Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
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users (IDUs) and soon thereafter in recipients of blood transfusions and in hemophiliacs. As the epidemiologic pattern of the disease unfolded, it became clear that a microbe transmissible by sexual (homosexual and heterosexual) contact and blood or blood products was the most likely etiologic agent of the epidemic.
Etiologic Agent
The etiologic agent of AIDS is HIV, which belongs to the family of human retroviruses (Retroviridae) . Nononcogenic lentiviruses cause disease in other animal species, including sheep, horses, goats, cattle, cats, and monkeys. The four recognized human retroviruses belong to two distinct groups: the human T lymphotropic viruses (HTLV) I and HTLV-II, which are transforming retroviruses; and the human immunodeficiency viruses, HIV-1 and HIV-2, which are cytopathic viruses. The most common cause of HIV disease throughout the world, and certainly in the United States, is HIV-1. HIV-1 comprises several subtypes with different geographic distributions (see below). HIV-2 was first identified in 1986 in West African patients and was originally confined to West Africa. However, a number of cases that can be traced to West Africa or to sexual contacts with West Africans have been identified throughout the world. HIV-2 is more closely related phylogenetically to the simian immunodeficiency virus (SIV) found in sooty mangabeys than it is to HIV-1.
Morphology of HIV
Electron microscopy shows that the HIV virion is an icosahedral structure containing numerous external spikes formed by the two major envelope proteins, the external gp120 and the transmembrane gp41 (Fig. 33.28). The virion buds from the surface of the infected cell and incorporates a variety of host proteins, including major histocompatibility complex (MHC) class I and II antigens into its lipid bilayer.
Fig. 33.28: Human immunodeficiency virus
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HIV is an RNA virus whose hallmark is the reverse transcription of its genomic RNA to DNA by the enzyme reverse transcriptase. The replication cycle of HIV begins with the high-affinity binding of the gp120 protein via a portion of its V1 region near the N terminus to its receptor on the host cell surface, the CD4 molecule . The CD4 molecule is a 55-kDa protein found predominantly on a subset of T lymphocytes that are responsible for helper or inducer function in the immune system . It is also expressed on the surface of monocytes/macrophages and dendritic/Langerhans cells.
Cellular activation plays an important role in the life cycle of HIV and is critical to the pathogenesis of HIV disease (see below). Following initial binding and internalization of virions into the target cell, incompletely reversetranscribed DNA intermediates are labile in quiescent cells and will not integrate efficiently into the host cell genome unless cellular activation occurs shortly after infection. Furthermore, some degree of activation of the host cell is required for the initiation of transcription of the integrated proviral DNA into either genomic RNA or mRNA. In this regard, activation of HIV expression from the latent state depends on the interaction of a number of cellular and viral factors. Following transcription, HIV mRNA is translated into proteins that undergo modification through glycosylation, myristylation, phosphorylation, and cleavage. The viral particle is formed by the assembly of HIV proteins, enzymes, and genomic RNA at the plasma membrane of the cells. Budding of the progeny virion occurs through the host cell membrane, where the core acquires its external envelope . The virally encoded protease then catalyzes the cleavage of the gag-pol precursor to yield the mature virion. Each point in the life cycle of HIV is a real or potential target for therapeutic intervention . Thus far, the reverse transcriptase and protease enzymes have proven to be susceptible to pharmacologic disruption.
Transmission
HIV is transmitted by both homosexual and heterosexual contact; by blood and blood products; and by infected mothers to infants either intrapartum, perinatally, or via breast milk. After approximately 20 years of scrutiny, there is no evidence that HIV is transmitted by casual contact or that the virus can be spread by insects, such as by a mosquito bite.
Sexual Transmission
HIV infection is predominantly a sexually transmitted disease (STD) worldwide. Although approximately 42% of new HIV infections in the United States are among men who have sex with men, heterosexual transmission is clearly the most common mode of infection worldwide, particularly in developing countries. Furthermore, the yearly incidence of new cases of AIDS attributed to heterosexual transmission of HIV is steadily increasing in the United States, mainly among minorities, particularly women in minority groups .
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Transmission by Blood and Blood Products
HIV can be transmitted to individuals who receive HIV-tainted blood transfusions, blood products, or transplanted tissue.
Maternal-fetal/Infant Transmission
HIV infection can be transmitted from an infected mother to her fetus during pregnancy or to her infant during delivery. This is an extremely important form of transmission of HIV infection in developing countries.
Transmission by other Body Fluids
There is no convincing evidence that saliva can transmit HIV infection, either through kissing or through other exposures, such as occupationally to health care workers. HIV can be isolated from saliva of only a small proportion of infected individuals.
Pathogenesis
The hallmark of HIV disease is a profound immunodeficiency resulting primarily from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper T cells, or inducer T cells. This subset of T cells is defined phenotypically by the presence on its surface of the CD4 molecule, ced HIV infection and cardiomyopathy.
Opportunistic Infections
1.Fungal infections like Candida, Cryptococcus, Histoplasma
2.Protozoal infections like Giardia, Cryptosporidia, Isospora
3.Bacterial infections like Shigella, Salmonella
4.Viral infections like CMV, Herpes etc.
5.Toxoplasma and Pneumocystis carinii is also common.
Treatment
The reverse transcriptase inhibitors include the nucleoside analogues zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir and the nonnucleoside reverse transcriptase inhibitors nevirapine, delavirdine, and efavirenz . These were the first class of drugs that were licensed for the treatment of HIV infection.
CHLAMYDIAL INFECTIONS
Trachoma is a chronic conjunctivitis associated with infection by C. trachomatis serovar A, B, Ba, or C. It has been responsible for an estimated 20 million cases of blindness throughout the world and remains an important cause of
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preventable blindness. Inclusion conjunctivitis is an acute ocular infection caused by sexually transmitted C. trachomatis strains (usually serovars D through K) in adults exposed to infected genital secretions and in their newborn offspring.
Epidemiology
Epidemiologically, two types of eye disease are caused by C. trachomatis. In trachoma-endemic areas where the classic eye disease is seen, transmission is from eye to eye via hands, flies, towels, and other fomites and usually involves serovar A, B, Ba, or C. In non-endemic areas, organisms of serovars D through K can be transmitted from the genital tract to the eye, usually causing only the inclusion conjunctivitis syndrome, occasionally with keratitis. Rarely, the eye disease acquired in this way progresses, with the development of pannus and scars similar to those seen in endemic trachoma. These cases may be referred to as paratrachoma to differentiate them epidemiologically from eye-to-eye- transmitted endemic trachoma.
Clinical Manifestations
Both endemic trachoma and adult inclusion conjunctivitis present initially as a conjunctivitis characterized by small lymphoid follicles in the conjunctiva. In regions with hyperendemic classic blinding trachoma, the disease usually starts insidiously before the age of 2 years. Reinfection is common and probably contributes to the pathogenesis of trachoma. Studies using PCR techniques indicate that chlamydial DNA is often present in the ocular secretions of patients with trachoma, even in the absence of positive cultures. Thus, persistent infection may be more common than was previously thought.
The cornea becomes involved, with inflammatory leukocytic infiltrations and superficial vascularization (pannus formation). As the inflammation continues, conjunctival scarring eventually distorts the eyelids, causing them to turn inward so that the inturned lashes constantly abrade the eyeball (trichiasis and entropion); eventually the corneal epithelium is abraded and may ulcerate, with subsequent corneal scarring and blindness. Destruction of the conjunctival goblet cells, lacrimal ducts, and lacrimal gland may produce a "dry-eye" syndrome, with resultant corneal opacity due to drying (xerosis) or secondary bacterial corneal ulcers.
Communities with blinding trachoma often experience seasonal epidemics of conjunctivitis due to H. influenzae that contribute to the intensity of the inflammatory process. In such areas the active infectious process usually resolves spontaneously in affected persons between 10 and 15 years of age, but the conjunctival scars continue to shrink, producing trichiasis and entropion and subsequent corneal scarring in adults. In areas with milder and less prevalent disease, the process may be much slower, with active disease continuing into adulthood; blindness is rare in these cases.
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Eye infection with genital C. trachomatis strains in sexually active young adults presents as the acute onset of unilateral follicular conjunctivitis and preauricular lymphadenopathy similar to that seen in acute adenovirus or herpesvirus conjunctivitis. If untreated, the disease may persist for 6 weeks to 2 years. It is frequently associated with corneal inflammation in the form of discrete opacities ("infiltrates"), punctate epithelial erosions, and minor degrees of superficial corneal vascularization. Very rarely, conjunctival scarring and eyelid distortion occur, particularly in patients treated for many months with topical glucocorticoids. Recurrent eye infections develop most often in patients whose sexual consorts are not treated with antimicrobials.
Diagnosis
The clinical diagnosis of classic trachoma can be made if two of the following signs are present:
1.Lymphoid follicles on the upper tarsal conjunctiva
2.Typical conjunctival scarring
3.Vascular pannus
4.Limbal follicles or their sequelae, Herbert's pits
The clinical diagnosis of endemic trachoma should be confirmed by laboratory tests in children with more marked degrees of inflammation. Intracytoplasmic chlamydial inclusions are found in 10 to 60% of Giemsastained conjunctival smears in such populations, but isolation in cell cultures, newer antigen detection testing, or chlamydial PCR is more sensitive. Follicular conjunctivitis in adult Europeans or Americans living in trachomatous regions is rarely due to trachoma.
Fig. 33.29: Immunofluorescence staining of chlamydiae
Treatment
Erythromycin and Tetracylines are effective.
INDEX
A
Abducens nerve 80 Acanthamoeba 414
characteristic features 414 lab diagnosis 415 pathogenesis 415
Accommodation 313
theories of mechanism 317
relaxation theory of Helmholtz 317 Tscherning theory 319
Acute inflammatory response 184 Adenovirus 421
clinical manifestations 421 laboratory diagnosis 422 treatment 422
Adrenergic inhibitors 298
alpha adrenergic inhibitors 299 beta adrenergic blockers 298 betaxolol 299
side effects 299 levobunolol 299
adverse effects 299 timolol 298
mechanism of action 298 Adrenergic stimulators 296
apraclonidine 297 mechanism of action 297 side effects 297 therapeutic uses 297
brimonidine 297 dipivefrine 296
adverse effects 296
clinical therapeutic uses 297 drug interaction 296
epinephrine 296 AIDS and HIV 422
etiology 423 morphology 423 pathogenesis 425 transmission 424
maternal-fetal/infant transmission 425
sexual transmission 424 transmission by blood and blood
products 425
transmission by other body fluids 425 treatment 425
Ancylostoma duodenale 399 clinical features 400 control 400
laboratory diagnosis 400 prevention 400 treatment 400
Angle of anterior chamber 21 development 22
Antiallergic drugs 244 antihistamines 244 side effects 245 decongestants 245 side effects 245
topical preparations 245 first generation 245 second generation 245 side effects 245
Antiamebic drugs 259 Antibiotics 249
drugs acting on bacterial DNA synthesis 253
drugs affecting cystoplasmic membrane 250
drugs affecting intermediary mechanism 253
pyrimethanine 253 sulfonamides 253 trimethoprim 253
drugs affecting protein synthesis 251 aminoglycosides 251 azithromycin 252 chloramphenicol 252 clindamycin 252
macrolides 252 neomycin 251 tetracyclines 251
drugs affecting the cell wall 249 bacitracin 250 cephalosporins 250 penicillins 249 vancomycin 250
Antifungal agents 258 amphotericin B 258 imidazoles 258 natamycin 258 polyenes 258
Antihypertensive agents 260 calcium channel antagonist 261
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direct acting vasodilators 262 diuretics 260
inhibitors of renin angiotensin system 262 parenteral antihypertensive agents 262 sympatholytic agents 261
Anti-inflammatory agents 16 antifibrotic agents 240 immunomodulators 243
cyclosporine A 243 dapsone 243 tacrolimus 243
immunosuppressants 240 immunosuppressive anti-neopalstic
agents 241 cytotoxic agents 242 fluorouracil 241 mitomycin C 241
non-steroidal anti-inflammatory drugs 239
steroids 237
different types of steroids in use 238 side effects 238
Antivirals 255
antiviral drugs for HIV infections 257 protease inhibitors 257
interferons 257 purine analogs 256
acyclovir 256 famcyclovir 256 foscarnet 256 gancyclovir 256 valacyclovir 256
pyrimidine analogs 255 idoxuridine 25 trifluridine 255 vidarabine 255
Aqueous humor 319 characteristics 319
conductivity 320 osmotic pressure 320 physical properties 319 reaction 320
viscosity 320 chemical composition 320 circulation 322
thermal circulation 322 uveoscleral outflow 323
formation 320
membrane permeability 321
Arrangement of nerve fibers 74 chiasma 74
optic nerve 74 optic radiation 75 optic tract 75 retina 74
visual cortex 75
B
Basal cell carcinoma 222 Best’s disease 204
Benign lesions of eyelid 212 adnexal lesions of eyelid 216
sebaceous adenoma 216 sebaceous carcinoma 216
benign epidermal lesions 212 benign sweat gland tumors 217
syringoma 217 dermoid cysts 213
inverted follicular keratosis 214 keratoacanthoma 215 lymphangioma 218
melanocytic lesions of eyelid 215 milia 212
neural tumors 218 neurofibroma 218
pilar tumors 217 pleomorphic adenoma 217
pseudocarcinomatous hyperplasia 214 seborrheic keratosis 214
squamous papilloma 213 vascular tumors 218
capillary hemangioma 218 cavernous hemangioma 218
Binocular vision 327 advantages 327 requisites 328
sensory mechanisms 328 Biochemistry of ocular tissue 126 Blastomycosis 390
clinical manifestations 391 diagnosis 391 pathogenesis 391 treatment 391
Blood aqueous barrier 142 Botulinum toxin 285 Bowen’s disease of eyelid 221 Bowman’s layer 133, 193 Bowman’s membrane 18
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Brucella 367 classification 369
clinical manifestations 369 complications 369 diagnosis 371
etiology 368 pathogenesis 368 treatment 371
Bruch’s membrane 36
C
Calcific band keratopathy 198 Calcium channel blockers 305 Candidiasis 383
clinical manifestations 384 diagnosis 385 pathogenesis 384 treatment 386
Carbonic anhydrase inhibitors 300 administration 300
dosage 300
mechanism of action 300 Causes for cataract formation 154
cortical cataract 154 lens metabolism 156 lipid metabolism 157 nuclear cataract 155
autosomal dominant disorders 155 autosomal recessive 155
Cellular synthesis of collagen 110 Cerebral cortex 83
Cerebral vessels supplying visual pathway 92 angular vein 94
branches of internal carotid 92 anterior cerebral artery 92 anterior choroidal artery 93 middle cerebral artery 92 posterior communicating artery 92
cavernous sinus 94
development of vascular system 95 venous drainage 93
Cestodes (tapeworms) 403 Chlamydial infections 425
clinical manifestations 426 diagnosis 427 epidemiology 426 treatment 427
Choroidal dystrophies 205 Choroidal vasculature 37
Chronic granulomatous inflammation 185 Ciliary muscle 316
Classification of anti-glaucoma drugs 293 classification of bacteria 342
bacterial cell 342 structure of cell wall 342
cultivation of bacteria 344 differential media 345 selective medium 345 transport medium 345
growth and nutrition of bacteria 343 newer classification 293
older classification 293 sterilization and disinfection 343
chemical methods 344 gaseous methods 344 physical methods 343
Coagulase negative staphylococci 348 micrococci 348
Staphylococcus epidermidis 348 Coccidioidomycosis 392
clinical manifestations 393 diagnosis 393 pathogenesis 392 treatment 393
Cogan’s microcystic dystrophy 193 Color vision 325
theories 325
Hering’s theory 326
Ladd Franklin’s theory 327 polychrmoatic theory 327 Young Helmholtz theory 325
Congenital anomalies 100 colobomata 102 cornea 100
iris 102
optic nerve 103 uveal tract 103
Congenital hereditary endothelial dystrophy 196
Conjunctival amyloidosis 200 Corneal dystrophies 191
bullous keratopathy 195
congenital hereditary stromal dystrophy 195
corneal edema 195
dystrophies of corneal stroma 194 Francosi Neetan’s fleck dystrophy 195 macular corneal dystrophy 194
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Schnyder’s crystalline dystrophy 195 topographic classification 191
anterior basement membrane dystrophy 193
Meesman’s dystrophy 193 primary gelatinous drop-like
dystrophy 194
Reis Bucklers dystrophy 193 Thiel-Behnke’s Honeycomb
dystrophy 193 Corneal layers 17 Corynebacterium diphtheriae 353
characters 353
clinical manifestations 355 complications 356 epidemiology 354 laboratory diagnosis 357 morphology 353 pathogenesis 354 pathology 354
prevention 358 toxoid 354 treatment 357
Cryptococcosis 393
clinical manifestations 394 diagnosis 394
etiologic agent 393 pathogenesis 394 pathology 394 treatment 395
Crystallins 151
aging process and effects 153 disulfide bond formation 153 glycation 153
peptide bond disruption 153 phosphorylation 153
genetic defects 152 molecular biology 152
Cycloplegics 270 atropine 270
clinical use 270 side effects 270 cyclopentolate 272 side effects 272
uses 272 homatropine 271 tropicamide 272
side effects 273 Cytotoxicity and tissue necrosis 188
D
Dalen Fuchs nodule 186 Defects in eyelids 104 Degeneration of conjunctiva 200 Degenerations of cornea 196 Descemet’s membrane 18, 133 Diabetes mellitus 308
alpha glucosidase inhibitors 310 biguanides 310
insulin preparations 308 insulin secretagogues 309 management 308 thiazolidinediones 310
Drugs used for dry eyes and corneal edema 246
mucolytic agents 247 tear stimulation 247 vinyl derivatives 247
E
Echinococcosis 407
clinical manifestations 408 diagnosis 409
endothelial dystrophies 195 treatment 409
Endothelial pumps 136 Enterobious vermicularis 397
characteristic features 397 clinical features 398 laboratory diagnosis 398 treatment 399
Epinephrine 268 ocular 268
Epithelial transport system 137 Epithelioid cells 226 Epithelium 17
limbus 19 development 20
Exposure keratopathy and Dellen 197 Extraocular muscles 55
action of the recti muscles 60 inferior oblique 61 superior oblique 60
actions of extraocular muscles 58 inferior rectus 59
lateral rectus 59 medial rectus 58 superior rectus 58
levator palpebrae superioris 63 structure 57
Index |
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Exudation 188 Eyeball 3 Eyebrows 11
Eyelids and adnexa 4 anatomy 4 canthi 4 embryology 4 muscular layer 6 structure of lids 5
superficial anatomy 4
F
Facial nerve 87 Filariasis 409
lymphatic filariasis 409 clinical features 409 diagnosis 410 treatment 410
onchocerciasis 411 clinical features 411 diagnosis 412 etiology 411 pathology 411 treatment 413
Fluorescein 282 clinical use 282
factors altering the fluorescein 282 intravenous fluorescein 283 topical preparations 282
Fluorexon 284
Foreign body giant cell 186 Frontal nerve 86
Fuch’s endothelial dystrophy 196 Fungal granuloma 191
Fusarium 387 diagnosis 387
modes of transmission 360 treatment 362
Gyrate atrophy 205
H
Hereditary retinal dystrophies 203
familial exudative vitreoretinopathy 203 lattice degeneration 203
Stickler syndrome 203 Wagner disease 203
Herpes viruses 417
clinical presentation 417 diagnosis 418
etiologic agent 417 pathogenesis 417 treatment 419
Histoplasma capsulatum 389 clinical manifestations 390 diagnosis 390
treatment 390 HMP shunt 122 Horopter 329 Hutchinson’s sign 87 Hyaluronic acid 112
Hyperosmotic agents 248, 302 contraindications 302 indications 302 mechanism of action 302
Hypersensitivity reactions 380 cytotoxic reaction 380 delayed reaction 381 immediate 380
immune complex reactions 381 reaction 380
Hypertensive and arteriosclerotic retinopathy 205
arteriolar sclerotic changes 206
G
Glands of lids 8 lymphatics 9 meibomian glands 8 nerve supply 9
Glial system of rating 44 accessory glia 44 blood supply 45 Muller’s cells 44
Gonococcus 359
clinical manifestations 360 laboratory diagnosis 362
I
Immunity 377
acquired immunity 377 active immunity 377 passive immunity 377
Increased vascular permeability 184 Indocyanine green 285
uses 285 Inflammation 183
acute inflammation 183 calor or heat 183