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

•Opportunistic microorganisms are often found within the sequestrum, just as in cats

•Animals with a history of sudden corneal exposure or acute keratoconjunctivitis sicca (KCS), and subsequent profound desiccation of the ocular surface, can develop necrosis and sequestration of their anterior corneal stroma

■One published report documents absolute KCS associated with development of an equine corneal sequestrum that was clinically and histologically indistinguishable from the feline disease.

RECURRENT EROSION SYNDROME (INDOLENT ULCER, BOXER ULCER,

SPONTANEOUS CHRONIC CORNEAL

EPITHELIAL DEFECTS) (Figs 8.21, 8.22)

This condition is very commonly encountered in dogs, but similar clinical presentation and pathology are seen in other species, including cats, horses and rabbits

•A strong breed predisposition has been documented for Boxer dogs, although all breeds can be affected

•In globes submitted for pathological assessment, this condition is very often found as an incidental finding and not the focus of clinical attention

•The characteristic clinical features of recurrent erosion include:

■Superficial ulcer/erosion that lacks stromal involvement

■A flap or lip of non-adherent epithelium surrounds the margins of the defect

■The ulcer resists healing and may persist for many weeks or often months if not treated appropriately

■Although the individual response to the presence of these lesions is highly variable, the degree of associated discomfort, extent of neovascularization and inflammatory response may be minimal, despite their chronicity

■Ulceration may recur in either eye

•Pathologic features of recurrent erosion include

■The adjacent, non-adherent epithelium exhibits dysmaturation and undergoes a morphologic change such that both its superficial and basal surfaces keratinize

■The basal lamina is essentially absent in the affected area, but fibronectin coats the exposed stroma

■There is a relatively thin, hyalinized, acellular zone in the superficial stroma and any inflammatory cellular infiltrate, fibroplasia or vascularization occurs deep to this acellular

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zone. The acellular layer might be as thin as 20 m and as thick as 100 m

•There are many similarities between recurrent erosion and corneal sequestration:

■The lack of epithelial attachment at the margins of the lesion

■The acellular superficial stroma which resists degradation and infiltration

■Occasionally the acellular superficial stroma will mineralize and behave like a sequestrum

■Development of corneal sequestra has been documented at the site of non-healing erosions in cats

•No single cause for this condition is recognized

■Although the initiating cause may be minor, superficial trauma, the syndrome’s characteristic morphologic features

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are not merely the result of chronic injury to, or a chronic defect in, the corneal surface

■Absence of basement membrane and abnormalities in the anterior stroma appear to play a key role in the lack of epithelial adhesion and delayed healing of these lesions. Surgical procedures that disrupt the abnormal basement membrane and anterior stroma, such as epithelial debridement, keratectomy, anterior stromal puncture

and grid keratotomy are generally required to promote healing. However, repeated surgical debridement does not lead to the formation of a condition similar to chronic erosion

■Altered patterns of corneal innervation and neuropeptides have been documented in dogs with recurrent erosions

■Altered expression of factors that promote epithelial migration and adhesion have been documented

■Some affected dogs demonstrate increased proteolytic activity in their tear fluid and respond to protease inhibitor therapy

■Severe stromal edema leading to lifting of the epithelium associated with subepithelial bullae can lead to several morphologic features similar to chronic erosion

•Florida keratopathy (Florida spots), focal corneal stromal opacification (Fig. 8.23)

■This condition is characterized by one or more localized round foci of corneal stromal opacification in dogs or cats with no symptoms of pain or inflammation

■Five globes with this condition have been examined at the COPLOW laboratory and, in contrast to a previous report, no evidence of abnormal morphology, or of associated pathologic organisms, has been found in any of our specimens by histopathology.

FUNGAL KERATITIS, EQUINE AND OTHER

SPECIES (Figs 8.24, 8.25)

There are 75 cases of fungal keratitis in horses in the COPLOW collection, which represents 10% of all equine submissions. There are 18 cases in dogs and two cases in cats.

Fungal keratitis is most frequently encountered in horses, particularly in certain geographic locations such as the South-Eastern United States. Fungal keratitis is relatively rare in most other domestic species.

The route of infection is not well documented, but it is widely believed that pre-existing disruption of the corneal epithelial barrier,

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or traumatic implantation of these opportunistic pathogens, is necessary to establish fungal keratitis.

However, epithelial microerosions have been identified in horses at an early stage in the development of mycotic keratitis, which may indicate that complete removal of the epithelial barrier may not be necessary to fungal colonization of the cornea.

•Aspergillus sp. are most commonly implicated but Fusarium sp. and others are also found.

Infection can be superficial stromal, deep stromal (at the level of Descemet’s membrane), or both superficial and deep. The clinical presentation of fungal keratitis is therefore highly variable:

•Ulcerative keratitis with variable stromal involvement. Often a plaque of white, yellow or brown material is present on the surface of the lesion

•Keratomalacia may occur, and may be a direct result of proteases liberated by fungal organisms (see below)

•Stromal abscess formation may occur deep in the cornea, and in some cases the abscess may be seen to bulge posteriorly into the anterior chamber

•Morphologic characteristics of fungal keratitis include:

■Suppurative inflammation or, more rarely, pyogranulomatous inflammation

■Presence of fungal hyphae within Descemet’s membrane

■Multiple breaks in Descemet’s membrane are often present near the site of fungal colonization

■Silver stains for fungi are often needed to help visualize the organisms

■It the original section does not sample the site with the organisms, it might be necessary to step-section deeply into the block in order to find the fungi

■Tissues containing fungal organisms often lack a significant neovascular response, and the production of anti-angiogenic factors by pathogenic fungi has been proposed

•Definitive identification of fungal organisms from histopathology or cytology is difficult, therefore isolation of the organism (which is time consuming) is often required for its identification. Recently, molecular genetic techniques have been used in the diagnosis of fungal keratitis.

KERATOMALACIA, COLLAGENOLYTIC KERATITIS, MELTING CORNEAL ULCER (Figs 8.26, 8.27)

Keratomalacia is a devastating disease process which occurs in all species.

•Horses are commonly presented with keratomalacia, secondary to microbial keratitis

•This is also seen in dogs but more rarely

–Brachycephalic dog breeds that typically have prominent globes and lagophthalmos (e.g. Shih Tzu, Pekingese, Pug) appear predisposed to severe keratomalacia.

Increased proteolytic activity occurs to some degree in most inflammatory conditions of the cornea, and in normal wound healing. Keratomalacia occurs when the lysis of stromal collagen proceeds rapidly and unchecked, overwhelming normal tissue mechanisms

of protease inhibition and resulting in liquefaction of the corneal stroma.

Topical corticosteroids potentiate the activity of proteases and predispose to microbial keratitis.

Serine proteases and matrix metalloproteases (MMPs) are released by certain micro-organisms, inflammatory cells and by native cells (including epithelial cells and keratocytes). A number of different pathogenic mechanisms may therefore be responsible for triggering keratomalacia, including:

•Microbial keratitis: Any form of microbial infection can incite an inflammatory response and can lead to liberation of endogenous proteases

•Bacterial keratitis: Bacteria are seen in histopathology only in the most early stages of disease and, in those cases, bacteria can be numerous. The lack of bacterial organisms in pathology submissions with keratomalacia may be due to prior therapy with antibiotics

–Certain bacteria, most notably Pseudomonas aeruginosa, produce exogenous MMPs and have a well-defined association with keratomalacia

–Mycotic keratitis (see above)

–Certain fungal organisms, e.g. Aspergillus and Fusarium spp., produce extracellular serine proteases

–Viral keratitis

•Chemical injury

■ Particularly alkali burns

•Trauma or acute, severe corneal desiccation

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•In many cases, the initiating cause cannot be determined histopathologically

Morphologic features of keratomalacia include:

•Abrupt qualitative change in the corneal stromal morphology

■The normal lamellar stroma is markedly altered

–Loss of lamellar architecture

–Loss of birefringence

–Collapse of the tissue owing to a loss of structural support because of the liquid nature of the affected tissue

■Usually collagenolytic lesions are rich in neutrophils, many of which are degenerate

•Descemetocele formation may be followed by corneal perforation and iris prolapse if keratomalacia is not controlled.

The prognosis for maintenance of vision in globes with perforations following keratomalacia is poorer than that for globes with traumatic, penetrating injury because of the increased likelihood of intraocular infection.

Comparative Comments

The discussion included in this chapter regarding superficial chronic keratitis, recurrent erosion syndrome, collagenolytic keratitis, corneal lysis, and corneal perforation is generally consistent with what the ocular pathologist notes in human eyes with similar conditions.

Infectious ulcerative keratitis may occur in humans, as in

other species, as a result of viral, bacterial, fungal, and protozoal infection.

•The most common viral pathogens affecting the human cornea are herpes simplex and herpes zoster

•Bacterial infections usually follow disruptions of the integrity of the surface epithelium

–The most important predisposing condition is trauma, including trauma from contact lenses, as well as bullous keratopathy and connective tissue disorders

–Syphilis may give rise to interstitial keratitis

–Bacterial crystalline keratopathy is a condition that results from suppression of the inflammatory response due to steroids in which there is unchecked bacterial proliferation in the stroma

White crystalline stromal opacities are seen clinically, and on microscopic examination, clumps containing massive numbers of bacteria occur in the stroma

•Fungal infections may also follow corneal trauma, particularly when plant material is introduced into the cornea

–In humans, mycotic keratitis is often seen in immunocompromised or debilitated patients and may be associated, as well, with the use of certain contact lens solutions

•In recent years, Acanthamoeba keratitis has become a growing problem in humans, associated with reusable contact lenses

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Comparative Comments (continued)

inappropriately cleaned, and with increasing contamination in tap water and swimming pools

–The Acanthamoeba exists in two forms, trophozoite and cyst

–It gives rise to a clinical picture similar to herpes keratitis but is resistant to treatment.

CORNEAL PERFORATION (see also Ch. 5)

COPLOW receives many enucleated globes from animals with perforating corneal lesions.

•Some are submitted in the immediate aftermath of perforation, when owners elect not to pursue further treatment on the grounds of cost, when given a poor prognosis for vision in the affected eye

•Some are submitted when severe endophthalmitis sets in

•Some are submitted when intractable glaucoma sets in.

It can be hard to recognize prior corneal perforation, particularly in globes that have extensive corneal scar tissue formation, but the following features are helpful (Fig. 8.28):

•Rupture of Descemet’s membrane

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•Full thickness corneal scar replacing the lamellar stroma

•Entrapment of pigmented uveal tissue within the stromal scar

•Anterior synechia, at the perforation site, or more extensively.

CORNEAL LYSIS, PERFORATION, AND IRIS PROLAPSE WITH EPITHELIALIZATION IN YOUNG CATS (Fig. 8.29)

There are four cases of young cats, ranging in age from 4 months to 7 years, in the COPLOW collection with subtotal lysis of the cornea followed by epithelialization of the prolapsed iris tissue.

•Both history and morphology suggest that affected cats experienced a catastrophic, destructive ocular event as a neonate, perhaps prior to eyelid opening (i.e. ophthalmia neonatorum)

•In all cases, the affected globe was small, wrinkled and aphakic, in the absence of significant inflammation or osseous metaplasia. Affected cats demonstrated minimal signs of discomfort

•While there is no specific evidence implicating FHV-1 infection as the cause of this syndrome, this would seem to represent a likely cause that warrants consideration.

EARLY LIFE CORNEAL PERFORATION, EARLY LIFE TRAUMA SYNDROME, AND ANTERIOR CHAMBER COLLAPSE SYNDROME (Fig. 8.30)

There are 59 cases in the COPLOW collection; including 27 cases in cats and 30 cases in dogs.

•Affected globes are from young animals, representing a range of species

■The age at enucleation varies widely, but is usually less than 1 year

•Generally, eyes are enucleated because they have glaucoma and marked buphthalmos

■A small proportion have phthisis bulbi and not buphthalmos

•They may or may not have a reported history of antecedent ocular disease, or ocular trauma early in life. It is important, but not easy, to distinguish this acquired syndrome from congenital

ocular malformation, i.e. syndromes associated with anterior segment dysgenesis

•Morphologic features leading to a diagnosis of early life corneal perforation include:

■Iris tissue broadly adherent to the posterior cornea

■Full thickness corneal scar tissue

■Pigmented uveal tissue entrapped in the fibrotic remnants of the corneal stroma

■Descemet’s membrane remains thin and is focally absent in segments of the diseased cornea

–Descemet’s membrane is often doubled, absent, or markedly attenuated

■Often, there is minimal uveal inflammation

■Lens abnormalities may include:

–Microphakia or aphakia

–Displaced lens remnants

–Remnants of empty wrinkled lens capsule may be found

Often, but not always, at or within the corneal scar.

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CORNEAL EPITHELIAL INCLUSION CYST

(see also Ch. 4)

•An uncommon, but important, differential consideration for corneal masses, such as dermoid, nodular granulomatous episclerokeratitis, corneal stromal abscess or corneal neoplasia

•These are predominantly acquired lesions and there is often a history of prior corneal disease such as corneal

ulceration, or of surgical or non-surgical trauma, prior to cyst development

•Clinical appearance is of smooth, raised mass or masses. The cysts are associated with a variable degree of neovascularization of the adjacent stroma and range in color from white to pale yellow or pink

•There is seldom any associated discomfort

•These intra-stromal cysts consist of a non-keratinized squamous epithelial lining and lumen that is filled with a serous fluid of varying viscosity, color and cellularity.

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INFLAMMATION DISRUPTING THE

ENDOTHELIUM, ENDOTHELIITIS

Corneal edema may accompany anterior uveitis of any cause, examples include:

•Equine recurrent uveitis

■Antigens common to both Leptospira spp. and the equine cornea have been implicated in the immunopathogenesis of recurrent uveitis in some horses

•Feline idiopathic lympho-plasmacytic uveitis

■Localized endothelial cell inflammation can be associated with localized corneal edema.

Specific viral infections are strongly associated with inflammation of the corneal endothelium:

•Canine ‘blue eye’, Canine adenovirus type-1 (CAV-1), infectious canine hepatitis) (Fig. 8.31)

■The descriptor ‘blue eye’ refers to the dense corneal edema which develops secondary to virus infection and