Contents

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 Superficial 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

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