The cornea is a highly organized, layered (lamellae) structure of collagen fibrils providing both high tensile strength to protect the eye and 70% of it refractive power. Although physical properties are closely linked to its primary optical function, its response to surgical interventions, and the results of routine eye tests such as intraocular pressure measurements, corneal biomechanics has not been a topic of major research interest. Topography, tonometry, pachymetry, and to a lesser extent optical coherence tomography (OCT), are the primary non- invasive tools used clinically for corneal disease screening and refractive surgery planning. It is clear from recent studies, however, that these systems are highly susceptible to experimental conditions and cannot be used to map fundamental corneal viscoelastic parameters. Indeed, there are no non-invasive measurement tools that can provide the information needed on every individual to develop a personalized biomechanical model of the cornea that could be used for screening, surgical planning, and treatment monitoring. Here we propose a tool based on optical coherence elastography (OCE) that can potentially replace pachymetry, tonometry, and topography with a single instrument, and may enable detailed, personalized models of cornea biomechanics. We will pursue a clinically translatable approach using dynamic OCE to provide spatial maps of fundamental viscoelastic properties at a spatial scale sufficient to potentially enable detailed biomechanical models of the cornea. This approach leverages several innovations developed by our team, including a phase-sensitive OCT (PhS-OCT) system providing displacement sensitivity better than 100 pm, non-contact and minimally contact mechanical stimulation approaches leveraging recent developments in acoustic radiation force (ARF) and photoacoustics (PA), and techniques to increase the inherent SNR of displacement measurements by one-two orders of magnitude using coded excitation and non-spherical lenses. The specific research plan includes five specific aims. In the first, we will enhance our current PhS-OCT system to improve spatial resolution and motion sensitivity while simultaneously decreasing overall imaging time. The initial move toward clinical translation will be in Aim 2 where both remote and non-contact methods will be investigated to launch broadband shear waves in the cornea. In parallel, we will explore a wide range of SNR enhancement techniques in Aim 3 to significantly increase overall SNR. In all cases, methods in Aims 2 and 3 will conform to all safety guidelines for both optical and ultrasonic exposure. Current methods to reconstruct the complex elastic modulus from dynamic displacement maps will be extended in Aim 4 to account for the bounded geometry of the cornea. Finally, we will study human donor corneas in Aim 5 to test whether OCE can provide maps of viscoelastic properties that can drive biomechanical models predicting corneal shape changes due to perturbations such as intraocular pressure variations and surgical interventions.
Although the physical properties of the cornea are closely linked to its primary optical function, and its progression in disease and response to surgical treatment, corneal biomechanics has not been a topic of major research interest. To date, there are no non-invasive clinical tools that can provide the information needed on every individual to develop a customized personal biomechanical model of the cornea that could be used for disease screening, refractive surgery planning, and treatment monitoring. We propose to develop a tool based on optical coherence elastography (OCE) that can potentially replace pachymetry, tonometry, and topography with a single instrument enabling detailed, personalized models of cornea biomechanics useful for a wide range of procedures including screening (e.g., sensitive myopia and glaucoma detection), surgical planning (e.g., optimized LASIK outcomes for all), and treatment monitoring (e.g., optimized collagen cross linking therapies for keratoconus and post-LASIK ectasia).
