiently flexible and varied in scope to incorporate mentees in Neurology at all levels of training. Public Health Statement: MS and optic neuritis are leading causes of visual loss among young and middle-aged adults in the U.S. This work will provide support for additional research and for mentoring of beginning clinician scientists in the development of improved testing methods for vision in these conditions.

National Institute of Health (NIH)
National Eye Institute (NEI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Special Emphasis Panel (ZEY1-VSN (01))
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Schron, Eleanor
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University of Pennsylvania
Schools of Medicine
United States
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Waldman, Amy T; Chahin, Salim; Lavery, Amy M et al. (2016) Binocular low-contrast letter acuity and the symbol digit modalities test improve the ability of the Multiple Sclerosis Functional Composite to predict disease in pediatric multiple sclerosis. Mult Scler Relat Disord 10:73-78
Galetta, Matthew S; Galetta, Kristin M; McCrossin, Jim et al. (2013) Saccades and memory: baseline associations of the King-Devick and SCAT2 SAC tests in professional ice hockey players. J Neurol Sci 328:28-31
Walter, Scott D; Ishikawa, Hiroshi; Galetta, Kristin M et al. (2012) Ganglion cell loss in relation to visual disability in multiple sclerosis. Ophthalmology 119:1250-7
Davies, Emma C; Henderson, Sam; Balcer, Laura J et al. (2012) Residency training: the King-Devick test and sleep deprivation: study in pre- and post-call neurology residents. Neurology 78:e103-6
Galetta, Kristin M; Graves, Jennifer; Talman, Lauren S et al. (2012) Visual pathway axonal loss in benign multiple sclerosis: a longitudinal study. J Neuroophthalmol 32:116-23
Galetta, Kristin M; Brandes, Lauren E; Maki, Karl et al. (2011) The King-Devick test and sports-related concussion: study of a rapid visual screening tool in a collegiate cohort. J Neurol Sci 309:34-9
Galetta, Kristin M; Calabresi, Peter A; Frohman, Elliot M et al. (2011) Optical coherence tomography (OCT): imaging the visual pathway as a model for neurodegeneration. Neurotherapeutics 8:117-32
Avery, Robert A; Liu, Grant T; Fisher, Michael J et al. (2011) Retinal nerve fiber layer thickness in children with optic pathway gliomas. Am J Ophthalmol 151:542-9.e2
Davies, Emma C; Galetta, Kristin M; Sackel, David J et al. (2011) Retinal ganglion cell layer volumetric assessment by spectral-domain optical coherence tomography in multiple sclerosis: application of a high-precision manual estimation technique. J Neuroophthalmol 31:260-4
Price, Raymond S; Balcer, Laura J; Galetta, Steven L (2010) Education research: a new system for reducing patient nonattendance in residents' clinic. Neurology 74:e34-6

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