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Fungal Endophthalmitis ............................ Mycosis of the Eye and Its Adnexa .. ............................ Developments in Ophthalmology Vol. 32 Series Editor W. Behrens-Baumann, Magdeburg ............................ Mycosis of the Eye and Its Adnexa W. Behrens-Baumann, Magdeburg with a contribution by R. RuÈchel,GoÈttingen 39 ®gures, 31 in color, and 39 tables, 1999 ............................ Prof. Dr. med. W. Behrens-Baumann Klinik fuÈr Augenheilkunde, Otto-von-Guericke-UniversitaÈt Leipziger Strasse 44, D±39120 Magdeburg This is a revised and extended translation of a former German version entitled Pilzerkrankungen des Auges by Wolfgang Behrens-Baumann The reproduction of the color illustrations in this book was made possible by a generous contribution from the Heinz Karger Memorial Foundation Continuation of `Bibliotheca Ophthalmologica', `Advances in Ophthalmology', and `Modern Problems in Ophthalmology' Founded 1926 as `Abhandlungen aus der Augenheilkunde und ihren Grenzgebieten' by C. Behr, Hamburg and J. Meller, Wien Former Editors: A. BruÈckner, Basel (1938±1959); H. J. M. Wewe, Utrecht (1938±1962); H. M. Dekking, Groningen (1954±1966); E. R. StreiV, Lausanne (1954±1979); J. FrancËois, Gand (1959±1979); J. van Doesschate, Utrecht (1967±1971); M. J. Roper-Hall, Birmingham (1966±1980); H. Sautter, Hamburg (1966±1980); W. Straub, Marburg a. d. Lahn (1981±1993) Library of Congress Cataloging-in-Publication Data Behrens-Baumann, Wolfgang. [Pilzerkrankungen des Auges, English] Mycosis of the eye and its adnexa / W. Behrens-Baumann; with a contribution by R. Ruchel. (Developments in ophthalmology; vol. 32) Includes bibliographical references and indexes. 1. Oculomycoses. I. Ruchel, R. II. Title. III. Series. [DNLM: 1. Eye Infections, Fungal ± drug therapy. 2. Eye Infections, Fungal ± diagnosis. W1 DE998NG v.32 1999] RE901.F8B4413 1999 617.7 ± dc21 ISSN 0250±3751 ISBN 3±8055±6915±7 (hardcover : alk. paper) Bibliographic Indices. This publication is listed in bibliographic services, including Current ContentsÔ and Index Medicus. Drug Dosage. The authors and the publisher have exerted every eVort 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 ¯ow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change 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. 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. Ó Copyright 1999 by S. Karger AG, P.O. Box, CH±4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel ISBN 3±8055±6915±7 ............................ Contents 1 1 An Overview of Fungal Pathogens of Ophthalmological Importance R. RuÈchel,GoÈttingen 1 1.1 Introduction 2 1.2 Zygomycota 4 1.3 Ascomycota 5 1.4 Basidiomycota 6 1.5 Deuteromycota 8 1.6 Indigenous Fungi Causing Invasive Mycoses 8 1.6.1 Candida albicans 11 1.6.2 Candida tropicalis 12 1.6.3 Candida parapsilosis 12 1.6.4 Candida glabrata (Torulopsis glabrata) and C. krusei 13 1.6.5 Rare Agents of Invasive Yeast Infections 13 1.6.6 Mixed Infections 13 1.6.7 Cryptococcus neoformans 15 1.6.8 Aspergillus fumigatus 17 1.6.9 Mucormycosis 19 1.6.10 Fusariomycosis 19 1.6.11 Scedosporium spp. 19 1.6.12 Histoplasmosis 20 1.7 Causative Agents of Super®cial Mycosis 21 1.8 Miscellaneous 21 1.8.1 Actinomycetales 22 1.8.2 Collection of Specimens and Culturing of Fungi 23 References 25 Glossary V 27 2 Antifungal Agents 27 2.1 Polyenes 27 2.1.1 Amphotericin B 30 2.1.2 Natamycin (Pimaricin) 30 2.1.3 Nystatin 31 2.2 Flucytosine 32 2.3 Azoles 32 2.3.1 Clotrimazole 33 2.3.2 Miconazole 34 2.3.3 Ketoconazole 35 2.3.4 Itraconazole 36 2.3.5 Fluconazole 37 2.3.6 Econazole, Voriconazole and Other Azole Antifungal Agents 37 2.3.6.1 Econazole 38 2.3.6.2 Voriconazole 38 2.3.6.3 Saperconazole and Thiabendazole 39 2.4 Miscellaneous Antifungal Agents 40 2.5 Recommended Drugs for Fungal Infections 41 References 52 3 Periocular Fungal Infections 52 3.1 Palpebral Involvement 52 3.2 Infections of the Lacrimal Ducts 54 3.3 Fungal Infections of the Orbit 56 3.3.1 Mucormycosis 58 3.3.1.1 Case Report 59 3.3.2 Aspergillus and Other Fungal Organisms 62 References 68 4 Mycoses of the Anterior Segment of the Eye 68 4.1 Prevalence of Fungi in the Conjunctival Flora 70 4.2 Fungal Conjunctivitis 70 4.3 Fungal Scleritis 71 4.4 Keratomycosis 73 4.4.1 Predisposing Factors 73 4.4.1.1 Corticosteroids 74 4.4.1.2 Antibiotics 75 4.4.1.3 Foreign Bodies 75 4.4.1.4 Postoperative Keratomycosis 76 4.4.1.5 Pre-Existing Eye Diseases 76 4.4.1.6 Contact Lenses Contents VI 77 4.4.1.7 Systemic Illness 77 4.4.1.8 Age, Sex, Climate and Season 78 4.4.2 Spectrum of Pathogens Causing Keratomycosis 78 4.4.3 Clinical Aspects of Keratomycoses 84 4.4.4 Further Diagnostic Measures in Keratomycosis 87 4.4.5 Histopathology of the Keratomycoses 88 4.4.6 Treatment of Keratomycosis 88 4.4.6.1 Medical Treatment 88 4.4.6.1.1 Antifungal Agents 89 4.4.6.1.2 Antifungal Agents Plus Corticosteroids 90 4.4.6.2 Surgical Treatment 92 4.4.7 Case Histories 92 4.4.7.1 Case 1 92 4.4.7.2 Case 2 94 4.4.7.3 Case 3 94 4.4.7.4 Case 4 94 4.4.7.5 Case 5 94 References 108 5 Fungal Endophthalmitis 108 5.1 Pathogenesis and Clinical Features 108 5.1.1 Endogenous Fungal Endophthalmitis 108 5.1.1.1 Pathogens 108 5.1.1.2 Causes 112 5.1.1.3 Clinical Features 116 5.1.1.3.1 Endogenous Aspergillus Endophthalmitis 117 5.1.1.3.2 Endogenous Cryptococcus Endophthalmitis 118 5.1.2 Exogenous Fungal Endophthalmitis 118 5.1.2.1 Causes 118 5.1.2.1.1 Postoperative Fungal Endophthalmitis 122 5.1.2.1.2 Fungal Endophthalmitis following Injury 122 5.1.2.1.3 Fungal Endophthalmitis following Keratomycosis or Scleritis 122 5.1.2.2 Clinical Features and Diagnosis 123 5.2 Treatment of Fungal Endophthalmitis 123 5.2.1 Drug Treatment 123 5.2.1.1 Local Antimycotic Therapy 124 5.2.1.2 Systemic Antimycotic Therapy 126 5.2.1.3 Surgical Treatment 129 References Contents VII 144 6 Histoplasmosis 144 6.1 Systemic Histoplasmosis 144 6.1.1 Epidemiology and Clinical Features 145 6.1.2 Diagnosis 145 6.1.2.1 Histoplasmin Skin Testing 146 6.1.2.2 Other Tests 147 6.2 Ocular Histoplasmosis 152 6.3 Treatment of Histoplasmosis 152 6.3.1 Treatment of Systemic Histoplasmosis 152 6.3.2 Treatment of Ocular Histoplasmosis 152 6.3.2.1 Drug Treatment 153 6.3.2.2 Photocoagulation and Surgical Treatment 154 6.4 DiVerential Diagnosis of Ocular Histoplasmosis 155 References 162 7 Experimental Findings in the Eye 162 7.1 Experimental Models of Keratomycosis 162 7.1.1 Development of DiVerent Models of Infection with Live Pathogens 162 7.1.1.1 Inoculation Technique and Immunosuppression 163 7.1.1.2 Strains Used for Infection 168 7.1.1.3 Antibiotics and Bacterial Superinfection 169 7.1.1.4 Immune Status of Experimental Animals 169 7.1.2 Keratomycosis Models Using Fungal Extracts 169 7.1.3 A Reproducible Model of Keratomycosis 171 7.2 Bioavailability of Antimycotic Agents 172 7.2.1 Amphotericin B 173 7.2.2 Bifonazole and Clotrimazole 173 7.2.3 Natamycin (Primaricin) 173 7.2.4 Fluconazole 174 7.2.5 Miconazole, Ketoconazole and Itraconazole 175 7.3 Experimental Toxicity of Antimycotic Agents 175 7.3.1 Corneal Toxicity 175 7.3.2 Retinal Toxicity 175 7.4 Treatment of Experimental Keratomycosis 175 7.4.1 Timing of Treatment 175 7.4.2 EVect of Antimycotic Agents on Experimental Keratomycosis 177 7.4.2.1 Amphotericin B 179 7.4.2.2 Bifonazole and Clotrimazole 179 7.4.2.3 Natamycin (Pimaricin) 179 7.4.2.4 Ketoconazole, Miconazole and Fluconazole 181 7.4.2.5 Miscellaneous Agents 181 7.4.3 Corticosteroids in the Treatment of Experimental Keratomycosis with Antimycotic Agents Contents VIII 182 7.4.4 Operative Treatment of Experimental Keratomycosis 183 7.5 Experimental Fungal Endophthalmitis 183 7.5.1 Experimental Endogenous Fungal Endophthalmitis 183 7.5.1.1 Experimental Models 185 7.5.1.2 Therapeutic Studies in the Endogenous Endophthalmitis Model 186 7.5.2 Experimental Exogenous Fungal Endophthalmitis 187 7.6 Experimental Histoplasmosis 189 References 197 Subject Index Contents IX OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO Dedicated to my wife Cordula and our daughters Verena and Corinna Chapter 1 ............................ An Overview of Fungal Pathogens of Ophthalmological Importance R. RuÈchel 1.1 Introduction Fungi were initially thought to be plants that lacked chlorophyll, but following the proposal of Whittaker [1], they are now considered to be an independent ®fth kingdom of life in parallel with the Monera (bacteria and certain prokaryotic algae), Protoctista (protozoa, nucleated algae, slime moulds, etc.), Plantae and Animalia. Fungi (mycetes) are eukaryotes, in con- trast to the bacteria (prokaryotes).
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