JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M12

 

Signalment (JPC #2839056): Collie

 

HISTORY: Tissue from a collie dog

 

HISTOPATHOLOGIC DESCRIPTION: Eye: There are diffuse dysplastic changes affecting the retina, sclera, iris/trabecular meshwork, and choroid. Multifocally, all layers of the retina are disorganized with the formation of multiple rosettes; detachment from the rounded, hypertrophied retinal pigment epithelium (“tombstoning”); an indistinct nerve fiber layer (with prominent Muller fibers), ganglion cell layer, and outer plexiform layer; thinning of the inner plexiform and nuclear layers (retinal atrophy) or coalescence of the nuclear layers. The choroid is diffusely and markedly thinned, composed of a thin fibrous stroma, few vessels, and extensive lack of pigmentation (choroidal hypoplasia); there is focally extensive thinning of the tapetum adjacent to the optic disc. There is a 10 x 15 mm retrobulbar cystic, thin-walled outpouching that contains numerous inward papillary projections and is multifocally lined by neuroectoderm (ectasia, staphyloma). This outpouching extends through a focally extensive defect in the sclera (coloboma) that extends from the optic disc to the ciliary body. There is multifocal extensive disruption of lens fiber architecture with replacement by numerous bladder cells, morgagnian globules, and reactive hyperplasia of the capsular lens epithelium with posterior migration of the epithelial cells (cataractous change). There are small amounts of eosinophilic granular to flocculant material within both the anterior and posterior segments that adhere to both the ciliary body and retina. There is ciliary body and iris atrophy. The iris is focally displaced rostrally and adhered to the cornea (anterior synechiae), obscuring the ciliary cleft. 

 

MORPHOLOGIC DIAGNOSIS: 1. Eye: Choroidal hypoplasia and hypopigmentation, diffuse, severe, with retinal detachment and atrophy, and cataractous change, Collie, canine.

2. Eye, optic nerve: Posterior scleral coloboma with scleral ectasia/staphyloma.

 

ETIOLOGY: Hereditary posterior segment anomaly (dysgenesis)

 

CONDITION: Collie eye anomaly (CEA)

 

GENERAL DISCUSSION:  

• Collie eye anomaly (CEA) is a canine inherited bilateral ocular disorder which shows a variety of manifestations of clinical lesions 

• CEA is common in collies (smooth and rough-coated), Shetland sheepdogs, Australian shepherds (similar to merle ocular dysgenesis syndrome), border collies, Lancaster heelers, and rarely in other non-collie breeds (beagle, dachshund, and German shepherd dog)

• There are four main lesions:
  • Choroidal hypoplasia
  • Coloboma; +/- sclera ectasia, posterior staphyloma
  • Retinal detachment and dysplasia
  • Intraocular (posterior segment) hemorrhage
• The earliest lesion of this anomaly is defective differentiation of primitive retinal  pigment epithelium (RPE) that forms rosette-like structures near the optic disc  
• All cases demonstrate a regionally defined area of choroidal hypoplasia (most consistent finding) and segmental tapetal aplasia lateral to the optic disc; coloboma may occur in up to 34% of cases which may result in retinal detachment and hemorrhage

 

PATHOGENESIS:

• An inherited autosomal recessive trait; the underlying genetic mutation, is a homozygous deletion in the canine NHEJ1 gene 
• Proper development of the eye requires obliteration of the intraretinal space and apposition of the pigment layer and neural retina
• CEA results from either: 1. Imperfect apposition of the pigment epithelium and neural retina or 2. Defective differentiation of the pigment epithelium (delayed closure of the optic fissure ; since pigment epithelium plays such a critical role in development of the eye, the primary defect is presumed to be in the retinal pigment epithelium 

 

TYPICAL CLINICAL (OPTHALMOSCOPIC) FINDINGS:

• Collie eye anomaly may be diagnosed as early as 5-10 weeks of age; after 12 weeks of age, it is hard to perform a diagnostic eye exam because the lesion can be covered up by pigment
• Bilateral lesions, although one eye may be worse than other
• Focal to diffuse choroidal and tapetal hypoplasia
• Optic nerve coloboma 
• Retinal folds or detachment with intraocular hemorrhage
• Retinal vessel tortuosity (no histological correlate)
• Enophthalmos, microphthalmos, and corneal stromal mineralization

 

TYPICAL GROSS FINDINGS:

• There are four gross lesions: Choroidal hypoplasia, posterior coloboma (+/- scleral ectasia), retinal detachment, vitreous/retinal hemorrhage
• Choroidal hypoplasia:

• Focally extensive to diffuse thinning and pallor (depigmentation) of the choroid usually adjacent to the optic disc at the tapetal-nontapetal junction

• Choroid and sclera will be translucent if transilluminated

• Choroidal vessels are fewer, wider, and abnormally arranged
• Normally bilateral, but often asymmetric

• Coloboma:

• Gray or pink indentations (variably sized) that are within or adjacent to the optic disk
• Retinal vasculature changes course or disappears at the edge of the coloboma
• Scleral ectasia or posterior staphyloma may occur when a large coloboma produces a bulge in the overlying sclera

• Retinal detachment:
  • Most often a sequela from coloboma; arises adjacent to the optic disk and extends out peripherally

• Subretinal, intraretinal, or preretinal intravitreal hemorrhage 
• Retinal separation, if present, is usually complete with two sites of attachment: at the optic disk and ora ciliaris; often has hemorrhage and retinal tears
• If the retina detaches from the ora ciliaris (retinal disinsertion), the folded retina will sink to the floor of the globe

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Earliest lesion is defective differentiation of primitive RPE to form rosette-like structures near the optic disc
• Choroidal hypoplasia:

• Fundamental lesion: Marked diffuse thinning of the choroid (choroid hypoplasia) with decreased pigmentation and a thin or absent tapetum
• Retinal pigment epithelium is poorly pigmented and may be vacuolated
• Tortuous vasculature

• Coloboma:
  • Lamina cribrosa or scleral defect with outward bulging or ectasia, often adjacent to the optic disc (but not in all cases)

• bulging of dysplastic neuroectoderm, continuous with retina, into the pit in the nerve head is a common presentation
• Neuroectoderm may show differentiation into ganglion cells, photoreceptor rosettes, glial cells, or pigment epithelium
• In large colobomas, choroid may be lacking and sclera thinned
• Rosette-like structures near or imbedded in the optic disk

• Retinal detachment:

• Retinal folds are visible as tubes in cross section; these indicate a retina that temporarily has outgrown the space available within the optic cup and correspond to vermiform streaks in fundus seen clinically; the folds gradually disappear as the eye matures and expands in diameter
• Hemorrhage
• May be focal or diffuse

• May also see pre-iridal fibrovascular membrane formation and hemorrhage into the posterior segment

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:

• Colobomas: Occur in all domestic species due to delayed fusion of the optic fissure; most often in blue-eyed or albino animals; Charolais cattle inherit colobomas as an autosomal dominant trait with incomplete penetrance; recent report in free-ranging white-tailed deer
• Choroidal hypoplasia: Occurs in a variety of dog breeds associated with color dilution 

• Other breed associated ocular abnormalities:
  • Merle ocular dysgenesis: Micropthalmia with abnormalities in the lens, sclera, and retina including coloboma formation, retinal detachment, and retinal dysplasia
  • Rocky Mountain horses: Micropthalmia, cornea globose, iris abnormalities, ciliary cysts, cataracts, etc. 
  • Doberman Pinscher and Staffordshire bull terrier (inherited): Persistent hyperplastic primary vitreous and persistent hyperplastic tunica vasculosa lentis; may also occur in other breeds

 

REFERENCES:

1. Clarke LL, Niedringhaus KD, Carmichael KP, Keel MK, Fenton H. Congenital ocular abnormalities in free-ranging white-tailed deer. Vet Pathol. 2018; 55(4):584-590. 
2. Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Congenital, developmental, or hereditary abnormalities in animals. In: Dubielzig RR, Ketring KL, McLellan GJ, Albert DM, eds. Veterinary Ocular Pathology: a comparative review. St Loius, MO: Saunders Elsevier; 2010;34-35.
3. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St Louis, MO: Elsevier; 2012:1429.
4. Narfstrom K, Ptersen-Jones SM. Diseases of the canine ocular fundus. In: Gelatt KN, Gilger BC, Kern TJ, eds. Veterinary Ophthalmology. 5^th ed. Aimes, IO: Wiley-Blackwell; 2013:1311-1316.
5. Ofri R. Retina. In: Maggs DJ, Miller PE, Ofri r, eds. Slatter’s fundamentals of veterinary ophthalmology. 4^th ed. St Louis, MO: Elsevier; 2008:303-304
6. Wilcock BP, Njaa BL: Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:412-414,419,422.

 

 

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