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Glaucoma is the leading cause of irreversible blindness worldwide and has a complex etiology associated with elevated intraocular pressure. Biomechanical forces induce vision loss through strain-induced damage to the retinal ganglion cells conducting visual information from the retina to the brain. This work tests the hypothesis that stiffening the peripapillary scleral (collagenous tissue adjacent to the optic nerve) protects against glaucomatous vision loss. A photocrosslinking approach was 1) developed to selectively stiffen the peripapillary sclera in vivo, 2) tested for efficacy in a rat animal model of glaucoma, and 3) simulated using a computational model to predict optimal photocrosslinking parameters. Scleral photocrosslinking was successfully targeted to the peripapillary sclera in vivo and found to have moderate treatment toxicity. In vivo studies in glaucomatous rats revealed that our treatment did not worsen …