Ординатура / Офтальмология / Английские материалы / Veterinary Ocular Pathology A Comparative Review_Dubielzig, Ketring, McLellan_2010

•There is an inherited predisposition to optic nerve colobomas in Basenji dogs (in which the colobomatous lesions may occur in isolation, or concurrently with persistent pupillary membranes) and in Hereford and Charolais cattle

•Optic nerve head colobomas may be classified according to their location as either ‘typical’, at the 6 o’clock position in the location of the fetal fissure, or ‘atypical’ if away from this location

Morphologic features of optic nerve colobomas

•The nerve head is widened and there is an outward bulging of vitreous

•A segmental defect in the lamina cribrosa and ectasia of the posterior sclera.

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Comparative Comments

As in the dog and cat, the major congenital anomalies of the optic nerve in humans are hypoplasia, colobomatous defects, and pits of the optic nerve head. Minor congenital anomalies include persistence of the hyaloid system on the disk, projection of vascular loops from the disk, myelination of the nerve fibers extending onto the retina, and pigmentation of the disk.

OPTIC NERVE SWELLING, TRAUMA

AND DEGENERATION

Papilledema (optic disc swelling, edema) (Fig. 12.6)

•Increased pressure in the calvarium or central nervous system for any reason can result in clinically apparent swelling and anterior displacement of the optic nerve head known as papilledema

■Papilledema may be recognized in association with CNS neoplasia, hydrocephalus, orbital masses and calvarial hyperostosis, causing direct compression of the optic nerve or increased CSF pressure

■Papilledema may be associated with variable visual and pupillary light reflex deficits

■Papilledema in dogs may be difficult to recognize clinically, due to the high degree of variation in the presence of myelination of canine optic nerve heads

•Globes with documented papilledema are seldom brought to the attention of a pathologist when the globe is available at necropsy. There are no examples of papilledema in the COPLOW collection.

Papilledema and optic nerve degeneration in Vitamin A deficient in cattle

The COPLOW collection contains a small series of cases of vitamin A deficient optic neuropathy in a one small group of cattle.

•Vitamin A deficiency optic neuropathy is well-documented in the veterinary literature

•In addition to causing night-blindness and progressive retinal degeneration in adult cattle, vitamin A deficiency in calves and young, growing cattle, is associated with papilledema and optic nerve degeneration

•Narrowing of the optic canals, due to excess bone deposition, thickening of the dura and increased CSF pressure

all contribute to compression, edema and ischemia of the optic nerves

•Malacia and demyelination of the optic nerve axons is associated with blindness and widely dilated pupils.

Glaucomatous optic neuropathy

•Initial swelling of the optic nerve head often precedes optic nerve degeneration in acute glaucoma, particularly in dogs

•Glaucomatous optic neuropathy is considered in detail in Chapter 13.

Optic nerve trauma and malacia in horses (Fig. 12.7)

•This condition is often preceded by a dramatic traumatic event, most commonly a backward fall and head trauma followed by vision loss

■If the traumatic event is not witnessed, or vision loss is not immediately noticed at the time of optic nerve damage, it may be hard to establish the relationship between the optic nerve lesion and the traumatic event

•Morphologic features of equine optic nerve trauma and malacia

■There will be total or segmental necrosis followed, very rapidly by gitter cells

■Gitter cells from the damaged nerve tissue migrate into the vitreous and are seen as white nodules/excrescences protruding anteriorly into the vitreous from the optic nerve head (exudative optic neuropathy)

–The clinical appearance of pale extrusions of optic nerve material into the vitreous is considered a poor prognostic indicator for recovery of vision after a traumatic event

■The end-stage optic nerve lesion involves profound atrophy and fibrosis of the neuropil (Fig. 12.8)

•The syndrome of optic nerve trauma in horses results in an end-stage appearance that is very similar to optic nerve ischemia and only the history can distinguish between the two

■Profound optic nerve atrophy with peri-papillary retinal degeneration has been reported in horses following episodes of profuse hemorrhage, and following surgical occlusion of the external and internal carotid and greater palatine arteries.

Comparative Comments

Vascular optic neuropathy is an important entity in human ophthalmology. This disorder can be divided into prelaminar, paralaminar, and retrolaminar vascular disease, depending on the site of ischemia.

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Optic nerve trauma and proptosis in dogs and cats (Figs 12.9, 12.10)

In 43 of the 80 canine globes in the COPLOW collection with a history of proptosis, there is optic nerve necrosis, malacia, fibrosis, or gliosis depending on the time between the proptosis and enucleation (see Ch. 5)

•There are only two feline globes enucleated after proptosis in the collection and both have optic nerve necrosis

■Traumatic proptosis is much less common in cats and dolichocephalic dogs than in brachycephalic dogs, and when it does occur it is generally accompanied by severe damage to ocular and optic nerve tissues as well as other signs of significant head trauma

•The most common finding is global necrosis of the optic nerve, commencing immediately, at the time of proptosis

■This could be due to ischemia, or crushing of the nerve tissue because of stretching and a drawing together of the dura mater

•Optic nerve trauma can also occur in the absence of globe proptosis, or in proptosed globes that are replaced surgically, and these are unlikely to be removed, or at least are unlikely to be examined by a pathologist. However, the clinical consequences are similar (Fig. 12.10)

•Trauma to the optic chiasm leading to contralateral blindness has been associated with excessive traction during enucleation procedures in the cat.

Comparative Comments

Human eyes with papilledema are frequently seen in the ocular pathology laboratory, particularly following autopsies.

•Papilledema denotes a swollen disk and is classically associated with an increase in intracranial pressure

–This leads to distension of the meningeal spaces about the nerve and compression of the nerve itself

–This constriction results in venous congestion, with leakage of serum into the nerve head, and impedance of axoplasmic flow anterior to the lamina cribrosa

–The swollen nerve head protrudes into the vitreous cavity and displaces the retina.

Physical injuries to the human optic nerve may be divided into:

•Orbital injuries, which produce proptosis and avulsion of the optic nerve

•Skull injuries, with fractures in the area of the optic foramen.

The pathologic picture of avulsion of the optic nerve shows extensive exudate and hemorrhage. Fractures or contusions in the area of the optic foramen are commonly seen and result in optic atrophy and blindness. Non-accidental injuries in infants (the shaken baby syndrome) may be followed by subdural and subarachnoid hemorrhage around the optic nerve, papilledema, and if the infant survives, optic atrophy. In addition, a variety of chemical injuries

and radiation injuries can occur, which also may lead to optic atrophy.

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INFLAMMATION OF THE OPTIC NERVE

(Figs 12.11, 12.12)

Inflammation of the optic nerve is seen quite frequently in clinical practice, often as a part of more generalized inflammatory processes involving the CNS, orbit or eye.

Clinical findings indicative of optic neuritis include

•Swelling and vascular congestion of the optic nerve head

•Indistinct margins of the optic nerve head and peripapillary retinal edema and/or exudates

•Detachment of the peripapillary retina

•Hemorrhages within the retina or on the surface of the optic nerve head

•Reduced vision with afferent pupillary light reflex deficits

•Inflammation that is confined to the retrobulbar optic nerve may result only in reduced or absent vision and altered pupillary light reflexes, in the absence of ophthalmoscopic abnormalities.

Specific inflammatory conditions primarily affecting the optic nerve are comparatively rarely encountered in a pathology service. In the absence of other signs of CNS, orbital or intraocular disease, idiopathic/presumed immune-mediated optic neuritis is unlikely to warrant either enucleation or euthanasia. In the COPLOW collection there are single cases of the following conditions:

Granulomatous meningoencephalitis (GME)

•Optic nerve involvement may occur in isolation, precede or occur in association with other, multifocal CNS lesions and

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associated clinical signs. Canine GME is a relatively common, and probably under-diagnosed, cause of both optic neuritis and of central blindness in dogs

•Definitive ante mortem diagnosis can be difficult, although elevated CSF protein with pleocytosis, and CT or MRI findings may be considered suggestive of GME

•Small dog breeds and females appear to be predisposed

•Longer survival times appear to be associated with focal GME, such as optic neuritis, than with the multifocal form

•Immunosuppressive therapy may restore vision in affected dogs, but a relapsing-remitting course is common despite therapy

Morphologic features include:

•Histiocytic cells forming cuffs around blood vessels and featuring reticulin fibers around individual histiocytic cells

The pathogenesis of this condition is unknown

Canine distemper optic neuritis

•The disease is associated with infection by Canine distemper virus (paramyxovirus)

•Optic neuritis may occur in isolation or be recognized before, concurrently, or after other systemic signs, such as respiratory, gastrointestinal or neurological, or signs of ocular disease, such as keratoconjunctivitis or retinochoroiditis

•Morphologic features include:

■Astrocytosis

■Loss of myelin

■Eosinophilic intranuclear inclusion bodies

Feline toxoplasmosis optic neuritis

•Despite the frequent reference to toxoplasmosis in the literature, there is only one case in the COPLOW collection in which toxoplasma organisms were identified

•Morphologic features include hemorrhage, malacia, and finding the organism bradyzoites

•The one affected cat had unilateral disease and eventually developed neurologic symptoms

•In veterinary patients, ocular toxoplasmosis appears to be more frequently associated with iridocyclitis and/or chorioretinitis. (Ocular toxoplasmosis is discussed in greater detail in

Chapter 9).

Comparative Comments

•Because of the optic nerve’s proximity and vascular continuity with the globe and the brain, optic nerve inflammation in the human is most often the result of extension from primary intraocular or intracranial inflammation

•Multiple sclerosis, sarcoidosis, a multisystem granulomatous disease, and Behçet’s disease, a multisystem vasculitis, can affect the optic nerve

•A variety of bacterial, viral, and fungal infections can involve the optic nerve and retina (neuroretinitis). Of these, Varicella

zoster-virus, Mucormycosis, Mycobacterium tuberculosis, Treponema pallidum, Toxoplasma gondii and Histoplasma capsulatum are the most important.

TUMORS OF THE OPTIC NERVE

Meningioma

•Canine orbital meningioma (see Ch. 6 for more detailed discussion) (Figs 12.13, 12.14)

■This is the most common variant involving the optic nerve

–There are 60 cases of canine orbital meningioma in the COPLOW collection, representing 1.5% of canine tumors in the collection

•Although the tumor originates from the arachnoid cap cells of the optic nerve, the tumor need not be anatomically located within the optic nerve meninges. However, the tumor always extends into the orbital connective tissues encircling the optic nerve

Morphologic features of canine orbital meningioma

•Aggregates of large polygonal cells infiltrating orbital adipose tissue

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Veterinary Ocular Pathology

A B

C D

•The cells can be hard to distinguish from epithelial cells but they are vimentin positive and cytokeratin negative

•There are often multiple foci of metaplastic bone, cartilage, or undifferentiated myxomatous stroma

Canine optic nerve meningioma by extension (Fig. 12.15)

•Within the COPLOW collection, there are five canine cases of meningioma with optic nerve involvement by extension from the cranial vault down the optic nerve

•The neoplasm spreads into the optic nerve by extension from the calvarium

•The tumor is limited within the confines of the dura mater, expanding the optic nerve thickness diffusely

•Optic nerve involvement is often bilateral

Morphologic features of canine optic nerve meningioma by extension include:

•The neoplastic tissue expands within the dura mater causing compression of the optic nerve

•Any of the morphologic subtypes that occur in the calvarium can be seen within the optic nerve meninges

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Figure 12.11  Optic neuritis or neoplasia masquerading as neuritis, feline. (A) DSH cat, 2 years old: this blind cat had bilateral neovascularization of the optic disc and peripapillary edema and vascularization. A cerebrospinal tap confirmed lymphosarcoma. (B) DSH cat, 10 years old: a proliferative mass obscures the optic disc. The tapetal retina shows multiple foci of inflammation. Lymphosarcoma was diagnosed on histopathology. (C) DSH cat, 2 years old: the swollen disc, peripapillary edema, infiltrate, and hemorrhage are the most significant lesions. Cryptococcosis was diagnosed from a cerebrospinal tap. (D) DSH cat,

8 years old: bilateral neovascularization of the optic disc was the only lesion found in this seizuring cat. Meningioma was the histopathologic diagnosis.

In addition to optic nerve meningioma in dogs and humans, there are sparse reports of optic nerve meningioma occurring in other species, including cattle and rats.

Optic nerve glioma (astrocytoma) (Figs 12.16, 12.17)

In the COPLOW collection, this disease is only represented in dogs

•It is unilateral and causes expansion of the optic nerve

•In all 11 cases in the COPLOW collection, the tumor lies near the globe and causes an inward bulging of the optic nerve head

•The tumor can also occur in the central retina and not involve the optic nerve (see Ch. 11), and extensive involvement of the optic chiasm has also been reported

Morphologic features of optic nerve glioma in dogs include:

•There is effacement of the optic nerve neuropil by spindle to stellate neoplastic cells

•The cytoplasmic processes of these cells form a tangle of fibrillar tissue

•The finding of tight, glomerular-like neovascular tangles within the tumor, or in the surrounding retina, can assist with the diagnosis

•Malignant forms with anaplastic cellular features are seen commonly. Cases that extend to the margins of the surgical resection in a biopsy specimen will often re-present with neurologic signs

•The tumor cells are positively labeled for glial fibrillary acidic protein (GFAP) on immunohistochemistry

•Classification system for gliomas/astrocytomas in dogs, from most to least differentiated forms:

■Astrocytoma

■Anaplastic astrocytoma

■Glioblastoma multiforme – considered most aggressive form.

Medulloepithelioma of the optic nerve head in horses (Fig. 12.18)

There is one case in the COPLOW collection

•Medulloepithelioma in the optic nerve head of young horses is very rare

•This is a mass which bulges anteriorly from the optic nerve head and also expands the optic nerve tissue. Exophthalmos and blindness may result

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