Project Summary/AbstractCorneal ulcers caused by infection are causing blindness and visual impairment in 4.2 million peopleworldwide annually and have been described as a silent epidemic. Corneal ulcers can be caused by severaldifferent organisms with those caused by fungi or Acanthamoeba parasites often associated with the worstoutcomes. Accurate and rapid diagnosis of the causative organism can prevent tissue damage leading toblindness. But clinical outcomes are often poor because the first-line diagnostic method slit lamp examinationis often inaccurate and the gold standard diagnostic method microbiological testing is time-consuming proneto false negatives and resource-intensive.We aim to develop a Portable In vivo Confocal Ophthalmoscope (PICO) that can provide accurate andrapid diagnosis in corneal ulcers. We have established a research team of leading ophthalmology andoptical engineering experts to achieve this goal: In vivo confocal microscopy (IVCM) is the only clinically-available imaging tool that can directly visualize causative organisms in the patients cornea. Dr. JayaChidambaram (Co-I University of Manchester UK) led the first prospective study to test laser-scanning IVCMin fungal and Acanthamoeba ulcer patients which established high diagnostic sensitivity (86-88%) andspecificity (81-98%). Further studies by others demonstrated similarly high diagnostic accuracy. Butwidespread adoption of IVCM has been hampered by the following weaknesses: 1) contact imaging 2) limitedfield of view (FOV) and speed and 3) high device cost (>$75000). While searching for a new approach toovercome these weaknesses Dr. Chidambaram began a collaboration with Dr. Dongkyun Kang (PIUniversity of Arizona) in 2019. Dr. Kangs team previously invented the worlds first smartphone-basedportable IVCM device (cost = ~ $4000) successfully imaged skin lesions from >350 patients in Uganda anddemonstrated imaging of cellular details of the cornea with similar image quality to the commercial IVCM.In this 3-year R01 project we will further innovate our skin portable IVCM technology to develop aPICO device that (1) enables non-contact corneal imaging (2) increases the FOV 12 times and speed 8times and (3) reduces the device cost >10 times compared to the commercial corneal IVCM device. We willdevelop a PICO prototype (Aim 1) and evaluate for corneal ulcer (fungal subtype) ex vivo (Aim 2).We envision that PICO will become a standard corneal imaging tool worldwide and will make significantimpacts on diagnosis and treatment monitoring of corneal ulcers and other major corneal diseases includingdry eye disease Fuchs endothelial dystrophy and corneal nerve evaluation to screen for peripheralneuropathy in Parkinsons disease and diabetes mellitus. Our proposal directly addresses several unmetneeds identified in the NEIs strategic plan including high-resolution imaging techniques to diagnose commoncorneal disorders and methods for early detection of corneal disease epidemics.