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

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Comparative Comments (continued)

–Also cholesterol and neutral fats are sometimes found as secondary lipid deposits following corneal inflammatory disease with new blood vessel formation

•The major human stromal dystrophies are:

–Granular dystrophy, in which keratohyaline deposits are noted

–Lattice dystrophy, in which fine-branching amyloid opacities are seen

–Avellino dystrophy (combined granular/lattice dystrophy)

–Macular dystrophy, in which there is proteoglycan deposition in all layers of the cornea except the epithelium

•Band keratopathy in humans conforms in appearance to the descriptions given here for other species

–Band keratopathy may follow any chronic local corneal disease or occur in association with systemic hypercalcemic states and in eyes with longstanding chronic inflammation.

Corneal endothelial dystrophies and degeneration (Fig. 8.9)

As with the other corneal dystrophies, it can be difficult to distinguish true endothelial dystrophy from acquired endothelial disease, which is much more commonly encountered. There are, however, several canine examples of endothelial dystrophy in the COPLOW collection.

•Endothelial dystrophy with multifocal defects in Descemet’s membrane in dogs less than 6 months old

■There are three such cases with bilateral disease in the COPLOW collection in three different breeds

■Euthanasia was elected in all three cases because of the severe, blinding nature of the corneal disease

■The affected corneas were markedly thickened and opaque

■Histopathology shows a relatively normal endothelium, but with multiple defects in Descemet’s membrane. Within these defective areas, endothelial cells may be seen to ‘colonize’ the posterior stroma

•Breed related corneal endothelial dystrophy and spontaneous corneal endothelial degeneration (attenuation)

■Boston Terriers and Chihuahuas are known to have a breed-related corneal endothelial dystrophy

■Mature adult dogs are typically presented with bilateral corneal edema that begins temporally and progresses to involve the entire cornea. Secondary corneal ulceration, due to rupture of epithelial bullae, is a common complication of profound corneal edema

Figure 8.8  Band keratopathy.

(A) Photomicrograph of a canine anterior cornea showing thickening and basophilia of the epithelial basal lamina typical of the mineralization seen in band keratopathy (arrow). (B) Photomicrograph of a canine anterior cornea showing mineralized basal lamina in an area of epithelial loss (arrow). (C) The mineralized basal lamina and anterior stroma in a dog cornea stain black with von Kossa stain.

■Affected dogs have corneal stromal edema and endothelial cell attenuation as a primary disease, without an identifiable underlying pathogenic mechanism

■In the COPLOW collection there are 12 cases which are considered to represent breed-related corneal endothelial dystrophy

–Five Boston Terriers, three Chihuahuas, three Puli, and one Poodle

■In all cases, the only morphologic finding was corneal endothelial cell attenuation, with profound corneal stromal edema and no apparent reason for the endothelial cell degeneration.

Comparative Comments

The endothelial dystrophies in humans appear different from those described above in young dogs. In man, the endothelial dystrophies have three factors in common:

1.The endothelial cells become sparse and irregular.

2.The abnormal endothelial cells produce excess collagen posterior to Descemet’s membrane, causing a multilaminar structure.

3.Excrescences form on Descemet’s membrane.

The most common endothelial dystrophy in humans is Fuchs’ dystrophy, which constitutes the common indication for corneal surgery for a corneal dystrophy.

Secondary degenerative endothelial diseases (Fig. 8.10)

Pathogenic mechanisms

•Postoperative/iatrogenic (see Ch. 4)

■Corneal endothelial attenuation is not uncommon as a postoperative complication following intraocular surgery, most notably, cataract surgery

•Any other disease process associated with tissue contact with the corneal endothelium such as anterior synechiae, or uveal masses such as neoplasms or cysts

■Inflammatory disease may also play a role in endothelial dysfunction in some of these disease processes

•Advanced age

■Corneal endothelial density reduces progressively with age and may ultimately fall below a critical density that is needed to maintain relative dehydration of the corneal stroma

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•Glaucoma

•Lens luxation

■Focal edema due to direct contact between the displaced lens and corneal endothelium

■Diffuse edema may be associated with secondary glaucoma.

Morphologic features of corneal endothelial degeneration

•The early changes are confined to endothelial attenuation, characterized by a reduction in cell density that is recognized as a ‘spreading’ of each individual endothelial cell, such that the distance between sampled nuclei is larger and the cell thickness is reduced

•Retrocorneal membrane formation

■More advanced or longer standing cases demonstrate spindle cell metaplasia of the endothelium, with or without collagen formation

•Duplication of Descemet’s membrane

■This phenomenon is seen in dogs and cats, but not in horses, after intraocular surgery, blunt trauma, lens luxation and in other conditions where the endothelium might be ‘stressed’

■Descemet’s is usually duplicated; with the new, posterior, Descemet’s being approximately the same thickness as the original, anterior Descemet’s membrane

■The mechanism responsible for duplication of Descemet’s membrane is unknown.

Severe corneal edema (corneal hydrops) associated with Descemet’s membrane rupture (Figs 8.11, 8.12)

•Most of the examples of this condition in the COPLOW collection are in cats (five cats), although the condition has been reported in other species including horses

•The rapidity of onset is reflected in the other term for the condition, ‘acute bullous keratopathy’

•The condition is characterized by rapidly developing, dense, relatively well-circumscribed corneal edema, with large coalescing bullae within the stroma and gross distortion of the corneal profile. Pronounced conical or globular forward protrusion of the anterior profile of the cornea ensues

•Histologically, rupture of Descemet’s membrane is a consistent finding, and is associated with marked stromal edema with little or no inflammation.

CHRONIC KERATITIS, SUPERFICIAL

Chronic keratitis represents a non-specific end result of many diverse pathogenic pathways, including:

•Physical irritation from contact with hair, inflammatory or neoplastic masses, or airborne particulate material

•Desiccation caused by:

■Exophthalmos or buphthalmos which impede eyelid closure and leads to inadequate distribution of the tear film

■Inability to blink related to neurologic lesions affecting the facial nerve

■Loss of corneal sensitivity related to lesions affecting the ophthalmic branch of the trigeminal nerve, with failure to initiate a protective blink or lacrimal response to irritation

■Disorders resulting in decreased secretion of the aqueous component of tears

–Chronic inflammation of the lacrimal and/or nictitans gland

–Atrophy of these glands or obstruction of their ducts, secondary to trauma, inflammation, chemical injury, or radiation damage

–Conjunctival xerosis or fibrosis

–Neurogenic disease

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■Qualitative tear film disorders including:

–Disorders of the conjunctiva resulting in inadequate mucin secretion

Chronic inflammation

Vitamin A deficiency, which causes squamous metaplasia with keratinization of mucus secreting epithelia

These disorders may also be associated with reduced secretion of aqueous tears

–Disorders of the eyelid margin

Resulting in inadequate secretion of tear film lipid by tarsal/meibomian glands

■Recurrent episodes of corneal ulceration for whatever reason

■Keratitis due to specific corneal pathogens, e.g., Moraxella bovis, Feline herpesvirus-1

■Immune-mediated disease

–The most commonly encountered breed-related condition being chronic superficial keratitis, previously known as pannus or Überreiter’s syndrome, in dogs (see below).

Morphologic features of chronic keratitis (Fig. 8.13)

The epithelial response (epidermalization) is dependant on an intact limbal epithelium because the stem cells for the cornea reside only in

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Figure 8.11  Corneal hydrops, clinical.

(A) DSH, 1 year old: the lateral view shows the increased corneal curvature due to the severe edema. (B) DSH, 2.5 years old: the protruding cornea is irregular in contour. (C) Pomeranian, 5 years old: diffuse stromal edema is present with associated large epithelial bullae (arrows). (D) Thoroughbred,

3 years old: the acute edema caused the irregular conical cornea.

the limbus. The components of the epithelial response in chronic superficial keratitis are:

•Hyperkeratosis

•Acanthosis

•Rete ridge formation

•Melanosis

The stromal response includes:

•Vascular in-growth from the limbus

•Reorganization of stromal collagen, with scarring

•Melanosis

•Inflammatory cell infiltration

■ Which depends on the stage of disease, prior therapy and the

nature of the inflammation locally at the time of sampling The basal lamina response:

•Marked thickening of the basal lamina may occur in response to repeated ulceration and re-epithelialization.

CHRONIC SUPERFICIAL KERATITIS

(CSK, PREVIOUSLY TERMED PANNUS OR ÜBERREITER’S SYNDROME) (Fig. 8.14)

•This is a chronic, progressive, immune-mediated inflammatory condition which spreads from the limbus across the

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superficial cornea, typically commencing in the temporal quadrant

•This bilateral condition has a predilection for the adult German Shepherd dog, Tervuren, Greyhound, Border Collie and Siberian Husky, although other breeds may be affected sporadically

•Ultraviolet light exposure has been implicated as a factor in the pathogenesis, and related environmental factors including altitude, sunlight exposure and dust may all adversely impact disease onset and severity.

Morphologic features of chronic superficial keratitis

•Lichenoid (interface) lymphoplasmacytic inflammation

•Superficial stromal fibrovascular proliferation and scarring, with subsequent melanosis

•Increased epithelial cell apoptosis

•Increased epithelial cell mitotic activity, but no associated epithelial erosion or ulceration.

The prognosis for achieving disease control and preserving vision may be poorer in those animals that show rapid onset of disease in early adulthood. However, most affected dogs show a favorable response to topical immunosuppressive therapy.

Figure 8.12  Feline corneal hydrops, pathology. (A–C) Three gross photographs of the same cat eye showing corneal hydrops and misshapen, markedly edematous corneal stroma. (D) Low magnification photomicrograph of the same cat eye showing edema, epithelial separation and a defect in Descemet’s membrane (arrow).

FELINE EOSINOPHILIC KERATITIS

(PROLIFERATIVE KERATITIS) (Figs 8.15, 8.16)

Feline eosinophilic keratitis is a relatively commonly encountered disease in companion animal veterinary practice. However, the disease is under-represented in a pathology collection because it is usually diagnosed on the basis of clinical and/or cytological findings alone. There are only 24 cases in the COPLOW collection, most of which are keratectomy specimens.

•Feline eosinophilic keratitis typically extends across the limbus as a kerato-conjunctivitis. Eosinophilic conjunctivitis and eyelid margin erosive lesions may also be seen in the absence of significant corneal disease

•Lesions are most often unilateral, although bilateral involvement does occur

•Grossly the disease appears as a vascularized, peri-limbal, raised, proliferative lesion, with an irregular surface that has characteristic superficial plaques of white material. Although localized, corneal involvement can be extensive

•An association between eosinophilic keratitis and Feline herpesvirus-1 infection has been demonstrated in some affected cats but virologic studies have not defined a consistent relationship between the presence of this virus and eosinophilic keratitis in all cases

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■Roles for mycoplasma and novel chlamydiae in feline conjunctival and corneal disease have also been proposed, but have not yet been specifically evaluated in eosinophilic/ proliferative keratitis

■Eosinophilic/proliferative keratitis, and FHV-1 stromal keratitis likely represent similar immune-mediated disorders of the feline cornea, that may or may not share the same inciting factors

•Eosinophilic keratitis generally shows a dramatic response to topical immunosuppressive therapy

•Morphologic features of feline eosinophilic keratitis:

■The epithelium is usually intact but, occasionally, an ulcerated surface may be lined by granular, acellular protein that likely represents granules liberated from eosinophils and/or mast cells. In addition to focal absence or thinning of the epithelium, hypertrophy and hyperplasia of the epithelium may also be seen

■The normal superficial lamellar stroma may be completely effaced

■Associated new corneal blood vessels can be large and may cross the lesion obliquely

■The inflammatory infiltrate is lympho-plasmacytic with variable numbers of eosinophils and mast cells

–Eosinophils often do not dominate the infiltrate and they may even be present in very small numbers.

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EQUINE EOSINOPHILIC KERATITIS, EQUINE SUPERFICIAL CORNEAL SEQUESTRUM,

OR EQUINE INDOLENT ULCER (Fig. 8.17)

These three conditions share similar clinical and morphologic features to an extent that, in the cases submitted to COPLOW, it has not been possible to distinguish one syndrome from another. There are 16 cases in the COPLOW collection, with clinical or morphologic features suggesting one or the other of these syndromes. However, samples are seldom submitted from cases with a clinical diagnosis of eosinophilic keratitis for histopathologic evaluation, because the diagnosis is frequently made by cytology.

•These conditions present as superficial recurrent or non-healing ulcers affecting the peripheral cornea

•Similar clinical and histopathological findings have been reported in horses with ocular onchocerciasis, in which microfilaria have been identified within the corneal or conjunctival tissues

•Morphologic features of the disease include:

■A failure of epithelial attachment

■A very thin hyper-eosinophilic band of material between the unattached epithelium and the more normal stroma

–This might be of stromal collagen origin or it might result from the degranulation of eosinophils

■Eosinophils and other inflammatory cells are seldom seen in samples submitted for pathology

–This may be because the cases with abundant eosinophils are readily diagnosed based on clinical appearance and cytologic findings.

FELINE CORNEAL SEQUESTRUM (FELINE CORNEAL NECROSIS, CORNEA NIGRUM) (Figs 8.18, 8.19)

This condition is a commonly recognized clinical entity in cats. There are 111 feline cases documented in the COPLOW collection

Key features of corneal sequestrum include:

•Superficial ulceration characterized by a lack of epithelial attachment

■Clinically, some cases fail to retain fluorescein dye suggesting that ulceration may not always be a feature of the disease. However, this may also reflect a failure of hydrophilic fluorescein dye to stain the relatively desiccated, hydrophobic sequestrum that is exposed

■In some cases, there is a history of chronic, superficial corneal erosion or ulceration preceding sequestrum formation

•Stromal pigmentation

■Brown pigmentation of the affected stroma is an early feature of the disease

■In some cases, stromal discoloration is evident under an intact epithelium

■The extent of pigmentation can range from barely detectable amber discoloration to dense, black opacity when observed clinically

■The precise nature of the dark pigment remains unknown. Different laboratory analyses of keratectomy specimens both support and refute the presence of iron or melanin within the diseased tissue

•Morphologic features of feline corneal sequestrum include:

■A localized superficial stromal defect characterized by superficial ulceration and brown to black discoloration of the diseased stroma

■The lesion typically involves just the anterior stroma, although in rare instances the sequestrum involves the full thickness of the cornea

■In addition to being discolored, the diseased stroma is devoid of keratocytes. The lamellar quality of the stroma is maintained but the normally distinct collagen lamellae appear to have blended together

■Neither blood vessels nor inflammatory cells enter the sequestered stroma, and its collagen appears to resist enzymatic degradation

■Opportunistic bacterial or fungal organisms are frequently seen, on or within the sequestered stromal tissue

■Varying degrees of inflammatory cell infiltration, blood vessel in-growth, collagen degradation, edema and granulation tissue formation occurs at the periphery and deep margins of the lesion

■Left untreated, the corneal epithelium will eventually undermine the sequestrum, causing the sequestrum to

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slough, with subsequent spontaneous healing. However, this is often a very protracted process that may take weeks or months. Lesions that extend very deeply into the

corneal stroma are unable to resolve spontaneously in this way

•The pathogenesis of corneal sequestration is poorly understood

■There is a breed predisposition for the Persian cat, in which the disease is more likely to involve both eyes

■In some cases, there may be a history of prior corneal insult, injury and/or ulceration that appears to incite the process of sequestrum formation

■There is strong, but equivocal evidence to support a

role for FHV-1 in the pathogenesis of corneal sequestration in non-predisposed breeds. Topical corticosteroid therapy may also predispose to corneal stromal sequestration in cats.

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CORNEAL SEQUESTRATION IN OTHER

SPECIES (Fig. 8.20)

Although seldom mentioned in the published literature, morphologic features of corneal sequestrum are seen occasionally in eyes or keratectomy specimens from other species, including dogs and horses. There are 42 cases of corneal sequestrum in dogs recorded in the COPLOW collection.

•As mentioned below, recurrent erosion syndrome shares several features with sequestration

•Equine eosinophilic keratitis and at least a subset of equine chronic superficial erosions have a superficial acellular protein membrane reminiscent of that seen in feline sequestrum

•Brown pigmentation of the sequestered stromal tissue is seldom seen in species other than the cat