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      Limbal Stem Cell Allografts and Corneal Transplant in a Patient with Severe Corneal Melting and Perforation due to Thermokeratoplasty and Cross-Linking Treatment Burn

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          Abstract

          Purpose

          To report corneal stem cell allografts in a patient with a persistent epithelial defect as well as corneal melting and perforation due to severe ultraviolet light burn and thermokeratoplasty treatment for keratoconus.

          Methods

          A 21-year-old female patient with corneal melting, perforation and a persistent epithelial defect in her left eye secondary to iatrogenic treatment for keratoconus, thermokeratoplasty and cross-linking was treated with penetrating keratoplasty, using a 9.0-mm diameter corneal graft and limbal stem cell allograft implants. At the end of the procedure, subtenonian injections of a combination of bevacizumab and triamcinolone were given.

          Results

          The patient had a favorable outcome 48 h after surgery, with an improvement of symptoms and a complete corneal healing. By the third week after surgery, she had a best-corrected visual acuity of 20/60 and a clear corneal graft, which remained stable for the 9 months of follow-up.

          Conclusions

          Treatment with limbal stem cell allografts and penetrating keratoplasty in a female patient with a large corneal defect and melting in her left eye was effective. Larger studies are warranted to explore the real impact of this procedure.

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          Most cited references6

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          Limbal stem cells of the corneal epithelium.

          Stem cells have certain unique characteristics, which include longevity, high capacity of self-renewal with a long cell cycle time and a short S-phase duration, increased potential for error-free proliferation, and poor differentiation. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. Stem cells for the cornea reside at the corneoscleral limbus. The limbal palisades of Vogt and the interpalisade rete ridges are believed to be repositories of stem cells. The microenvironment of the limbus is considered to be important in maintaining the stemness of stem cells. Limbal stem cells also act as a "barrier" to conjunctival epithelial cells and normally prevent them from migrating on to the corneal surface. Under certain conditions, however, the limbal stem cells may be partially or totally depleted, resulting in varying degrees of stem cell deficiency with resulting abnormalities in the corneal surface. Such deficiency of limbal stem cells leads to "conjunctivalization" of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. This results in ocular discomfort and reduced vision. Partial stem cell deficiency can be managed by removing the abnormal epithelium and allowing the denuded cornea, especially the visual axis, to resurface with cells derived from the remaining intact limbal epithelium. In total stem cell deficiency, autologous limbus from the opposite normal eye or homologous limbus from living related or cadaveric donors can be transplanted on to the affected eye. With the latter option, systemic immunosuppression is required. Amniotic membrane transplantation is a useful adjunct to the above procedures in some instances.
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            Limbal stem cell transplantation: new progresses and challenges.

            Patients with limbal stem cell deficiency (LSCD) suffer from photophobia and a severe loss of vision uncorrectable by conventional PKP. This literature review shows that new strategies can be formulated for treating LSCD. Early cryopreserved amniotic membrane transplantation (AMT) as a temporary biological bandage with sutures or with sutureless ProKera in the acute stage of chemical burn and Stevens-Johnson syndrome prevents the occurrence of LSCD by preserving and expanding the remaining limbal epithelial stem cells. Similarly, remaining limbal stem cells can also be expanded in corneal surfaces with partial or nearly total LSCD if corneal pannus is removed and AMT is performed as a graft with or without sutures by the use of fibrin glue. Moreover, AMT as a temporary bandage and a graft using fibrin glue can also facilitate corneal surface reconstruction by reducing the size of a conjunctival limbal autograft (CLAU) to one 60 degrees graft for unilateral total LSCD as well as promote the success of a keratolimbal allograft (KLAL) for bilateral total LSCD. The latter success is further dictated by effective systemic immunosuppression and by measures to restore the ocular surface defenses, suppress conjunctival inflammation, and correct cicatricial complications so that a stable tear film can be maintained before surgery. This review also summarizes recent findings and outlines future challenges that we need to overcome in squamous metaplasia, that is, another major type of ocular surface failure.
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              Epithelial transplantation for the management of severe ocular surface disease.

              First, to present a new classification of epithelial transplantation procedures for ocular surface disease; second, to present our experience with a keratolimbal allograft procedure for limbal stem cell deficiency; and third, to make recommendations for the indications and postoperative management of epithelial transplantation procedures. A review of all epithelial transplantation procedures was performed. A classification of these procedures based on the source of donor tissue and the tissue transplanted was proposed. In addition, a review of 25 eyes of 21 patients who underwent a keratolimbal allograft was completed. Ocular surface stability, improvement of visual acuity, success of subsequent keratoplasties, and preoperative risk factors were evaluated. Results were compared with those of other epithelial transplantation procedures for ocular surface disease. On the basis of the results of published studies, as well as ours, a recommendation for the indication of the various procedures was made. Epithelial transplantation for ocular surface disease can be classified as one of the following procedures: conjunctival autograft (CAU), conjunctival allograft (CAL), conjunctival limbal autograft (CLAU), cadaveric conjunctival limbal allograft (c-CLAL), living related conjunctival limbal allograft (lr-CLAL), or keratolimbal allograft (KLAL). Evaluation of our keratolimbal allograft patients revealed that 18 of 25 eyes (72%) developed a stable ocular surface. Fifteen eyes (60%) demonstrated a significant improvement in visual acuity. Persistent epithelial defects and symblephara were successfully managed with this procedure. Six of 13 (46%) subsequent keratoplasties were successful. Patients with limbal deficiency due to Stevens-Johnson syndrome had a significantly worse outcome. Patients with preoperative conjunctival keratinization also had a significantly worse outcome. Indications for epithelial transplantation are as follows: For patients with unilateral cicatrizing conjunctival disease, the first option should be CAU. For patients with unilateral limbal deficiency, CLAU is the procedure of choice. For patients with bilateral disease Ir-CLAL should be considered first. If this procedure is not available, then consideration of KLAL is warranted. Classification of the various epithelial transplantation procedures based on anatomy is useful for an accurate comparison and discussion of the procedures. KLAL is a useful technique in the management of severe ocular surface disease due to limbal deficiency. However, patients with preoperative conjunctival keratinization have a poor prognosis. Consideration of a CLAU or a Ir-CLAL should be made for ocular surface disease on the basis of whether the disease is unilateral or bilateral. The importance of HLA and ABO typing, as well as the protocol for immunosuppression in the allograft procedures for limbal deficiency, needs further study.
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                Author and article information

                Journal
                Case Report Ophthalmol
                Case Report Ophthalmol
                COP
                Case Reports in Ophthalmology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                1663-2699
                Sep-Dec 2012
                23 October 2012
                23 October 2012
                : 3
                : 3
                : 364-369
                Affiliations
                Instituto Oftalmologico Privado, Irapuato, Mexico
                Author notes
                *Leopoldo Garduño-Vieyra, MD, Blvd. Lazaro Cardenas 1851, Colonia San Pedro, Irapuato, Guanajuato CP 36520 (Mexico), E-Mail polo80@ 123456hotmail.com
                Article
                cop-0003-0364
                10.1159/000343771
                3506062
                23185178
                066182e3-17b8-46ec-80be-9c885be660b2
                Copyright © 2012 by S. Karger AG, Basel

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No-Derivative-Works License ( http://creativecommons.org/licenses/by-nc-nd/3.0/). Users may download, print and share this work on the Internet for noncommercial purposes only, provided the original work is properly cited, and a link to the original work on http://www.karger.com and the terms of this license are included in any shared versions.

                History
                Page count
                Figures: 3, References: 6, Pages: 6
                Categories
                Published online: October, 2012

                Ophthalmology & Optometry
                thermal burn,stem cells,corneal melting,thermokeratoplasty
                Ophthalmology & Optometry
                thermal burn, stem cells, corneal melting, thermokeratoplasty

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