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      A Review of Structural and Biomechanical Changes in the Cornea in Aging, Disease, and Photochemical Crosslinking

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          Abstract

          The study of corneal biomechanics is motivated by the tight relationship between biomechanical properties and visual function within the ocular system. For instance, variation in collagen fibril alignment and non-enzymatic crosslinks rank high among structural factors which give rise to the cornea's particular shape and ability to properly focus light. Gradation in these and other factors engender biomechanical changes which can be quantified by a wide variety of techniques. This review summarizes what is known about both the changes in corneal structure and associated changes in corneal biomechanical properties in aging, keratoconic, and photochemically crosslinked corneas. In addition, methods for measuring corneal biomechanics are discussed and the topics are related to both clinical studies and biomechanical modeling simulations.

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          The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults

          The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration.
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            Risk assessment for ectasia after corneal refractive surgery.

            To analyze the epidemiologic features of ectasia after excimer laser corneal refractive surgery, to identify risk factors for its development, and to devise a screening strategy to minimize its occurrence. Retrospective comparative and case-control study. All cases of ectasia after excimer laser corneal refractive surgery published in the English language with adequate information available through December 2005, unpublished cases seeking treatment at the authors' institution from 1998 through 2005, and a contemporaneous control group who underwent uneventful LASIK and experienced a normal postoperative course. Evaluation of preoperative characteristics, including patient age, gender, spherical equivalent refraction, pachymetry, and topographic patterns; perioperative characteristics, including type of surgery performed, flap thickness, ablation depth, and residual stromal bed (RSB) thickness; and postoperative characteristics including time to onset of ectasia. Development of postoperative corneal ectasia. There were 171 ectasia cases, including 158 published cases and 13 unpublished cases evaluated at the authors' institution. Ectasia occurred after LASIK in 164 cases (95.9%) and after photorefractive keratectomy (PRK) in 7 cases (4.1%). Compared with controls, more ectasia cases had abnormal preoperative topographies (35.7% vs. 0%; P<1.0x10(-15)), were significantly younger (34.4 vs. 40.0 years; P<1.0x10(-7)), were more myopic (-8.53 vs. -5.09 diopters; P<1.0x10(-7)), had thinner corneas before surgery (521.0 vs. 546.5 microm; P<1.0x10(-7)), and had less RSB thickness (256.3 vs. 317.3 microm; P<1.0x10(-10)). Based on subgroup logistic regression analysis, abnormal topography was the most significant factor that discriminated cases from controls, followed by RSB thickness, age, and preoperative corneal thickness, in that order. A risk factor stratification scale was created, taking all recognized risk factors into account in a weighted fashion. This model had a specificity of 91% and a sensitivity of 96% in this series. A quantitative method can be used to identify eyes at risk for developing ectasia after LASIK that, if validated, represents a significant improvement over current screening strategies.
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              The Genetic and Environmental Factors for Keratoconus

              Keratoconus (KC) is the most common cornea ectatic disorder. It is characterized by a cone-shaped thin cornea leading to myopia, irregular astigmatism, and vision impairment. It affects all ethnic groups and both genders. Both environmental and genetic factors may contribute to its pathogenesis. This review is to summarize the current research development in KC epidemiology and genetic etiology. Environmental factors include but are not limited to eye rubbing, atopy, sun exposure, and geography. Genetic discoveries have been reviewed with evidence from family-based linkage analysis and fine mapping in linkage region, genome-wide association studies, and candidate genes analyses. A number of genes have been discovered at a relatively rapid pace. The detailed molecular mechanism underlying KC pathogenesis will significantly advance our understanding of KC and promote the development of potential therapies.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                29 March 2019
                2019
                : 7
                : 66
                Affiliations
                [1] 1Cole Eye Institute, Cleveland Clinic , Cleveland, OH, United States
                [2] 2Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , Cleveland, OH, United States
                [3] 3Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of CWRU , Cleveland, OH, United States
                [4] 4Department of Biomedical Engineering, Case Western Reserve University , Cleveland, OH, United States
                [5] 5Department of Pediatrics, Case Western Reserve University , Cleveland, OH, United States
                Author notes

                Edited by: Brittany Coats, The University of Utah, United States

                Reviewed by: Henrique de Amorim Almeida, Polytechnic Institute of Leiria, Portugal; Seok Hyun (Andy) Yun, Harvard Medical School, United States

                *Correspondence: William J. Dupps bjdupps@ 123456outlook.com

                This article was submitted to Biomechanics, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2019.00066
                6459081
                31019909
                7e229e00-2ab4-4b7f-89e1-c1bd9dfc6ddb
                Copyright © 2019 Blackburn, Jenkins, Rollins and Dupps.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 November 2018
                : 07 March 2019
                Page count
                Figures: 5, Tables: 8, Equations: 0, References: 172, Pages: 16, Words: 13771
                Funding
                Funded by: National Eye Institute 10.13039/100000053
                Categories
                Bioengineering and Biotechnology
                Review

                cornea biomechanical properties,cornea,aging,crosslinking,crosslinking (cxl) corneal collagen,keratoconus

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