Clinical Translation of Dynamic OCE for Corneal Biomechanical Assessment
Purpose: Determining corneal mechanical properties is required for understanding and diagnosing corneal shape changes caused by ocular disease, degeneration, or refractive surgery, yet remains a long-standing challenge. This dissertation aims to clinically translate dynamic optical coherence elastography (OCE) for spatially-resolved quantification of human corneal biomechanics in vivo. Methods: An air-pulse–based OCE system was adapted for noninvasive clinical assessment of corneal elastic modulus. Corneal mechanical waves generated by low-pressure (0.3mmHg) air-pulse stimulation were imaged using high-speed, phase-senstive OCT. Frequency-dependent corneal wave-speed dispersion was measured, and compared to established Rayleigh–Lamb model. Dispersion-independent approximate Rayleigh–Lamb wave (aRLW) speeds were used to estimate corneal elastic modulus and then applied to 1) evaluating alignment between corneal toricity and biomechancial anisotropy in astigmatism and 2) mapping biomechanical heterogeneity in keratoconus. Results: Air-pulse generated broadband, high-frequency (>5 kHz) corneal waves were detected with 0.19 nm sensitivity. The air-pulse OCE system achieved ~0.29 kPa mechanical resolution and spatio-mechanical resolutions of 35 μm laterally and 15 μm axially. Corneal wave-speed dispersion (1–29m/s at 1kHz, plateau 12.2–15.9m/s > 4 kHz) was consistent with Rayleigh–Lamb model. Dispersion-independent aRLW speeds produced repeatable elastic moduli with ~40% lower variance. Biomechanical anisotropy closely aligned with corneal topography, with aRLW-speeds higher/stiffer along the steep meridian (12.97±1.6 m/s; 43.81±1.63D) than the flat meridian (9.03±1.8 m/s; 42.45±1.7D). In keratoconus, aRLW-speeds were lowest in the steeper-cone region (8.55±1.51 m/s) compared with the apex (10.83±1.34 m/s) and superior cornea (14.54±2.1 m/s). Conclusions: This work established air-pulse OCE as a clinical tool for spatially-reolved, in vivo quantification of corneal biomechanics. By characterizing corneal wave-speed dispersion and applying Rayleigh–Lamb model, this work provides the physical basis for linking OCE-metrics to intrinsic corneal elasticity, addressing a limitation that previously prevented direct mechanical interpretation in corneal-OCE. Dispersion-independent aRLW speeds yielded repeatable stiffness estimates that quantitatively differentiated normal from keratoconic corneal regions and revealed directional anisotropy associated with astigmatism—capabilities unattainable with current clinical instruments—establishing OCE-metrics as biomechanical markers for disease-related weakening and structural asymmetry. Collectively, these advances position OCE as a clinically viable technology for diagnosing, monitoring, and guiding treatment of corneal biomechanical disorders.
Biomechanical Anisotropy, Mechanical Spatial Heterogeneity, Mechanical Resolution, Phase Sensitive Optical Coherence Tomography, Mechanical Testing, Clinical Research, Astigmatism, Keratoconus, Cornea, Optical Coherence Elastography, Biomechanical Properties, Clinical Translation, Microliter Air Pulse, Mechanical Wave Speed Dispersion, Mechanical Waves
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