While it is recognized that keratoconus involves a generalized mechanical weakening of the central cornea leading to corneal steepening and cone formation, the mechanism underlying this change has yet to be identified. We have recently received National Institute of Health support from the National Eye Institute to begin to unravel this unknown mechanism.
Using ultra fast lasers, called femtosecond lasers, we have developed new technology that allows us to non-invasively probe corneal collagen structure and mechanical strength. Since collagen is the principal structural protein of the cornea that provides strength and determines shape, we can for the first time test the hypothesis that keratoconus involves an acquired or genetic structural/mechanical weakening leading to progressive corneal steepening.
Thus far, 3-dimensional imaging using femtosecond lasers to generate second harmonic (SHG) signals (A harmonic is a signal or wave whose frequency is an integral (whole-number) multiple of the frequency of some reference signal or wave.) from collagen have shown that the normal human cornea contains a unique population of transversely oriented collagen bundles, called ‘Sutural Lamellae’, that insert into the most anterior portion of the cornea and then pass deeper, interweaving with other collagen, and ultimately ‘suturing’ the cornea into its shape (see movie below). 3-Dimensional imaging of SHG signals in keratoconus shows that these ‘Sutural Lamellae’ are severely disrupted and in some corneas are completely absent.
We are currently developing an elastic microscope using femtosecond laser light to induce what is called ‘Laser Induce Optical Breakdown’ of tissue (LIOB), to generate very small bubbles (1/1000 of a millimeter in diameter) that can be probed using acoustic radiation to measure tissue strength. Using LIOB coupled with SHG imaging, we will be able to precisely map the regional differences in corneal collagen structure and mechanical strength to determine if the loss of ‘Sutural Lamellae’ underlies the loss of mechanical strength in keratoconus.
Our long term goal is to develop a clinical instrument that will allow us to measure the mechanical strength of the cornea and determine the presence of ‘Sutural Lamellae’. If our hypothesis is correct, then this new instrument may be able to detect early, subclinical cases of keratoconus to enable earlier intervention. More importantly, future studies could help determine how keratoconus develops and be used to define susceptible patient populations for genetic testing.
by Tibor Juhasz and James V. Jester, PhD.
University of California ~ Irvine
Department of Ophthalmology
About Dr Jester:
Dr. James Jester, a professor in UC Irvine’s Department of Ophthalmology, is a recognized international leader in the cell biology of corneal wound healing and scarring. He has had a major impact in this field of research.
For about a year, Dr. Jester has been involved in studies involving corneal wound healing using three-dimensional microscopes to create images of eye tissue. In the studies, the scientists have shown that scar tissue in the cornea can be three-dimensionally imaged, measured, and in many cases prevented. Dr. Jester and his team are also studying corneal crystallins – water soluble proteins – and their role in helping keep the cornea healthy, clear and transparent.
Dr. Jester has a Ph.D. in Experimental Pathology with postdoctoral training in Experimental Ocular Pathology from the Doheny Eye Institute in Los Angeles and the National Eye Institute, National Institutes of Health in Bethesda, Maryland. Dr. Jester has authored over 200 peer-reviewed research papers as well as various articles and book chapters on cornea, corneal wound healing, and other related subjects.