BOOK
The Eye E-Book
John V. Forrester | Andrew D. Dick | Paul G McMenamin | Fiona Roberts | Eric Pearlman
(2015)
Additional Information
Book Details
Abstract
The Eye: Basic Sciences in Practice provides highly accessible, concise coverage of all the essential basic science required by today’s ophthalmologists and optometrists in training. It is also essential reading for those embarking on a career in visual and ophthalmic science, as well as an invaluable, current refresher for the range of practitioners working in this area.
This new fourth edition has now been fully revised and updated in line with current curricula, key research developments and clinical best practice. It succinctly incorporates the massive strides being made by genetics and functional genomics based on the Human Genome Project, the new understanding of how the microbiome affects all aspects of immunology, the remarkable progress in imaging technology now applied to anatomy and neurophysiology, as well as exciting new molecular and other diagnostic methodologies now being used in microbiology and pathology. All this and more collectively brings a wealth of new knowledge to students and practitioners in the fields of ophthalmology and visual science.
- The only all-embracing textbook of basic science suitable for trainee ophthalmologists, optometrists and vison scientists – other books concentrate on the individual areas such as anatomy.
- Attractive page design with clear, colour diagrams and text boxes make this a much more accessible book to learn from than many postgraduate textbooks.
- Presents in a readable form an account of all the basic sciences necessary for an understanding of the eye – anatomy, embryology, genetics, biochemistry, physiology, pharmacology, immunology, microbiology and infection and pathology.
- More on molecular pathology.
- Thorough updating of the sections on pathology, immunology, pharmacology and immunology.
- Revision of all other chapters.
- More colour illustrations.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| The Eye | i | ||
| Copyright page | iv | ||
| Table of Contents | v | ||
| Preface | vii | ||
| Acknowledgements | viii | ||
| 1 Anatomy of the eye and orbit | 1 | ||
| Anatomical terms of reference | 1 | ||
| Osteology of the skull and orbits | 1 | ||
| General arrangement and features of the skull | 1 | ||
| Osteology of the orbit | 1 | ||
| The walls of the orbit | 2 | ||
| Features of the orbital roof | 2 | ||
| 2 Embryology and early development of the eye and adnexa | 103 | ||
| Introduction | 103 | ||
| General embryology | 103 | ||
| Ocular embryology: general introduction | 103 | ||
| Genetic regulation of eye development | 110 | ||
| Eye field transcription factors | 110 | ||
| Periocular mesenchyme is derived from a mixture of neural crest and mesoderm | 111 | ||
| The neural retina and retinal pigment epithelium are derived from neuroepithelium | 112 | ||
| Axes in the neural retina | 113 | ||
| Retinal morphogenesis (Fig. 2-8) | 114 | ||
| Macula and foveal development | 115 | ||
| Peripheral retina | 117 | ||
| Development of retinal vasculature | 117 | ||
| Development of the retinal pigment epithelium | 117 | ||
| Optic nerve and disk development | 118 | ||
| Development of the fibrous coat of the eye | 119 | ||
| Development of the sclera | 119 | ||
| Development of the cornea | 119 | ||
| Development of the intraocular contents | 120 | ||
| Lens development (Fig. 2-13) | 120 | ||
| Development of the vitreous and hyaloid system | 121 | ||
| Development of the uveal tract | 124 | ||
| The choroid | 124 | ||
| The ciliary body | 124 | ||
| The iris | 126 | ||
| Development of the anterior chamber angle and aqueous outflow pathways | 127 | ||
| Development of the extraocular muscles | 129 | ||
| Development of the eyes and surrounding structures is influenced by the pattern of development of the skull, pharyngeal arches and face | 129 | ||
| Further Reading | 129 | ||
| Further Reading | 129.e7 | ||
| 3 Genetics | 130 | ||
| Chromosomes and cell division | 130 | ||
| Chromosomes | 130 | ||
| Cell division | 130 | ||
| Mitosis (Box 3-1) | 130 | ||
| Meiosis: formation of gametes | 131 | ||
| Genetic makeup | 132 | ||
| Molecular genetics (DNA and genes) | 132 | ||
| How genes work: decoding DNA | 133 | ||
| Regulating gene expression is constantly active, has multiple pathways and is influenced by environment (epigenetics) | 135 | ||
| Ordering of DNA and accessibility for transcription | 135 | ||
| Non-coding RNA and RNA-binding proteins constantly regulate gene expression | 135 | ||
| Spliceosomes | 135 | ||
| Chromosome defects and gene mutations | 135 | ||
| Structural chromosomal abnormalities | 136 | ||
| Gene mutations | 137 | ||
| Clinical genetics | 137 | ||
| Autosomal inheritance | 137 | ||
| X-linked disorders | 137 | ||
| Mitochondrial inheritance | 138 | ||
| Multifactorial inheritance | 138 | ||
| Disease associations | 139 | ||
| Genetic polymorphisms | 139 | ||
| Population genetics | 140 | ||
| Gene frequency | 140 | ||
| Genetic linkage and linkage analysis | 140 | ||
| Linkage equilibrium and disequilibrium | 141 | ||
| Mendelian randomization identifies causal modifiable environmental risk to disease | 141 | ||
| Epigenetics (Box 3-7) | 141 | ||
| Understanding the human genome: DNA analysis | 142 | ||
| Cloning | 142 | ||
| Refining technology: molecular analysis of human genes and mutations | 142 | ||
| Southern and Northern blotting | 142 | ||
| DNA polymorphisms | 143 | ||
| Restriction fragment length polymorphism | 143 | ||
| Variable number of tandem repeats polymorphism | 143 | ||
| Polymerase chain reaction | 143 | ||
| Genomics, transcriptomics and proteomics | 143 | ||
| Finding and tracking the gene through families | 146 | ||
| Molecular biology and clinical medicine | 146 | ||
| Gene probes | 146 | ||
| Molecular and cell biology: controlling cell destiny | 146 | ||
| Using molecular biological technology to detect apoptosis | 147 | ||
| Gene therapy | 147 | ||
| Genes, cell differentiation and cell-based therapies | 148 | ||
| Molecular genetics and ophthalmology | 150 | ||
| The X chromosome | 150 | ||
| Retinitis pigmentosa (Fig. 3-13) | 151 | ||
| X-linked retinitis pigmentosa | 151 | ||
| Autosomal dominant retinitis pigmentosa | 153 | ||
| Choroideraemia | 153 | ||
| Norrie’s disease | 154 | ||
| Retinoblastoma | 154 | ||
| Albinism | 155 | ||
| Oculocutaneous albinism | 155 | ||
| Ocular albinism | 155 | ||
| Myotonic dystrophy | 155 | ||
| Mitochondrial inheritance | 156 | ||
| Leber’s hereditary optic neuropathy | 156 | ||
| Other mitochondrial disorders | 156 | ||
| Further Reading | 156 | ||
| Further Reading | 156.e1 | ||
| 4 Biochemistry and cell biology | 157 | ||
| Introduction | 157 | ||
| The continuing advance of ‘omics’ | 159 | ||
| Cells and tissues | 160 | ||
| The cell | 160 | ||
| General structure | 160 | ||
| The plasma membrane | 161 | ||
| Endoplasmic reticulum and Golgi apparatus | 164 | ||
| Mitochondria | 164 | ||
| The nucleus | 169 | ||
| The intracellular matrix | 169 | ||
| Microfilaments. | 169 | ||
| Intermediate filaments. | 173 | ||
| Group 3 cytoskeletal fibres. | 174 | ||
| Septins. | 177 | ||
| Intracellular signalling mechanisms | 177 | ||
| The extracellular matrix | 178 | ||
| Extracellular matrix proteins determine the structural nature of the tissue | 178 | ||
| Non-structural proteins | 184 | ||
| Glycosaminoglycans occur in the extracellular matrix bound to core proteins as proteoglycans | 186 | ||
| Extracellular matrix molecules are intimately involved in cell adhesion | 186 | ||
| Epithelial and endothelial cells bind via transmembrane complexes to each other and to the basement membrane | 189 | ||
| Mesenchymal cells bind to the matrix via focal adhesion sites | 189 | ||
| Biochemical pathways that affect ocular function | 189 | ||
| Glucose metabolism and tissue glycation | 189 | ||
| Glucose enters cells by facilitated diffusion | 190 | ||
| Excessive levels of glucose may impair cellular metabolism | 191 | ||
| Excessive levels of glucose lead to glycation of proteins | 191 | ||
| Glucose and lipid metabolism | 193 | ||
| Oxidation/reduction and free radical production | 193 | ||
| Lipids and lipid peroxidation | 194 | ||
| The ocular surface | 198 | ||
| The tear film | 198 | ||
| Tear film lipids have unique characteristics | 198 | ||
| Lacrimal gland secretion provides the aqueous component of tears | 199 | ||
| The mucous layer stabilizes the aqueous layer by providing a hydrophilic contact surface | 200 | ||
| Tear secretion is under psychoneuroendocrine control | 201 | ||
| The conjunctiva | 201 | ||
| The epithelium is more than a simple covering layer for the conjunctiva | 201 | ||
| The conjunctival stroma is highly vascular and contains aqueous veins | 202 | ||
| The lids | 202 | ||
| Cornea and sclera | 203 | ||
| The cornea | 203 | ||
| Corneal transparency is a function of its relative acellularity and matrix structure | 203 | ||
| The epithelium. | 203 | ||
| Matrix factors affecting transparency: collagen. | 204 | ||
| Glycosaminoglycans. | 205 | ||
| Swelling pressure versus hydration. | 206 | ||
| Cellular factors affecting transparency: (1) keratocytes. | 207 | ||
| Cellular factors affecting transparency: (2) leucocytes. | 207 | ||
| Cellular factors affecting transparency: (3) the endothelium. | 207 | ||
| Transport of water out of the cornea is a dual process. | 208 | ||
| Optical factors affecting image formation. | 209 | ||
| Metabolism of corneal cells | 209 | ||
| Oxidative metabolism and glucose utilization. | 209 | ||
| Oxygen handling by the cornea. | 209 | ||
| Effects of contact lens wear on corneal physiology. | 210 | ||
| Cell turnover and wound healing in the cornea | 211 | ||
| The epithelium. | 211 | ||
| Limbal corneal stem cells. | 211 | ||
| The stroma. | 212 | ||
| The endothelium. | 213 | ||
| Vascularization. | 214 | ||
| Vitamin A and the cornea. | 215 | ||
| The sclera | 215 | ||
| Matrix factors. | 215 | ||
| Bulk fluid transport and the uveal effusion syndrome. | 215 | ||
| Uveal tract | 216 | ||
| The iris | 216 | ||
| Physiology | 216 | ||
| Blood flow in the iris | 216 | ||
| The ciliary body | 217 | ||
| Functions of the ciliary body | 217 | ||
| Blood flow in the ciliary body | 217 | ||
| Ciliary muscle and accommodation | 217 | ||
| Blood–aqueous barrier | 218 | ||
| Eicosanoids in the iris/ciliary body | 220 | ||
| Detoxification and antioxidation in the anterior segment | 220 | ||
| The cytochrome P450 system is the major drug detoxification (CYP) system in the eye. | 220 | ||
| The ciliary body is the main source of antioxidant systems in the anterior segment. | 220 | ||
| The choroid | 221 | ||
| Functions of the choroid | 221 | ||
| Vascular function. | 221 | ||
| Non-vascular functions. | 222 | ||
| Lymphoid function. | 222 | ||
| Aqueous humour dynamics | 222 | ||
| Aqueous humour is secreted by the ciliary body epithelium | 222 | ||
| Composition of aqueous humour | 222 | ||
| Neural/autonomic control of aqueous secretion | 223 | ||
| Cholinergic mechanisms are not involved in control of intraocular pressure | 223 | ||
| Adrenergic receptors regulate IOP via adenylate cyclase | 225 | ||
| Nucleotides and nucleotide receptors | 225 | ||
| Circadian regulation of aqueous humour formation | 225 | ||
| Is guanylate cyclase involved in intraocular pressure control? | 225 | ||
| Aqueous humour outflow from the eye | 225 | ||
| Control of outflow at the trabecular meshwork | 226 | ||
| Metabolism of trabecular meshwork cells | 226 | ||
| Uveoscleral drainage | 227 | ||
| Episcleral circulation | 227 | ||
| An intraocular pressure-independent link between aqueous production and aqueous outflow? | 228 | ||
| Does aqueous contain components that contribute to flow resistance? | 228 | ||
| The lens | 228 | ||
| Lens transparency | 228 | ||
| The epithelium | 228 | ||
| The organization of the lens fibre cells underpins the transmission properties of the lens | 228 | ||
| The crystallins | 230 | ||
| Cytoskeletal proteins of the lens | 232 | ||
| Membrane lipids and proteins | 233 | ||
| Extracellular matrix | 234 | ||
| Semipermeable membranes and physiology of the lens | 234 | ||
| Lens metabolism | 235 | ||
| Carbohydrate | 235 | ||
| Protein | 235 | ||
| Lipid | 236 | ||
| Redox systems in the lens microenvironment | 236 | ||
| Ageing in the lens and cataract formation | 237 | ||
| Reduced vision in cataract is caused by increased light scatter by lens proteins | 237 | ||
| Cataract formation is caused by any insult to the lens | 238 | ||
| Age-related cataract formation is multifactorial | 238 | ||
| Mechanism of age-related cataract formation: a failure of chaperone function | 240 | ||
| The vitreous | 240 | ||
| The vitreous body is a true connective tissue containing collagen, gags and cells | 240 | ||
| The matrix | 240 | ||
| Vitreous cells | 241 | ||
| Physicochemical properties of the vitreous gel | 241 | ||
| The viscoelasticity of the vitreous protects the retina during eye movement and deformations of the globe | 241 | ||
| Vitreous retards bulk flow of fluid and diffusion of small molecules | 241 | ||
| The retina | 242 | ||
| The neural retina is highly organized in layers | 242 | ||
| Metabolic function in the retina | 242 | ||
| Glucose metabolism in the retina | 242 | ||
| Protein metabolism in the retina | 243 | ||
| The retina contains a high content of lipid (20%) | 245 | ||
| Blood flow in the retina | 245 | ||
| The blood–retinal barrier regulates the passage of molecules into the retina | 245 | ||
| Retinal blood flow may be partly under autonomic control | 245 | ||
| Photoreceptors | 246 | ||
| Metabolism and turnover | 246 | ||
| Photoreceptor cell-specific proteins | 249 | ||
| Melanopsin comes of age | 250 | ||
| Photoreceptors are easily damaged but readily regenerate | 251 | ||
| The interphotoreceptor matrix is the biological glue for retinal adhesion | 253 | ||
| The retinal pigment epithelium | 254 | ||
| The RPE is a pluripotent cell | 254 | ||
| Photoreceptor function is critically dependent on a healthy RPE layer | 256 | ||
| The RPE is polarized with tight junctions, but transport is bidirectional | 257 | ||
| The chemistry of the visual response | 258 | ||
| Photochemical reactions in the retina | 258 | ||
| Rhodopsin, vitamin A and photoreceptor turnover | 258 | ||
| Phototransduction: the conversion of light energy to an electrochemical response | 259 | ||
| Phototransduction is a biological cascade | 261 | ||
| Does phosphoinositide metabolism have a role in phototransduction? | 261 | ||
| Renewal of photoreceptors is associated with accumulation of lipofuscin pigment in the RPE cells | 261 | ||
| RPE lysosomes contain a battery of enzymes capable of degrading complex lipid–glycoprotein aggregates | 262 | ||
| Synaptic events between photoreceptors and cells of the inner nuclear layer | 262 | ||
| Two types of bipolar cell | 263 | ||
| Neurotransmitters and neuromodulators | 265 | ||
| Glutamate is the major neurotransmitter in the retina | 265 | ||
| Horizontal and amacrine cells | 266 | ||
| Dopamine exerts a neuromodulatory effect on retinal function | 267 | ||
| Conclusion | 268 | ||
| Further Reading | 268 | ||
| Further Reading | 268.e1 | ||
| 5 Physiology of vision and the visual system | 269 | ||
| Introduction | 269 | ||
| Do I have good vision? | 269 | ||
| Flicker can be used to determine limits of vision | 271 | ||
| Motion detection is also a feature of rod vision | 271 | ||
| Sensing colour | 271 | ||
| There are many hues but only three primary colours | 272 | ||
| Chromaticity is semiquantified ‘colouredness’ | 272 | ||
| Shape, form and depth perception (and more) help to ‘shape’ vision | 273 | ||
| Light detection and dark adaptation | 273 | ||
| What are the limits of detectable light? | 273 | ||
| Thresholds and the frequency of seeing | 274 | ||
| What is the minimal stimulus for vision? | 274 | ||
| Dark adaptation curve and retinal sensitivity | 274 | ||
| Melatonin and circadian rhythms | 276 | ||
| Are two small stimuli equivalent to one large one (summation)? | 277 | ||
| Spatial summation | 278 | ||
| Temporal summation | 278 | ||
| Detection of minimum stimulus for motion displacement | 279 | ||
| Binocular summation | 279 | ||
| Visual acuity and contrast sensitivity | 279 | ||
| Visual acuity is not simply a function of cone activity | 279 | ||
| Limits of and limitations on acuity | 280 | ||
| Contrast sensitivity | 283 | ||
| Does the retinotopic arrangement of fibres in the cortex have a bearing on acuity? | 285 | ||
| Best-corrected visual acuity: effects of external factors | 285 | ||
| Pupil size and visual acuity testing in infants | 286 | ||
| Eye movements | 286 | ||
| Binocular viewing and the probability theory of visual perception | 287 | ||
| Electrophysiology of the visual system | 287 | ||
| The electrical response is initiated by phototransduction | 287 | ||
| Electrophysiology of single retinal cells | 288 | ||
| How does the photochemical change in the receptor produce the spike discharge in the retinal neurone? | 291 | ||
| Retinal connections, circuitry and neurotransmitters | 291 | ||
| Retinal connections | 291 | ||
| Clinical visual electrophysiology | 296 | ||
| Resting potential and the electro-oculogram | 298 | ||
| The electroretinogram | 298 | ||
| The multifocal ERG | 299 | ||
| The visual evoked potential | 299 | ||
| Flicker | 301 | ||
| Colour vision | 302 | ||
| Colorimetry and colour discrimination | 302 | ||
| Different colours have different luminosity | 302 | ||
| Spectral sensitivity curves | 302 | ||
| Photochromatic interval | 303 | ||
| Cone thresholds | 303 | ||
| Colour detection requires more than one type of photoreceptor | 303 | ||
| Trichromatic theory of colour vision | 303 | ||
| Psychophysical evidence for three cone photoreceptors | 303 | ||
| Molecular evidence for three receptors | 304 | ||
| Convergence, Young–Helmholtz and Hering | 305 | ||
| Responses between photoreceptors and neural cells | 305 | ||
| Ganglion cell responses and opponent colour theory | 306 | ||
| Colour constancy | 306 | ||
| Colour blindness | 307 | ||
| Monochromatism | 307 | ||
| Dichromatism | 308 | ||
| Anomalous trichromatism | 308 | ||
| Achromatopsia | 308 | ||
| Visual perception | 308 | ||
| Monocular versus binocular vision | 309 | ||
| Positioning objects in space | 309 | ||
| Measuring by eye | 311 | ||
| Are two eyes better than one? | 312 | ||
| Stereopsis and depth perception | 313 | ||
| The horopter | 313 | ||
| Measuring stereopsis | 314 | ||
| Image disparity and stereopsis | 317 | ||
| Retinal rivalry and ocular dominance | 317 | ||
| Colour processing | 318 | ||
| Shape detection | 319 | ||
| Contribution of texture analysis and motion detection to depth perception | 319 | ||
| Division of labour in the visual system: parcellation and the human connectome | 321 | ||
| Imaging studies | 321 | ||
| The magnocellular and parvocellular pathways subserve different functions | 321 | ||
| The striate cortex and the prestriate cortex shuffle information between them in the build-up to a perceived image | 322 | ||
| Parcelling out the processing in V1 | 323 | ||
| Is the visual cortex organized for hierarchical neural processing or for functional specialization? | 324 | ||
| Physiology of ocular movement | 326 | ||
| Types of movement | 326 | ||
| Uniocular eye movements | 326 | ||
| Binocular eye movements | 327 | ||
| Saccades | 327 | ||
| Pursuit | 327 | ||
| Control of eye movement | 329 | ||
| The fixation reflex | 329 | ||
| Oculovestibular reflexes are eye movement responses to positional changes in the relationship between the head and the trunk | 329 | ||
| Rolling eye movements are due to oculovestibular and oculocervical reflexes | 330 | ||
| The midbrain is a coordinating centre for reflex eye movement and connects input from multiple sources | 330 | ||
| The superior colliculus is involved in both perception and eye movement control | 331 | ||
| Cortical centres regulate complex eye movements | 333 | ||
| The cerebellum | 334 | ||
| Ocular movements during natural activity | 335 | ||
| Neural versus mechanical control of eye movement? | 335 | ||
| Conclusion | 336 | ||
| Further Reading | 337 | ||
| Further Reading | 337.e1 | ||
| 6 General and ocular pharmacology | 338 | ||
| Introduction | 338 | ||
| Pharmacokinetics: drug trafficking in the body | 338 | ||
| Basic concepts | 338 | ||
| Drug absorption | 340 | ||
| The rate of passage (diffusion) through a cell membrane can be predicted by Fick’s law | 340 | ||
| Active transport | 340 | ||
| Drug absorption is dependent on a drug’s lipid solubility | 340 | ||
| Drug properties | 340 | ||
| The rate of drug absorption varies with the route of administration | 341 | ||
| Drug distribution | 341 | ||
| Drugs are metabolized to facilitate clearance | 342 | ||
| Metabolized drugs are excreted in urine and bile | 343 | ||
| Renal excretion | 343 | ||
| Glomerular filtration. | 343 | ||
| Secretion. | 343 | ||
| Reabsorption. | 343 | ||
| Biliary excretion | 343 | ||
| Pharmacodynamics: drug handling by the body | 344 | ||
| Drug–receptor interactions | 344 | ||
| Ion channels | 344 | ||
| Second messengers | 345 | ||
| Cyclic adenosine monophosphate (cAMP) | 345 | ||
| Calcium is a major mediator of cellular activity | 345 | ||
| Regulation of protein synthesis | 346 | ||
| Ligand–receptor affinity determines selectivity | 346 | ||
| Genetic control of drug handling influences response | 346 | ||
| P450 gene. | 347 | ||
| Ocular pharmacology: drug handling by cells and tissues of the eye | 347 | ||
| Mechanisms of ocular drug absorption | 347 | ||
| Factors influencing delivery of drugs to the eye | 347 | ||
| Routes of administration | 347 | ||
| Conjunctiva. | 347 | ||
| Precorneal tear film and cornea | 348 | ||
| Delivery methods of ocular medication | 349 | ||
| Residence in the conjunctival sac | 349 | ||
| Drug vehicles affect drug delivery | 350 | ||
| Solutions | 350 | ||
| Semisolids (ointments) | 350 | ||
| Slow-release preparations | 350 | ||
| Ocular inserts. | 350 | ||
| Collagen shields. | 350 | ||
| Soft contact lens. | 351 | ||
| Intravitreal inserts. | 351 | ||
| Advanced ocular delivery systems | 351 | ||
| New ophthalmic delivery system (NODS) | 351 | ||
| Particulates | 351 | ||
| Liposomes | 351 | ||
| Ocular iontophoresis | 352 | ||
| Intracameral and intravitreal administration | 352 | ||
| Intravitreal delivery of drugs has revolutionized care for vascular retinal disorders | 352 | ||
| Drugs administered systemically also penetrate the eye | 353 | ||
| Topical medications and preservatives | 354 | ||
| Reconstituting the tear film | 354 | ||
| Tear substitutes | 354 | ||
| Mucolytics | 355 | ||
| Ocular drugs and the autonomic nervous system | 355 | ||
| The parasympathetic system | 355 | ||
| Parasympathomimetics mimic the action of acetylcholine | 355 | ||
| Parasympathetic antagonists affect the pupil and ciliary muscle separately and are exploited therapeutically | 356 | ||
| The sympathetic system | 357 | ||
| The control of intraocular pressure is facilitated by similar and opposite effects of adrenergic receptors | 358 | ||
| Clinical control of intraocular pressure exploits the adrenergic system | 359 | ||
| The histaminergic system: histamine is released from conjunctival mast cells during allergic reactions | 359 | ||
| Antihistamines | 360 | ||
| Sodium cromoglicate | 361 | ||
| Eicosanoids affect multiple ocular functions | 361 | ||
| Serotonin: a potent neurotransmitter | 363 | ||
| Serotonin receptor subclasses mediate different effects | 363 | ||
| 5-HT antagonists | 363 | ||
| Glucocorticoids | 363 | ||
| Immunosuppressant agents: combating ocular inflammatory disease | 364 | ||
| Biologics | 365 | ||
| Local anaesthetics: an integral part of ophthalmic examination and surgery | 366 | ||
| Local anaesthetics affect excitable membranes | 366 | ||
| Local anaesthetics have both local and systemic side-effects | 368 | ||
| Ocular toxicity from systemic administration of drugs | 368 | ||
| Uveal tract | 368 | ||
| Photosensitization | 368 | ||
| Oculotoxic drugs | 369 | ||
| Further Reading | 369 | ||
| Further Reading | 369.e1 | ||
| 7 Immunology | 370 | ||
| Introduction | 370 | ||
| Overview of the immune system | 370 | ||
| Cells and molecules of the immune system | 373 | ||
| The myeloid system and innate immunity | 377 | ||
| Neutrophilic granulocytes | 377 | ||
| Myeloid mononuclear cells | 377 | ||
| Other granulocytes | 378 | ||
| The lymphoid system and acquired immunity | 380 | ||
| T cells | 380 | ||
| B cells | 380 | ||
| Blurring the margins between innate and adaptive immunity | 381 | ||
| Natural killer cells | 381 | ||
| Lymphoid tissue inducer cells | 381 | ||
| Innate lymphoid cells | 382 | ||
| Initial response of the host to injury (the innate immune response) | 382 | ||
| The acute inflammatory response | 382 | ||
| The acute inflammatory response goes through three phases: | 382 | ||
| Tissue damage and the release of mediators | 382 | ||
| Vascular changes | 386 | ||
| Leucocyte activation and adhesion to the endothelium | 386 | ||
| Adhesion of leucocytes to the endothelium thus involves a series of molecular events | 386 | ||
| Leucocyte migration into the tissues and chemotaxis | 387 | ||
| Phagocytosis and removal of damaged tissue and microorganisms | 389 | ||
| Activation of innate immune cells by microorganisms | 389 | ||
| NK, NKT and γδT cells also express PRRs and mediate innate immunity | 390 | ||
| Effector cells in the inflammation response | 392 | ||
| Resolution of inflammation | 392 | ||
| Chronic inflammation | 393 | ||
| The systemic response to acute inflammation: the acute-phase reaction | 394 | ||
| Development of adaptive immunity and immunological memory | 395 | ||
| Antigen recognition is made possible by antigen-presenting cells | 395 | ||
| T cells respond to antigen by clonal expansion | 395 | ||
| T and B cells participate in the effector response | 396 | ||
| How does the organism deal with intracellular antigen? | 396 | ||
| Effector mechanisms | 396 | ||
| Antibodies | 396 | ||
| All five antibody isotypes have similar basic structure | 396 | ||
| Special features of H and L chains | 396 | ||
| Antigen–antibody binding | 397 | ||
| Monoclonal and polyclonal antibodies | 399 | ||
| Cytokines are the effector elements released by cells during innate and adaptive immune responses | 399 | ||
| What makes a cytokine a cytokine? | 399 | ||
| Cytokines involved in specific immune reactions | 401 | ||
| Cytokines involved in lymphomyeloid cell maturation | 402 | ||
| Cytokine receptors and cytokine receptor antagonists | 402 | ||
| Some cytokines play a bigger role in inflammation than others | 403 | ||
| Chemokines and chemokine receptors | 404 | ||
| Complement | 405 | ||
| What is complement and what does it do? | 405 | ||
| Complement has the following effects: | 405 | ||
| The classical complement cascade | 406 | ||
| The alternative pathway | 408 | ||
| Collectin activation of complement | 408 | ||
| Cytolysis and the membrane attack complex | 408 | ||
| Regulation of complement activation | 408 | ||
| Complement activation is usually incomplete: implications for age-related macular degeneration | 409 | ||
| Cellular mechanisms of tissue damage | 410 | ||
| The delayed-type hypersensitivity reaction is the hallmark of cell-mediated immunity | 411 | ||
| Inflammatory (M1-like) macrophages cause tissue damage: alternatively activated (M2-like) macrophages are more likely to promote healing | 411 | ||
| Do cytotoxic T and NK cells induce cellular damage by making holes in the cell membrane? | 412 | ||
| Organization of the immune system | 412 | ||
| Functional anatomy of lymphoid organs | 412 | ||
| Bone marrow stem cells produce all blood cells | 413 | ||
| The thymus regulates T-cell development and maturation | 413 | ||
| Lymph nodes are designed for antigen trapping | 414 | ||
| The spleen receives antigen from all sources (lymphatics and blood) | 415 | ||
| Tertiary lymphoid organs | 416 | ||
| The mucosal immune system | 416 | ||
| The immune system as a police force | 416 | ||
| Dendritic cells are the major surveillance cells of the afferent lymphoid system | 416 | ||
| Trafficking of cells to and from the lymphoid system depends on specific cell surface adhesion molecules | 418 | ||
| What turns a lymphocyte on? | 419 | ||
| Where are memory cells found? | 420 | ||
| What turns a lymphocyte off? | 420 | ||
| T regulatory cells. | 420 | ||
| Antigen recognition | 421 | ||
| The APC makes the antigen recognizable | 421 | ||
| Processing by APCs is under tight cellular control | 422 | ||
| Making the antigen presentable: the MHC molecule as candy wrapper | 423 | ||
| The major histocompatibility system | 424 | ||
| What are MHC antigens and where are they found? | 424 | ||
| Organization of the MHC genes in the genome | 426 | ||
| Regulation and transcription of the MHC genes | 427 | ||
| T-cell activation | 427 | ||
| The TCR and antigen binding | 427 | ||
| The right time and the right place for T-cell activation | 430 | ||
| What are γδT cells and what is their role? | 431 | ||
| Superantigens | 431 | ||
| Antigens can be presented by other MHC and MHC-like molecules | 432 | ||
| Co-stimulation: presentation of antigen requires ‘help’ from other molecules | 432 | ||
| Co-stimulatory molecules | 433 | ||
| Getting the message across: cell signalling through the immunological synapse | 435 | ||
| Action of drugs on cell activation | 437 | ||
| B-cell activation | 437 | ||
| Antigens, B cells, and T cells: which does what? | 437 | ||
| Antigen recognition by B cells | 437 | ||
| B cells as antigen-presenting cells | 438 | ||
| B-cell differentiation | 438 | ||
| Antibody generation during B-cell ontogeny | 439 | ||
| Somatic mutations occur in the CDR of the V genes | 439 | ||
| Genetic control of antibody production | 439 | ||
| Immunological tolerance and autoimmunity | 439 | ||
| What is tolerance? | 441 | ||
| Sites of tolerance induction | 441 | ||
| Mechanisms of tolerance induction | 442 | ||
| Clonal deletion | 442 | ||
| Anergy | 442 | ||
| Active suppression by specific lymphocytes: T-regulatory cells | 443 | ||
| T-cell tolerance is different from B-cell tolerance | 443 | ||
| Failed tolerance | 444 | ||
| Autoimmune disease is the dysfunction or damage of tissue caused by immune responses to autoantigens | 444 | ||
| Parasitic infections persist by giving false signals to the immune system | 444 | ||
| Allergy and immediate hypersensitivity | 445 | ||
| Atopy, asthma and allergic eye disease | 445 | ||
| Mast cells and mast cell degranulation | 446 | ||
| Immunoglobulin and helper T cells | 447 | ||
| Mechanism of disease production in allergic disease | 448 | ||
| Mast cells also have a protective role | 448 | ||
| Organ and tissue transplantation | 450 | ||
| Tumours induce immune responses | 451 | ||
| The eye and the immune system | 453 | ||
| The innate immune system and the eye | 453 | ||
| The adaptive immune system and the first line of defence in the eye | 453 | ||
| Progressive ocular surface disease | 454 | ||
| Cicatrizing disease of the conjunctiva | 454 | ||
| Keratitis and ‘melting’ corneal ulcers | 455 | ||
| Inflammatory disorders of the orbit and sclera | 456 | ||
| The eye as a privileged site: what does this mean for the survival of corneal grafts? | 457 | ||
| Intraocular inflammation | 459 | ||
| The role of the immune system in ageing and degeneration in the eye | 460 | ||
| Conclusion | 461 | ||
| Further Reading | 461 | ||
| Further Reading | 461.e1 | ||
| 8 Microbial infections of the eye | 462 | ||
| Introduction | 462 | ||
| Microbes in the environment | 462 | ||
| Host defences at the ocular surface | 463 | ||
| Physical barriers | 463 | ||
| Epithelium | 463 | ||
| Resident macrophages and dendritic cells in the cornea | 464 | ||
| Pathogen recognition receptors and recruitment of neutrophils | 464 | ||
| Toll-like receptors (TLR) | 464 | ||
| NOD-like receptors | 464 | ||
| C-type lectins | 467 | ||
| Neutrophils | 467 | ||
| Adaptive immunity to microbial infection | 469 | ||
| Ocular infections worldwide | 469 | ||
| Contact lenses | 469 | ||
| Viral infections of the eye | 471 | ||
| Herpes stromal keratitis | 471 | ||
| Primary infection. | 471 | ||
| Angiogenesis and lymphangiogenesis. | 471 | ||
| Latency. | 471 | ||
| Viral retinitis | 472 | ||
| Bacterial infections of the eye | 473 | ||
| Ocular surface | 473 | ||
| Pseudomonas aeruginosa virulence factors. | 473 | ||
| Streptococcus pneumoniae. | 474 | ||
| Staphylococcus aureus. | 474 | ||
| Contact lens-related corneal inflammation. | 474 | ||
| Bacterial endophthalmitis | 474 | ||
| Fungal infections of the eye | 475 | ||
| Corneal infection with Aspergillus and Fusarium | 475 | ||
| Contact lens-associated fungal keratitis. | 475 | ||
| Treatment of fungal keratitis. | 475 | ||
| Pathogenesis of fungal keratitis. | 475 | ||
| Corticosteroids. | 477 | ||
| Protozoan causes of ocular disease | 477 | ||
| Acanthamoeba keratitis | 477 | ||
| Acanthamoeba virulence factors. | 478 | ||
| Host response to Acanthamoeba. | 478 | ||
| Acanthamoeba as a ‘Trojan horse’. | 478 | ||
| Toxoplasmosis | 478 | ||
| Host response. | 479 | ||
| Ocular toxoplasmosis. | 480 | ||
| Helminth causes of ocular infection | 480 | ||
| Toxocariasis | 480 | ||
| Ocular infections in developing countries | 480 | ||
| Onchocerciasis (river blindness) | 480 | ||
| Life cycle and parasite burden | 480 | ||
| Pathogenesis | 480 | ||
| Endosymbiotic Wolbachia bacteria | 481 | ||
| Onchocerciasis control | 481 | ||
| Loa loa (loiasis, Eyeworm) | 482 | ||
| Trachoma | 482 | ||
| Trachoma in Australia | 483 | ||
| Conclusion | 483 | ||
| Further Reading | 485 | ||
| Further Reading | 485.e1 | ||
| 9 Pathology | 486 | ||
| Introduction | 486 | ||
| Cell and tissue damage | 486 | ||
| Agents or conditions that can cause direct damage to ocular cells and tissues | 486 | ||
| Reduced oxygen supply | 486 | ||
| Physical agents | 486 | ||
| Chemical agents | 487 | ||
| Toxins | 487 | ||
| Viruses | 488 | ||
| Dysregulated immunity | 488 | ||
| Nutritional deficiencies | 488 | ||
| Genetic abnormalities | 488 | ||
| Chromosomal abnormalities | 488 | ||
| Single gene defects. | 488 | ||
| Mechanism of cell death | 489 | ||
| Necrosis | 489 | ||
| Apoptosis | 489 | ||
| Sublethal cell injury | 490 | ||
| Hydropic swelling. | 490 | ||
| Atrophy. | 490 | ||
| Hypertrophy. | 490 | ||
| Metaplasia. | 490 | ||
| Healing and repair | 490 | ||
| Healing in the cornea usually leads to a corneal opacity (scar) | 491 | ||
| Iris | 492 | ||
| Lens | 492 | ||
| Retina | 492 | ||
| Choroid | 492 | ||
| Sclera | 492 | ||
| Optic nerve | 492 | ||
| Inflammation | 492 | ||
| What happens in acute inflammation? | 492 | ||
| How does infection cause inflammation? | 494 | ||
| Bacteria | 494 | ||
| Pyogenic infection. | 494 | ||
| Chronic infection. | 494 | ||
| Viruses | 495 | ||
| Herpes simplex keratitis. | 495 | ||
| Herpes zoster ophthalmicus. | 495 | ||
| Acute retinal necrosis. | 496 | ||
| Progressive outer retinal necrosis. | 496 | ||
| Cytomegalovirus retinitis. | 497 | ||
| Chlamydia | 497 | ||
| Fungi | 497 | ||
| Protozoal and metazoal infections | 498 | ||
| Toxoplasma gondii. | 498 | ||
| Acanthamoeba spp. | 498 | ||
| Toxocara canis. | 499 | ||
| Other parasites | 499 | ||
| Inflammation may occur without infection | 499 | ||
| Granulomatous inflammation | 499 | ||
| Reactions to endogenous materials | 500 | ||
| Reactions to exogenous non-biological materials | 500 | ||
| Non-granulomatous inflammation | 500 | ||
| Inflammation due to autoimmune disease | 500 | ||
| Sjögren syndrome | 500 | ||
| Rheumatoid eye disease | 501 | ||
| Other ocular surface disease | 501 | ||
| Lens-induced uveitis | 501 | ||
| Sympathetic ophthalmia | 502 | ||
| Vasculitis | 503 | ||
| Temporal (giant cell) arteritis. | 503 | ||
| Takayasu’s disease. | 503 | ||
| Polyarteritis nodosa. | 503 | ||
| Wegener’s granulomatosis. | 503 | ||
| Systemic lupus erythematosus | 503 | ||
| Metabolic disease | 504 | ||
| Diabetes | 504 | ||
| Thyroid eye disease | 504 | ||
| Disorders of amino acid metabolism | 504 | ||
| Homocystinuria | 504 | ||
| Cystinosis | 505 | ||
| Ageing, degeneration and dystrophies | 505 | ||
| Ageing | 505 | ||
| Degeneration | 505 | ||
| Composition/type of degeneration | 505 | ||
| Hyalinization. | 505 | ||
| Fatty degeneration. | 506 | ||
| Elastic fibre degeneration. | 506 | ||
| Pinguecula and pterygium. | 507 | ||
| Calcification. | 507 | ||
| Amyloid | 507 | ||
| Systemic amyloid deposition | 507 | ||
| Localized amyloid deposition | 507 | ||
| The exfoliation syndrome (pseudoexfoliation syndrome) | 508 | ||
| Degenerative vascular disease | 508 | ||
| Hyalinization. | 508 | ||
| Vaso-occlusive disease. | 508 | ||
| Microvascular occlusion. | 509 | ||
| Macrovascular occlusion. | 510 | ||
| Cataract | 511 | ||
| Cataract associated with ageing. | 511 | ||
| Secondary cataract. | 512 | ||
| Glaucoma | 512 | ||
| Primary open-angle glaucoma. | 512 | ||
| Primary closed-angle glaucoma. | 512 | ||
| Secondary glaucoma. | 513 | ||
| Age-related macular degeneration and disciform degeneration of the macula | 513 | ||
| Dystrophies | 514 | ||
| Retinal dystrophies | 514 | ||
| Retinitis pigmentosa. | 514 | ||
| Vitelliform dystrophy (Best disease). | 515 | ||
| Stargardt’s disease (fundus flavimaculatus). | 515 | ||
| Corneal dystrophies | 515 | ||
| Epithelial dystrophies. | 516 | ||
| Corneal dystrophies of Bowman’s layer. | 516 | ||
| Stromal dystrophies. | 516 | ||
| Lattice dystrophy. | 516 | ||
| Macular dystrophy. | 516 | ||
| Granular corneal dystrophy. | 517 | ||
| Combined granular–lattice dystrophy (Avellino dystrophy). | 517 | ||
| Endothelial dystrophies. | 517 | ||
| Congenital hereditary endothelial dystrophy. | 518 | ||
| Iridocorneal endothelial syndrome. | 518 | ||
| Posterior polymorphous dystrophy. | 518 | ||
| Fuchs’ endothelial dystrophy. | 518 | ||
| Neoplasia | 518 | ||
| Pathogenesis of neoplasia | 519 | ||
| Premalignancy | 519 | ||
| Carcinogenesis | 519 | ||
| Oncogenes and tumour suppressor genes | 521 | ||
| Tumour spread and metastases | 521 | ||
| Hamartomas | 521 | ||
| Haemangiomas | 521 | ||
| Naevi | 521 | ||
| Choristomas | 522 | ||
| Dermoid | 522 | ||
| Phakomatous choristoma | 522 | ||
| Teratoma | 522 | ||
| Benign epithelial tumours | 523 | ||
| Benign tumours of surface epithelium | 523 | ||
| Benign tumours of adnexal glands | 523 | ||
| Malignant epithelial tumours | 523 | ||
| Basal cell carcinoma | 523 | ||
| Squamous cell carcinoma | 523 | ||
| Sebaceous gland carcinoma | 525 | ||
| Malignant melanoma | 525 | ||
| Conjunctiva | 525 | ||
| Uveal melanoma | 525 | ||
| Iris melanomas. | 526 | ||
| Ciliary body and choroidal melanomas. | 526 | ||
| Neural tumours | 526 | ||
| Neurofibroma and schwannoma | 526 | ||
| Malignant peripheral nerve sheath tumours | 529 | ||
| Retinoblastoma | 529 | ||
| Astrocytic hamartoma | 531 | ||
| Glioma | 531 | ||
| Meningioma | 533 | ||
| Tumours derived from muscle | 533 | ||
| Leiomyoma/leiomyosarcoma | 533 | ||
| Rhabdomyoma/rhabdomyosarcoma | 533 | ||
| Vascular tumours | 533 | ||
| Haemangiomas | 534 | ||
| Epithelioid haemangioma | 534 | ||
| Kaposi sarcoma | 534 | ||
| Other connective tissue tumours | 534 | ||
| Lymphoid tumours | 534 | ||
| Lacrimal gland tumours | 536 | ||
| Pleomorphic adenoma (benign mixed tumour) | 536 | ||
| Adenoid cystic carcinoma | 537 | ||
| Other malignant epithelial tumours | 537 | ||
| Lacrimal sac tumours | 537 | ||
| Metastatic tumours | 537 | ||
| Disorders misdiagnosed as neoplasms | 537 | ||
| Cysts | 537 | ||
| Eyelid. | 537 | ||
| Conjunctiva. | 537 | ||
| Orbit. | 537 | ||
| Pseudoepitheliomatous hyperplasia | 538 | ||
| Idiopathic orbital inflammation | 538 | ||
| Further Reading | 538 | ||
| Further Reading | 538.e1 | ||
| Index | 539 | ||
| A | 539 | ||
| B | 540 | ||
| C | 541 | ||
| D | 544 | ||
| E | 545 | ||
| F | 546 | ||
| G | 546 | ||
| H | 547 | ||
| I | 548 | ||
| J | 549 | ||
| K | 549 | ||
| L | 550 | ||
| M | 551 | ||
| N | 552 | ||
| O | 553 | ||
| P | 554 | ||
| Q | 555 | ||
| R | 555 | ||
| S | 556 | ||
| T | 558 | ||
| U | 559 | ||
| V | 559 | ||
| W | 560 | ||
| X | 560 | ||
| Y | 560 | ||
| Z | 560 |