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

■Iridal abnormalities, that include:

–Iris hypoplasia

–Dilator muscle hypoplasia, so that the pupils are miotic and resistant to pharmacologic mydriasis

–Abnormal, circumferential position of the granula iridica (corpora nigra)

–Abnormal iris surface contour

–Irido-corneal adhesions.

–Abnormalities of the irido-corneal drainage angle

–Widened palpebral fissures

■Ciliary cysts

■Nuclear cataracts

■Lens subluxation.

Persistent hyperplastic primary vitreous (PHPV) and persistent hyperplastic tunica vasculosa lentis (PHTVL) (Fig. 3.14)

•There is a sporadic occurrence in any breed, but PHPV/PHTVL is considered to be inherited in the Doberman Pinscher and Staffordshire Bull terrier breeds.

•Specimens rarely submitted for evaluation

■ There are only 12 cases logged into the COPLOW collection

– Three of the 12 are in Doberman Pinschers

•The primary vitreous, including the hyaloid vasculature and the tunica vasculosa lentis, provide a blood supply to the fetal lens, and in dogs completely regress shortly after birth

•In dogs with PHPV/PHTVL, the first observable abnormalities are seen about halfway through gestation (30–33 days), when the hyaloid vasculature and tunica vasculosa lentis appear over-developed relative to normal, and a retro-lental membrane may first be recognized

■The abnormalities are usually centered on the vitreous but there can be variable involvement of the whole retro-lental vascular system, and anterior tunica vasculosa lentis

■In moderate and severe cases, tissue may be recognized that would not be identified in the normal primary vitreous

–Cartilage

–Pigmented tissue

–Nests of glial tissue

■Posterior lenticonus, cataract and posterior lens capsule defect is often seen

■Intralenticular hemorrhage is sometimes seen

–Although hemorrhage within the lens is a good morphologic marker for a congenital abnormality of the fetal hyaloid vasculature, it does not discriminate between PHPV, PHTVL, and persistent hyaloid artery

■Retinal detachment may be seen in severe cases

–Retinal detachment can lead to pre-iridal fibrovascular membrane, and contribute to neovascular glaucoma or anterior segment hemorrhage

–Retinal dysplasia may accompany PHPV, as has been reported in the Miniature Schnauzer as a recessively inherited condition, and as a familial trait in the Bouvier des Flandres.

Retinal dysplasias (Fig. 3.15)

•An important hereditary abnormality in dogs, retinal dysplasia, is seldom encountered as a genetic disease in other species

•Globes with retinal dysplasia in isolation are almost never submitted to the diagnostic ocular pathology laboratory

■The only cases identified in the COPLOW collection are those in which retinal dysplasia accompanies other abnormalities of serious consequence to ocular health and/or vision

■Because so few cases are seen in a pathology collection, and because the only cases seen are in a special context, a diagnostic ocular pathologist has little beyond generalities to add to the understanding of these developmental disorders

•Definition: the disorganized development of retinal tissue

■Solitary or multi-focal disease

•Many breeds of dog are affected, and the reader is referred to the most recent edition of Ocular Disorders Presumed To Be Inherited in Purebred Dogs, with regular updates available from the Canine Eye Registration Foundation (CERF)

•Retinal dysplasia is characterized funduscopically as welldemarcated, linear, curvilinear or larger, geographic foci, that may be raised or wrinkled, and may be accompanied by pigment disturbance or evidence of associated retinal degeneration. In some cases, funduscopic lesions may not be readily identifiable until secondary degenerative changes become apparent

■Linear lesions are generally considered to represent ‘folds’, which some consider as a distinct entity not qualified to be considered as dysplasia, in the absence of significant tissue disorganization

–Some feel that simple retinal folds in puppies are likely to disappear with the subsequent maturation and physical enlargement of the globe

■Geographic lesions are likely to include retinal lesions beyond just folding

–Rosettes

–Thickening or thinning

–Jumbling of the retinal layers

–Focal retinal detachment, or local changes in the RPE, with accompanying retinal degeneration.

The vitreoretinopathies – vitreoretinal dysplasia (Figs 3.16, 3.17)

By virtue of the blinding effect of retinal detachment, intraocular hemorrhage and the risk of neovascular glaucoma, vitreoretinopathy is more often seen in the pathology laboratory than retinal dysplasia alone, with 58 cases logged into the COPLOW collection.

•Congenital, inherited retinal detachment/non-attachment is recognized in Bedlington and Sealyham terriers. For a comprehensive breakdown of the breeds affected by vitreoretinal dysplasia, the reader is referred to the most recent edition of

Ocular Disorders Presumed To Be Inherited in Purebred Dogs, with

regular updates available from the Canine Eye Registration Foundation (CERF)

•This diagnosis is made when there is abnormal development of both the vitreous and the retina. Because the two tissues are so intimately connected, disease of one impacts the health of the other

•The vitreous body is formed by scant spindle cells, a connection to the retina by attachment to the inner limiting membrane (a basal lamina secreted by retinal Müller cells), and hyaluronic acid secreted by the ciliary epithelium

•The vitreous changes seen include:

■Areas of liquid vitreous which can only be recognized on gross examination, prior to embedding

■Areas of more dense, organized, or ‘solid’ vitreous

–These areas create traction on the retina and can be associated with subsequent retinal detachment

–Traction on the retina from the abnormal vitreous can be associated with broad peripheral retinal disinsertion (tearing) or with more localized peripheral retinal tears. Retinoschisis is also sometimes recognized. Abnormal cellular membranes on the inner retinal surface are often seen in vitreoretinopathies

–Areas of solid vitreous can be best seen with an Alcian blue stain, and they often stain positively for collagen with a trichrome stain

•Retinal detachment, and resulting retinal hypoxia, leads to the release of vasoproliferative cytokines, particularly vascular endothelial growth factor (VEGF), which stimulate pre-iridal fibrovascular membrane (PIFVM) formation. This, in turn, leads to peripheral anterior synechiae and neovascular glaucoma and/ or hemophthalmos.

•Vitreoretinopathy of the Shih Tzu dog

■Vitreoretinopathy in this breed is often not recognized until neovascular glaucoma is seen secondary to retinal detachment

■There are 30 cases of Shih Tzu vitreoretinopathy in the COPLOW collection (Figs 3.16, 3.17)

–In this breed, the disease is usually presented in middleaged dogs, rather than very young dogs

–The detection of vitreous changes often requires either careful attention to the gross morphology at the time of globe trimming, or an Alcian blue stain

–The vitreous is usually liquid in much of the posterior segment but condensed at the inner retinal surface

–Retinoschisis is often seen in the detached retina

■There is traction and peripheral retinal tearing leading to local or extensive retinal detachment (rhegmatogenous retinal detachment and giant retinal tears)

■The formation of peripheral retinal tears associated with vitreous degeneration and traction may represent a good comparative model for the study of pathogenesis, treatment and prevention of peripheral rhegmatogenous retinal detachment in humans

■By the time affected globes are removed, they frequently have neovascular glaucoma or intraocular hemorrhage associated with the formation of pre-iridal fibrovascular membranes and peripheral anterior synechiae

■Although these cases might not find their way to the pathologist until complete retinal detachment and disinsertion leads to neovascular glaucoma, they are regularly presented to veterinary ophthalmologists. In recent years surgical re-attachment of the retina has become an option.

Oculo-skeletal dysplasia syndrome (Figs 3.18, 3.19)

There are seven cases of oculo-skeletal dysplasia in the COPLOW collection.

•Seen in Labrador retrievers and Samoyeds

•Autosomal dominant inheritance with incomplete penetrance has been postulated

■Heterozygous animals usually have mild retinal dysplasia

■Homozygous animals have skeletal changes and mild to severe retinal dysplasia

–There is a correlation between the phenotypic severity of the ocular and the skeletal manifestations of the disease. Animals with severely affected eyes generally have pronounced chondrodysplastic dwarfism

–Skeletal abnormalities affect the growth plate and result in shortened and hypoplastic chondrocyte columns

–Ocular changes

The least affected eyes have focal or multifocal retinal dysplasia and prominent vitreous strands

Mildly affected globes have focal retinal detachment and a combination of liquefied areas in the vitreous and thick vitreous strands attached to the inner retina

Severely affected globes have complete retinal detachment, with disinsertion and wrinkling of the peripheral retina inward towards the optic disc

–Decreased amounts of type II collagen in the vitreous of affected Labrador retrievers. Type II collagen is a component of the growth plate as well as normal vitreous

–The end-stage ocular disease occurs when the retinal detachment leads to pre-iridal fibrovascular membranes and subsequent neovascular glaucoma, and intraocular hemorrhage.

Congenital cataract (lens opacity) and other congenital abnormalities of the lens

Normal lens structure (Fig. 3.20) (see Ch. 10)

•Nucleus and cortex

•Lens capsule (anterior and posterior)

•Lens epithelium

•Lens fibers

•Anterior and posterior sutures.

Congenital lens abnormalities other than cataract

Aphakia

•Primary aphakia, no lens anlage developed

■This extremely rare abnormality occurs in combination with other anterior segment abnormalities (see anterior segment dysgenesis) and/or microphthalmos

•Secondary aphakia, early lens extrusion, resorption or destruction

■Early life trauma or inflammation

■Wrinkled remnants of lens capsule may be seen if the tissue is sectioned in the appropriate plane.

•Histologically there is thinning, or rupture, of the posterior capsule and a posterior bulging of the posterior polar lens cortex

•Often seen in combination with persistent hyaloid artery or PHPV/PHTVL.

Lens coloboma and microphakia (Fig. 3.21)

•These conditions may represent abnormalities of the zonular suspensory apparatus, rather than primary abnormalities in lens development

•Often associated with other congenital abnormalities such as uveal colobomata, retinal detachment, anterior segment dysgenesis and PHPV/PHTVL.

Posterior lenticonus and lentiglobus (Fig. 3.22)

•Posterior protrusion and increased curvature of the posterior pole of the lens

•Seen as a breed-related problem in Cavalier King Charles Spaniels but seen sporadically in many breeds of dog and in many species, and is often associated with cataract

•Clinically the cataract is in focus on the posterior pole of the lens, which has a globular appearance

Development of anterior lens features on the posterior pole

•This unusual phenomenon happens when other features, such as PHPV/PHTVL or dysplastic retinal tissue, make broad contact with the posterior pole of the lens, and the posterior lens differentiates like the anterior pole

•The lens epithelium wraps around to the posterior pole (posterior migration)

•The posterior capsule becomes thick

•The epithelium, displaced to the posterior pole, forms a second posterior nuclear bow.

Congenital cataract (Fig. 3.23)

•Congenital cataract should imply that the cataract is present at birth. However, animals are seldom evaluated at birth, therefore