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      Persistent Corneal Epithelial Defects: A Review Article

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          Abstract

          Persistent corneal epithelial defects (PEDs or PCEDs) result from the failure of rapid re-epithelialization and closure within 10-14 days after a corneal injury, even with standard supportive treatment. Disruptions in the protective epithelial and stromal layers of the cornea can render the eye susceptible to infection, stromal ulceration, perforation, scarring, and significant vision loss. Although several therapies exist and an increasing number of novel approaches are emerging, treatment of PEDs can still be quite challenging. It is important to treat the underlying causative condition, which may include an infection, limbal stem cell deficiency, or diabetes, in order to facilitate wound healing. Standard treatments, such as bandage contact lenses (BCLs) and artificial tears (ATs), aim to provide barrier protection to the epithelial layer. Recently-developed medical treatments can target the re-epithelialization process by facilitating access to growth factors and anti-inflammatory agents, and novel surgical techniques can provide re-innervation to the cornea. PEDs should be treated within 7-10 days to avoid secondary complications. These interventions, along with a step-wise approach to management, can be useful in patients with PEDs that are refractory to standard medical treatment. In this review, we discuss the epidemiology, etiology, diagnosis, current and novel management, and prognosis of persistent epithelial defects.

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          Progress in corneal wound healing.

          Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.
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            Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency.

            To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). Thirty-one eyes of 26 consecutive patients had cytologically proven limbal deficiency resulting from chemical burns (14 eyes); Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5 eyes); contact lens-induced keratopathy (3 eyes); aniridia (3 eyes); multiple surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based on the severity of limbal deficiency, group A (mild), comprising 10 eyes, received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT; and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating keratoplasty. All patients except those in group A received continuous oral cyclosporine. Except for the 2 eyes with atopy, all amniotic membrane-covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced inflammation, vascularization, and scarring, and the surfaces became smooth and wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7 eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft rejection was noted in 3 (14%) of 21 eyes of groups B and C. For partial limbal deficiency with superficial involvement, AMT alone is sufficient and hence superior to ALT because there is no need to administer cyclosporine. For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct the perilimbal stroma, with reduced inflammation and vascularization, which collectively may enhance the success of ALT.
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              Overview of the Cornea: Structure, Function, and Development.

              The cornea is a transparent tissue with significant refractive and barrier functions. The epithelium serves as the principal barrier to fluid and pathogens, a function performed through production of tight junctions, and constant repopulation through differentiation and maturation of dividing cells in its basal cell layer. It is supported posteriorly by basement membrane and Bowman's layer and assists in maintenance of stromal dehydration. The stroma composes the majority of corneal volume, provides support and clarity, and assists in ocular immunity. The posterior cornea, composed of Descemet membrane and endothelium, is essential for stromal dehydration, maintained through tight junctions and endothelial pumps. Corneal development begins with primitive formation of epithelium and lens, followed by waves of migration from cells of neural crest origin between these two structures to produce the stroma and endothelium. Descemet membrane is secreted by the latter and gradually thickens.
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                Author and article information

                Journal
                Med Hypothesis Discov Innov Ophthalmol
                mehdiophth
                Medical Hypothesis, Discovery and Innovation in Ophthalmology
                Medical Hypothesis, Discovery & Innovation Ophthalmology
                2322-4436
                2322-3219
                Autumn 2019
                : 8
                : 3
                : 163-176
                Affiliations
                [1 ] McGovern Medical School, Health Science Center, University of Texas, Houston, TX, USA
                [2 ] Hoopes Durrie Rivera Research Center, Hoopes Vision, Draper, UT, USA
                [3 ] John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, School of Medicine, University of Utah Salt Lake City, UT, USA
                [4 ] Utah Lions Eye Bank, Murray, UT, USA
                Author notes
                Correspondence to: Professor Majid Moshirfar, MD, Hoopes Durrie Rivera Research Center, Hoopes Vision, 11820 S. State Street Suite, #200, Draper, UT 84020; Phone: 801-568-0200; Fax: 801-563-0200; E-mail: cornea2020@me.com
                Article
                mehdiophth-8-163
                10.1016/s0886-3350(13)80283-0
                6778469
                31598519
                23943f12-a4e1-4fe8-871b-3870114644fe
                © 2019, Author(s).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License ( http://creativecommons.org/licenses/by/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

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                Review Article

                ophthalmic solutions,fibronectin,thymosin beta-4,epidermal growth factor,insulin-like growth factor i,growth factor,albumins

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