Breakthrough imaging technique offers non-invasive early detection of corneal diseases

Our eyes guide us through the world and allow us to see the beauty around us. Unfortunately, vision loss associated with age-related degeneration of the eye is a reality for many people. The transparent tissue at the front of the eye, called the cornea, is a key element in focusing the light we see at the back of the eye (the retina) and creating a clear and sharp image. Various ocular diseases can cause degeneration of the cornea and its periphery ring, known as the limbus, this results in the cornea changing its shape and becoming opaque (significantly less transparent to visible light).Such charges are some of the major causes of vision loss that affect billions of people around the world. The World Health Organization (WHO) has determined that vision impairment poses an enormous global financial burden with annual global costs of productivity losses estimated to be $411 billion USD in 2020. While some of the mechanisms for this decline are well understood, early detection of corneal diseases, at the stage when they affect the cornea at a cellular level, can help ophthalmologists administer treatment early enough to cure the disease or at least significantly slow down its progression.

Waterloo Physics and Astronomy’s Prof. Bizheva leads a research group hoping to change this and allow doctors to detect and treat corneal diseases early, before the cloudy veil of late-stage degeneration robs patients of their vision. In a recent paper published in Biomedical Optics Express (full citation below), they demonstrate a huge step toward this goal. They have developed an optical imaging modality that can image a large volume of the cornea in three dimensions with enough resolution to see individual cells. The technology is very fast (it acquires 1 volumetric image in a quarter of a second) and the procedure is completely non-contact (the imaging probe does not touch the eye's surface, or do anything else that might make your skin crawl). The publication that described the imaging system and what it can do, was the most downloaded paper in the Biomedical Optics Express journal for the year 2022.

Laser diagramThe new imaging technique is based on Optical Coherence Tomography (OCT). To understand what OCT is and how it works, think back to the Michelson interferometer you would have encountered in Modern Physics and in Optics. Light generated on a broadband laser is incident on a beam splitter that divides the beam into two different paths. Each path ends in a mirror, so the light returns to the beam splitter from each path. Each returning beam can either reflect or transmit at the beam splitter. The two beams interfere in the beam splitter when they return and the fraction that goes out the fourth, so far unused, side of the beamsplitter is determined by the difference in length for the two paths. Suppose both paths have identical lengths. In that case, the light leaving the fourth side interferes constructively and 100% of the light leaves the fourth side. But if one path changes length by half a wavelength (i.e., a change of less than 0.5 micrometers for visible light), then none of the light will leave the fourth side. Even smaller length changes can be detected by measuring intermediate values between 100% and 0%.

OCT uses many different wavelengths of light to allow for precise distance measurements in such an interferometer. In Prof. Bizheva’s work, instead of a mirror, of the optical beams is projected onto a person’s cornea. The reflections from cellular structures at different depths in the cornea act as many tiny interferometers with different path lengths. The many different wavelengths used in OCT allow all of those “mirrors” positions to be determined with high precision (roughly one micrometer resolution) from the surface of the eye to more than a millimeter deep below the surface. Combining several other techniques to make Line Scanning Spectral Domain OCT (LS-SD-OCT), the Bizheva group is able to capture the readings of a million tiny interferometers, at a rate of 2500 frames per second! This gives the speed to fully map a cubic millimeter of cornea in a matter of seconds, fast enough to correct small distortions due to a living person’s natural eye movements, which is a topic of current work in the group.

Work continues to improve the new technique further and to eventually see it used to diagnose corneal disorders early enough to correct them. Moreover, the same technique could be critical in guiding surgeons’ hands to the exact spots where therapies will be most effective.

The paper Line-scanning SD-OCT for in-vivo non-contact, volumetric, cellular resolution imaging of the human cornea and limbus was published in Biomedical Optics Express, volume 13, pages 4007-4020 in 2022 []. The authors were Le Han, a PhD student who built the system and conducted the measurements, Bingyao Tan, a former PhD student now a research associate at Nanyang Technological University, Zohreh Hosseinaee, a former PhD student now a post-doctoral fellow at UC Berkeley, an MSc student who now works on similar topics in industry, Denise Hileeto, an Associate Prof. at the UW School of Optometry and Vision Sciences, and Kostadinka Bizheva, professor of Physics and Astronomy at the University of Waterloo.  The research was funded by the Natural Sciences and Engineering Research Council, Canadian Institutes of Health Research, and the Transformative Quantum Technologies program of the Canada First Research Excellence Fund.