This application requests a career development award for an academic neuro-ophthalmologist with a scientific interest in idiopathic intracranial hypertension (IIH), a potentially blinding condition that most commonly affects young women. This award will provide the candidate with the necessary mentorship, training and experience to propel her to the level of independent patient oriented researcher focused on advancing diagnosis, clinical care and outcomes of IIH. The candidate is an accomplished early career physician-scientist. In the short term she seeks research career development in the areas of clinical research &epidemiology, visual psychophysics &electrophysiology and neuro-ophthalmic imaging. She will develop her knowledge and capabilities in these areas through coursework, guided study, practical experience and mentored research. This will form the foundation upon which she will build an independent research program in IIH. From this vantage point she will pursue her long term goal of improving clinical care for IIH and other neuro-ophthalmic conditions both as an independent researcher with a strong translational research program and as an expert clinician caring directly for patients. The environment created by the Department, Medical School and Institution is characterized by clinical and research expertise and productivity. There is a proven track record of effectively nurturing early career physician scientists in the fields of ophthalmology and vision research. Departmental and Medical School leadership are committed to providing material, financial and intellectual support to ensure the candidate's development and success. There is a significant clinical need for non-invasive biomarkers that will improve diagnosis and management of IIH. The objective of the research project is to establish physiologically based markers of retinal ganglion cell (RGC) function and retinal vasculature as markers of IIH that detect abnormalities, monitor treatment and distinguish peripheral vision outcomes. This objective will be accomplished with two specific aims: 1. To test the hypothesis that RGC function is impaired and retinal vascular diameters are enlarged in IIH subjects as compared to visually normal control subjects: Electrophysiological and pupil light response based measures of RGC function and image based measures of retinal blood vessel diameter will be compared between IIH subjects with elevated intracranial pressure and control subjects. This will establish that these markers are abnormal in the IIH population. 2. To test the hypothesis that RGC function impairment and retinal vascular dilation recover in IIH subjects with short and long term treatment: Electrophysiological and pupil light response based measures of RGC function and image based measures of retinal blood vessel diameter will be compared within IIH subjects when intracranial pressure is elevated, immediately following short term intracranial pressure lowering by lumbar puncture and following long term intracranial pressure lowering by standard clinical therapy. This will establish that these markers change with treatment of IIH. The results of the proposed study will lay the scientific and technical foundation for the development of these markers as clinical tools and clinical trial outcome measures of IIH. Furthermore, the results will advance scientific understanding of the pathophysiology underlying optic nerve dysfunction and injury in IIH. The project has broader significance because the knowledge gained and technical capabilities developed will have applications to other diseases at the intersection of neurology and ophthalmology such as glaucoma and cerebrovascular disease. The research career development and mentoring plan will transform the candidate into an independent researcher who will make long-lasting contributions to vision science.

Public Health Relevance

Idiopathic intracranial hypertension (IIH), defined by elevated pressure in the brain without other cause, can produce irreversible blindness by compromising the function of the optic nerve, which transmits visual information from the eye to the brain. Markers that predict vision loss in IIH have been elusive and this leads to uncertainty on the part of treating physicians regarding initiation and escalation of therapy. This work will aim to establish objective, non-invasive markers of IIH that improve diagnosis, facilitate monitoring and inform treatment decisions. The career development goals of the principal investigator include developing expertise in use of functional and structural measures of the visual pathways for study of IIH. The results will help treating physicians to improve clinical care of patients with IH.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1-VSN (01))
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Agarwal, Neeraj
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University of Illinois at Chicago
Schools of Medicine
United States
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MacIntosh, Peter W; Jain, Sachin; Moss, Heather E et al. (2014) A school of red herring. Surv Ophthalmol 59:664-70