PROJECT SUMMARY The long-term goal of this project is to improve diagnosis and management of keratoconus. The efficacy of corneal crosslinking for progressive keratoconus has generated interest in detecting the disease at an earlier stage in hopes of preventing progression leading to vision loss. Yet, there is currently no clinical evidence supporting the benefits of early treatment of keratoconus with crosslinking. The primary barrier in designing studies that address this question is the lack of diagnostic technology to identify keratoconus in the early stages. The project addresses this technological need. Current keratoconus diagnosis relies primarily on measurements of corneal shape. Since shape changes are secondary to microstructural alterations, a method to image the corneal microstructure could enable detection of keratoconus at an earlier stage. Alterations in the corneal epithelium and Bowman’s layer are among the first histophatologic signs of keratoconus. Our goal is to develop the first widefield OCT imaging modality to quantify structural and optical alterations of the epithelium and Bowman’s layer from the center to the periphery of the cornea. The technology will then be used to prove that alterations in Bowman’s layer and epithelium can be quantified across the entire cornea in keratoconus subjects. The project has two specific aims: Aim 1: To develop Widefield Corneal Microlayer Tomography (wCMT). The technology is based on high-resolution OCT combined with a new beam scanning approach to enable widefield imaging of the cornea. We will develop OCT image processing tools to generate the first volumetric thickness and optical scattering maps of the epithelium and Bowman’s layer over the entire cornea. The system and software will be tested on healthy and keratoconus subjects. Aim 2: To map the alterations of Bowman’s layer and epithelium over the entire cornea with wCMT in keratoconus. We will prove that wCMT can quantify alterations in Bowman’s layer and epithelium from the center to the periphery of the cornea. Data acquired on control subjects and patients with early-stage to moderate keratoconus will be used to prove that wCMT can detect alterations in Bowman’s layer and epithelium from the early stage of the disease. In the long term, the technology will have an important positive impact as it lays the foundation for the discovery of structural biomarkers that will enable the detection of keratoconus at an earlier stage.