Ocular Parasites

Anne J. Gemensky-Metzler

Parasites are an often overlooked cause of ocular disease in large animals. Ocular parasitic diseases can threaten vision and reduce the economic value of the animal through decreased function, decreased production, or both.

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.¹ The larvae do not appear to have a predilection for ocular tissues; rather, the eye is involved as part of a generalized subcutaneous migration. Prevalence of onchocerciasis appears to vary with region of the world. One study concluded that 50% of horses with cutaneous onchocerciasis will have ocular involvement,² whereas in another study roughly 50% of horses evaluated had dermal microfilariae, and of those 40% had ocular abnormalities consistent with onchocerciasis.³

The pathogenesis of ocular onchocerciasis in horses remains unclear, but an immune-mediated inflammatory response to microfilariae has been implicated. In humans, keratoconjunc­tivitis and uveitis associated with local presence of Onchocerca volvulus microfilariae occur only after the microfilariae die. The endosymbiont Wolbachia pipientis bacteria are released, inducing an intense host immune response with subsequent dermal pruritus, uveitis, and often blindness.^4,5 Studies of the immunopathogenesis of O.

Ocular onchocerciasis occurs mostly in adult horses.⁷ The older the host, the greater 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 similar­sized punctate, subepithelial corneal opacities are often present. Corneal lesions are often wedge 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.¹

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).

Chorioretinitis reportedly is a manifestation of posterior segment involvement. Active lesions are recognized ophthal- moscopically by hyporeflective areas representing chorioretinal edema and inflammatory exudates, usually observed around the optic disk in a “butterfly-shaped” pattern.^1,3 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 typically 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.^8,9 The presence of eosinophils in corneal and conjunctival scrapings is suggestive of a parasite etiology, but 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 bacterial or fungal corneal stromal abscesses. 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. Recently, concurrent treatment with doxycycline has been found to improve efficacy of ivermectin therapy by sterilizing adult female worms through elimination of the symbiotic Wolbachia bacteria.¹⁰ Furthermore, by eliminating the Wolbachia, the subsequent dermal and ocular inflammatory response when microfilariae die is reduced.^6,11

In horses, microfilaricide therapy has also been associated with increased ocular inflammation. Therefore treatment is directed at first controlling the inflammatory reaction with systemic antiinflammatory medications and then eliminating the parasite.¹² Corticosteroids have been the mainstay of this initial antiinflammatory treatment and may be given topically, subconjunctivally, or systemically, depending on the severity of the inflammation, extent of ocular and dermal involvement, and temperament of the horse. Like ivermectin, moxidectin has been found to be 100% effective in treatment of Onchocerca spp. microfilaria-associated dermatitis in horses, but without inducing the dermal edema seen after treatment with ivermec- tin.^13,14 Systemic NSAIDs or corticosteroids are indicated to treat and/or prevent severe uveitis with concurrent Onchocerca dermatitis and before larvicidal therapy. The antiprostaglandin activity of NSAIDs like phenylbutazone (2.2 to 4.4 mg/kg PO q12-24h) and flunixin meglumine (0.5 to 1.1 mg/kg PO, IM, or IV q12-24h) is beneficial, especially when corneal ulceration prohibits topical use of corticosteroids.

When keratoconjunctivitis or uveitis is severe and/or refrac­tory to systemic antiinflammatory treatment, topical application of corticosteroids may be indicated. However, since the corneal infiltrates associated with onchocerciasis are clinically indis­tinguishable from infectious organisms, extreme caution should be exercised when prescribing or administering topical or subconjunctival corticosteroids in horses. Because of superior solubility, 1% prednisolone acetate and 0.1% dexamethasone sodium phosphate are the preferred topical corticosteroid preparations. Depending on severity, lesions may be treated two to four times daily. Subconjunctival corticosteroids are also beneficial but must be used with caution if corneal ulceration exists. Therapy is tapered as the inflammation is controlled.

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

Because systemic ivermectin or moxidectin therapy is not effective in killing adult worms, routine deworming is recom­mended to eliminate microfilariae and prevent maturation to adult worms.¹⁵ Adult worms may survive in the nuchal ligament of horses for extended periods of time.⁷

Ocular Habronemiasis

Equine ocular habronemiasis occurs when larvae from Hab- ronema 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 for feeding.

■ Clinical Signs Ocular lesions typically consist of raised, proliferative, nonhealing wounds present at the medial canthus or, less commonly, at other periocular sites. 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.¹⁶ 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 squamous cell carcinoma, sarcoids, phycomycosis, onchocerciasis, foreign body reaction, eosinophilic granuloma, and exuberant granulation tissue. Identification by PCR of Habronema DNA in the excised tissue may support a diagnosis of habronemiasis.¹⁷

■ Treatment Until recently, routine treatment was topical, with systemic therapy reserved for severe or refractory cases. However, oral ivermectin (0.2 mg/kg) and moxidectin (0.4 mg/ kg) kill both adults and larvae in the stomach and have become the treatment of choice. Lesions begin to regress in 7 days and are usually healed by 1 to 5 weeks after treatment if reinfestation is prevented.^18,19 Other effective larvicides include trichlorfon and diethylcarbamazine (DEC).

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

Ocular Thelaziasis

Thelazia spp. nematodes in the conjunctival sac of large animals are considered commensal but can cause clinical ocular disease. Thelazia spp. have a worldwide distribution, with Thelazia Iacrymalis found more often in horses and Thelazia gulosa, Thelazia rhodesii, and Thelazia skrjabini found more frequently in cattle.²⁰ The infection rate for cattle and horses in the United States is estimated at 15% to 38%, with horses younger than 3 years of age affected more often than adult horses.^21-24 The complete life cycle of the parasite is unknown, but Musca autumnalis (face fly) and other Musca species serve as the intermediate host or vector.²⁵

■ Clinical Signs Most horses and ruminants infested with Thelazia show no clinical signs. However, chronic conjunctivitis, follicular conjunctivitis, conjunctival cysts, and superficial keratitis can occur, especially in the summer months when flies are active.²⁶ The disease is often mild but can progress to cause corneal neovascularization, edema, and ulceration. Dacryocystitis due to 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

24 27 theoretically may lead to keratoconjunctivitis sicca.²⁴,

■ Diagnosis Direct visualization of the adult Thelazia worms in the conjunctival sac or flushing the nasolacrimal system is diagnostic. The parasites are motile unless a topical neuro­muscular blocking agent 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 0.2 mg/kg are effective in eliminating Thelazia.^28-30 It is unclear whether ivermectin therapy is effective in eliminating Thelazia in horses, and efficacy of newer drugs such as doramectin or moxidectin has not been reported.²⁸ Alternatively, the parasites may be removed manually with saline flushes or forceps after topical anesthetic is administered, followed by topical ophthalmic organophosphate therapy.³⁰

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, bighorn sheep, and elk, however, the migrating microfilariae can cause a hypersensitivity reaction in facial and ocular capillaries.^31,32

■ 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. Ophthalmoscopic changes indicative of chorioretinitis and optic neuritis are common and include retinal edema, pigment changes in the tapetal and nontapetal fundus, optic disk edema, and optic disk atrophy.³¹

■ 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 (100 to 300 mg/kg PO), diethyl­carbamazine (100 mg/kg PO), and stibophen (5 to 10 mg/kg IM for 3 to 10 days). The efficacy of ivermectin to treat Elaeophora is unknown. 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 ivermectin, moxidectin, or eprinomectin.^33-35 Visible larvae may be mechanically removed. The nasal botfly Gedoelstia hassleri is reported to cause conjunctival and corneal 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 fever, anemia, weight loss, edema of the ventral abdomen and limbs, sudden death, and ocular signs such as conjunctival edema, hyperemia, and petechiation.³⁶ Sheep and goats experimentally infected with Trypanosoma brucei can develop keratoconjunctivitis and panu­veitis, including chorioretinitis and optic neuritis.^37,38 Dem­onstration of the organism in blood smears is diagnostic. Quinapyramine sulfate and chloride has been effective in treating many horses, but persistent or recurrent infections have raised concern about possible drug resistance.^36,39

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 ovis and Trypanosoma brucei cause uveitis in sheep. Ocular manifestations of these diseases are discussed in the Corneal and Conjunctival Parasitism section earlier.

Toxoplasma Iridocyclitis and Retinitis

Although seropositivity for Toxoplasma gondii is common in horses and donkeys in some countries, associated clinical disease is uncommon and has not been reported in cattle or horses. However, the intracellular protozoan parasite Toxoplasma gondii can cause ocular disease in small ruminants. Invasion and replication in the retina and uveal tract lead to retinitis, chorioretinitis, and anterior uveitis.

■ Clinical Signs The most common ocular findings with ocular toxoplasmosis are iridocyclitis and retinitis.^40,41 Retinitis is the primary posterior segment lesion, with secondary involve­ment of the choroid. Retinal degeneration, clumping of pigment in the retinal pigment epithelium and choroid, and optic disk 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.

■ Diagnosis and Treatment Toxoplasmosis is most commonly diagnosed by one of a variety of serologic tests for IgG and IgM antibodies or by histopathologic identification through biopsy or necropsy. Antibodies for IgG take more time to develop and may persist for years after an active infection has resolved while IgM antibodies rise and disappear sooner after recovery. Thus, titers for both IgG and IgM should be evaluated and a paired sample taken 2 to 4 weeks later may differentiate past infection or exposure (lower titers with either a decrease or no change) from active infection (a 4-16-fold increase or sustained high titers).⁴⁰ Toxoplasmosis may be treated using sulfadiazine and pyrimethamine. Treatment may be beneficial during active infection when organisms are multiply­ing but is rarely effective in completely eliminating infection or clearing a subclinical infection because of the tissue encyst-

40

ment of organisms.⁴⁰

Miscellaneous Intraocular Parasites are often centrally blind. No treatment exists, and the disease is typically fatal.