Project Summary/Abstract In recent years, patient centered outcomes (PCOs) have rapidly gained a prominent role in clinical trials throughout medicine, and ophthalmology is following this trend. There is, however, little uniformity in the measures currently in use, even though the FDA has been emphasizing the importance of standardizing clinical trial outcomes for over a decade. Several visual functioning questionnaires (VFQs) and standardized reading tests are available, calibrated in multiple languages. However, for other visually guided (instrumental) activities of daily living – (I)ADLs –, whether related to information gathering, visually guided action, wayfinding, or detail discrimination (the 4 visual domains generally recognized in low vision rehabilitation), there currently are no standardized performance assessments. One reason for this is the difficulty to create uniform real- world visual activities: They depend on available tools, test conditions, and other factors that may be difficult to reproduce across sites, let alone in countries with different customs, tools/utensils, measures, etc. The current proposal fills this void by developing and calibrating a broad set of visual performance measures in virtual reality (VR). It is built on 5 years of experience our team has gained through the development of 3 reliable sets of activities in VR for a population with ultra-low vision, i.e., VA”20/1600. In this proposal, we address the much broader low vision population with 20/00” VA”20/0 or restricted peripheral fields (<20° diameter). We start out with an inventory of relevant (I)ADLs, calibrated in the form of a 125-item VFQ. From these items we select activities for the functional assessment, in all 4 visual domains. All activities will be created in virtual reality (VR), and participants will perform these while wearing a wide-screen VR headset with built-in hand and eye tracking. A subset of the activities will also be created as real-world tests to allow comparison of the two test modalities. Each activity will comprise 2 or 5 steps that are pass/fail scored; scores are analyzed using the method of successive dichotomizations (MSD). Effects of auditory and haptic complements to the visual information in VR will also be examined. In Aim 1, we will develop and calibrate the VFQ, administered to 300 low vision respondents. In Aim 2, 20 activities in real-world and VR modalities will be compared in 150 participants across 3 participating centers. In Aim 3, 60 activities in VR will be calibrated in 225 participants across the 3 centers, and in Aim 4, the contribution(s) of auditory and/or haptic feedback will be studied, also in 225 participants. Psychometric analyses will yield calibrated item (difficulty) measures for the VFQ and the activities in VR. The Low Vision Assessment in Virtual Reality (LVAVR) will consist of up to 60 activities, the VFQ of up to 125 items. Both instruments will be made available for clinical and research u...