PROJECT SUMMARY There is a critical need for developing markers and predictors of both high intracranial pressure (ICP) and response to high ICP treatment, that will guide clinicians to appropriately personalize treatment for idiopathic intracranial hypertension (IIH) by targeting aggressive interventions to patients who are not responding to conservative treatments or are at risk of vision loss. This application seeks to develop measurements of retinal vascular changes in the posterior eye as novel clinically-relevant biomarkers to meet this need. These are promising biomarker candidates based on preliminary data. Furthermore, they are specific, objective, quantitative and can be derived from non-invasive technologies. The long-term goal of this research is to understand the time course and variability of retinal vascular changes associated with ICP changes. Though some retinal vascular changes in association with ICP have been described, others have not been systematically studied. Furthermore, how retinal vascular changes relate to other eye changes associated with ICP is poorly understood. Our central hypothesis is that retinal vascular changes in response to ICP treatment precede other ophthalmic changes and that these predict treatment response over the longer term. The objective of this proposal is to perform a secondary analysis of fundus photos collected as part of the NIH funded Idiopathic Intracranial Hypertension Treatment Trial (IIHTT, clinicaltrials.gov identifier NCT01003639) to define retinal vascular changes occurring during IIH treatment in the context of other markers of disease. The first aim is to define the spectrum of retinal vascular changes that occur during medical treatment of IIH by comparing retinal vascular features extracted from fundus photographs at baseline and study conclusion. The second aim is to establish early retinal vascular change as a marker of response to medical treatment in IIH by studying how changes between initial study visits (0-1 month) predict outcomes at 6 months.