Project Grant R01EY036042

BIOMECHANICS OF THE HUMAN OPTIC NERVE HEAD FOR GLAUCOMA BIOMARKERS. - SUMMARY GLAUCOMA IS A LEADING CAUSE OF BLINDNESS IN THE UNITED STATES AND WORLDWIDE. THE DISEASE IS CHARACTERIZED BY THE DEATH OF RETINAL GANGLION CELLS AFTER THE INITIAL INJURY TO THEIR AXONS IN THE OPTIC NERVE HEAD AND BY EXTENSIVE CHANGES IN THE STRUCTURE OF THE CONNECTIVE TISSUES OF THE OPTIC NERVE HEAD. THERE IS CONSENSUS THAT THE INTRAOCULAR PRESSURE GENERATES A BIOMECHANICAL RESPONSE IN THE TISSUES OF THE OPTIC NERVE HEAD THAT IS FUNDAMENTAL TO THE DEVELOPMENT OF GLAUCOMA AXON DAMAGE. MECHANICAL DEFORMATION AND REMODELING OF THE OPTIC NERVE HEAD IN RESPONSE TO A LONG-TERM IOP ELEVATION CAN DAMAGE THE RETINAL GANGLION CELL AXONS BOTH DIRECTLY AND INDIRECTLY THROUGH MECHANICAL ACTIVATION OF THE ASTROCYTES AND LAMINA CRIBROCYTES AND DISRUPTION OF BLOOD FLOW FROM THE DISTORTION OF BLOOD VESSELS. THE CELLS OF THE OPTIC NERVE HEAD CAN ALSO REACT TO CHANGES IN THE MECHANICAL PROPERTIES OF THE CONNECTIVE TISSUE STRUCTURES OF THE OPTIC NERVE HEAD IN WAYS THAT COMPROMISE THE PHYSIOLOGICAL SUPPORT FOR THE AXONS. THE SCIENTIFIC PREMISE OF THE PROPOSED STUDY IS THAT BIOMECHANICAL BEHAVIORS AND PROPERTIES OF THE TISSUES OF THE OPTIC NERVE HEAD WILL PREDICT THE RISK OF AXON INJURY IN OPEN ANGLE GLAUCOMA. IN AIM 1, WE WILL IMAGE THE EYES OF HUMAN SUBJECTS WITH PRIMARY OPEN ANGLE GLAUCOMA AT DIFFERENT STAGES USING AN OPTICAL IMAGING METHOD CALLED SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY. IMAGES WILL BE ACQUIRED BEFORE AND AFTER A CHANGE IN THE INTRAOCULAR PRESSURE TO MEASURE THE DEFORMATION USING DIGITAL VOLUME CORRELATION. THE IOP WILL BE CHANGED BY LASER SUTURE LYSIS AS PART OF THE POST-OPERATIVE CARE OF PATIENTS WHO HAVE HAD RECENT TRABECULECTOMY SURGERY AND BY STARTING OR STOPPING GLAUCOMA MEDICATION. IN AIM 2, WE WILL DEVELOP PATIENT-SPECIFIC FINITE ELEMENT MODELS. THE MODELS WILL BE USED TO ANALYZE THE DEFORMATIONS MEASURED IN AIM 1 TO DETERMINE THE PATIENT-SPECIFIC MECHANICAL PROPERTIES OF THE TISSUES OF THE OPTIC NERVE HEAD. THE MECHANICAL PROPERTIES AND STRAINS WILL BE ANALYZED TO DETERMINE HOW THEY VARY WITH AGE, SEX, RACE, STAGE OF GLAUCOMA DAMAGE, AND THE RATE OF PAST PROGRESSION. IN AIM 3, WE WILL ANALYZE THE OUTCOMES IN AIMS 1 AND 2 TO IDENTIFY POTENTIAL BIOMECHANICAL MARKERS FOR PROSPECTIVE LONGITUDINAL STUDIES TO EVALUATE THE ABILITY OF THE BIOMECHANICAL MARKERS TO PREDICT GLAUCOMA PROGRESSION. WE WILL ALSO REIMAGE THE EYES OF PARTICIPATING PATIENTS TO MEASURE REMODELING TO THE STRUCTURE AND MECHANICAL PROPERTIES OF THE OPTIC NERVE HEAD. THESE STUDIES WILL DETERMINE WHETHER THE DEFORMATIONS AND MATERIAL PROPERTIES OF THE TISSUES OF THE OPTIC NERVE HEAD, MEASURED BY CURRENT IMAGING, IMAGE ANALYSIS AND MODELING METHODS, ARE PREDICTIVE OF GLAUCOMA PROGRESSION AND ENHANCE FUNDAMENTAL UNDERSTANDING OF HOW THE TISSUES REMODEL IN OPEN ANGLE GLAUCOMA.