CORNEAL AND CONJUNCTIVAL PARASITISM

Ocular Onchocerciasis

Ocular disease caused by Onchocerca cervicalis is the result of aberrant migration of noninfective microfilariae into the palpebral, conjunctival, and corneal tissues.483 The larvae do not appear to have a predilection for ocular tissues; rather, the eye is involved merely as part of a generalized subcutaneous migration. Approximately 50% of horses with cutaneous onchocerciasis will have ocular involvement.484

The pathogenesis of ocular onchocerciasis remains unclear. In humans, keratoconjunctivitis and uveitis associated with local presence of Onchocerca volvulus microfilariae occur only after the microfilariae die. Because Onchocerca microfilariae are typically found in equine ocular tissues without evidence of inflammation, a similar mechanism is probably involved. Therefore, some change in the parasite and/or in the host’s immune response likely occurs to incite an inflammatory response.

Ocular onchocerciasis occurs mostly in adult horses. The older the host, the greater is the exposure to the vector and the parasite, and presumably the greater the potential for ocular migration of microfilariae. Furthermore, increased immune sensitivity may occur with increased exposure to dead microfilariae.

Clinical Signs

Conjunctivitis and keratoconjunctivitis concentrated at the temporal limbus are the most common manifestations of ocular onchocerciasis. Acutely, chemosis and hyperemia of the conjunctiva occur, accompanied by increased lacrimation and blepharospasm. Small, raised, white nodules (0.5 to 2 mm in diameter) in the limbal conjunctiva and similar-sized punctate, subepithelial corneal opacities are often present. Corneal lesions are often wedged shaped, with the base of the triangle at the limbus, and are characterized by varying degrees of superficial and deep neovascularization and cellular stromal infiltrates. Untreated, the lesions progressively enlarge, although the rate of progression and the severity of the disease vary. With chronicity, patches of depigmentation (vitiligo) occur in the perilimbal bulbar conjunctiva. Recurrent episodes of keratoconjunctivitis are common.

Migration and subsequent death of microfilariae in the uveal tract result in uveal inflammation. Both the anterior and the posterior uveal tract may be involved. The clinical signs of Onchocerca uveitis include apparent photophobia, epiphora, miosis, aqueous flare, inflammatory cells in the anterior chamber, and globe hypotonicity. However, these signs are not specific for onchocerciasis, and other etiologies must be considered (see Table 39-2).

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Chorioretinitis reportedly is a common manifestation of posterior segment involvement. Active lesions are recognized ophthalmoscopically by hyporeflective areas, representing chorioretinal edema and inflammatory exudates, usually observed around the optic papilla in a “butterfly-shaped” pattern.485 However, aqueous and vitreous opacification often precludes accurate assessment of the fundus.

Diagnosis

Characteristic clinical signs are highly suggestive of Onchocerca keratoconjunctivitis, but definitive diagnosis requires corneal or conjunctival biopsy. Conjunctival biopsy may be collected after topical anesthesia, whereas general anesthesia is necessary for partial-thickness lamellar keratectomies to obtain corneal biopsies. A single, 3- to 5-mm biopsy is divided into two samples. One sample is placed on a slide with physiologic saline, minced, and warmed to 37° C (98.6° F) to stimulate larvae movement and therefore enhance their detection. Slides are examined repeatedly over the next hour for migrating microfilariae. The organisms are 200 to 240 mm long and 4 to 5 mm in diameter, with a short, unsheathed tail. The other half of the biopsy specimen is placed in 10% buffered neutral formalin for histopathologic examination.

The presence of microfilariae in ocular tissue does not substantiate a diagnosis of Onchocerca keratoconjunctivitis unless evidence of a host inflammatory response exists. The cytologic response is usually pleomorphic, with neutrophils, lymphocytes, plasma cells, and eosinophils present. Varying degrees of neovascularization, pigmentation, lamellar disorganization, collagen degeneration, and calcification are present in the cornea. The overlying epithelium becomes thickened and keratinized. The presence of eosinophils in corneal and conjunctival scrapings is suggestive of a parasite etiology; however, Onchocerca microfilariae are rarely found. Definitive diagnosis of Onchocerca as the cause of uveitis is rarely possible.

The differential diagnosis for equine keratoconjunctivitis also includes squamous cell carcinoma, habronemiasis, and mycotic infections. Because horses with ocular Onchocerca have a generalized larval migration, they may also have dermatitis, especially of the ventral thorax.

Treatment

In humans chronically infected with O. volvulus, systemic ivermectin therapy decreases ocular microfilaria burden and improves associated ocular disease. In horses, however, microfilaricide therapy has been associated with increased ocular inflammation. Therefore, treatment is directed at first controlling the inflammatory reaction and then eliminating the parasite.486,487 Corticosteroids are the mainstay of this initial antiinflammatory treatment and may be given topically, subconjunctivally, or systemically, depending on the severity of the inflammation, the extent of ocular and dermal involvement, and the temperament of the horse.

Because of superior solubility, prednisolone acetate* and dexamethasone alcohols† are the preferred topical corticosteroid preparations. Mild lesions without concurrent uveitis are treated four to six times daily. When keratoconjunctivitis is severe or when uveitis is present, hourly application may be indicated. Subconjunctival corticosteroids are also beneficial but must be used with caution if corneal ulceration exists or is possible. Therapy is tapered as the inflammation is controlled.

Systemic corticosteroids are indicated for severe uveitis, with concurrent Onchocerca dermatitis, and before larvicidal therapy. Prednisolone, at an initial dose of 0.5 to 1 mg/kg daily for 5 to 7 days, is tapered as the inflammation decreases. Refractory cases have been treated for extended periods with 0.25 mg/kg prednisone every other day.488 The antiprostaglandin activity of NSAIDs such as phenylbutazone and flunixin meglumine is also beneficial, especially when corneal ulceration prohibits the topical use of corticosteroids.

Elimination of the microfilariae is recommended once inflammation is controlled (see Chapter 40). The use of topical antibiotics is also recommended to prevent bacterial infection when corneal or conjunctival epithelial ulceration is present. With uveal involvement, topical mydriatic/cycloplegic agents such as atropine are indicated to relieve ciliary spasm and reduce the risk of posterior synechia formation.

Ocular Habronemiasis

Equine ocular habronemiasis occurs when larvae from Habronema muscae, Habronema microstoma, or Draschia megastoma are deposited on ocular tissues. Flies serving as intermediate hosts for Habronema are attracted to moist areas of the body, including the conjunctiva, for feeding; ocular discharge and periocular wounds provide additional sites. As the flies feed, Habronema larvae are deposited on the surface of ocular tissues, migrate into the tissues, and produce a local granulomatous inflammatory reaction. Equine habronemiasis occurs worldwide.

Clinical Signs

Ocular lesions typically consist of raised, proliferative, nonhealing wounds present at the medial canthus. The lesions are friable and pruritic and bleed easily. Lesions often contain small (1 to 2 mm), yellow, caseated nodules (“sulfur granules”). Fistulous tracts and subdermal nodules may develop below the medial canthus. Corneal neovascularization, edema, and ulceration can occur as a result of altered lid function and irritation to the cornea from contact with the rough, irregular surface of the lesion. Corneal involvement increases the degree of ocular pain and blepharospasm.

Habronemiasis lesions are typically seasonal, occurring in the warm summer months when the fly population increases. Certain horses appear to be predisposed to developing cutaneous and ocular habronemiasis, and recurrence may be seen in these animals each summer.

Diagnosis

Demonstration of the larvae in the granulomatous lesions or fistulous tracts is diagnostic. Biopsies of the affected tissue are directly examined for Habronema larvae and may also be submitted for histopathologic examination. Cytologic examination of conjunctival scrapings reveals a mixed inflammatory response, with neutrophils, eosinophils, and macrophages predominating; however, Habronema larvae are usually not seen. The differential considerations for these lesions include neoplasia (especially squamous cell carcinoma), sarcoids, phycomycosis, onchocerciasis, foreign body reaction, and exuberant granulation tissue.

Treatment

Until recently, routine treatment was topical, with systemic therapy reserved for severe or refractory cases. However, oral ivermectin (0.2 mg/kg) has become the treatment of choice. Lesions begin to regress in 7 days and are usually healed by 4 to 6 weeks after treatment. Other effective larvicides include trichlorfon, ronnel, and diethylcarbamazine (DEC).

Topical, intralesional, and systemic corticosteroids may be used to decrease the inflammatory response to the larvae, but with ivermectin larvicidal treatment, they may not be needed. Topical antibiotics are indicated and topical corticosteroids avoided if corneal ulceration is present. Debridement and drainage of granulomatous areas and fistulous tracts may increase topical drug penetration and prevent abscess formation. Fly control and prompt treatment of disorders causing ocular discharge or exposure of fresh tissue are important in prevention of habronemiasis.

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Ocular Thelaziasis

Thelazia nematodes in the conjunctival sac of large animals are considered commensal but can cause clinical ocular disease. Thelazia species have a worldwide distribution, with Thelazia lacrymalis found more often in horses and Thelazia gulosa, Thelazia rhodesii, and Thelazia skrjabini found more frequently in cattle. The infection rate for cattle and horses in the United States is estimated at 15% to 38%, with horses less than 3 years of age affected more often than adult horses. The complete life cycle of the parasite is unknown, but Muscae autumnalis (face fly) and other Muscae species serve as the intermediate hosts.

Clinical Signs

Most horses and ruminants infested with Thelazia show no clinical signs. However, chronic conjunctivitis, conjunctival cysts, and superficial keratitis can occur, especially in the summer months when flies are active. The disease is often mild but can progress to cause corneal neovascularization, edema, and ulceration. Dacryocystitis from parasite migration in the nasolacrimal system occurs and is more common in cattle than horses. Migration into the lacrimal gland and its ducts is seen and theoretically may lead to keratoconjunctivitis sicca.489

Diagnosis

Direct visualization of the adult Thelazia worms in the conjunctival sac or nasolacrimal flushings is diagnostic. The parasites are motile unless topical anesthetic is used. Adult Thelazia are 8 to 18 mm long and milky white, and their cuticle contains prominent transverse striations.

Treatment

In cattle, both ivermectin and doramectin given systemically at 200 mg/kg are effective in eliminating Thelazia.490,491 It is unclear if ivermectin therapy is effective in eliminating Thelazia in horses.491 Alternatively, the parasites may be removed manually with saline flushes or forceps after topical anesthetic is administered, followed by topical ophthalmic organophosphate therapy.492

Ocular Elaeophoriasis

Elaeophoriasis, or “sore head,” is a disease of sheep that is caused by the nematode Elaeophora schneideri. Adult Elaeophora organisms are found in the common carotid and internal maxillary arteries of deer, where microfilariae are produced and migrate into the capillaries of the face and head. Biting flies of the genera Hybomitra and Tabanus transmit the microfilariae to new hosts. The disease is most prevalent in the fall and winter in western parts of the United States where sheep are grazed at high altitudes. Elaeophora infections in deer are usually not associated with clinical signs. In small domestic ruminants and elk, however, the migrating microfilariae can cause a hypersensitivity reaction in facial and ocular capillaries.

Clinical Signs

Migration of Elaeophora microfilariae in ocular capillaries leads to local inflammation. Although the uveal tract is affected more often, sheep with elaeophoriasis may develop chronic keratoconjunctivitis evidenced by epiphora, blepharospasm, conjunctival hyperemia, chemosis, and corneal opacities. Clinical signs of anterior uveitis caused by Elaeophora are nonspecific and include epiphora, blepharospasm, miosis, clouding of the anterior chamber, and cataract formation. Funduscopic changes indicative of chorioretinitis and optic neuritis are common and include retinal edema, pigment changes in the tapetal and nontapetal fundus, optic disc edema, and optic disc atrophy.493

Diagnosis and Treatment

Diagnosis depends on demonstrating the microfilariae in skin or conjunctival biopsies. Treatment of heavily parasitized animals may cause death by occlusion of the carotid arteries with Elaeophora adults. Drugs used in treatment include piperazine (50 mg/kg orally), DEC (100 mg/kg), and stibophen (35 mL intravenously). The efficacy of ivermectin to treat Elaeophora is unknown, but it is poor against other filarides. Symptomatic treatment of keratitis and uveitis is indicated.

Ocular Manifestations of Nasal Bots

Larvae of the arthropod Oestrus ovis, the sheep botfly, can aberrantly migrate up the nasolacrimal duct and enter the conjunctival sac, causing local inflammation. Conjunctival migration is accompanied by epiphora, conjunctival hyperemia, and chemosis. Finding the larvae within the conjunctival sac is diagnostic. Treatment consists of mechanical removal and topical or systemic organophosphates. The nasal botfly Gedoelstia hassleri is reported to cause ocular lesions in horses in South Africa.

Ocular Manifestations of Trypanosomiasis and Piroplasmosis

Many species of the protozoal blood parasite Trypanosoma can infect horses and ruminants, causing edema, hyperemia, and petechiation of the conjunctiva. Sheep infected with Trypanosoma brucei can develop keratoconjunctivitis and panuveitis, including chorioretinitis and optic neuritis. Demonstration of the organism in blood smears is diagnostic.

Other blood protozoans, including Babesia and Theileria, can also cause conjunctival edema, petechiation, icterus, swollen eyelids, and blood-stained tears.

Uveal and Retinal Parasitism

Onchocerciasis, Elaeophoriasis, and Trypanosomiasis

Onchocerca cervicalis causes equine parasitic uveitis and chorioretinitis, and Elaeophora and Trypanosoma cause uveitis in sheep. Ocular manifestations of these diseases are discussed under Corneal and Conjunctival Parasitism.

Toxoplasma Iridocyclitis and Retinitis

The intracellular protozoan parasite Toxoplasma gondii can cause ocular disease in large animals. Invasion and replication in the retina and uveal tract lead to retinitis, chorioretinitis, and anterior uveitis. The acquired form of toxoplasmosis in ruminants, however, is often not associated with clinical signs, and ocular lesions are uncommon. Toxoplasmosis is rare in horses.

Clinical Signs

The most common ocular findings with ocular toxoplasmosis are iridocyclitis and retinitis.494 Retinitis is the primary posterior segment lesion, with secondary involvement of the chorioid. Retinal degeneration, clumping of pigment in the retinal pigment epithelium and chorioid, and optic disc avascularity are seen ophthalmoscopically; however, these lesions are not pathognomonic for toxoplasmosis. Orbital pain and swelling may result from parasitic invasion of extraocular muscles and orbital fat.

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Diagnosis and Treatment

MISCELLANEOUS INTRAOCULAR PARASITES

The most common intraocular parasite in horses is Setaria, with Setaria digitata found more frequently within the eyes of horses than Setaria equina. Ocular infestation is presumed to result from aberrant migration of the larval stage. Although Setaria causes minimal inflammation in the peritoneal cavity, it can cause serious intraocular inflammation. Diagnosis is by visualizing the parasite in the aqueous humor. Treatment involves symptomatic antiinflammatory therapy and surgical removal.

Other filarides found free within the anterior chamber of horses’ eyes include Dirofilaria immitis and Onchocerca cervicalis. Diagnosis and treatment are the same as for Setaria. Severe endophthalmitis resulting from intraocular infection with the free-living nematode Halicephalobus has been reported in a horse.495 The ocular disease was accompanied by a fatal encephalopathy. Diagnosis was based on finding the parasite during microscopic examination of intraocular tissues.

The canine cestodes, Echinococcus granulosa and Echinococcus multilocularis, may form intraocular hydatid cysts in horses and ruminants, thereby producing extensive inflammation and retinal detachment. There is no medical treatment, and surgical removal is often impossible. Diagnosis is made on histopathologic examination of affected tissues.

Coenurus cerebralis, the intermediate form of Taenia multiceps and Taenia serialis, can develop in the CNS of sheep, causing a disease known as “sturdy” or “gid.” Besides having abnormal gait, affected animals are often centrally blind. No treatment exists.

OCULAR NEOPLASIA

STEVEN M. ROBERTS

A wide variety of tumor types may involve the ocular or periocular tissues of food animals. Except for the most common neoplasms, limited information is available regarding treatment modalities, drug dosages, overall prognosis, and prevention or control. The tendency has been to adapt information and methods used in other areas of medicine for use in large animals. Table 39-3 lists potential presenting signs and corresponding ocular neoplastic conditions or related differential diagnoses for horses, cattle, sheep, and goats. Table 39-4 categorizes ocular neoplasms that have been reported in the literature for each of these species. The greatest amount of information pertains to the horse.

Table 39-3 Ocular Neoplasia and Differential Diagnoses by Species Based on Presenting Clinical Signs

image image image

Table 39-4 Ocular Neoplasms Reported in Large Animal Species

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Despite the variety of primary and secondary neoplasms affecting the ocular and periocular tissues, most tumors produce similar effects on the eye, with tissue distortion and loss of function being the initial concerns. Strategic therapy and management goals may vary from curative or palliative (e.g., eliminating discomfort by enucleation) for individuals to elimination of the problem (e.g., culling from the herd) for a population. Specific tumor treatment options are often similar for neoplasms involving a particular ocular region or location; when designing a management plan, however, the specific histologic tumor type is important in determining prognosis. Classification of a tumor as “benign” versus “malignant” or “localized” (e.g., equine sarcoid) versus “systemic” (e.g., lymphosarcoma) greatly influences treatment options and management approaches. The following discussion addresses the major tumors of concern in large animals and briefly surveys miscellaneous tumors that have been associated with ocular signs.

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OCULAR SQUAMOUS CELL CARCINOMA

Definition and Etiology

Bovine ocular squamous cell carcinoma (OSCC), also commonly called “cancer eye,” represents the most economically important neoplasm of large animals. It is the most common tumor affecting cattle in North America, and according to estimates from federally inspected abattoirs in the United States, 12.5% of all bovine carcass condemnations were caused by OSCC.496 The economic impact includes carcass condemnations, production losses, treatment expenditures, and management costs.

Ocular SCC arises from the epithelial surfaces of the conjunctiva (corneoscleral junction, nictitating membrane, and palpebra) or cornea. The etiology is probably multifactorial, with genetic, environmental, and viral factors being proved or suspected.496-498 In particular, increasing levels of solar irradiation and decreasing amounts of circumocular pigmentation are linked to an increased prevalence of OSCC.499,500

Equine OSCC is the most prevalent equine ocular neoplasm (followed by equine sarcoid) and typically occurs in horses with unpigmented eyelids.498,501 The amount of perilimbal and nictitating membrane pigmentation represents another important causal factor in cattle and horses that has received little attention but should be considered on prepurchase and health examinations (see Chapters 1 and 2).

Clinical Signs and Differential Diagnoses

The gross appearance depends not only on the anatomic tumor site (because this determines the overall interaction between epithelium and underlying connective tissue elements) but also the stage of malignancy. In general, premalignant squamous cell tumors are small, white, elevated, hyperplastic plaques or papilloma-like structures with verrucous surfaces (Fig. 39-29). In contrast, malignant tumors are more irregular, nodular, pink, erosive, and necrotic in nature (Fig. 39-30). Necrotic tumors often have a characteristic foul odor. Squamous cell carcinomas that invade the orbit may become massive and eventually aggressively invade bone. Often the gross appearance allows a diagnosis to be established, but at times, cytology or histology is necessary to differentiate among benign tumors, carcinoma in situ, and invasive SCC. Bovine OSCC typically involves (in decreasing order of frequency) the lateral limbus, eyelid margins (especially the lower), nictitating membrane, and medial canthal regions.496,497 Similar tissues are involved in horses, although some reports suggest that the nictitating membrane is more frequently involved than the corneoscleral junction.498,502 Clinical signs resulting from metastatic lesions are not common, although lymphatic tissues may become infiltrated with neoplastic cells.

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Fig 39-29 Bovine ocular squamous cell carcinoma (OSCC). Note the small, premalignant, hyperplastic plaque involving the medial limbus and the large, malignant, nodular mass on the lower eyelid. The large mass is becoming ulcerated and necrotic.

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Fig 39-30 Bovine OSCC involving the cornea and conjunctiva. Note the irregular and invasive growth into the cornea. The surface is rough and necrotic.

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Despite the characteristic appearance of lesions, differential considerations (especially in the horse) include adenocarcinoma, adenoma, angiosarcoma, basal cell tumor, conjunctival follicular hyperplasia, dermoid, fibroma, fibrosarcoma, granulation tissue, habronemic blepharoconjunctivitis, lymphosarcoma, mastocytoma, plasma cell tumors, sarcoid, and schwannoma (see Tables 39-3 and 39-4).

Pathophysiology

The tumor in all species develops through a series of premalignant stages (i.e., hyperplastic plaques or epidermal plaques and papillomas) to progress over months and years to a carcinoma in situ and finally an invasive squamous cell carcinoma. Neoplastic lesions may arise without notable precursor stages. It is unlikely that tumors arise in the cornea unless previous vascularization has occurred.503 Spontaneous regression of 30% to 50% of bovine precancerous lesions may occur,496 and in rare cases, early OSCC may regress spontaneously. Tumors arising at the limbus are confounded by the dense and poorly vascularized sclera and cornea, thus hindering metastasis to extraocular sites. Nictitating membrane tumors extend to the base of the membrane and cartilage more rapidly, with spread into the orbit and surrounding bones occurring much sooner than with tumors involving the globe. Although metastasis will eventually occur, extensive extraocular spread is limited in cattle by the practice of sending most affected animals to slaughter. Horses demonstrate multiple tumor locations and local invasion in up to 50% of cases.502,503 Metastasis beyond extraocular sites is rare in horses.

Epidemiology

Although OSCC has been reported in a wide variety of cattle breeds, the Hereford breed (either purebred or crossbred) is most often diagnosed with this tumor as a result of the common use of this breed as a range animal and the strong genetic trait for a white face. Thus, selective breeding for partially to fully pigmented periocular skin greatly reduces the occurrence of this tumor.496 The tumor is more common in older cattle, with the peak age prevalence being 7 to 8 years. Exposure to increasing levels of actinic radiation raises the prevalence of bovine OSCC.499 The prevalence of ocular squamous cell tumors, including nonmalignant tumors, involving Hereford herds in regions with abundant sunlight can range from 20% to 40%. Research performed in cattle herds suggests that a high plane of nutrition or a lower-than-normal body weight in cows for the first 2 years acts to increase the prevalence.496 The intriguing possibility that bovine OSCC may be induced by viruses (e.g., papillomavirus) warrants further research.

Equine OSCC in North America demonstrates an increased prevalence with increasing longitude (°W), altitude, and mean solar irradiation.501 Breeds with a greater risk of developing OSCC include draft breeds, especially the Belgian (odds ratio [OR] = 21.7), Appaloosa (OR = 7.9), paint and pinto (OR = 4.5), and grade horses (OR = 3.1). Coat colors showing an increased risk include white (OR = 26.7), creamello/palomino (OR = 13.7), gray (OR = 6.7), red/white and strawberry/white (OR = 4.7), buckskin (OR = 4.4), and chestnut/sorrel (OR = 3.8).501

Necropsy Findings

Depending on the extent of involvement, gross changes are noted that involve the globe, conjunctiva and nictitating membrane, orbit, bones of the orbit, and regional cervical lymph nodes. In rare instances, metastasis to thoracic and abdominal organs can occur.

Treatment and Prognosis

Numerous modalities are available, and applications depend on availability of instrumentation, location and extent of the tumor, and value and intended function of the animal. Choices include radiofrequency hyperthermia,* cryonecrosis, intralesional injection of biologic response modifiers (BRMs; e.g., allogeneic OSCC extract, mycobacterial cell wall fraction,† Propionibacterium acnes‡), intralesional chemotherapy with cisplatin§ (with or without initial debulking),504,505 radiotherapy (cesium-137, cobalt-60, gold-198, iridium, strontium-90), and surgical removal (local excision, enucleation, and exenteration with or without salivary gland and lymph node resection). Intralesional use of cisplatin (1 mg/cm3 of tumor volume) is highly effective, but multiple injections are necessary (four times at 2- to 3-week intervals). Handling of the drug and animal after treatment must adhere to U.S. Occupational Safety and Health Administration (OSHA) guidelines,506 and animals must not be used for food consumption. Appropriate precaution should be followed with extralabel use of cytotoxic drugs. Surgical debulking with adjunctive cryonecrosis or radiofrequency hyperthermia is an effective and affordable treatment modality. Cryonecrosis is achieved with liquid nitrogen, using a probe or spray delivery system to freeze the tissues to −30° C (−22° F) twice, with complete thawing between freeze cycles. Radiofrequency hyperthermia is performed with piercing or surface probes to heat the tissues to 50° C (122° F) for 30 seconds. Multiple treatment sites are necessary for lesions larger than 0.5 cm in diameter.

Because recurrence rates range between 30.4% and 42.4%,498,502 the willingness of the owner to return the animal for follow-up treatment is a significant determinant in overall survival. Financial constraints were the most common reason for cessation of treatment. Many horses that die as a consequence of OSCC are euthanized at the owner’s request. The overall prognosis is determined by the degree of neoplastic involvement of normal tissue, but a guarded prognosis is warranted. If treatment is to be undertaken, intervention should begin at the earliest stages of tumor development. In animals destined for slaughter, the guidelines for condemnation of bovine carcasses affected with OSCC shown in part A of Box 39-2 should be considered.

Box 39-2 Guidelines for Inspection (Antemortem and Carcass) and Disposal of Animals, Carcasses, and Parts Affected with Neoplasia

From Code of Federal Regulations, Title 9, Chapter 3, Parts 309.6, 311.11, and 311.12 (1-1-87 edition).

A Epithelioma of the eye
1 Any animal found on antemortem inspection to be affected and the eye has been destroyed or obscured by neoplastic tissue and which shows extensive infection, suppuration, and necrosis, usually accompanied by foul odor, or any affected animal with cachexia, regardless of extent, shall be condemned.
2 Carcasses of animals with the eye or orbital region affected will be condemned if the affection has:
a Involved the osseous structures of the head with extensive infection, suppuration, and necrosis;
b Metastasized from the eye or orbital region to any lymph node (including the parotid lymph node), internal organs, muscles, skeleton, or other structure, regardless of the extent of the primary tumor; or
c Regardless of extent is associated with cachexia or evidence of absorption or secondary changes.
3 Carcasses of animals affected to a lesser degree than above may be passed for human food after removal and condemnation of the head, including the tongue, provided the carcass is otherwise normal.
B Neoplasms
1 An individual organ or other part of a carcass affected with a neoplasm shall be condemned. If there is evidence of metastasis or that the general condition of the animal has been adversely affected by the size, position, or nature of the neoplasm, the entire carcass shall be condemned.
2 Carcasses affected with malignant lymphoma shall be condemned.

Prevention and Control

In cattle, factors such as genetics, UV light, and environmental factors (e.g., wind, dust) are known to be involved in OSCC. Ocular viral infection may also be contributory. If possible, affected animals should be culled as soon as possible because most production situations preclude environmental factor modification. Specific preventive measures have not been systematically evaluated in horses, but recommendations include reducing UV light exposure, using protective fly masks in horses (to decrease solar irradiation and environmental irritants), tattooing lightly pigmented periocular skin, and avoiding breeds thought to have an increased risk of tumor development.

OCULAR MANIFESTATIONS OF LYMPHOSARCOMA

Definition and Etiology

Lymphosarcoma is a fatal systemic neoplastic disease of the lymphoreticular tissue. The adult or enzootic form of bovine lymphosarcoma is likely the most devastating and common neoplasm of dairy cattle. This is a systemic disease with ocular manifestations rather than a pure ophthalmic problem. (See Chapter 37 for specific information regarding bovine lymphosarcoma and the bovine leukemia virus.) Lymphosarcoma represents the most common cause of orbital neoplasia in cattle,507 excluding OSCC that involves the orbit by local extension. Lymphosarcoma may affect horses508 and goats. The etiology in horses and goats is unknown.

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Clinical Signs and Differential Diagnoses

Clinical signs are usually associated with exophthalmos caused by orbital disease. Neoplastic lymphoid cell infiltration behind the globe results in exophthalmos, subsequent exposure keratitis, and eventual proptosis507 (Fig. 39-31). One report has documented intraocular lymphosarcoma in a Holstein cow as the presenting sign of generalized lymphosarcoma.509 Subtle exophthalmos is often overlooked because of the natural exophthalmic state of some dairy breeds. Typically, these animals present with a history that suggests an acute onset of exophthalmos, when actually orbital involvement has been present for a time. Clinical signs associated with the exophthalmos and exposure keratitis include corneal edema, vascularization, ulceration, epidermalization, conjunctival hemorrhage, chemosis, and ocular discharge. These signs may develop, progress, and change quickly once corneal protection is compromised. Other physical examination findings are discussed in Chapter 37. Differential considerations for exophthalmos include orbital cellu-litis, trauma, retrobulbar hemorrhage, retrobulbar soft tissue masses, chronic sinusitis, and sinus neoplasia (see Tables 39-3 and 39-4).

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Fig 39-31 Orbital lymphosarcoma. Diffuse orbital involvement causing exophthalmos and secondary exposure keratitis of the right eye.

Clinical Pathology

Definitive diagnosis is achieved by cytologic samples obtained with a spatula after topical anesthesia496 or specimens excised for biopsy and fixed in formalin. Benign lesions typically contain superficial, anucleated, keratinized squamous cells and deeper epithelial cells with enlarged nuclei and coarse chromatin clumping. Biopsies of these lesions show that the basal layer or basement membrane has not been invaded. Malignant OSCC lesions are composed of pleomorphic cells with bizarre shapes, large hyperchromatic nuclei containing large clumps of chromatin, and prominent nucleoli. On biopsy examination, invasion across the basement membrane is noted, and keratin-pearl formation or marked anaplasia is usually present.503 In the event of regional lymphatic involvement, fine-needle aspiration or preferably a biopsy may demonstrate neoplastic infiltration.

Equine lymphosarcoma involving the eye also represents a systemic disease with ocular manifestations. Other systemic manifestations are discussed in Chapter 37. Ocular lesions include uveitis, nictitating membrane masses, chemosis and conjunctivitis, and neoplastic infiltration of the eyelids and orbit.509 Differential considerations should include any chronic inflammatory disease, equine infectious anemia, equine piroplasmosis, and infectious causes of uveitis (see Table 39-2).

Necropsy Findings

As with the clinical signs, necropsy findings are variable. In cattle, orbital involvement is common, with lymphoid tumors being firmly attached to the periorbita and walls of the orbit. Extraocular muscles are frequently infiltrated with tumor cells. The globe itself is typically not involved.503 Ocular lesions occur less often in horses than in cattle. In the horse the globe (uveal tract) can be involved, in addition to extraocular tissues. As with other systemic neoplastic diseases, multiple organ involvement is expected with lymphosarcoma.

Treatment and Prognosis

This systemic disease may be treated palliatively or systemically in an attempt to achieve remission for a time. Enucleation provides palliative treatment, and chemotherapy with corticosteroids, vincristine, and L-asparaginase may induce remission. Extralabel use of these cytotoxic drugs must be approached with extreme caution, and treated animals must not be used for food consumption. Most cattle with orbital lymphosarcoma either die or are euthanized in terminal stages of disease within 6 months of the original diagnosis.507 Horses can have a much more protracted disease course, with many presenting because of chronic illness of up to 12 months’ duration.508 The overall prognosis is unfavorable, regardless of the species involved.

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Prevention and Control

Control of bovine lymphosarcoma depends on efforts to eradicate bovine leukemia virus, a monumental task in most cases. In other large animal species, prevention and control recommendations for lymphosarcoma are not possible until the etiology can be identified. If animals are destined for slaughter, the guidelines for condemnation of bovine carcasses affected with lymphosarcoma as shown in part B of Box 39-2 should be followed.

OCULAR MANIFESTATIONS OF EQUINE SARCOID

Definition and Etiology

Equine sarcoid is a locally aggressive, nonmalignant, fibroblastic tumor of the equine skin (see Chapter 40). It appears to be the most common equine neoplasm, with 14.7% of ocular and adnexal tumors in the horse being sarcoids (all involved the eyelids).510 This neoplasm develops more frequently in sites predisposed to trauma and areas that come into contact with existing sarcoids, and it does not metastasize to internal organs.

Clinical Signs and Differential Diagnoses

Sarcoids involving the eyelids are classified according to the scheme used for cutaneous lesions: verrucous, fibroblastic, mixed, or occult. Tumors of the eyelids may appear smooth and nodular, crusted and nodular, ulcerated, or pedunculated (Figs. 39-32 and 39-33). Regardless of their appearance, the tumors are nonregressing. Periocular sarcoids are subject to trauma; thus the verrucous type frequently transforms into the fibroblastic type with surface ulceration. It is difficult to differentiate sarcoid from fibroma, fibrosarcoma, neurofibroma, neurofibrosarcoma, schwannoma, or nonneoplastic granulation tissue (see Tables 39-3 and 39-4).

image

Fig 39-32 Equine sarcoid. The upper eyelid exhibits a smooth, nodular mass typical of many periocular sarcoids.

image

Fig 39-33 Equine sarcoid involving the medial aspect of eyelid. At examination or during treatment, sarcoids may become ulcerated. This tumor became ulcerated after one injection of a Mycobacterium cell wall preparation but subsequently resolved.

Treatment and Prognosis

Problematic lesions can be treated by a variety of modalities, none of which is uniformly successful. Often, multiple treatment sessions are required for tumor control. Treatment modalities include surgical excision (50% success rate), cryonecrosis (30% success rate), radiofrequency hyperthermia (RDM Hypertherm), intralesional injection of BRMs (bacille Calmette-Guérin),510 chemotherapy with intralesional cisplatin (Platinol; with or without initial debulking),503,504 radiation therapy (cesium-137, cobalt-60, gold-198, iridium, strontium-90), and chemotherapy (5-fluorouracil) combined with surgical excision. BRM therapy has not proved as successful for sarcoids located at other body sites. An available commercial Mycobacterium product (Normagen) can be used, but it does not demonstrate the clinical efficacy seen with previously used research preparations. If the sarcoid is static, flat, and hairless, it may be best left alone because any trauma, surgical or otherwise, could increase the growth rate and invasiveness of the lesion. Response to therapy varies on the basis of tumor location, duration, severity, and previous therapeutic measures.

Treatment of periocular sarcoid with BRMs shows particular promise but has the disadvantage of requiring a potentially long course of treatment, involving a series of intralesional injections. Intratumoral use of cisplatin is highly effective (see Chapter 40). Successful treatment measures exist for equine sarcoid, and if a complete treatment protocol is followed, the prognosis is favorable. As with any neoplastic disease, at the first evidence of recurrence, the animal should be reevaluated.

MISCELLANEOUS TUMORS WITH OCULAR INVOLVEMENT

The tumors previously discussed represent the most significant ocular or periocular neoplasms of large animals. However, to the individual animal or owner, any tumor type represents a significant problem. Thus, clinicians must remember that numerous primary and secondary neoplastic processes can involve the eye and surrounding tissues. Secondary tumors may be either metastatic masses or locally invasive masses extending from sites near the eye. The greatest variety of ocular neoplastic disease has been reported in the horse (see Table 39-4).

Adnexal tumors that have been reported include adenoma, adenocarcinoma, basal cell carcinoma, fibroma, fibrosarcoma, hemangioma,511 hemangiosarcoma,512 lymphosarcoma, melanocytoma, melanoma, papilloma, plasma cell tumors, and schwannoma. Few reports address treatment of these tumors thoroughly.

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Surgical excision of small lesions, cryosurgery, radiation therapy, intralesional cisplatin,504,505 and medical treatment with cimetidine513,514 have been used successfully on select tumors. Oral cimetidine (2.5 mg/kg three times daily for an initial 3-month period) is useful as a means of melanoma control. If lesions are progressively enlarging, cimetidine has been particularly successful in arresting or resolving tumor lesions. This treatment is also a useful adjunct to cryonecrosis, surgical excision, or chemotherapy. The prognosis is poor for malignant masses because metastatic disease or local recurrence usually results. This is especially true with angiosarcomas502 that involve primarily the conjunctiva but may also involve the corneoscleral junction. Limited success with angiosarcoma treatment has been achieved in a case of equine orbital lymphangiosarcoma through enucleation and chemotherapy with intravenous vincristine (four doses of 1.3, 1.3, 1.2, and 1 mg/m2 of body surface area on days 0, 7, 14, and 51, respectively) and prednisone. Seven years after treatment, the horse showed no signs of recurrence. An additional case of conjunctival and nictitating membrane malignant hemangiosarcoma was treated by local excision and perioperative intratumoral cisplatin. Follow-up demonstrated tumor lysis and no recurrence after 6 months.

Any tumor involving the nasal and paranasal cavities has the potential to involve the ocular structures as the result of orbital spread. Enzootic adenocarcinoma in sheep is an example of this type of process. Although infrequently noted, exophthalmos secondary to orbital invasion of this tumor has been reported.515 Primary orbital neoplasia in the form of a multilobular osteoma (chondroma rodens) has been reported in the horse516 and reminds one that a space-occupying mass (neoplasia) can affect the eye by causing progressive exophthalmos.

Neoplasia involving the CNS, diencephalon, or occipital cortex can result in a central blindness, abolished pupillary light responses, and mydriasis. Other forms of intracranial neoplasia can secondarily involve the eye as a result of cranial nerve dysfunction. For example, an intracranial schwannoma caused exposure ulcerative keratitis in a cow that presented with left facial paresis.517

Reports of neoplasia involving the globe, all in horses, describe the clinical, histologic, and treatment aspects of epibulbar melanocytoma,518 intraocular melanoma,519,520 and medulloepithelioma.521 Optic nerve tumors have included neuroepithelial tumors and meningiomas. In the intraocular cases the globe was rendered nonfunctional by the neoplastic process, and the involved eye was subsequently enucleated. An optic nerve neuroepithelial tumor displayed metastatic spread as a result of extension into the brain through the optic foramen, causing brain compression.522 Although documented cases of these miscellaneous ocular neoplasms are not widespread, they must be taken into consideration as possible causes of large animal ocular neoplasia.

Other than vascular tumors, most ocular tumors do not display a severe metastatic threat. Although enucleation may be curative, histologic evaluation of excised tissues and long-term patient follow-up are necessary if accurate epidemiologic and prognostic data are to be available. Once an accurate diagnosis has been made, the clinician and owner must determine, in light of all available medical information and the proposed use of the animal, whether treatment should be curative or palliative or whether elimination of the problem from the herd should be of greater concern than care of the individual animal.

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* Vicryl, Ethicon, Somerville, NJ.

* Port-A-Cul, Becton Dickinson, Sparks MD.

* Natacyn, Alcon Laboratories, Fort Worth, TX.

† Diflucan, Pfizer, Exton, PA.

* Voltaren, Novartis, East Hanover, NJ.

* Activase, Genentech, South San Francisco, CA.

* Roxane Laboratories, Columbus, OH.

* Viroptic, Burroughs-Wellcome, Research Triangle Park, NC.

* Bausch & Lomb, Tampa, FL.

† Banamine, Schering-Plough, Kenilworth, NJ.

* 1% suspension, Falcon Ophthalmics, Fort Worth, TX.

† 0.1% solution/0.05% ointment, Alcon Laboratories, Fort Worth, TX.

‡ Kenalog, Westwood-Squibb Pharmaceuticals, Buffalo, NY.

§ Depo-Medrol, Upjohn, Kalamazoo, MI.

* Butazolidin, Cooper’s Animal Health, Kansas City, MO.

† Bausch & Lomb Pharmaceuticals, Tampa, FL.

‡ Falcon Ophthalmics, Fort Worth, TX.

* Pred-Forte, Allergan Pharmaceuticals, Irvine, CA.

† Maxitrol, Alcon Laboratories, Fort Worth, TX.

* RDM Hypertherm, RDM International, Phoenix, AZ.

† Normagen, Fort Dodge Laboratories, Fort Dodge, IA.

‡ ImmunoRegulin, ImmunoVet, Tampa, FL.

§ Platinol, Bristol-Meyers, Wallingford, CT.