Project Grant R01EY035647

NONCONTACT IN VIVO GUIDANCE OF CORNEAL COLLAGEN CROSSLINKING THERAPY WITH OPTICAL COHERENCE TOMOGRAPHY AND ACOUSTIC MICRO-TAPPING ELASTOGRAPHY - ABSTRACT. KERATOCONUS (KC) IS THE MOST COMMON AND ONE OF THE MOST SERIOUS FORMS OF CORNEAL ECTASIA. CORNEAL THINNING AND DEFORMATION OF CORNEAL GEOMETRY LEADS TO ITS NEAR-CONICAL SHAPE. CORNEAL SHAPE AND THICKNESS ARE CURRENTLY USED TO CHARACTERIZE ECSTATIC CHANGES, AND OPTICAL COHERENCE TOMOGRAPHY (OCT) IS THE MOST ACCURATE TOOL FOR THAT. ALTHOUGH CORNEAL SHAPE CAN BE USED TO CALCULATE REFRACTIVE POWER, IT CANNOT BE USED ALONE TO PREDICT DISEASE PROGRESSION. IN FACT, ELASTIC MODULI CHANGES IN THE CORNEA ARE A DRIVER OF ECTASIA. CORNEAL COLLAGEN CROSSLINKING (CXL) IS A MINIMALLY INVASIVE PROCEDURE THAT CAN POTENTIALLY SLOW THE PROGRESSION OF ECTASIA [1-4]. UV LIGHT MODIFIES THE MICROSTRUCTURE OF CORNEA SOAKED IN RIBOFLAVIN AND FORMS ADDITIONAL CHEMICAL BONDS BETWEEN COLLAGEN FIBERS IN THE STROMA LEADING TO INCREASED CORNEAL STIFFNESS. HOWEVER, THERE IS CURRENTLY NO INSTRUMENT THAT CAN PROVIDE NONCONTACT, ACCURATE ASSESSMENT OF CORNEAL ANISOTROPIC ELASTIC MODULI. INDEED, THE CORNEA IS A BOUNDED MEDIUM OF HIGHLY ORGANIZED COLLAGEN FIBRILS RESULTING IN ITS HIGHLY ANISOTROPIC MECHANICAL BEHAVIOR, REQUIRING DETAILED TECHNIQUES AND MODELS TO MAP ITS ELASTIC MODULI. THE GOAL OF THIS PROJECT IS TO DEVELOP A NON-CONTACT, NON-INVASIVE CLINICAL TOOL BASED ON OPTICAL COHERENCE TOMOGRAPHY AND ELASTOGRAPHY (OCE) TO SIMULTANEOUSLY MAP GEOMETRY (CURVATURE AND THICKNESS) AND IMAGE ELASTIC IN- AND OUT-OF-PLANE MECHANICAL MODULI OF CORNEA FOR LONGITUDINAL PRE-AND POST-OPERATIVE DIAGNOSTICS OF KC PROGRESSION AND EVALUATE CXL SURGERY OUTCOMES. WE HYPOTHESIZE THAT QUANTIFYING CORNEAL ELASTICITY IN VIVO WILL ENABLE SIGNIFICANT INNOVATION, PROVIDING A BASIS TO BUILD AN INDIVIDUALIZED BIOMECHANICAL MODEL OF THE EYE, MONITOR PROGRESSION OF KC AND OTHER ECTATIC CHANGES IN THE CORNEA, GUIDE CUSTOMIZED TREATMENT PLANS, AND BOTH PREDICT AND EVALUATE REFRACTIVE SURGERY OUTCOMES. SA1 WILL FOCUS ON OPTIMIZING OUR UNIQUE AMT-OCE SYSTEM FOR IN VIVO ELASTICITY MEASUREMENTS IN KC PATIENTS, BUILDING IT ON A SLIT-LAMP BASED PLATFORM AND COMBINING IT WITH OCT TOPOGRAPHY. IN SA2, WE WILL MAP BASELINE ELASTIC PROPERTIES IN RABBIT CORNEA PRE- AND POST-CXL TO CONFIRM THAT ELASTIC PROPERTY CHANGES DUE TO THE PROCEDURE CAN BE QUANTIFIED. LEVERAGING THE RESULTS OF SA1, SA3 WILL FOCUS ON BASELINE MODULI IN HEALTHY VOLUNTEERS MATCHING THE MOST LIKELY DEMOGRAPHIC OF KC PATIENTS TO DETERMINE WHETHER MODULI DEPEND ON RACE AND IOP AND DEFINE DIAGNOSTIC CRITERIA FOR KC. FINALLY, IN SA4 WE WILL PERFORM CORNEA MODULI MAPPING IN KC PATIENTS LONGITUDINALLY PRE- AND POST-CXL TO COMPREHENSIVELY COMPARE THEM TO THOSE IN NORMAL SUBJECTS. THIS PROJECT BUILDS ON THE RIGOR OF OUR PREVIOUS RESEARCH WHERE (I) WE INVENTED A FULLY NON-CONTACT SYSTEM TO LAUNCH MECHANICAL WAVES IN THE CORNEA AND TRACK THEIR PROPAGATION WITH FAST OCT [5, 6]. (II) WE SHOWED THAT THE CORNEA IS HIGHLY ANISOTROPIC AND DEVELOPED A PROPER MODEL OF CORNEAL BIOMECHANICS [7, 8]. (III) WE TESTED OUR APPROACH IN EX VIVO AND IN VIVO STUDIES AND VALIDATED OUR RESULTS WITH MECHANICAL TESTS [7-10]. WE ALSO OBTAINED STATISTICALLY SIGNIFICANT PRELIMINARY DATA FOR CXL TREATED HUMAN CORNEA EX VIVO [9].