High-throughput optical coherence microscopy for diagnostic evaluation of corneal disease

PROJECT SUMMARY Optical coherence tomography (OCT) is uniquely able to achieve high depth resolution of several microns while imaging a large 3-dimensional (3D) volume. It is already widely used by ophthalmologists to diagnose diseases of the cornea and guide treatments. We aim to extend the range of applications further by pushing the envelope on the ultrahigh-resolution front. The specific aims are to: (1) Develop and validate ultrahigh-resolution OCT microscopy (OCM) using short-wavelength light sources. The recent availability of visible coherent light sources enables the development of OCT microscopy with a higher transverse resolution, potentially better than the current standard for corneal microscopy (in vivo corneal confocal microscopy or IVCM). We will develop an ultrahigh-speed line-scan spectral-domain OCT with dynamic focusing. The goal is to achieve one-micron resolution non-contact volumetric corneal imaging within a few seconds, enabling greater ease of use, faster scan times, and the ability to visualize more clinically relevant microscopic structures within the cornea compared to IVCM. (2) Explore the diagnostic potential of ultrahigh-resolution OCM for infectious keratitis and keratoconus. These are two of the most common causes of corneal blindness globally. IVCM can visualize large corneal pathogens (fungus and amoeba), but not bacteria which are the most common cause of infectious keratitis. IVCM is also not capable of visualizing collagen bundles within the cornea, the site of the primary structural changes caused by keratoconus. Our preliminary findings indicate OCM can visualize fungus and bacteria in addition to larger corneal pathogens as well as collagen bundles in rabbit corneas. Identification of these structures could significantly improve the diagnosis of infectious keratitis and keratoconus. The theoretically superior usability of OCM compared to IVCM may also enable wider adoption of corneal microscopy. We will complete pilot ex vivo and in vivo clinical studies comparing OCM against IVCM for the diagnosis of infectious keratitis and keratoconus. Earlier determination of the correct diagnosis would allow for faster initiation of targeted therapy and improved visual outcomes in these common, potentially blinding conditions.