E-Book, Englisch, 576 Seiten, Web PDF
Dartt / Bex / D'Amore Ocular Periphery and Disorders
1. Auflage 2011
ISBN: 978-0-12-382083-9
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark
E-Book, Englisch, 576 Seiten, Web PDF
ISBN: 978-0-12-382083-9
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark
This selection of articles from the Encyclopedia of the Eye is the first single-volume overview presenting articles on the function, biology, physiology, and pathology of the structures of the ocular periphery, as well as the related disorders and their treatment. The peripheral structures are implicated in a number of important diseases, including optic neuritis, thyroid eye disease, and strabismus. The volume offers a basic science background of these topics rather than a strictly clinical focus. - The first single volume to integrate comparative studies into a comprehensive resource on the neuroscience of the ocular periphery - Chapters are carefully selected from the Encyclopedia of the Eye by the world's leading vision researchers - The best researchers in the field provide their conclusions in the context of the latest experimental results
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Ocular Periphery and Disorders;4
3;Copyright Page;5
4;Contents;6
5;Contributors;10
6;Introduction;14
7;Section I: Extraocular and Eyelid Muscles: Structure, Function, and Pathophysiology;16
7.1;Eyelid Anatomy and the Pathophysiology of Blinking;18
7.1.1;Glossary;18
7.1.2;Organization of the Eyelid System;18
7.1.3;Modifiability of the Blink System;21
7.1.4;Benign Essential Blepharospasm and Hemifacial Spasm;22
7.1.5;Further Reading;23
7.2;Differentiation and Morphogenesis of Extraocular Muscles;24
7.2.1;Glossary;24
7.2.2;Introduction;24
7.2.3;Origins of Extraocular Muscles;24
7.2.4;Determination of Eye Muscle Precursors;26
7.2.5;Molecular Signatures and Muscle Differentiation;27
7.2.6;Muscle Morphogenesis;29
7.2.7;Summary;31
7.2.8;Further Reading;31
7.3;Extraocular Muscles: Extraocular Muscle Anatomy;32
7.3.1;Glossary;32
7.3.2;Gross Anatomy of the EOM within the Orbit;32
7.3.3;Histological Anatomy of the EOMs;36
7.3.3.1;Overall Organization;36
7.3.3.2;Innervation;36
7.3.3.3;Skeletal Muscle Fiber Types;37
7.3.3.4;Myosin Isoform Complexity in the EOM;37
7.3.3.5;Nonuniform Expression of MyHC Isoforms along the Muscle Length;38
7.3.3.6;Other Molecules Heterogeneously Expressed;40
7.3.4;Continuous Remodeling in Normal Adult EOM;40
7.3.5;Acknowledgments;41
7.3.6;Further Reading;41
7.4;Extraocular Muscles: Extraocular Muscle Metabolism;42
7.4.1;Glossary;42
7.4.2;Insights from Gene Expression Profiling;42
7.4.3;Lactate: An Oxidizable Substrate for the Extraocular Muscle;43
7.4.4;Creatine Kinase, the Missing ATP Buffer in the Extraocular Muscle;43
7.4.5;Mitochondrial Content in the Extraocular Muscles;44
7.4.6;Mitochondria as Calcium Sinks in the Extraocular Muscle;45
7.4.7;Are Extraocular Muscle Mitochondria Different?;45
7.4.8;Matching Mitochondrial Capacity to Contractile Function;46
7.4.9;Matching Energy Supply to Demand;47
7.4.10;Acknowledgments;47
7.4.11;Further Reading;47
7.5;Extraocular Muscles: Proprioception and Proprioceptors;48
7.5.1;Glossary;48
7.5.2;Proprioception;48
7.5.3;Muscle Spindles;49
7.5.3.1;Occurrence, Distribution, and Number of Muscle Spindles;49
7.5.3.2;Structure of Muscle Spindles;49
7.5.3.3;Function of Muscle Spindles;50
7.5.4;Golgi Tendon Organs;50
7.5.4.1;Occurrence, Distribution, and Number of Golgi Tendon Organs;50
7.5.4.2;Structure of Golgi Tendon Organs;51
7.5.4.3;Function of Golgi Tendon Organs;51
7.5.5;Palisade Endings;51
7.5.5.1;Occurrence, Distribution, and Number of Palisade Endings;51
7.5.5.2;Structure of Palisade Endings;52
7.5.5.3;Molecular Characteristics of Palisade Endings;52
7.5.5.4;Function of Palisade Endings;52
7.5.6;Further Reading;53
7.6;Abnormal Eye Movements due to Disease of the Extraocular Muscles and Their Innervation;54
7.6.1;Glossary;54
7.6.2;Introduction;54
7.6.3;Effects of Disorders of the EOMs on Eye Movements;54
7.6.4;Effects of Disorders of the Neuromuscular Junction on Eye Movements;55
7.6.5;Effects of Disorders of the Oculomotor, Trochlear, and Abducens Nerves on Eye Movements;57
7.6.6;Effects of Disorders of the Brainstem Circuitry on Eye Movements;57
7.6.6.1;Horizontal Movements;57
7.6.6.2;Vertical Movements;58
7.6.7;Congenital Misalignment of the Eyes (Infantile Strabismus) and Attendant Nystagmus;58
7.6.8;Effect of Visual System Disorders on Eye Movements;59
7.6.9;Infantile Forms of Nystagmus in Individual with Normal Visual Systems;59
7.6.10;Conclusions;59
7.6.11;Further Reading;59
7.7;Extraocular Muscles: Functional Assessment in the Clinic;60
7.7.1;Glossary;60
7.7.2;Normal Eye Movements;60
7.7.2.1;Ocular Motility Assessment in the Clinic;61
7.7.2.2;Clinical Treatment for Primary Eye Motility Disorders;62
7.7.3;Acknowledgments;63
7.7.4;Further Reading;63
8;Section II: Structure and Function of the Tear Film, Ocular Adnexa, Cornea and Conjunctiva in Health and Pathogenesis in Disease;64
8.1;Tear Film;66
8.1.1;Glossary;66
8.1.2;The Role of the Tear Film;66
8.1.3;Structure and Thickness of the Tear Film;66
8.1.4;The Lipid Layer;67
8.1.5;Tear Evaporation;68
8.1.6;The Aqueous Layer;68
8.1.7;Tear Production;69
8.1.8;The Mucin Layer;70
8.1.9;Tear Distribution and Stability;70
8.1.10;Tear Film Osmolarity;72
8.1.11;Drainage of Tears;73
8.1.12;Absorption of Tears by the Ocular Surface;74
8.1.13;Further Reading;74
8.2;Meibomian Glands and Lipid Layer;75
8.2.1;Glossary;75
8.2.2;Overview;75
8.2.3;The Lipid Layer of the Tear Film;76
8.2.4;Meibomian Glands;77
8.2.4.1;Anatomy and Histology;77
8.2.4.2;Development;78
8.2.4.3;Composition of Meibomian Lipids;78
8.2.4.4;Meibomian Lipid Turnover and Synthesis;78
8.2.5;Pathology of the Meibomian Gland;79
8.2.5.1;Chronic Blepharitis;80
8.2.5.2;Chalazion;81
8.2.5.3;Surgical Damage;81
8.2.5.4;Contact Lenses and the Lipid Layer;81
8.2.6;Further Reading;81
8.3;Lacrimal Gland Overview;83
8.3.1;Glossary;83
8.3.2;Anatomy of the Main Lacrimal Gland;83
8.3.3;Cell Types within the Lacrimal Gland;83
8.3.3.1;Acinar Cells;83
8.3.3.2;Ductal Cells;83
8.3.3.3;Myoepithelial Cells;84
8.3.3.4;Bone-marrow-derived Cell Population;84
8.3.4;Innervation of the Lacrimal Gland;84
8.3.5;Blood Supply;85
8.3.6;Contents of Lacrimal Fluid;85
8.3.7;Mechanisms of Protein Secretion in the Lacrimal Gland;85
8.3.8;Mechanisms and Regulation of Electrolyte and Water Secretion by the Lacrimal Gland;87
8.3.8.1;Acinar Cells;87
8.3.8.2;Ductal Cells;88
8.3.9;Conclusion;88
8.3.10;Further Reading;88
8.4;Lacrimal Gland Hormone Regulation;89
8.4.1;Glossary;89
8.4.2;Gender-Related Dimorphisms;89
8.4.3;Sex Steroids;90
8.4.3.1;Androgens;90
8.4.3.2;Estradiol and Progesterone;92
8.4.4;Prolactin;92
8.4.4.1;Exocrine Products and Autocrine/Intracrine and Paracrine Mediators;92
8.4.5;Influences of Prolactin, Estradiol, and Progesterone during Pregnancy;93
8.4.6;Reproductive Hormone Influences on Other Mucosal Immune System Tissues;94
8.4.7;Counterpoises between Contradictory Signals;95
8.4.8;Further Reading;97
8.5;Lacrimal Gland Signaling: Neural;98
8.5.1;Glossary;98
8.5.2;Anatomy of the Lacrimal Gland;98
8.5.3;Neural Control of Lacrimal Gland Secretion;98
8.5.4;Signal Transduction Pathways Activated in the Lacrimal Gland;99
8.5.4.1;Cholinergic Agonist-Activated Signal Transduction Pathways;99
8.5.4.1.1;PLC-coupled signaling pathway;99
8.5.4.1.2;PLD-coupled signaling pathway;101
8.5.4.1.3;MAPK-coupled signaling pathway;102
8.5.4.2;VIP-Activated Signal Transduction Pathways;102
8.5.4.2.1;Adenylate cyclase-coupled signaling pathway;102
8.5.4.2.2;MAPK-coupled signaling pathway;103
8.5.4.3;a1-Adrenergic Agonist-Activated Signal Transduction Pathways;103
8.5.4.3.1;Ca2+- and PKC-coupled signaling pathways;103
8.5.4.3.2;MAPK-coupled signaling pathway;104
8.5.4.3.3;NO-coupled signaling pathway;104
8.5.5;Further Reading;104
8.6;Lids: Anatomy, Pathophysiology, Mucocutaneous Junction;106
8.6.1;Glossary;106
8.6.2;Anatomy;106
8.6.3;Pathophysiology;107
8.6.3.1;Dermatochalasis;107
8.6.3.2;Ptosis;108
8.6.3.3;Retraction;108
8.6.3.4;Entropion;109
8.6.3.5;Trichiasis;110
8.6.3.6;Distichiasis;110
8.6.3.7;Ectropion;110
8.6.3.8;Floppy Lid Syndrome;110
8.6.3.9;Common Malignant Eyelid Tumors;110
8.6.3.10;Benign Eyelid Tumors;112
8.6.3.11;Inflammatory and Infectious Disorders of the Lids;112
8.6.4;Further Reading;113
8.7;Overview of Electrolyte and Fluid Transport Across the Conjunctiva;114
8.7.1;Glossary;114
8.7.2;Introduction;114
8.7.3;Conjunctival Epithelium;115
8.7.4;Bioelectric Studies on the Isolated Rabbit Conjunctiva;117
8.7.5;Electrolyte Transport Systems of the Rabbit Conjunctiva;118
8.7.6;Regulation of Epithelial Ion Transport in Rabbit Conjunctiva;119
8.7.7;Fluid Transport Studies across Isolated Rabbit Conjunctiva;120
8.7.8;Further Reading;122
8.8;Conjunctival Goblet Cells;123
8.8.1;Glossary;123
8.8.2;Goblet Cell Development;123
8.8.3;Function of Conjunctival Goblet Cells;124
8.8.4;Control of Goblet Cell Proliferation and Mucin Secretion;125
8.8.4.1;Goblet Cell Proliferation;126
8.8.4.2;Goblet Cell Mucin Secretion;127
8.8.5;Clinical Implications of Mucin Deficiency on the Ocular Surface;128
8.8.5.1;Sjögren Syndrome;129
8.8.5.2;Vitamin A Deficiency;129
8.8.5.3;Topical Preservatives;129
8.8.5.4;Ocular Cicatrical Pemphigoid;129
8.8.5.5;Laser-assisted In Situ Keratomileusis;129
8.8.5.6;Ocular Allergies;129
8.8.6;Summary;130
8.8.7;Further Reading;130
8.9;Ocular Mucins;131
8.9.1;Glossary;131
8.9.2;Introduction;131
8.9.3;Mucin Architecture;131
8.9.3.1;Mucin Families;133
8.9.3.1.1;Surface-associated mucins;133
8.9.3.1.2;Secreted mucins;133
8.9.3.2;Biosynthesis and Turnover;134
8.9.3.2.1;Synthetic pathways;134
8.9.3.2.2;Glycosylation;135
8.9.3.2.2.1;Glycosyltransferases;135
8.9.3.2.3;Turnover;135
8.9.3.2.3.1;Recycling;135
8.9.3.2.4;Degradation;136
8.9.3.3;Control of Secretion;136
8.9.3.4;Individual Variation;136
8.9.4;Mucin Function;136
8.9.4.1;Gel Formation;137
8.9.4.2;Anchoring to the Ocular Surface;138
8.9.4.3;Physical and Chemical Barriers;138
8.9.4.4;Lubrication;139
8.9.4.5;Tear Breakup;139
8.9.4.6;Antimicrobial Activity;139
8.9.4.7;Immune Protection;139
8.9.5;Clinical Relevance and Pathology;139
8.9.5.1;Contact Lens Wear;139
8.9.5.2;Dry Eye Syndromes;140
8.9.6;Further Reading;140
8.10;Tear Drainage;141
8.10.1;Glossary;141
8.10.2;History;141
8.10.3;Development;141
8.10.4;Anatomy and Dimensions;142
8.10.5;Comparative Anatomy;142
8.10.6;Tear Transport through Canaliculi;143
8.10.7;Tear Transport through Lacrimal Sac and Nasolacrimal Duct;144
8.10.8;Innate Immune Mechanisms;145
8.10.9;Adaptive Immune Mechanisms;145
8.10.10;Absorption of Tear Fluid Components;146
8.10.11;Conclusions;146
8.10.12;Further Reading;147
8.11;Cornea Overview;148
8.11.1;Glossary;148
8.11.2;Anatomy of the Layers;148
8.11.2.1;Epithelium;148
8.11.2.2;Epithelial Basement Membrane;148
8.11.2.3;Bowman's Membrane;148
8.11.2.4;Stroma;149
8.11.2.5;Descemet's Membrane;149
8.11.2.6;Endothelium;149
8.11.3;Function;149
8.11.3.1;Protective Barrier;149
8.11.3.2;Transparency;149
8.11.4;Disease Processes;150
8.11.4.1;Epithelial Disease;150
8.11.4.1.1;Epithelial staining patterns;150
8.11.4.1.2;Epithelial iron deposition;150
8.11.4.1.3;Band keratopathy;151
8.11.4.1.4;Chemical/thermal burns;151
8.11.4.1.5;Medication toxicity;151
8.11.4.1.6;Thygeson's punctate keratitis;151
8.11.4.2;Subepithelial Disease;151
8.11.4.2.1;Epithelial basement membrane dystrophy;151
8.11.4.2.2;Subepithelial infiltrates;151
8.11.4.3;Stromal Disease;152
8.11.4.3.1;Infection;152
8.11.4.3.2;Dystrophies;152
8.11.4.3.3;Degenerations;152
8.11.4.3.4;Descemet's copper deposition;153
8.11.4.4;Endothelial Disease;153
8.11.4.4.1;Fuchs' dystrophy;153
8.11.4.4.2;Pseudophakic bullous keratopathy;153
8.11.5;Surgery;153
8.11.5.1;Surgical Intervention of Epithelial Disease;154
8.11.5.1.1;Amniotic membrane graft;154
8.11.5.1.2;Conjunctival flap;154
8.11.5.1.3;Corneal glue;154
8.11.5.1.4;Disodium ethylenediaminetetraacetic acid chelation;154
8.11.5.1.5;Limbal stem cell transplant;154
8.11.5.1.6;Phototherapeutic keratectomy;154
8.11.5.1.7;Pterygium excision;154
8.11.5.1.8;Stromal puncture;155
8.11.5.1.9;Tarsorrhaphy;155
8.11.5.2;Surgical Intervention of Stromal Disease;155
8.11.5.2.1;Anterior lamellar keratoplasty;155
8.11.5.2.2;Penetrating keratoplasty;155
8.11.5.2.3;Corneal biopsy;155
8.11.5.2.4;Corneal laceration repair;155
8.11.5.2.5;Refractive surgery;155
8.11.5.2.6;Prosthetic keratoplasty;156
8.11.5.3;Surgical Intervention of Endothelial Disease;156
8.11.5.3.1;Descemets Stripping Automated Endothelial Keratoplasty;156
8.11.6;Further Reading;157
8.12;Corneal Epithelium: Cell Biology and Basic Science;158
8.12.1;Glossary;158
8.12.2;The Corneal Epithelium Has Vital Functions in Vision;158
8.12.3;The Apical Squames Possess Specializations to Promote Tear Film Spreading;159
8.12.4;The Epithelial Basal Cells Adhere to the Underlying Basement Membrane via tight Adhesive Junctions called Hemidesmosomes;160
8.12.5;The Palisades of Vogt;161
8.12.6;Bowman's Layer Is an Acellular Zone Located Immediately under the Corneal Epithelial Basement Membrane;161
8.12.7;The Collagen- and Proteoglycan-Rich Corneal Stroma with Its Stromal Cells, Descemet's Membrane, and the Corneal Endothelial Cells are all Vital to the Health of the Cornea;161
8.12.8;The Avascular Cornea;163
8.12.9;Further Reading;164
8.13;Corneal Nerves: Anatomy;165
8.13.1;Glossary;165
8.13.2;Origins of Corneal Nerves;165
8.13.3;Architecture of the Corneal Innervation;165
8.13.3.1;Limbal Plexus;165
8.13.3.2;Stromal and Subepithelial Plexuses;166
8.13.3.3;Subbasal Nerve Plexus;167
8.13.3.4;Intraepithelial Nerve Terminals;168
8.13.4;Corneal Nerve Neurochemistry;169
8.13.5;Corneal Nerve Remodeling;170
8.13.6;Corneal Nerve Regeneration after Ocular Surgery;170
8.13.6.1;Refractive Surgery;171
8.13.6.2;Cataract Surgery;171
8.13.6.3;Penetrating Keratoplasty;171
8.13.6.4;Mechanisms of Nerve Regrowth;172
8.13.7;Further Reading;172
8.14;Corneal Nerves: Function;173
8.14.1;Glossary;173
8.14.2;Functional Properties of Corneal Sensory Receptors;173
8.14.3;Response of Corneal Receptors to Local Inflammation;176
8.14.4;Effects of Injury on Corneal Nerves;177
8.14.5;Sensitivity of the Intact Cornea;177
8.14.6;Sensitivity of the Injured Cornea;177
8.14.7;Further Reading;178
8.15;Corneal Epithelium: Wound Healing Junctions, Attachment to Stroma Receptors, Matrix Metalloproteinases, Intracellular Communications;179
8.15.1;Glossary;179
8.15.2;Corneal Epithelial Wound Healing: Introduction;179
8.15.3;Corneal Epithelial Wound Healing: Phases of Wound Healing Process;179
8.15.4;Corneal Nerves;181
8.15.5;Corneal Epithelial Wound Healing: Cell-Cell and Cell-Matrix Junctions;181
8.15.5.1;Cell-Cell Junctions: Gap Junctions;181
8.15.5.2;Cell-Cell Junctions: Tight Junctions;182
8.15.5.3;Cell-Cell Junctions: Adherens Junctions;182
8.15.5.4;Cell-Cell Junctions: Desmosomes;182
8.15.5.5;Cell-Matrix Junctions: Hemidesmosomes and Adhesion Complexes;182
8.15.6;Secreted Factors Involved in Corneal Epithelial Wound Healing;183
8.15.7;Matrix Metalloproteinases;184
8.15.8;Corneal Epithelial Wound Healing: Conclusion;184
8.15.9;Further Reading;185
8.16;Corneal Epithelium: Transport and Permeability;186
8.16.1;Glossary;186
8.16.2;Introduction;186
8.16.3;Corneal Hydration Control and Transparency;186
8.16.4;Importance of Transport Mechanisms to Epithelial Function;187
8.16.5;Primary and Secondary Ionic Transport Mechanisms;188
8.16.6;Coupling of Ionic Transport Mechanisms to Stromal Deturgescence;188
8.16.7;Other Transport Mechanisms;189
8.16.7.1;Receptor-Mediated Control of Corneal Epithelial Ionic Transport Functions;190
8.16.7.2;Cell-Volume Control and Epithelial Renewal;190
8.16.7.3;Ca2+ Channel and Pump Activity;190
8.16.7.4;K+, Cl-, and Na+ Channels;191
8.16.8;Summary;191
8.16.9;Further Reading;191
8.17;Stem Cells of the Ocular Surface;193
8.17.1;Glossary;193
8.17.2;The Ocular Surface;193
8.17.2.1;Anatomy;193
8.17.2.2;Development;194
8.17.2.3;Homeostasis and Repair;194
8.17.3;Properties of Stem Cells;195
8.17.4;Stem Cells in the Corneal Epithelium;195
8.17.4.1;Characteristics of Limbal Stem Cells;195
8.17.4.2;Limbal Stem Cell Niche;196
8.17.4.3;Limbal Stem Cell Deficiency;196
8.17.4.4;Understanding the Role for LSC in Corneal Homeostasis;197
8.17.5;Conjunctival Stem Cells;197
8.17.6;Corneal Stromal Stem Cells;198
8.17.7;Corneal Endothelial Stem Cells;198
8.17.8;Conclusions;198
8.17.9;Acknowledgments;199
8.17.10;Further Reading;199
8.18;The Surgical Treatment for Corneal Epithelial Stem Cell Deficiency, Corneal Epithelial Defect, and Peripheral Corneal Ulcer;200
8.18.1;Glossary;200
8.18.2;Introduction;200
8.18.3;Corneal Epithelial Transplantation for Total Stem Cell Deficiency;201
8.18.3.1;In Vivo Expansion of Corneal Epithelial Cells (Keratolimbal Allografts);201
8.18.3.1.1;History and concept of ocular surface reconstruction;201
8.18.3.1.2;Indications;201
8.18.3.1.3;Surgical procedure;201
8.18.3.1.4;Postoperative management;202
8.18.3.1.5;Other surgical procedures;202
8.18.3.2;Ex Vivo Expansion of Corneal Epithelial Cells;202
8.18.3.2.1;History and concepts;202
8.18.3.2.2;AM as a suitable carrier for corneal epithelial cell culture;202
8.18.3.2.3;Cell culture procedure;203
8.18.3.2.4;Indications;203
8.18.3.2.5;Surgical procedure;204
8.18.3.2.6;Postoperative management;204
8.18.3.2.7;Clinical outcome of allogeneic cultivated corneal epithelial transplantation;204
8.18.3.3;Ex Vivo Expansion of Oral Mucosal Epithelial Cells;204
8.18.3.3.1;Concept;204
8.18.3.3.2;Cell culture procedure;204
8.18.3.3.3;Indications;205
8.18.3.3.4;Surgical procedure and postoperative medications;205
8.18.3.3.5;Clinical outcome of cultivated autologous oral mucosal epithelial transplantation;205
8.18.4;Phototherapeutic Keratectomy for Corneal Epithelial Disorders;206
8.18.4.1;PTK for Corneal Epithelial Defect;206
8.18.4.1.1;Indications;206
8.18.4.1.2;Surgical procedure;206
8.18.4.1.3;Postoperative management;206
8.18.5;Tectonic Lamellar Keratoplasty for Peripheral Corneal Ulcers;206
8.18.5.1;Concept;206
8.18.5.2;Rheumatoid Arthritis;206
8.18.5.3;Mooren's Ulcer;206
8.18.6;Further Reading;207
8.19;Refractive Surgery;208
8.19.1;Glossary;208
8.19.2;Short Historical Background of Corneal Refractive Surgery;209
8.19.3;The LASIK Procedure;210
8.19.4;Corneal Refractive Surgery, Wound Healing, and Haze;210
8.19.5;Corneal Refractive Surgery, Optical Aberrations, and Visual Quality;210
8.19.6;Causes for Spherical Aberration Increase Following Corneal Refractive Surgery;212
8.19.7;Corneal Biomechanical Effects in Refractive Surgery;213
8.19.8;Other Side Effects and Complications of PRK and LASIK;213
8.19.9;Safety, Efficacy, and Satisfaction of LASIK;213
8.19.10;Toward an Optimization of the Corneal Refractive Surgery Procedure;214
8.19.11;Further Reading;215
8.20;Refractive Surgery and Inlays;216
8.20.1;Glossary;216
8.20.2;Introduction;216
8.20.3;Radial Keratotomy;216
8.20.4;Photorefractive Keratectomy;217
8.20.5;Laser-assisted in situ Keratomileusis;217
8.20.6;Laser-Assisted Subepithelial Keratectomy;218
8.20.7;Epithelial Laser in situ Keratomileusis (epi-LASIK);219
8.20.8;Femtosecond Laser in situ Keratomileusis (FS-LASIK);219
8.20.9;Treatment of Hyperopia;219
8.20.10;General Side Effects of Laser Refractive Surgery;220
8.20.11;Wave front and Laser Refractive Surgery;220
8.20.12;Corneal Inlays;220
8.20.13;Intracorneal Rings (ICR);221
8.20.14;Conclusion;221
8.20.15;Further Reading;221
8.21;Contact Lenses;222
8.21.1;Glossary;222
8.21.2;Introduction;222
8.21.3;Types of Contact Lenses;222
8.21.4;How Contact Lens Wear Affects the Ocular Surface;224
8.21.4.1;Effects of Contact Lens Wear on the Corneal and Limbal Epithelium;224
8.21.4.2;Alteration of the Lens: Cornea Resurfacing Mechanism;225
8.21.4.3;Adverse Events;225
8.21.4.3.1;Inflammation;225
8.21.4.3.2;Infection;225
8.21.4.3.3;Mechanical effects;226
8.21.5;Current Hot Topics in Contact Lens Research;226
8.21.5.1;Contact Lens Care Products;226
8.21.5.2;Corneal Infection;226
8.21.5.3;Orthokeratology;226
8.21.6;Summary;227
8.21.7;Further Reading;227
8.22;Imaging of the Cornea;228
8.22.1;Glossary;228
8.22.2;Slit-Lamp Biomicroscopy;228
8.22.3;Specular Microscopy;229
8.22.4;Confocal Microscopy;230
8.22.5;Ultrasound Biomicroscopy;230
8.22.6;Anterior Segment Optical Coherence Tomography;232
8.22.7;Acknowledgments;233
8.22.8;Further Reading;233
8.23;The Corneal Stroma;234
8.23.1;Glossary;234
8.23.2;Stromal Anatomy;235
8.23.3;Stromal Development;235
8.23.4;Stromal Cells;237
8.23.5;Transparency;238
8.23.6;Stromal Extracellular Matrix;238
8.23.7;Conclusion;240
8.23.8;Acknowledgments;240
8.23.9;Further Reading;240
8.24;Corneal Dystrophies;241
8.24.1;Glossary;241
8.24.2;Introduction;241
8.24.3;Anterior Dystrophies;241
8.24.3.1;Epithelial and EBM Dystrophies;241
8.24.3.1.1;EBM Dystrophy;241
8.24.3.1.2;Meesman's;242
8.24.3.2;Bowman's Layer Dystrophies;242
8.24.3.2.1;Reis-Buckler's;242
8.24.3.2.2;Thiel-Behnke;242
8.24.3.3;Stromal Dystrophies;243
8.24.3.3.1;Lattice;243
8.24.3.4;Granular;244
8.24.3.4.1;Granular type 1;244
8.24.3.4.2;Granular type 2;244
8.24.3.5;Macular;245
8.24.3.6;Rare Stromal Dystrophies;245
8.24.3.6.1;Gelatinous drop-like dystrophy;245
8.24.3.6.2;Schnyder's crystalline dystrophy;245
8.24.3.6.3;Central cloudy dystrophy;246
8.24.3.6.4;Congenital hereditary stromal dystrophy;246
8.24.3.6.5;Posterior amorphous dystrophy;246
8.24.3.6.6;Fleck dystrophy;246
8.24.4;Posterior Dystrophies;246
8.24.4.1;Fuchs' Endothelial;246
8.24.4.2;Posterior Polymorphous Membrane;247
8.24.4.3;Congenital Hereditary Endothelial Dystrophy;247
8.24.5;Further Reading;248
8.25;Corneal Imaging: Clinical;249
8.25.1;Glossary;249
8.25.2;Introduction;249
8.25.3;Confocal Microscopy;249
8.25.3.1;Historical Overview;249
8.25.3.2;How it Works;249
8.25.3.3;Clinical Applications;250
8.25.3.3.1;The normal cornea;250
8.25.3.3.2;Pachymetry;251
8.25.3.4;Applications in Pathology;251
8.25.3.4.1;Other applications;252
8.25.4;Anterior Segment OCT;252
8.25.4.1;Historical Overview;252
8.25.4.2;How it Works;253
8.25.4.3;Clinical Applications;253
8.25.5;Conclusion;259
8.25.6;Further Reading;270
8.26;Corneal Scars;271
8.26.1;Glossary;271
8.26.2;Introduction;272
8.26.3;Ocular Wound Healing;275
8.26.4;Corneal Wound Healing;276
8.26.4.1;Cell-Cell Communication;276
8.26.4.1.1;Cytokines and GFs;276
8.26.4.1.2;TGF-ß signaling pathways;278
8.26.4.2;Cell-ECM Communication;279
8.26.4.2.1;Suppressing or amplifying factors;279
8.26.4.2.2;Bone marrow-derived stem cells;280
8.26.4.2.3;Cellular responses;280
8.26.4.3;Three Phases of Corneal Wound Healing;281
8.26.4.3.1;Inflammatory phase (lasts up to 2-4weeks after injury);281
8.26.4.3.2;Active wound-healing phase (lasts up to 4-6months after injury);282
8.26.4.3.3;Remodeling phase (occurs from 4-6months to 3-4years after injury);282
8.26.4.3.4;Termination of the fibrotic repair response (about 3-4years after injury);282
8.26.5;Modulation of Scarring;283
8.26.5.1;Currently Available Scar-Reducing Therapies;283
8.26.5.2;Emerging Scar-Reducing Therapies;284
8.26.6;Conclusion;285
8.26.7;Acknowledgments;285
8.26.8;Further Reading;285
8.27;Corneal Endothelium: Overview;287
8.27.1;Glossary;287
8.27.2;Anatomy;287
8.27.2.1;General Description;287
8.27.2.2;Cell-to-Cell Junctions;287
8.27.3;Embryology;288
8.27.3.1;Initial Development;288
8.27.3.2;Role of Transcription Factors;289
8.27.4;Biochemistry and Metabolism;290
8.27.4.1;Glucose and Energy Metabolism;290
8.27.4.2;Cell Division and Replenishment;291
8.27.4.3;Cytokines and Immune Privilege;292
8.27.4.4;Proteins Synthesized for External Transport;293
8.27.5;The Role of the Corneal Endothelium in Deturgescence;294
8.27.5.1;Introduction;294
8.27.5.2;The Biochemistry of Active Deturgescence;294
8.27.5.3;The Physiological Control of Active Deturgescence;295
8.27.6;Genetic Diseases of the Corneal Endothelium;296
8.27.6.1;Fuchs' Endothelial Dystrophy;296
8.27.6.2;Related Posterior Membrane Dystrophies;296
8.27.7;Further Reading;296
8.28;Regulation of Corneal Endothelial Function;298
8.28.1;Glossary;298
8.28.2;Corneal Endothelial Function;298
8.28.2.1;Stromal Swelling Pressure and Maintenance of Transparency;298
8.28.2.2;Endothelial Barrier Function;298
8.28.3;Nutrition/Waste Removal;299
8.28.4;Corneal Endothelial Transport;299
8.28.4.1;Active Transport;299
8.28.4.2;Bicarbonate/Carbonic Anhydrase;300
8.28.4.3;Anion Transporters and Channels;300
8.28.4.4;Aquaporin-1 (AQP1);301
8.28.4.5;Pump Mechanism;301
8.28.5;Barrier Integrity;301
8.28.5.1;MLC Phosphorylation and Actomyosin Contraction;302
8.28.5.2;Effect of MLC Phosphorylation on Corneal Endothelium Barrier Integrity;302
8.28.5.3;Transplantation Failure and Tumor Necrosis Factor;303
8.28.6;Regulation of Transport Activity and Barrier Integrity;303
8.28.6.1;Adenosine, Soluble Adenylate Cyclase, and c303
8.28.6.2;Role of cAMP-PKA axis in the Regulation of Barrier Integrity;304
8.28.7;Summary and Perspective;304
8.28.8;Further Reading;304
8.29;Regulation of Corneal Endothelial Cell Proliferation;305
8.29.1;Glossary;305
8.29.2;Background;305
8.29.3;Cell Cycle Progression, G1/S Transition and its Cell Cycle Regulators;305
8.29.4;G1 Phase Cell Cycle Arrest in CECs in vivo;306
8.29.4.1;Cell-Cell Contact Inhibition;306
8.29.4.2;The Presence of Antiproliferative TGF-ß2 in the Aqueous Humor;308
8.29.4.3;The Interaction Between CECs and Extracellular Matrix;308
8.29.5;What Do We Know From Primary and Subcultured CECs;308
8.29.5.1;Age-Related Decrease in Sensitivity to Mitogen or Growth Factors in Cultured HCECs;308
8.29.5.2;Comparison of Proliferative Capacity of HCECs from Central and Peripheral Regions;309
8.29.5.3;Overexpression of E2F2 Promotes Proliferation of CEC;309
8.29.5.4;PKC Signaling Pathways in Regulating Proliferation of CECs;309
8.29.5.5;FGF-2 Signaling Pathway;309
8.29.6;Summary;309
8.29.7;Further Reading;309
8.30;Artificial Cornea;311
8.30.1;Glossary;311
8.30.2;The Need for Artificial Corneas;311
8.30.3;Desired Characteristics for an Implantable AC;312
8.30.4;Synthetic Artificial Corneas or Keratoprosthesis;313
8.30.5;Self-Assembled Corneal Equivalents;314
8.30.6;Bioengineered ACs that Address Regeneration;315
8.30.7;Future Directions;317
8.30.8;Further Reading;317
8.31;Drug Delivery to Cornea and Conjunctiva: Esterase- and Protease- Directed Prodrug Design;318
8.31.1;Glossary;318
8.31.2;Topical Ocular Drug Delivery;318
8.31.3;Role of Cornea in Topical Drug Delivery;320
8.31.4;Role of Conjunctiva in Ocular Drug Delivery;323
8.31.4.1;Transconjunctival Pathway;325
8.31.4.2;Subconjunctival Delivery;328
8.31.5;Conclusion;328
8.31.6;Further Reading;328
8.32;Knock-Out Mice Models: Cornea, Conjunctiva, Eyelids and Lacrimal Gland;330
8.32.1;Glossary;330
8.32.2;Introduction;330
8.32.2.1;Transgenesis;330
8.32.2.2;Gene Targeting;330
8.32.2.2.1;Tissue-specific gene ablation using Cre-LoxP system;331
8.32.2.2.2;Pitfalls of Cre-LoxP system: Cryptic Cre expression by germ cells during gametogenesis;331
8.32.2.2.3;Inducible Cre-LoxP system;331
8.32.3;Strategies of Cornea-Specific Genetic Modification: Transgenic and Knock-Out/Knock-In Mice;332
8.32.3.1;Identification of Ocular-Surface Tissue-Specific Promoter;332
8.32.3.1.1;Stromal keratocyte-specific promoter;332
8.32.3.1.2;Corneal-epithelium-specific promoter;333
8.32.3.1.3;Ocular-surface epithelium-specific Pax6 promoter (Pax6OS);333
8.32.3.2;Ocular Surface Tissue-Specific Driver Mouse Lines;333
8.32.3.2.1;Corneal stroma-specific mouse lines;333
8.32.3.2.2;Corneal-epithelium-specific mouse lines;334
8.32.3.2.3;Ocular surface tissue-specific Pax6OS-rtTA mouse line;336
8.32.4;Roles of Growth Factors on Ocular Surface Tissue Morphogenesis during Development and Wound Healing Elucidated from Transgenic ;336
8.32.4.1;TGFß Receptor Signaling Pathways during Development and Corneal Wound Healing;338
8.32.4.1.1;Role of TGFß2 on development;338
8.32.4.1.2;Role of TGF-ß signaling in wound healing of corneal epithelium;338
8.32.4.2;Role of FGF7 in Maintenance of Corneal Homeostasis;338
8.32.4.3;EGFR/EGF, TGFa Signaling Pathways on Eyelids Morphogenesis;339
8.32.5;Conclusion: The Clinical Relevance of Tet-ON Mouse Models in Elucidating Pathophysiology of Ocular Surfaces Diseases;340
8.32.6;Acknowledgments;340
8.32.7;Further Reading;341
8.33;Gene Therapy for the Cornea, Conjunctiva, and Lacrimal Gland;342
8.33.1;Glossary;342
8.33.2;Introduction;342
8.33.3;Corneal Gene Therapy Methods;342
8.33.3.1;Viral Vectors;345
8.33.3.2;Nonviral Vectors;346
8.33.4;Use of Gene Therapy to Treat Corneal Diseases;347
8.33.4.1;Corneal Graft Rejection;347
8.33.4.2;Corneal Wound Healing;347
8.33.4.3;Corneal Alkali Burn;348
8.33.4.4;Corneal Scarring or Haze;348
8.33.4.5;Corneal Neovascularization;349
8.33.4.6;Corneal Dystrophies;349
8.33.4.7;Other Corneal Disorders;349
8.33.4.8;Lacrimal Gland Gene Therapy;349
8.33.4.9;Conjunctiva Gene Therapy;350
8.33.5;Acknowledgments;350
8.33.6;Further Reading;351
9;Section III: Immune Regulation of the Cornea and Conjunctiva and its Dysregulation in Disease;352
9.1;Adaptive Immune System and the Eye: Mucosal Immunity;354
9.1.1;Glossary;354
9.1.2;Organized Inductive Sites;355
9.1.3;Effector Sites;356
9.1.3.1;Specialized Niches;356
9.1.4;Transfer of Immunoglobulins to the Milieu Extérieur;358
9.1.4.1;pIgR and dIgA;358
9.1.4.2;Acute Regulation of pIgR Traffic;358
9.1.4.3;A Mechanism That Constitutively Secretes Autoantigens to the Stroma;359
9.1.4.4;FcgammaRn and IgG1;360
9.1.5;Mucosal Tolerance and Response to Infection;360
9.1.6;Implications for Ocular Surface Pathophysiology;360
9.1.7;Further Reading;361
9.2;Adaptive Immune System and the Eye: T Cell-Mediated Immunity;362
9.2.1;Glossary;362
9.2.2;Innate and Adaptive Immunity;362
9.2.2.1;Antigen Trafficking, Processing, and Presentation to T cells;363
9.2.2.1.1;T-cell activation;363
9.2.2.1.2;T cell differentiation and effector function;365
9.2.2.1.3;T-cell immune responses in the eye;367
9.2.3;Further Reading;368
9.3;Innate Immune System and the Eye;369
9.3.1;Glossary;369
9.3.2;Introduction;369
9.3.3;Passive Innate Defense System;369
9.3.3.1;Anatomic and Physical Barriers;369
9.3.3.1.1;Eyelids and eyelashes;369
9.3.3.1.2;Tear film;369
9.3.3.1.3;Corneal epithelium;370
9.3.3.1.4;Posterior lens capsule;370
9.3.3.1.5;Retinal pigment epithelium;370
9.3.3.2;Chemical Barriers;371
9.3.3.2.1;Lysozyme;371
9.3.3.2.2;Secretory phospholipase A2;371
9.3.3.2.3;Cathelicidin (LL-37);371
9.3.3.2.4;Defensins;371
9.3.3.2.5;Lactoferrin;372
9.3.3.2.6;Lipocalin-A;372
9.3.3.2.7;Secretory IgA;372
9.3.3.2.8;Complement;372
9.3.4;Active Innate Defense System;372
9.3.4.1;Pattern Recognition Receptors;372
9.3.4.1.1;Toll-like receptors;372
9.3.4.1.2;NOD-like receptors;372
9.3.4.1.3;Complement;373
9.3.4.2;Cytokines, Chemokines, and Effector Cells;374
9.3.4.2.1;Initiation and amplification;374
9.3.4.2.2;Clearing the pathogen;374
9.3.4.3;Innate Immune Privilege;374
9.3.4.4;Link between Innate and Adaptive Immunity;374
9.3.5;Conclusion;375
9.3.6;Further Reading;375
9.4;Dynamic Immunoregulatory Processes that Sustain Immune Privilege in the Eye;376
9.4.1;Glossary;376
9.4.2;Introduction;376
9.4.3;Induction of ACAID;377
9.4.3.1;Ocular Phase of ACAID;377
9.4.3.2;Thymic Phase of ACAID;377
9.4.3.3;Splenic Phase of ACAID;377
9.4.3.4;Sympathetic Nervous System and ACAID;377
9.4.3.5;ACAID T Regulatory Cells;378
9.4.3.6;What is the Relevance of ACAID?;379
9.4.4;Vitreous Cavity-Associated Immune Deviation;379
9.4.5;Ocular Regulatory Cells Induced In Situ;379
9.4.6;Conclusions;380
9.4.7;Further Reading;380
9.5;Immunosuppressive and Anti-Inflammatory Molecules that Maintain Immune Privilege of the Eye;382
9.5.1;Glossary;382
9.5.2;Immunosuppression and Anti-Inflammatory Activity in Aqueous Humor;382
9.5.3;The Immunoregulatory and Immunosuppressive Factors of The Immune-Privileged Eye;383
9.5.3.1;Transforming Growth Factor-Beta;383
9.5.3.2;Alpha-Melanocyte-Stimulating Hormone;384
9.5.3.3;Other Neuropeptides;385
9.5.3.4;Other Molecules;385
9.5.4;Application of the Lessons of Immune Privilege;386
9.5.5;Conclusion;386
9.5.6;Further Reading;387
9.6;Antigen-Presenting Cells in the Eye and Ocular Surface;388
9.6.1;Glossary;388
9.6.2;Introduction;388
9.6.3;Antigen-Presenting Cells of the Ocular Surface;389
9.6.3.1;Corneal APCs;389
9.6.3.1.1;Epithelial Langerhans cells;389
9.6.3.2;Stromal APCs;390
9.6.3.3;Corneal APCs in Inflammation;391
9.6.3.4;The Function of APCs in Corneal Transplantation;392
9.6.3.5;The Function of APCs in Microbial Keratitis;392
9.6.4;Conjunctival APCs;392
9.6.4.1;Role of APCs in Allergic Eye Disease;393
9.6.5;APCs of the Uvea;393
9.6.5.1;Anterior Chamber-Associated Immune Deviation;393
9.6.5.2;Role of APCs in Age-Related Macular Degeneration;393
9.6.5.3;Role of APCs in EAU;394
9.6.6;APCs of the Retina;394
9.6.7;APCs of the Sclera;394
9.6.8;Conclusions;395
9.6.9;Further Reading;395
9.7;Dry Eye: An Immune-Based Inflammation;396
9.7.1;Glossary;396
9.7.2;Defining the Problem;396
9.7.2.1;Epidemiology of Dry Eye;396
9.7.2.2;Dry Eye Syndrome in Peri- and Post- menopausal Women;397
9.7.2.3;Patients on Anti-androgen Therapy;397
9.7.3;Clinical Features of Dry Eye;397
9.7.3.1;Chronic Pain;397
9.7.3.1.1;Ocular surface neuropathy in dry eye;397
9.7.3.1.2;Comorbidities;397
9.7.3.2;Quality of Life Impact;398
9.7.4;How We Secrete Normal Tears;398
9.7.4.1;The Lacrimal Functional Unit;398
9.7.4.1.1;The general role of the LFU in homeostasis and disease;398
9.7.5;Events on the Ocular Surface;399
9.7.5.1;Environmental Impact on the Ocular Surface;399
9.7.5.1.1;Afferent arm of the immune response: immunoregulation;400
9.7.5.1.2;Efferent arm of the immune response: immunoregulation;400
9.7.5.1.3;Afferent arm of the immune response during autoimmune-based inflammation;401
9.7.5.1.4;Efferent arm of the immune response during autoimmune-based inflammation;402
9.7.6;Past, Future, and Current Therapies;403
9.7.6.1;Artificial Tears;403
9.7.6.2;Corticosteroids;403
9.7.6.3;Cyclosporine;403
9.7.6.4;Mucin Secretagogues;403
9.7.6.5;Tetracyclines;404
9.7.7;Further Reading;404
9.8;Penetrating Keratoplasty;405
9.8.1;Glossary;405
9.8.2;Penetrating Keratoplasty: Indications and Survival;405
9.8.3;Corneal Immune Privilege;405
9.8.3.1;Immune-Privileged Tissue;405
9.8.3.2;Immune-Privileged Site;406
9.8.4;Clinical Features of Corneal Graft Rejection;406
9.8.5;Pathogenesis of Rejection;407
9.8.5.1;Afferent Mechanisms and Components;407
9.8.5.1.1;Histocompatibility antigens;407
9.8.5.1.2;Direct and indirect alloantigen recognition;407
9.8.5.1.3;T-lymphocyte activation;408
9.8.5.2;Effector Mechanisms;408
9.8.5.2.1;T lymphocytes;408
9.8.5.2.2;Macrophages;409
9.8.5.2.3;NK cells;409
9.8.5.2.3.1;Breakdown of immune privilege?;409
9.8.6;Treatment of Rejection;409
9.8.7;Prevention of Rejection;409
9.8.8;Further Reading;410
9.9;Immunopathogenesis of HSV Keratitis;411
9.9.1;Glossary;411
9.9.2;Natural History of Herpes Stromal Keratitis;411
9.9.3;Eradication of Replicating HSV-1 from the Corneal Epithelium;411
9.9.4;HSV-1 Colonization of Sensory Ganglia;412
9.9.5;Herpes Stromal Keratitis;412
9.9.5.1;T Cells in HSK;412
9.9.5.2;Cytokines and Their Role in HSK;412
9.9.5.3;Antigen-Presenting Cells in HSK;413
9.9.5.4;Chemokine Involvement in HSK;413
9.9.5.5;Angiogenesis in HSV-1 Stromal Keratitis;414
9.9.6;Models of HSK Pathogenesis;414
9.9.7;Epidemiology and Pathogenesis of Human HSK;414
9.9.8;Management of Human HSV Stromal Keratitis and Implications on Pathogenesis;415
9.9.9;Acknowledgments;415
9.9.10;Further Reading;415
9.10;Immunopathogenesis of Onchocerciasis (River Blindness);416
9.10.1;Glossary;416
9.10.2;The Role of Endosymbiotic Wolbachia Bacteria in Onchocerciasis;416
9.10.3;Role of Wolbachia in Pathogenesis - Evidence from Infected Individuals;416
9.10.4;The Role of Wolbachia in the Pathogenesis of ocular onchocerciasis - Lessons from the Murine Model of O. volvulus/Wolbach;417
9.10.5;Wolbachia and TLRs in the Cornea;417
9.10.6;Identification of a Wolbachia TLR2/TLR6 Ligand;418
9.10.7;Conclusion;419
9.10.8;Acknowledgments;419
9.10.9;Further Reading;420
9.11;Immunopathogenesis of Pseudomonas Keratitis;421
9.11.1;Glossary;421
9.11.2;Introduction;421
9.11.3;PMN, Cytokines, and Chemokines;422
9.11.4;T Cells and IL-12;423
9.11.5;IL-18 and IFN-.;423
9.11.5.1;IFN-. and SP;423
9.11.6;Neuropeptides;423
9.11.6.1;SP;423
9.11.6.2;VIP;424
9.11.7;TLR;424
9.11.8;Apoptosis;425
9.11.8.1;Neuropeptides;425
9.11.9;New Animal Model;426
9.11.10;Further Reading;426
9.12;Immunobiology of Acanthamoeba Keratitis;428
9.12.1;Glossary;428
9.12.2;Introduction;428
9.12.3;Anatomical and Physiological Barriers to Corneal Infections with Acanthamoeba;429
9.12.4;Innate Immune System and Resistance to Acanthamoeba Infections;429
9.12.4.1;Role of Macrophages in the Resistance to Acanthamoeba Infections;429
9.12.4.2;Role of Neutrophils in the Resistance to Acanthamoeba Infections;429
9.12.4.3;Humoral Factors of the Innate Immune System that Affect Resistance to Acanthamoeba Infections;430
9.12.5;Adaptive Immune System and Resistance to Acanthamoeba Infections;430
9.12.5.1;Role of the Mucosal Immune System in Resistance to AK;431
9.12.5.2;Evading the Adaptive Immune Response;431
9.12.6;Anti-Disease Vaccine for AK;432
9.12.7;Conclusions;433
9.12.8;Further Reading;433
9.13;Molecular and Cellular Mechanisms in Allergic Conjunctivitis;434
9.13.1;Glossary;434
9.13.2;Ocular Allergies;434
9.13.2.1;Seasonal Allergic Conjunctivitis;434
9.13.2.2;Perennial Allergic Conjunctivitis;434
9.13.2.3;Vernal Keratoconjunctivitis;435
9.13.2.4;Atopic Keratoconjunctivitis;435
9.13.3;Cellular Mechanisms in Ocular Allergy;436
9.13.3.1;Conjunctival MCs;436
9.13.3.2;Conjunctival Eosinophils and Neutrophils;437
9.13.3.3;Conjunctival Lymphocytes;437
9.13.3.4;Conjunctival Epithelial Cells;438
9.13.3.5;Conjunctival Fibroblasts;439
9.13.4;Molecular Mechanisms;439
9.13.4.1;Costimulatory Molecules in Ocular Allergy;439
9.13.4.1.1;IgE in ocular allergy;439
9.13.4.2;Cytokines and Chemokines in Ocular Allergy;440
9.13.5;Further Reading;440
9.14;Pathogenesis of Fungal Keratitis;441
9.14.1;Glossary;441
9.14.2;Contact-Lens-Associated Fungal Keratitis;441
9.14.3;Biofilm Formation in Contact-Lens-Associated Keratitis;441
9.14.4;Keratitis Caused by Candida;441
9.14.5;Fungal Keratitis Associated with Trauma;442
9.14.5.1;Role of Matrix Metalloproteinases in Fungal Keratitis;442
9.14.5.2;Role of Innate Immunity in Fungal Keratitis;442
9.14.6;Murine Model of Aspergillus Keratitis;443
9.14.7;Conclusions;444
9.14.8;Acknowledgments;444
9.14.9;Further Reading;445
9.15;Conjunctiva Immune Surveillance;446
9.15.1;Glossary;446
9.15.2;Conjunctival Morphology and Function Are Closely Interacting for Immune Surveillance;447
9.15.2.1;Epithelial Defense Mechanisms;447
9.15.2.1.1;Epithelial morphology and function;447
9.15.2.2;Epithelial Immune Surveillance Takes Care of Environmental Antigens;447
9.15.2.2.1;Physical and physicochemical barriers keep antigens outside;447
9.15.2.2.2;The mechanical washing effect of the tear film wipes away antigens and detritus;448
9.15.2.2.3;Epithelial innate immune defense factors;448
9.15.2.2.3.1;PRRs on epithelial cells provide an externalalarm system;448
9.15.2.2.3.2;The conjunctival epithelium secretes diverse AMPs;450
9.15.2.2.3.3;Conventional antibacterial factors are surprisinglyversatile defense tools;450
9.15.2.3;Conjunctival Lamina Propria: Morphology and Function of the Diffuse Mucosal Immune System;450
9.15.2.3.1;Diffusely arranged lymphoid and innate cells contribute to conjunctival immune surveillance;450
9.15.2.3.2;Different subtypes of lymphocytes occur in the conjunctiva;450
9.15.2.3.3;The conjunctiva contributes actively to the secretory immune system;451
9.15.2.3.3.1;Local conjunctival plasma cells produce mainly the anti-inflammatory IgA;451
9.15.2.3.3.2;SIgA performs diverse protective and antiinflammatory functions at the ocular surface;451
9.15.2.4;Lamina Propria Leukocytes Provide Immediate Innate Response against Invading Pathogens and can Orchestrate an Inflammatory Reac;451
9.15.2.4.1;Protective functions of conjunctival lamina propria leukocytes;452
9.15.2.5;HEVs Provide the Regulated Immigration of Bone-Marrow-Derived Cells into the Tissue;452
9.15.3;Conjunctival Lymphoid Follicles Have a Typical Morphology and Function;452
9.15.4;The Topographical Distribution of CALT is in the Right Place to Assist Corneal Immune Surveillance;452
9.15.5;CALT is a Part of the Complete Eye- Associated Lymphoid Tissue;453
9.15.6;Mechanisms of Conjunctival Immune regulation;453
9.15.6.1;CALT Is Physiologically Biased to Tolerogenic, Anti-Inflammatory Responses;453
9.15.6.2;Deregulation of EALT Is a Central Component of Inflammatory Ocular Surface Disease;455
9.15.7;Further Reading;457
9.16;Defense Mechanisms of Tears and Ocular Surface;459
9.16.1;Glossary;459
9.16.2;Introduction;459
9.16.3;Defense Mechanisms of Tears;459
9.16.4;Defense Mechanisms of the Ocular Surface Epithelia;462
9.16.4.1;Mechanical/Physical Defenses;462
9.16.4.2;Pathogen Recognition;463
9.16.4.3;Antimicrobial Peptides;463
9.16.4.4;Other Contributions to Ocular Surface Epithelial Defense;465
9.16.5;Concluding Remarks;465
9.16.6;Acknowledgments;465
9.16.7;Further Reading;466
9.17;Corneal Epithelium: Response to Infection;467
9.17.1;Glossary;467
9.17.2;Introduction;467
9.17.2.1;Basic Structure and Function;467
9.17.3;Corneal Infection;468
9.17.4;TLRs and TLR-Related Molecules;468
9.17.5;Cytokines/Chemokines;469
9.17.6;Antimicrobial Molecules;469
9.17.6.1;ß-Defensins;469
9.17.6.2;Cathelicidins;470
9.17.7;Complement System;470
9.17.8;Secretory IgA;470
9.17.9;Adhesion Molecules;470
9.17.10;Neuropeptides;471
9.17.10.1;Innervation of the Corneal Epithelium;471
9.17.10.1.1;Substance P;471
9.17.10.1.2;Vasoactive intestinal peptide;471
9.17.11;Thymosin-ß4;472
9.17.12;Conclusion;472
9.17.13;Further Reading;473
9.18;Inflammation of the Conjunctiva;474
9.18.1;Glossary;474
9.18.2;Inflammation;474
9.18.3;The Conjunctiva and Cornea;475
9.18.4;Tear Fluid: A Reservoir of Inflammatory Cells and Modulators;475
9.18.5;Allergic Reactions in the Conjunctiva;476
9.18.6;Infection of the Conjunctiva or Cornea;477
9.18.7;Tear Fluid as a Diagnostic Indicator of Inflammation;477
9.18.8;Connection of the Conjunctiva and Cornea via Tear Fluid;478
9.18.9;Further Reading;479
9.19;Concept of Angiogenic Privilege;480
9.19.1;Glossary;480
9.19.2;Introduction: Angiogenesis and Lymphangiogenesis;480
9.19.3;Corneal Angiogenic Privilege;480
9.19.3.1;Corneal Avascularity;480
9.19.3.2;Angiogenic and Anti-Angiogenic Molecules Involved in Corneal Neovascularization;481
9.19.3.2.1;Vascular endothelial growth factors;481
9.19.3.2.1.1;Vascular endothelial growth factor;482
9.19.3.2.1.2;VEGF-C and VEGF-D;482
9.19.3.2.2;Basic fibroblast growth factor;482
9.19.3.2.3;Inhibitory PAS (Per/Arnt/Sim) domain protein;482
9.19.3.3;Cornea and Corneal Epithelium;483
9.19.3.4;Limbal Barrier Function;483
9.19.3.5;Angiogenic Privilege and Immune Privilege;483
9.19.4;Further Reading;484
9.20;Corneal Angiogenesis;485
9.20.1;Glossary;485
9.20.2;Introduction;485
9.20.3;Angiogenesis;485
9.20.4;Etiology and Epidemiology of Corneal NV;485
9.20.5;Clinical Manifestations;486
9.20.6;Mechanisms Underlying the Maintenance of Corneal Avascularity;486
9.20.7;Corneal Angiogenic Privilege: The Balance between Angiogenesis and Anti- Angiogenesis;488
9.20.7.1;Angiogenic Molecules;488
9.20.7.1.1;Vascular endothelial growth factor;488
9.20.7.1.2;Basic fibroblast growth factor;489
9.20.7.1.3;Matrix metalloproteinases;490
9.20.7.1.4;Lipid mediators;490
9.20.7.2;Anti-Angiogenic Molecules;490
9.20.7.2.1;Angiostatin;490
9.20.7.2.2;Endostatin and neostatins;490
9.20.7.2.3;Pigment-epithelial-derived factor;490
9.20.7.2.4;Arresten, canstatin, and tumstatin;490
9.20.8;Therapy;491
9.20.8.1;Medical Treatments;491
9.20.8.2;Surgical Treatment;491
9.20.9;Further Reading;492
9.21;Avascularity of the Cornea;493
9.21.1;Glossary;493
9.21.2;Corneal Histology;493
9.21.3;Corneal Avascularity and Optical Clarity;494
9.21.4;Endogenous Anti-Angiogenic Mechanisms;494
9.21.5;Loss of Corneal Avascularity;496
9.21.6;Immune Privilege of the Avascular Cornea;496
9.21.7;Corneal Transplant and Avascularity;496
9.21.8;Corneal Alymphaticity and Allograft Rejection;496
9.21.9;The Avascular Cornea as an Angiogenesis Study Platform;497
9.21.10;Conclusions;497
9.21.11;Further Reading;497
10;Section IV: Visual Acuity Related to the Cornea and its Disorders;500
10.1;Pupil;502
10.1.1;Glossary;502
10.1.2;Advantages of a Mobile Pupil;502
10.1.3;Overview of the Pathways Controlling Pupil Diameter;502
10.1.4;Iris Musculature;504
10.1.5;Pupillary Light Reflex;504
10.1.5.1;Description;504
10.1.5.2;Afferent Pathway;504
10.1.5.2.1;Intrinsically photosensitive retinal ganglion cells;505
10.1.5.2.2;Pretectal olivary nucleus;505
10.1.5.3;Efferent Pathway;506
10.1.5.4;Sympathetic Influences on the PLR;506
10.1.6;The Pupillary Near Response;506
10.1.6.1;Description;506
10.1.6.2;Efferent Pathway of the PNR;506
10.1.6.3;Afferent Influences on the PNR;506
10.1.7;Additional Cortical Influences on Pupillary Responses;507
10.1.7.1;Visually Mediated Cortical Influences on Pupillary Behavior;507
10.1.7.2;Task-Evoked Pupillary Responses;507
10.1.8;Influence of Alertness on Pupillary Behavior;507
10.1.8.1;Arousal;507
10.1.8.2;Sleep;508
10.1.8.3;Ascending Neuromodulatory Systems;508
10.1.9;Acknowledgments;508
10.1.10;Further Reading;508
10.2;Acuity;509
10.2.1;Glossary;509
10.2.2;Detection and Resolution Acuity;509
10.2.3;Measurement of Visual Acuity;509
10.2.4;Reporting Visual Acuity;511
10.2.5;Optical and Neural Limits on Visual Acuity;511
10.2.6;Visual Acuity across the Retina;512
10.2.7;Visual Acuity over Life;512
10.2.7.1;Visual Standards;512
10.2.8;Hyperacuity;512
10.2.9;Dynamic Visual Acuity;513
10.2.10;Further Reading;513
10.3;Contrast Sensitivity;515
10.3.1;Glossary;515
10.3.2;Contrast-Detection Threshold;515
10.3.3;Psychophysical Assessment of Vision;515
10.3.4;Spatial Frequency Channels;516
10.3.5;Contrast Sensitivity Function;517
10.3.6;Temporal Contrast Sensitivity;518
10.3.7;Further Reading;520
10.4;Astigmatism;521
10.4.1;Glossary;521
10.4.2;The Definition and Etymology of Astigmatism;521
10.4.3;Ocular Astigmatism: Prevalence and Age-Related Changes;522
10.4.4;The Origin of Ocular Astigmatism;522
10.4.5;Image Formation and Refractive Specification in Astigmatism;523
10.4.5.1;Standard Notation for Specifying Astigmatic Refraction;523
10.4.5.2;Ocular Image Formation in Astigmatism;524
10.4.5.3;Classification of Ocular Astigmatism;524
10.4.5.4;Astigmatic Blurring and Visual Perception;524
10.4.5.5;Oblique Astigmatism;526
10.4.5.6;Ocular Astigmatism During Near Work;526
10.4.5.7;Specialized Notations for Specifying Astigmatic Refraction;527
10.4.6;The Measurement of Ocular Astigmatism;528
10.4.6.1;Keratometry;528
10.4.6.2;Wave Front Analysis;528
10.4.7;The Correction of Ocular Astigmatism;530
10.4.7.1;Spectacles;530
10.4.7.2;Contact Lenses;530
10.4.7.3;Surgery;530
10.4.7.4;Not Correcting Ocular Astigmatism;531
10.4.8;Summary;531
10.4.9;Further Reading;531
10.5;Myopia;532
10.5.1;Glossary;532
10.5.2;Definition of Myopia: Health and Economic Implications;532
10.5.3;Natural History of Myopia;533
10.5.4;Structural Correlates, Molecular and Anatomical Changes in Myopia;533
10.5.5;Classifications of Myopia;534
10.5.6;Epidemiology of Myopia;535
10.5.7;Etiology of Myopia;535
10.5.8;Correction and Prevention: Clinical Management of Myopia;537
10.5.8.1;Positive Additions for Nearwork;538
10.5.8.2;Contact Lenses;538
10.5.8.3;Vision Therapy and Biofeedback Training;538
10.5.8.4;Pharmacological Treatment;539
10.5.8.5;Correction and Prevention: Clinical Management of Myopia?;539
10.5.9;Further Reading;539
10.6;Amblyopia;540
10.6.1;Glossary;540
10.6.2;What Is Amblyopia?;540
10.6.3;Amblyopia Is a Significant Public Health Problem;540
10.6.4;Types of Amblyopia;540
10.6.5;The Site(s) of Amblyopia;540
10.6.6;Sensitive Periods for the Development of Amblyopia;541
10.6.7;Traditional Treatment of Amblyopia;541
10.6.7.1;Clinical Studies;542
10.6.7.2;Experimental Treatment of Amblyopia Beyond the Sensitive Period;542
10.6.8;Perceptual Learning as a Clinical Tool for Treating Amblyopia;543
10.6.9;Acknowledgments;543
10.6.10;Further Reading;543
10.7;Hyperopia;544
10.7.1;Glossary;544
10.7.2;Definition and Classifications of Hyperopia;544
10.7.3;Prevalence;545
10.7.4;Normal Time Course of Hyperopia;545
10.7.5;Clinical Presentations of Hyperopia;546
10.7.6;Risks of Uncorrected Hyperopia;546
10.7.7;Importance of Early Detection of Significant Hyperopia;546
10.7.8;Examination Techniques of Hyperopia;546
10.7.9;Management of Hyperopia;547
10.7.10;Conclusion;549
10.7.11;Further Reading;549
11;Subject Index;550
