JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
Signalment (#2165081): 1 year-old New Zealand White rabbit
HISTORY: S-M04a: This rabbit had a two week history of buphthalmos and a one day history of excessive lacrimation, corneal ulcer and bilateral marked scleral injection.
HISTOPATHOLOGIC DESCRIPTION: Eye: Changes within the narrowed filtration angle are characterized by a continuous iris stroma that spans the iridocorneal angle and loss of the uveoscleral trabecular meshwork within the ciliary cleft (trabecular hypoplasia) (Note these changes are partially obscured by artifactual separation). Diffusely there is mild to marked thinning of the retina with loss of the afferent nerve fiber layer. Few remaining ganglion cells are shrunken and hyperchromatic with pyknotic nuclei. Diffusely there is variable thinning of the inner and outer plexiform nuclear layers with accentuation of the Muller fibers (retinal atrophy). There is marked cupping of the optic nerve head with scattered spongiosis and few dilated myelin sheaths. Diffusely the fibers of the corneal substantia propria are separated by clear space and lymphatics within the sclera are ectatic (edema). There is atrophy of the choroid, ciliary body and iris, and the sclera is markedly thin.
MORPHOLOGIC DIAGNOSIS: Eye: Goniodysgenesis, with retinal atrophy, optic nerve cupping, uveal tract atrophy, scleral thinning and corneal edema, New Zealand White rabbit, lagomorph.
CONDITION: Primary (congenital) glaucoma; goniodysgenesis
Signalment (#1505464): A 7 year-old Bassett Hound
HISTORY: S-M04b: This dog had a sudden onset of buphthalmia of the right eye.
HISTOPATHOLOGIC DESCRIPTION: There is goniodysgenesis, characterized by a continuous iris stroma that spans the iridocorneal angle and inserts into the termination of Descemet’s membrane (imperforate pectinate ligament), increased connective tissue within the uveal trabecular meshwork, and loss of the uveoscleral drainage angle (trabecular hypoplasia). The anterior aspect of the corneal epithelium is attenuated, and the lateral aspects of the corneal epithelium are hyperplastic, up to 13 cell layers thick, with intracellular edema (hydropic degeneration), intercellular edema (spongiosis), and multifocal superficial squamous keratinization. Multifocally, small caliber blood vessels extend from the limbus into the corneal stroma (corneal vascularization). Within the stroma surrounding the blood vessels are moderate numbers of neutrophils (keratitis) and multifocal aggregates of brown, granular pigment (melanin). Multifocally, corneal stroma is separated by increased clear space (corneal edema). Multifocally, within the anterior chamber and vitreous body, there are few to moderate numbers of neutrophils admixed with an eosinophilic proteinaceous exudate (hypopyon). The pupillary margin is everted with protrusion of the posterior iris pigment layer through the pupil (ectropion uveae). Within the retina, there is multifocal mild to moderate retinal atrophy, characterized by loss of the nerve fiber layer; ganglion cells that are swollen, have clumped Nissl substance and central chromatolysis (dengeneration) there is loss and degeneration of the inner nuclear cell layer, and blending of the inner and outer plexiform layers. The retina is multifocally elevated from the multifocally hypertrophied retinal pigment epithelium (retinal detachment). There is mild cupping of the optic nerve, which contains few dilated axonal sheaths and rare spheroids. Focally, the sclera is markedly expanded by ectatic lymphatics, abundant eosinophilic homogenous fluid (edema), hemorrhage, and congested blood vessels. Multifocally, the bulbar and palpebral conjunctiva is expanded by a cellular infiltrate composed of lymphocytes, plasma cells, macrophages and neutrophils, markedly congested blood vessels, hemorrhage and ectatic lymphatics (edema). The conjunctival epithelium is hyperplastic, with acanthosis, spongiosis, and intraepithelial neutrophilic pustules (conjunctivitis and blepharitis).
MORPHOLOGIC DIAGNOSIS: 1. Eye: Goniodysgenesis, with retinal atrophy, multifocal, moderate, and detachment, basset hound, canine.
- Eye: Uveitis and keratoconjunctivitis, neutrophilic, multifocal, moderate, with hemorrhage and edema.
CONDITION: Glaucoma (primary); Goniodysgenesis
- Glaucomas are a group of related diseases characterized by a prolonged increase in intraocular pressure (IOP) resulting in various degenerative changes within the ocular tissues, including functionally significant injury to the optic nerve and retina
- Glaucoma is common in dogs, less common in cats, occasional in horses, and rare in other species
- Normal aqueous humor production and drainage
- Produced by the ciliary body and processes > posterior chamber > through the pupil > anterior chamber (nourishes the lens and cornea) > drainage through fenestrations in the pectinate ligament > uveal and corneoscleral trabecular meshwork > canal of Schlemm > scleral venous plexus > systemic circulation
- Also removed through the iris stroma and ciliary muscle into the choroid (amount varies by species)
- The ciliary cleft extends 360 degrees around the iridocorneal angle; blockage of most of it is required for the development of glaucoma
- Glaucomas are classified foremost as primary and secondary
- Primary glaucoma is genetic, bilateral, commonly associated with abnormal development of the pectinate ligament, trabecular meshwork, ciliary cleft, or any combination of these structures (congenital goniodysgenesis), without concurrent ocular or systemic disease; seen almost exclusively in dogs
- Secondary glaucoma (acquired) accounts for the majority of cases in animals, is usually unilateral, and as a result of concurrent ocular or systemic disease, especially anterior synechia resulting from iris bombe, an expanding neoplasm (uveal melanocytoma) behind or within the iris, pupillary obstruction by vitreal prolapse that occurs subsequent to anterior lens luxation, or from adhesion of an inflamed iris to the cornea
- Development of a pre-iridal fibrovascular membrane is the most common cause
- Primary and secondary glaucoma can be further classified as open or closed, based on the iridocorneal angle (ICA).
- Open angle: increased IOP despite iridocorneal angle and sclerociliary cleft open and devoid of abnormalities; the heritable disease in beagles is a model for human primary open angle glaucoma
- Closed angle: increased IOP with an abnormality in trabecular meshwork and/or pectinate ligament
- Both increased IOP and degenerative structural changes must be present to warrant a diagnosis of glaucoma
- Goniodysgenesis (refers to all developmental defects of the filtration angle): The two types most common in dogs include:
- Pectinate ligament dysplasia (imperforate pectinate ligament)
- Usually bilateral but clinically initially present in only one eye
- Characterized by continuation of mature iris stroma across the uveal trabecular meshwork with insertion at the terminal edge of Descemet’s membrane
- Trabecular hypoplasia: Arrested maturation of the trabecular meshwork resulting in increased dense (primitive mesenchymal) tissue filling the filtration angle
- Blockage of the flow of aqueous humor anywhere along the outflow system can result in increased IOP > sustained IOP causes atrophy of retina, optic nerve cupping, and other secondary changes
TYPICAL CLINICAL FINDINGS:
- Common clinical and gross findings with glaucoma include buphthalmos; increased IOP; cataract; failure of eyelids to cover the cornea (lagophthalmos); corneal edema, erosion and/or ulceration; scleral injection; mydriasis; tearing of Descemet's membrane (Haab's striae); subluxation or luxation of the lens; anterior or posterior synechiae; segmental iridal atrophy to aniridia; impaired vision; and blindness
- Buphthalmos is more common in young animals and in animals with thin scleras (rats, rabbits, cats, dogs) that can stretch more readily
- Cats generally present with mydriasis, anisocoria, subtle corneal edema and buphthalmia in contrast to dogs which have overt ocular vascular injection and corneal edema
- May demonstrate high vitreal concentration of glutamate and taurine due to ischemic damage to retinal cells
TYPICAL GROSS FINDINGS:
- Buphthalmos; cataract; failure of eyelids to cover the cornea (lagophthalmos); corneal edema, erosion and/or ulceration; scleral injection; mydriasis and lens subluxation (partial displacement) or luxation (displacement into the anterior or posterior segment); anterior lens luxation can be a cause of secondary glaucoma or a sequela of glaucoma, due to rupture of zonular ligament
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Cupping of the optic disk is pathognomonic when present (absence does not rule out glaucoma as it may take up to 7 days to develop); often more pronounced in cats and rabbits
- Secondary effects: Dilated axonal sheaths; axonal degeneration and loss
- Retinal lesions are characteristic and a reliable method for histological diagnosis
- Atrophy begins in nerve fiber and ganglion layers
- Loss of nerve fibers unmasks the normally inconspicuous Muller fibers
- In dogs, progresses to loss of inner nuclear layer
- Outer nuclear layer and photoreceptors can remain unaffected for extended periods of time
- Exact pathogenesis of retinal atrophy unknown; contributing factors include:
- Pressure-induced ischemic damage after collapse of blood vessels in retina, optic nerve, or choroid
- Interference with ganglion cell nutrition by impairment of axoplasmic flow caused by IOP at lamina cribrosa (the mesh-like structure in the posterior sclera where the optic nerve exits the eye)
- Direct damage to ganglion cells by elevated local production of excitatory amino acids, especially glutamate, from injured optic nerve and retina
- Tapetal sparing: The superior retina, especially overlying the tapetum lucidum, often shows less degenerative changes than the inferior retina; the cause of this sparing effect is unknown
- Dogs with high-pressure glaucoma may develop full-thickness retinal atrophy
- Collapse of uveal trabecular meshwork
- Buphthalmos: thin sclera and anterior chamber anterior-posterior dimension increased
- Increased aqueous pressure injures the corneal endothelium, results in: diffuse edema, eventual fibrosis and vascularization; Corneal striae (breaks in Descemet’s membrane) – most frequent in horses
- Failure of lids to cover enlarged globe > corneal desiccation and eventual ulceration > secondary corneal cutaneous metaplasia and/or ulceration
- Atrophy of ciliary processes
- Migration of corneal endothelium across the face of the pectinate ligament and onto the surface of the iris
- Corneal neovascularization and keratitis
- Scleral thinning
ADDITIONAL DIAGNOSTIC TESTS:
- Tonometry (single measurement of IOP)
- Tonography (evaluates functional integrity of the aqueous outflow tract).
- Gonioscopy (reveals structural filtration angle abnormalities)
- Exophthalmos due to retrobulbar masses
- Dogs: Breeds with primary glaucoma include beagles, Basset hounds, Norwegian elkhounds, Siberian huskies, Bouvier des Flandres, Welsh springer spaniels, Great Danes, Chows, Dandie Dinmont terriers, Samoyeds
- Rabbits: Congenital glaucoma of New Zealand White rabbits:
- Inherited autosomal recessive defect in the bu gene
- Usually evident by 3-5 months of age and results in non-painful, uni- or bilateral buphthalmia with subsequent corneal opacity
- Absence or underdevelopment of the outflow channels results in impaired drainage of aqueous humor, increased IOP, buphthalmia, increased corneal diameter and corneal protrusion
- Often incomplete penetrance, resulting in normal homozygous animals
- Small litter sizes and poor neonatal survival are common because of close linkage of the bu gene with a semilethal locus
- Cats: The most common causes are diffuse iridal melanomas, other neoplasms, and idiopathic lymphocytic-plasmacytic anterior uveitis; Siamese and Burmese cats may be predisposed to primary glaucoma; aqueous humor misdirection syndrome tends to cause glaucoma in older, female cats
- Cattle: Although rare, congenital and secondary glaucoma from infectious and neoplastic processes have been reported
- Horse: Alternate means of draining aqueous humor from the eye due to thick pectinate fibers and inconspicuous corneoscleral trabecular meshwork and scleral plexus; secondary glaucoma from anterior uveitis and intraocular neoplasia most commonly recognized
- Rats: Wistar and Brown Norway: Popular inducible models for retinal ganglion cell (RGC) atrophy of Primary Open Angle Glaucoma (POAG) in humans
- Chickens: Light-induced glaucoma occurs in chicks raised under continuous light; changes include increased IOP, buphthalmos, retinal atrophy and blindness, retinal detachment, peripheral anterior synechiae, globe rupture, fibrosis, and osseous metaplasia
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- Jones ML, Beck AP, Dubielzig RR. Bilateral buphthalmia in a 4-Month-Old Texas longhorn steer. Vet 2012;50(1): 212-214.
- Labelle P. The eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2017:1288-1292.
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