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

Aspiration or injection sites (Fig. 4.13)

•Injection or aspiration sites are often sampled as part of the protocol in studies involving intraocular injection or aspiration

•Although properly performed injections or aspirations have a low rate of complications, no procedure is entirely ‘safe’. It is instructive to look at the local tissue reactions that occur at the site of such a common and, seemingly, innocuous procedure

•Lesions that may be seen at aspiration or injection sites include:

■Disruption of scleral collagen

■Phagocytosis of hypodermic needle lubricant, recognized as refractile, non-staining material

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■Glial and spindle cell proliferation within the vitreous

■Vitreous prolapse into the site (this is more likely with aspiration techniques)

■Epithelial down-growth.

Comparative Comments

Following the advent of microscopic surgery, iris incarceration or prolapse, suture problems, and wound dehiscence are extremely rare occurrences in human eyes submitted to the pathology laboratory.

TISSUE EFFECTS OF ELECTROCAUTERY,

CRYOSURGICAL AND LASER APPLICATIONS

The effects of electrocautery (Fig. 4.14)

•Used for surgical cutting and hemostasis

•Electrocautery creates a tissue artifact that the pathologist needs to be aware of when interpreting histopathological findings

■Electrocautery affects the tissue immediately in contact with the device, regardless of the tissue type

■These effects are seen at surgical margins where electrical energy was used for cutting or hemostasis

■Electrocautery imparts a coagulation effect on connective tissues, seemingly fusing the collagen and other protein structures

■The effect on epithelia is to cause cells to elongate into a distorted, spindle cell profile.

The effects of cryotherapy

•Used for focal ablation of ciliary body tissue in glaucoma; for retinopexy in the treatment or prevention of retinal detachment; treatment of mass lesions, including corneal, limbal and adnexal neoplasms, and in the management of distichiasis. Cryogens used in ophthalmic practice include liquid nitrogen, nitrous oxide and carbon dioxide. The advantages and disadvantages of different cryogens and cryosurgical instruments are important considerations in their selection for specific ophthalmic applications

•Cryotherapy affects a sphere of tissue within a radius extending from the application device

•The radius of the ice ball generated and the rate of freezing is diminished in highly vascular tissues because the flow of blood moderates the temperature of the tissues. Pigmentation does not significantly influence tissue cryobiology

•Freezing causes cell lysis, cellular dehydration and thermal shock with ischemic/and coagulation necrosis, with subsequent removal of the affected cellular components. Freezing has little effect on the qualitative nature of the connective tissues, such as the sclera. Eventually stromal elements and epithelium may ‘grow back’, but return of more complex tissue organization is incomplete

•The acute effects of cryotherapy are tissue edema and necrosis which stimulates a granulation tissue response

•The end effects are atrophy and disorganization of the affected tissues.

The effects of surgical laser (Figs 4.15, 4.16)

Diode lasers

•Penetrate deeply into the tissues until preferentially absorbed by pigmented tissue, when their energy is converted to heat

•May be delivered through the clear cornea without causing significant damage to the corneal endothelium

•Morphologic consequences of diode laser use:

■The effect occurs by thermal coagulation of tissues within a certain radius of where the heat energy is generated (usually pigmented tissue)

■Collagen is affected by a coagulation reaction much like electrocautery

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■Cellular tissues undergo coagulation necrosis followed by resorption

■With time, stromal tissue might reform, but complex elements of tissue reorganization do not occur. The end result is an atrophic scar

•Uses of diode lasers

■Cyclophotocoagulation for glaucoma (Fig. 4.15) transscleral or endoscopic delivery of laser energy is used to elicit focal ablation of ciliary body tissue

–The goal of cyclophotocoagulation is to destroy the aqueous-producing ciliary body epithelium

–The effects of cyclophotocoagulation are different in dogs with brown versus blue irides:

In heavily pigmented dogs, much of the energy is absorbed by, and destroys, the pigmented tissues of ciliary stroma just inside the sclera. This results in necrosis and ablation of pigmented stroma, inner sclera, ciliary nerves, blood vessels, and ciliary muscles, but not ciliary epithelium

In blue-eyed dogs, the light energy passes through the non-pigmented sclera and ciliary stroma and is absorbed directly by the pigmented ciliary epithelium,

creating a local ablation which is more focused on the target tissue

■Retinopexy (Fig. 4.16)

–Transpupillary or transscleral delivery typically used for this application in veterinary patients

–Lesions produced are inconsistent, due to variations in pigmentation of the ocular fundus in dogs, particularly in tapetal region

*

A B

Figure 4.16  Transscleral laser cyclophotocoagulation. (A) Photomicrograph showing transscleral laser cyclophotocoagulation in a dog with a pigmented ciliary body. The cauterized tissue is centered on the inner sclera adjacent to the first pigmented tissue in the lasered field (black arrows). (B) Photomicrograph showing transscleral cyclophotoablation in a blue-eyed dog. The cauterized tissue is around the pigmented epithelial cells. The laser energy is converted to heat by the melanin pigment of the ciliary epithelium (white arrows).

–By the transpupillary route, optimal energy delivery is characterized by outer retinal necrosis and RPE migration, with minimal gliosis or inflammation. Excessive energy settings may be associated with pan-retinal and choroidal necrosis, and with focal retinal detachment

–Transscleral delivery is associated with mild perivascular scleritis and scleral thinning, choroidal thinning and variable retinal degeneration with RPE migration

■Ablation of pigmented mass lesions

–Ablation of epibulbar and iris melanoma

–Rupture of pigmented uveal cysts

–Treatment of hypertrophic and cystic corpora nigra in horses

–The corneal endothelium may sustain localized damage as a result of thermal energy released by the treated pigmented masses.

CO2 laser

•Less commonly used in veterinary ophthalmology

•Does not penetrate tissues

Figure 4.15  Laser retinopexy. Gross photograph of a canine globe, taken immediately after surgery, showing laser retinopexy sites.

•Used to create a controlled surgical ablation of surface tissues, this application has been applied to the management of corneal squamous cell carcinoma and eyelid neoplasia in veterinary patients

•The characteristic morphologic change is a narrow line of coagulated collagen seen at the incision site.

Nd:YAG laser

•For cyclophotoablation in the management of canine glaucoma

■Cataract formation appears to be a more common complication following cyclophotoablation with Nd:YAG, than with diode laser

•For the ablation of pigmented mass lesions

•Used in the Q-switched mode, the Nd:YAG laser has a photodisruptive tissue effect that has been used for:

■Laser posterior capsulotomies in the treatment of lens capsular opacities following cataract surgery

■Iridotomies, synechiotomies and sclerostomies

■For the rupture of pigmented uveal cysts

■Treatment of cystic corpora nigra in horses.

Photodynamic therapy

Photodynamic therapy makes use of light energy combined with chemical photosensitive agents which amplify the tissue effect. If the photosensitive agent is administered intravascularly the light-induced effect will center on blood vessels potentially destroying the blood supply to a neoplasm. Since less light energy is used and the damage is more localized the morphologic affects are limited.

Comparative Comments

Few complications are encountered in humans as a result of electrocautery, cryoapplication, or surgical laser treatment.

Lens surgery

Surgery to remove the lens in cases of lens luxation:

There are 42 canine globes in the COPLOW collection that were enucleated following surgery to remove the lens.

•Relatively common complications are related to:

■Integrity of the surgical wound

–There are seven cases of corneal perforation

■Postoperative inflammation (uveitis or endophthalmitis)

–There are 22 cases of severe inflammation in the COPLOW collection

■Attenuation of the corneal endothelium, resulting in corneal edema, that may reflect pre-existing trauma by contact with

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Veterinary Ocular Pathology

an anteriorly luxated lens, or as a result of endothelial touch during intraocular surgery (as discussed above)

•Anterior prolapse of the destabilized, and often degenerate, vitreous may contribute to:

■Glaucoma

■Retinal detachment, related to vitreous traction.

Phacoemulsification or manual extracapsular extraction surgery for cataract (Figs 4.17, 4.18)

There are 117 cases of globes removed following cataract surgery in the COPLOW collection, 113 in dogs and four in cats.

•In cataract surgery patients, non-specific complications of intraocular surgery relate to:

■The integrity and healing of the surgical wound

■Inflammation (that may reflect exacerbation of pre-existing lens-induced uveitis, or endophthalmitis related to intraoperative contamination)

■Attenuation of the corneal endothelium (see above)

■The formation of intra-vitreal traction bands, leading to retinal detachment

■Formation of pre-iridal fibrovascular membranes and neo-vascular glaucoma (see above)

•Complications directly associated with metaplasia, proliferation, and migration of lens epithelial cells after phacoemulsification, or manual extracapsular, cataract surgery include:

A B

C D

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■Lens epithelial cell metaplasia

–The cell undergoes a transformation to a mesenchymal, spindle cell/myofibroblast-like morphology, with extracellular collagen deposition

–With time, the metaplastic cells ‘disappear’, and only the collagen remains

■Lens epithelial cell proliferation

–Proliferating cells remain attached to the lens capsule, but they can form pronounced nodules of spindle cells

■Lens epithelial cell migration after cataract surgery

–Residual lens epithelial cells remaining after cataract surgery can migrate to the posterior capsule, leading to posterior capsular opacification

This complication is less likely to occur if a prosthetic intraocular lens is inserted into the capsular bag, and is influenced by the material from which the prosthetic lens is manufactured, as well as the lens design

–Lens epithelial cells can also migrate outside the lens capsule

These cells continue to remain attached to tissue surface. They can cause pre-iridal membranes and, particularly when there is evidence of posterior lens capsule rupture, can incorporate the ciliary processes or extend across the anterior vitreous face. These lens epithelial cell membranes can contribute to traction bands leading to retinal detachment

–Lens epithelial migration and proliferation outside the capsular bag rarely happens in human globes but is seen

Figure 4.17  Elschnig’s pearls, capsular opacities. (A) Labrador Retriever cross, 5 years old: a large area of Elschnig’s

pearls can be seen. (B) German Shepherd Dog, 11 years old: Elschnig’s pearls are present at the arrows. Severe capsular opacities are also present. (C) Old English Sheepdog, 8 years old: anterior and posterior capsular opacities are present inferiorly. (D) Boston Terrier, 7 years old: the arrows point to the margins of the intraocular lens (IOL). Diffuse capsule opacities reduce the tapetal reflex.

in both dogs and cats after surgical or spontaneous trauma (see Ch. 5)

■Cataract ‘re-growth’ secondary to lens epithelial proliferation and lens fiber differentiation may occur (Elschnig’s pearls and Soemmerring’s ring cataract)

•There are only four cats in the COPLOW collection whose eyes were removed after cataract surgery, however, two of the four had feline post-traumatic ocular sarcoma, spindle cell variant (see Ch. 5).

Comparative Comments

Cataract surgery is the most commonly performed surgical procedure of any type in humans, and lens epithelial proliferation and migration are commonly encountered but rarely contribute to loss of the eye.

•The intent of the surgical procedure is to provide an alternate route for the drainage of aqueous from the anterior chamber. This is accomplished by placement of a device which consists of a narrow tube implanted into the anterior chamber, through which aqueous humor typically drains into a subconjunctival bleb, or reservoir, from which it is absorbed into the circulation. This sub-conjunctival reservoir is generally maintained by a variably shaped plate that

is anchored to the sclera. Alternate routes for aqueous drainage from anterior chamber implants include the frontal sinus

•Cyclo-destructive procedures such as transscleral or endoscopic laser cyclophotocoagulation or cyclocryotherapy (as discussed previously) may be combined with, precede, or follow drainage implant surgery, and will contribute to pathological findings in subsequently enucleated globes

Glaucoma drainage implant surgery (Fig. 4.19)

•Globes may be enucleated after drainage implant placement because of surgical or mechanical complications contributing to failure of the procedure

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Comparative Comments

Lens epithelial migration and proliferation outside the capsular bag rarely happens in human globes.

•Implant failure is often associated with the formation of fibrin or, ultimately, scar tissue, which obstructs the capillary effect of the anterior chamber tube, or results in obliteration of the filtering bleb

■A great deal of effort may be required on the part of the pathologist to obtain sections required to

determine the cause of implant failure, particularly if

the location of the device is not marked on the enucleated globe

•Other relatively common postoperative complications include inflammation, dehiscence of the implant or conjunctival incision, epithelial growth into the reservoir, cataract, and corneal endothelial attenuation.

Comparative Comments

Complications from glaucoma valve surgery in humans parallel those seen in animal eyes.

Intrascleral prostheses and evisceration surgery (Figs 4.20–4.22)

Evisceration with intrascleral prosthesis placement is a common surgical alternative to enucleation in the management of severe, untreatable ocular disease in veterinary patients. The most common indication for evisceration is intractable glaucoma in an irreversibly blind eye.

Advantages

Advantages of evisceration and intrascleral prosthesis over enucleation include:

•The superior cosmetic outcome

•Many owners express a psychological hostility to the removal of the eye and this procedure seems to offer what seems like a more acceptable compromise.

Disadvantages

Disadvantages of evisceration and intrascleral prosthesis over enucleation include:

•Complexity of surgical procedure relative to enucleation

■Usually done only by a specialist

■Additional expense

•Suboptimal specimen available for pathological evaluation

•Corneal health is a significant postoperative concern, affecting patient comfort, the ability of the corneoscleral shell to retain a prosthesis and the cosmetic outcome

•If the intrascleral prosthesis fails, a second surgical procedure is required, with the possibility of attendant complications that might adversely affect the health of the animal.

Reasons for corneoscleral shell failure, from the perspective of the COPLOW archive, are consistent with previously published reports (see references), and include:

•Dogs: 1448 evisceration specimens and 60 corneoscleral shell/ intrascleral prosthesis failures submitted (4.1%)

■38 of 60 cases: inflammatory disease, including severe inflammation within the corneoscleral shell, with or without epithelial down-growth (11 cases) (Fig. 4.21)

■22 of 60 cases: re-growth of neoplasm

–Of 1448 evisceration specimens, a diagnosis of neoplasia was made in 146 (10%) (Fig. 4.22)

–All but two of the 22 cases with intrascleral prosthesis failure related to recurrence of neoplasia involved malignant tumors

■13 of 60 cases: failure of the corneoscleral shell, including wound dehiscence, severe keratitis, corneal abscessation, and one case with a corneal stromal cyst

•Cats: 76 eviscerations and 11 corneoscleral shell/intrascleral prosthesis failures (14.5%)

■2 of 11 cases: inflammatory disease within the corneoscleral shell

■9 of 11 cases: re-growth of malignant neoplasia

–17 evisceration samples had tumors (22.4%).

Our experience highlights the importance of appropriate case selection for evisceration with intrascleral prosthesis placement:

•Evisceration does not represent a good option in cats

■The ratio of corneoscleral shell failures to evisceration samples in the COPLOW collection is 14.5%

■Of corneoscleral shell failures, 82% were due to the re-growth of malignant tumors, with life-threatening potential

•Evisceration with intrascleral prosthesis is a reasonable option in dogs with a history of a well-defined ocular disease like primary glaucoma with confirmed goniodysgenesis. The procedure may also be considered in dogs where a thorough ocular exam, in combination with other clinical diagnostic findings, can essentially rule out neoplasia or severe, active intraocular inflammation

•Evisceration with intrascleral prosthesis is not a good option in dogs with conditions precluding a thorough ocular exam and making it ostensibly impossible to clinically rule out neoplasia or significant, active intraocular inflammation

•Caution should be exercised when considering this procedure in dogs with suspected intraocular neoplasia, or with pre-existing corneal disease, or other disease that may compromise the integrity or healing of the corneoscleral shell.

Common lesions observed in corneoscleral shells submitted from animals that had intrascleral prostheses include:

•Stromal keratitis

■Most corneoscleral shells submitted had some degree of corneal vascular infiltrate

•Retrocorneal membrane

■The corneal endothelium was absent from almost every corneoscleral shell examined

■The endothelium is replaced by an avascular, lamellar, collagen rich, spindle cell membrane that is not only adjacent to the cornea, but lines the interior of the globe

■Remnant uveal tissue

–Most corneoscleral shells examined contained some remnant uveal tissue

–The remnant uveal tissue does not seem to have a major, adverse effect on postoperative outcome

–Perhaps surprisingly, these uveal tissue remnants do not undergo fibrosis.

Comparative Comments

The most serious complications following evisceration surgery in humans are the development of sympathetic ophthalmia, an entity limited to humans, and the return or extension of a previously unrecognized tumor. Otherwise, problems following intrascleral prostheses and evisceration are similar to those described for animal eyes.