Histologic Basis of Ocular Disease in Animals

Bruce Grahn, DVM, Diplomate ACVO, ABVP, is Professor Emeritus in the Department of Small Animal Clinical Sciences at the Western College of Veterinary Medicine, University of Saskatchewan in Saskatoon, Canada.

Robert Peiffer, DVM, PhD, Diplomate ACVO, is Professor Emeritus of ophthalmology and pathology at the University of North Carolina in Chapel Hill, North Carolina, USA.

Brian Wilcock, DVM, PhD, is a Professor Emeritus in the Department of Pathobiology at the Ontario Veterinary College in Guelph, Ontario, Canada and Owner of Histovet Surgical Pathology in Guelph, Ontario, Canada.

Foreword xiii


Acknowledgements xv


1 Fixation and processing of ocular tissues 1


Fixatives 1


Fixation and sectioning artifacts 2


Fixation techniques 3


Trimming the fixed globe 5


Electron microscopy 13


References 14


2 General pathology of the eye 15


Adaptations characterized by changes in cell size, number, or appearance 15


Neoplasia 19


Nomenclature 23


Distinguishing benign from malignant 25


Prognostication 27


Unsuccessful adaptation: cellular degeneration, necrosis, and apoptosis 27


Calcification, pigmentation, and cystic change 30


Ocular inflammation 32


Ocular manifestations of acute inflammation 34


Chronic inflammation 39


Ocular manifestations of chronic inflammation 39


Immune privilege 41


Lymphocytic-plasmacytic endophthalmitis 42


The sequelae of intraocular inflammation and other injuries 43


Limited regenerative ability 43


Susceptibility to scarring 43


Further reading 46


3 Congenital anomalies 49


Introduction 49


Defective organogenesis 50


Defective early organogenesis 50


Anophthalmos and cystic globe 53


Anophthalmos and microphthalmos 54


Cyclopia and synophthalmos 56


Congenital anomalies of lens 56


Congenital retinal nonattachment 63


Aniridia - iridal hypoplasia or aplasia 63


Coloboma 63


Defective later organogenesis 64


Neurectodermal defects 64


Multifocal retinopathies 71


Multiple ocular anomalies (MOA) in Rocky Mountain horses 71


Anomalies of surface ectodermal origin that develop during later organogenesis 73


Congenital adnexal cysts 73


Dermoids 73


Defects of neural crest migration and mesenchymal differentiation that develop in later organogenesis 73


Congenital corneal disease 73


Congenital disorders of neurocrest and mesenchymal tissues that manifest in the uvea during later organogenesis 74


Persistent pupillary membranes (PPMs) 74


Congenital glaucoma 75


Uveal hypoplasia 78


Collie eye anomaly (CEA) and related defects 78


Persistence of embryonic vasculature 81


References 83


4 Histopathology of ocular trauma 89


Perforating and penetrating wounds of the globe and ocular tissues 89


Perforating wounds of the globe 89


Traumatic intraocular hemorrhage 89


Expulsive subchoroidal hemorrhage 90


Sequelae of intraocular hemorrhage 90


Posttraumatic inflammation 95


Phacoclastic endophthalmitis and traumatic cataract 95


Infectious endophthalmitis 95


Trauma to individual ocular tissues 95


Orbit and optic nerve 95


Cornea/sclera 95


Uvea 100


Lens 101


Vitreous and retina 101


Globe as a whole 101


Reaction to foreign materials 101


Complications of ocular surgery 102


Chemical and thermal burns 102


Effects of radiant energy 103


References 103


5 Diseases of the eyelid, conjunctiva, lacrimal, and nasolacrimal systems 105


Eyelids 105


Structural disorders 105


Dermoids 105


Hamartomas 105


Subconjunctival fat prolapse 105


Entropion, ectropion, and medial canthal pocket syndrome 105


Distichiasis, districhiasis, and ectopic cilia 106


Inflammatory disease 108


Pyogranulomatous (granulomatous) blepharitis 108


Juvenile sterile granulomatous dermatitis and lymphadenitis (juvenile cellulitis) 110


Chalazion 110


Medial canthal erosion syndrome 111


Proliferative pox virus blepharitis in birds 111


Parasitic eyelid disorders 111


Demodicosis 111


Cnemidocoptes pilae (scaly beak) infestation of avian species 113


Eyelid tumors and neoplasms 113


Cystic apocrine hyperplasia (hidrocystomas, sudoriferous cysts, and apocrine cysts) 113


Granular cell tumor 113


Meibomian (tarsal gland) adenoma 115


Melanocytoma and melanoma 115


Histiocytoma 118


Mast cell tumor 118


Peripheral nerve sheath tumors 118


Equine sarcoid 121


Squamous cell carcinoma 122


Diseases of the conjunctiva 123


General pathology of the conjunctiva 124


Congenital conjunctival abnormalities 124


Infectious conjunctivitis 126


Herpesvirus 126


Chlamydophila (chlamydia) 126


Rickettsia rickettsi 126


Moraxella bovis 126


Parasitic conjunctivitis 126


Noninfectious inflammatory disease 127


Episclerokerataconjunctivitis 127


Lipogranulomatous conjunctivitis of cats 127


Eosinophilic conjunctivitis 128


Miscellaneous conjunctival disorders 128


Conjunctival overgrowth in rabbits (pseudopterygium) 128


Membranous (ligneous) conjunctivitis 129


Conjunctival neoplasms 129


Conjunctival lymphoma 129


Conjunctival mast cell tumors 130


Conjunctival melanoma and melanocytoma 130


Viral papillomas 133


Conjunctiva squamous papilloma 133


Conjunctival squamous cell carcinoma 133


Conjunctival vascular neoplasia 133


Miscellaneous neoplasms of the third eyelid 133


Lacrimal and nasolacrimal disorders 136


Neoplasms of the gland of the third eyelid 136


Prolapsed gland of the third eyelid 138


Keratoconjunctivitis sicca (KCS) 138


Dacryops and canaliculops 138


References 138


6 Diseases of the cornea 143


Corneal wound healing 143


Epithelial wound healing 143


Stromal wound healing 147


Endothelial wound healing 149


Epithelial and fibrous ingrowth 151


Healing of corneal grafts 152


Nonspecific corneal responses to insult 152


Corneal vascularization 152


Corneal pigmentation 154


Corneal edema 154


Keratitis 154


Epithelial alterations of keratitis 154


Stromal alterations of keratitis 156


Endothelialitis 158


Specific inflammatory corneal disease 159


Immune?mediated nonulcerative keratitis 159


Immune?mediated ulcerative keratitis 159


Superficial punctate keratitis (punctate erosive corneal dystrophy) 159


Chronic superficial keratitis (pannus) 159


Eosinophilic keratitis 161


Miscellaneous corneal disorders: corneal sequestrum, indolent corneal ulceration, corneal dystrophy, corneal lipid infiltrates, and corneal degeneration 161


Corneal sequestrum 161


Indolent ulceration (boxer ulcer, spontaneous corneal epithelial defects) 164


Corneal dystrophies, corneal lipid infiltrates, and corneal calcific/lipid degeneration 165


Miscellaneous corneal disease 167


Corneal neoplasia 172


References 177


7 Diseases of the episclera and sclera 181


Primary episcleral and scleral inflammatory disorders: a brief introduction 181


Secondary scleritis 181


Scleral neoplasia 182


Limbal melanocytoma 184


Episcleritis (episclerokeratitis, episclerokeratoconjunctivitis) 185


Scleritis and necrotizing scleritis a continuum or separate conditions? 189


Non?necrotizing scleritis 193


Necrotizing scleritis 195


Parasitic episcleral disease (onchocerca vulpis/lienalis) 195


References 196


8 Histologic manifestations of disorders of the uvea 197


Normal aging changes 203


Degenerative diseases of the uvea 205


Uveal atrophy 205


Uveal cysts 205


Cystoid degeneration of the pars plana ciliary epithelium 205


Pre?iridal fibrovascular membranes (PIFMs) 208


Heterotopic bony metaplasia of the ciliary body in guinea pigs 208


Uveitis 210


The nomenclature of uveitis 210


The intraocular events of uveitis 210


The etiologic implications of inflammatory exudates 216


Immune privilege 218


Consequences of uveitis 218


Histologic basis of the common infectious, idiopathic, and immune?mediated uveitis syndromes in domestic animals 221


Lens?induced uveitis 221


Phacolytic uveitis 223


Phacoclastic uveitis 224


Equine recurrent uveitis 227


Feline lymphocytic-plasmacytic uveitis 231


Pigmentary uveitis/pigmentary glaucoma of dogs 231


Equine heterochromic iridocyclitis with secondary keratitis 233


Vogt-Koyanagi-Harada?like or uveodermatologic syndrome in dogs 233


Uveal xanthogranuloma in miniature schnauzers 235


Uveitis associated with specific infectious agents 235


Viruses 235


Feline infectious peritonitis 235


Canine adenovirus?associated uveitis 238


Canine distemper virus?associated uveitis 239


Bovine malignant catarrhal fever (MCF)?associated uveitis 239


Bovine viral diarrhea mucosal disease?associated uveitis 239


Ovine bluetongue 239


Equine viral arteritis (EVA)?associated uveitis 239


West Nile?associated avian uveitis 239


Hog cholera 239


Bacteria 240


Fungi 241


Other infectious causes for endophthalmitis 245


Algal endophthalmitis 246


Protozoan endophthalmitis 246


Metazoan parasitic uveitis 246


References 250


9 Histologic basis of glaucoma 255


Introduction 255


The gross, subgross, and histologic lesions of elevated IOP 255


Retinal changes 257


Optic nerve changes 262


Classification of canine glaucoma and introduction to open and closed angles 266


Congenital glaucoma 267


Primary glaucoma 270


Open angle glaucoma of beagle dogs 274


Primary (congenital) glaucoma in New Zealand white rabbit 274


Secondary glaucoma 274


Pre?iridal Fibrovascular Membrane 274


Posterior Synechia with Pupillary Block 275


Vitreous degeneration, syneresis, and anterior chamber prolapse 275


Trabecular obstruction by tumor 278


Other causes of secondary glaucoma in dogs 278


Glaucoma in cats 283


Glaucoma in horses 284


References 286


10 Histologic manifestations of acquired and inherited diseases of the lens 289


Embryology and anatomy of the lens 289


Physiology of the lens 292


Pathology of the lens 292


Aging changes 294


Cataract 294


The classification of cataracts 294


The histopathology of cataract 294


The pathogenesis of cataracts 299


Etiologies of cataract 299


Lens luxation 302


Inherited lens zonular dysplasia 303


References 305


11 Acquired diseases of the vitreous 307


Primary disorders of the vitreous 310


Vitreous degeneration 310


Asteroid hyalosis 315


Posterior vitreous detachment 315


Synchisis scintillans 315


Uveal and neuroectodermal pigment and cysts within the vitreous and incidental parasitic encounters 317


Neovascularization 317


Conditions with secondary vitreous involvement 317


Vitritis 317


Vitreous hemorrhage 319


References 322


12 Histologic manifestations of retinal disease 325


Introduction 325


Retinal diseases by histologic pattern 328


Retinal atrophy 329


Inner retinal atrophies 329


The pathogenesis of retinal degeneration secondary to glaucoma 329


Retinal atrophy secondary to non?glaucomatous optic nerve injury and vascular disease 335


Optic nerve hypoplasia/aplasia 336


Outer retinal (photoreceptor) atrophies 336


Inherited photoreceptor dysplasias and degenerations 336


Retinal detachment 340


Toxic and nutritional retinopathies 346


Fluoroquinolone?induced retinal degeneration 346


Vitamin A deficiency 347


Vitamin E deficiency 347


Taurine deficiency 347


Light?induced retinal degeneration 347


Sudden acquired retinal degeneration (SARD) and immune mediated retinopathy (IMR) of dogs 352


Diseases targeting the retinal pigment epithelium 352


Retinal pigment epithelial dystrophy (central progressive retinal atrophy) 352


Hereditary retinal pigment epithelial disorders (congenital stationary night blindness of briard dogs, multifocal retinopathies) 352


Canine multifocal retinopathy 354


Retinal pigment epithelial dysplasia in the royal college of surgeons rat 354


Localized chorioretinal atrophy in rats 354


Retinitis 354


Bystander retinitis 356


Retinitis as a manifestation of neurologic disease 356


Histophilus somni (formerly Hemophilus somnus) infection in cattle 356


Canine distemper 356


Retinal lesions reflecting noninfectious systemic disease 357


Retinal lesions of systemic hypertension 357


Retinal lesions resulting from inborn errors in the intermediary metabolism (lysosomal storage diseases and others) 357


Retinal injury from thermal energy 358


Retinal neoplasms 358


Medullopitheliomas 360


Retinoblastoma 360


References 360


13 Acquired diseases of the optic nerve 367


Intraocular disorders with associated optic neuropathy 367


Glaucomatous optic neuropathy 367


Endophthalmitis and ascending optic neuritis 372


Canine distemper optic neuritis 372


Orbital disorders that affect the optic nerve 372


Proptotic optic neuropathy 372


Orbital cellulitis/abscess with optic nerve sepsis 372


CNS conditions that affect the optic nerve 372


Optic nerve disorders 376


Granulomatous meningoencephalitis 376


Unilateral granulomatous optic neuritis 376


Optic neuropathy in horses 376


Feline optic neuropathies 376


Other causes of optic neuritis 378


Toxic optic neuropathy 378


Vitamin A deficiency 379


Primary optic nerve neoplasms 381


Meningioma 381


Optic nerve gliomas 382


Peripapillary medulloepitheliomas 382


Lymphosarcoma and other metastatic neoplasms 382


References 384


14 Acquired diseases of the orbit 387


Introduction 387


Inflammatory disease 387


Extraocular myositis 388


Lacrimal adenitis 389


Orbital trauma/hematoma 390


Zygomatic sialocoele 391


Orbital cysts and post?enucleation orbital mucocoeles 393


Parasitic orbital disease 396


Orbital neoplasia 396


Multilobular tumor of bone (multilobular osteochondroma) 398


Primary orbital osteoma and osteosarcoma 402


Lacrimal adenoma and adenocarcinoma 404


Harderian gland adenomas and adenocarcinomas 404


Rhabdomyosarcoma 404


Orbital myofibroblastic sarcoma 404


Vascular anomalies 406


References 406


15 Intraocular neoplasia 409


Non?neoplastic hyperpigmented lesions 410


Benign melanocytic neoplasia 410


Uveal melanocytoma 410


Uveal melanocytosis (melanosis) 415


Malignant uveal melanomas 415


Canine and feline uveal malignant melanoma 415


Diffuse iris melanoma of cats 417


Iris and ciliary epithelial neoplasia 422


Medulloepithelioma and retinoblastoma (primitive neuroectodermal tumors) 426


Primary ocular sarcomas of cats and rabbits 428


Schwannomas of blue eyed dogs 430


Osteosarcoma and chondrosarcoma 430


Miscellaneous primary intraocular tumors 432


Metastatic uveal neoplasia 433


Lymphosarcoma 433


Secondary intraocular neoplastic extension from primary nasal and orbital and adnexal neoplasms 435


References 436


Index 443