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      Corneal endothelial cell dysfunction: etiologies and management

      review-article
      Therapeutic Advances in Ophthalmology
      SAGE Publications
      corneal endothelial dysfunction, etiologies, human corneal endothelium, management

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          Abstract

          A transparent cornea is essential for the formation of a clear image on the retina. The human cornea is arranged into well-organized layers, and each layer plays a significant role in maintaining the transparency and viability of the tissue. The endothelium has both barrier and pump functions, which are important for the maintenance of corneal clarity. Many etiologies, including Fuchs’ endothelial corneal dystrophy, surgical trauma, and congenital hereditary endothelial dystrophy, lead to endothelial cell dysfunction. The main treatment for corneal decompensation is replacement of the abnormal corneal layers with normal donor tissue. Nowadays, the trend is to perform selective endothelial keratoplasty, including Descemet stripping automated endothelial keratoplasty and Descemet’s membrane endothelial keratoplasty, to manage corneal endothelial dysfunction. This selective approach has several advantages over penetrating keratoplasty, including rapid recovery of visual acuity, less likelihood of graft rejection, and better patient satisfaction. However, the global limitation in the supply of donor corneas is becoming an increasing challenge, necessitating alternatives to reduce this demand. Consequently, in vitro expansion of human corneal endothelial cells is evolving as a sustainable choice. This method is intended to prepare corneal endothelial cells in vitro that can be transferred to the eye. Herein, we describe the etiologies and manifestations of human corneal endothelial cell dysfunction. We also summarize the available options for as well as recent developments in the management of corneal endothelial dysfunction.

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          Most cited references157

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          Descemet-stripping automated endothelial keratoplasty.

          To evaluate the speed of visual recovery in 16 consecutive patients with corneal endothelial dysfunction who received Descemet-stripping automated endothelial keratoplasty (DSAEK). This is a retrospective study of a novel method for small-incision endothelial transplantation (DSAEK). Endothelial replacement was accomplished with Descemet stripping of the recipient and insertion of a posterior donor tissue that had been prepared with a microkeratome. Best spectacle-corrected visual acuity (BSCVA) by manifest refraction, endothelial counts, and dislocation rates were measured up to 12 months after DSAEK. Sixteen consecutive patients underwent uncomplicated DSAEK. Three patients had known optic nerve or macular disease precluding vision better than 20/200. Of the remaining 14 patients, 11 had BSCVA of 20/40 by postoperative week 12 (7 by week 6). The remaining 2 were 20/50 by weeks 6 and 12. All 14 patients were 20/40 or better at 1 year. One patient had a primary graft failure, and surgery was repeated with 20/40 BSCVA at 1 year. The dislocation rate was 25%. The average cell count between 7 and 10 months was 1714. The average pachymetry was 682. DSAEK surgery allows rapid, excellent BSCVA visual recovery. The rate of visual recovery is more rapid than usually found with penetrating keratoplasty.
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            Proliferative capacity of corneal endothelial cells.

            The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic "pump" functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the in vivo induction of transient corneal endothelial cell division or the in vitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new treatments to restore corneal clarity. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Long-term graft survival after penetrating keratoplasty.

              To determine long-term graft survival rates and causes of secondary graft failures for a large series of penetrating keratoplasties (PKPs). Retrospective, noncomparative case series. Longitudinal review of 3992 consecutive eyes that underwent PKP at a large tertiary care referral center from 1982 through 1996. Data were collected retrospectively from August 1982 through December 1988 and prospectively thereafter. Three thousand six hundred forty primary grafts and 352 regrafts. Corneal graft survival and etiology of graft failures. Patients were evaluated preoperatively and at 1, 3, 6, 9, 12, 18, and 24 months after transplant, then at yearly intervals. Mean recipient age was 67 years (range, 1-98 years). The predominant indications for PKP were pseudophakic bullous keratopathy (32%) and Fuchs' dystrophy (23%). Graft failure occurred in 10% (385) of the eyes. The most common causes of secondary graft failure were endothelial failure (29%) or immunologic endothelial rejection (27%). Survival of first time grafts was 90% at 5 years and 82% at 10 years. Initial regrafts had significantly lower 5-year and 10-year survival rates, 53% and 41%, respectively. The highest 5-year and 10-year survival rates were noted in primary grafts for eyes with a preoperative diagnosis of keratoconus (97% and 92%, respectively), or Fuchs' dystrophy (97% and 90%, respectively). Primary grafts for aphakic bullous keratopathy without intraocular lens placement had the lowest 5-year survival rate, 70%. The 5-year and 10-year survival rates in this series demonstrate that PKP is a safe and effective treatment for the corneal diseases commonly transplanted in the United States. However, endothelial failure and immunologic graft rejection were persistent risks over the long term, supporting the need for continued patient follow-up. Regrafts, aphakic eyes without intraocular lens placement at the time of transplant, and corneas with deep stromal vascularization had reduced graft survival rates. Pseudophakic bullous keratopathy grafts with a retained posterior chamber intraocular lens were at increased risk of endothelial failure compared with primary grafts done for other causes or compared with pseudophakic bullous keratopathy grafts done with intraocular lens exchange.
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                Author and article information

                Journal
                Ther Adv Ophthalmol
                Ther Adv Ophthalmol
                OED
                spoed
                Therapeutic Advances in Ophthalmology
                SAGE Publications (Sage UK: London, England )
                2515-8414
                07 December 2018
                Jan-Dec 2018
                : 10
                : 2515841418815802
                Affiliations
                [1-2515841418815802]Ophthalmic Research Center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran 16666, Iran
                Author notes
                Article
                10.1177_2515841418815802
                10.1177/2515841418815802
                6293368
                30560230
                165761d7-c150-4e51-9cb4-27a54b97183d
                © The Author(s), 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 24 April 2018
                : 31 October 2018
                Categories
                Review
                Custom metadata
                January-December 2018

                corneal endothelial dysfunction,etiologies,human corneal endothelium,management

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