Corneal ulcers caused by infection are causing blindness and visual impairment in 4.2 million people
worldwide annually and have been described as a “silent epidemic”. Corneal ulcers can be caused by several
different organisms, with those caused by fungi or Acanthamoeba parasites often associated with the worst
outcomes. Accurate and rapid diagnosis of the causative organism can prevent tissue damage leading to
blindness. But clinical outcomes are often poor because the first-line diagnostic method, slit lamp examination,
is often inaccurate, and the gold standard diagnostic method, microbiological testing, is time-consuming, prone
to false negatives, and resource-intensive.
We aim to develop a Portable In vivo Confocal Ophthalmoscope (PICO) that can provide accurate and
rapid diagnosis in corneal ulcers. We have established a research team of leading ophthalmology and
optical 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 patient’s cornea. Dr. Jaya
Chidambaram (Co-I, University of Manchester, UK) led the first prospective study to test laser-scanning IVCM
in fungal and Acanthamoeba ulcer patients, which established high diagnostic sensitivity (86-88%) and
specificity (81-98%). Further studies by others demonstrated similarly high diagnostic accuracy. But
widespread adoption of IVCM has been hampered by the following weaknesses: 1) contact imaging, 2) limited
field of view (FOV) and speed, and 3) high device cost (>$75,000). While searching for a new approach to
overcome these weaknesses, Dr. Chidambaram began a collaboration with Dr. Dongkyun Kang (PI,
University of Arizona) in 2019. Dr. Kang’s team previously invented the world’s first smartphone-based,
portable IVCM device (cost = ~ $4,000), successfully imaged skin lesions from >350 patients in Uganda, and
demonstrated 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 a
PICO device that (1) enables non-contact corneal imaging, (2) increases the FOV 12 times and speed 8
times, and (3) reduces the device cost >10 times compared to the commercial corneal IVCM device. We will
develop 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 significant
impacts on diagnosis and treatment monitoring of corneal ulcers and other major corneal diseases, including
dry eye disease, Fuch’s endothelial dystrophy, and corneal nerve evaluation to screen for peripheral
neuropathy in Parkinson’s disease and diabetes mellitus. Our proposal directly addresses several unmet
needs identified in the NEI’s strategic plan, including high-resolution imaging techniques to diagnose common
corneal disorders, and methods for early detection of corneal disease epidemics.