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      Comorbidity of Keratoconus and Fuchs’ Corneal Endothelial Dystrophy: A Review of the Literature

      * , ,
      Ophthalmic Research
      S. Karger AG
      Cornea, Fuchs’ dystrophy, Keratoconus

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          Introduction: Comorbidity of keratoconus (KC) and Fuchs’ corneal endothelial dystrophy (FD) has been sporadically reported in the literature since the early nineties. This review summarizes findings from the related literature while examining the possibilities related to the concurrent development of these disorders and the clinical significance for the clinician. Methods: NLM/PubMed, Ovid, Google Scholar, Cornea, and Cochrane database were reviewed for research papers presenting cases of comorbid KC and FD published between January 1990 and July 2019. Results: Fifteen papers which presented 69 cases were included in the study. Most cases were women (56.5%), involvement was bilateral (59.4%), and the age range was wide (15–82 years) with a normal distribution. Incidence is expected to be approximately 1 per 100,000. FD is the most frequent comorbid corneal dystrophy diagnosed in KC patients. There are 4 distinct possibilities for the cooccurrence of KC and FD, the most likely being that of chance. Conclusion: The overall incidence of these disorders found in combination is very low and, in absence of other conclusively proven hypotheses, most likely attributable to chance. The treatment plan should be tailored to the needs of the individual patient, since the diagnosis can be made in any stage of life and could be part of a more complex presentation that includes another pathology of the cornea or senile cataract. The inclusion of preoperative topography and specular microscopy as routine in cataract preoperative assessment would protect against any postoperative complications in these patients.

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          Most cited references29

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          Is Open Access

          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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            Atopy and keratoconus: a multivariate analysis.

            The primary goal of this study was to determine if atopy is a risk factor for keratoconus. Other potential risk factors were also studied and included age, sex, race, eye rubbing, mitral valve prolapse, handedness, collagen vascular disease, ocular trauma, pigmentary retinopathy, Marfan's syndrome, Down's syndrome, and a history of contact lens wear. A case-control study was designed (n=120) with incident cases assembled from the years 1985-99. Controls were chosen from the same person-time experience as cases and were picked from a source population with multiple outcomes ensuring that none was knowingly related to any of the potential exposures being studied. Atopy was defined based on the UK working group 1994 definition (at least 4/6 criteria = complete, 3/6 criteria = incomplete, and at least 1/6 criteria = partial). Keratoconus was defined based on clinical criteria and previously published I-S values. Multiple logistic regression was used in the analysis to obtain the odds ratios as the measure of association. In the univariate associations, there was an association between keratoconus and atopy as well as eye rubbing and family history of keratoconus. However, in the multivariate analysis, only eye rubbing was still a significant predictor of keratoconus (odds ratio = 6.31 p = 0.001). This study supports the hypothesis that the most significant cause of keratoconus is eye rubbing. Atopy may contribute to keratoconus but most probably via eye rubbing associated with the itch of atopy. No other variable measured was significantly associated with the aetiology of keratoconus.
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              Keratoconus: an inflammatory disorder?

              Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

                Author and article information

                Ophthalmic Res
                Ophthalmic Research
                S. Karger AG
                July 2020
                23 December 2019
                : 63
                : 4
                : 369-374
                2nd Department of Ophthalmology, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece
                Author notes
                *Ioanna Mylona, MD, MSc, 2nd Department of Ophthalmology, Papageorgiou General Hospital, Agiou Pavlou 76, Pavlos Melas, GR–564 29 Thessaloniki (Greece), milona_ioanna@windowslive.com
                Author information
                505579 Ophthalmic Res 2020;63:369–374
                © 2019 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 08 October 2019
                : 18 December 2019
                Page count
                Tables: 1, Pages: 6
                Systematic Review

                Vision sciences,Ophthalmology & Optometry,Pathology
                Fuchs’ dystrophy,Cornea,Keratoconus
                Vision sciences, Ophthalmology & Optometry, Pathology
                Fuchs’ dystrophy, Cornea, Keratoconus


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