© 2009 American College of Veterinary Ophthalmologists

Veterinary Ophthalmology

(2009)

12

, 1, 56–60

Blackwell Publishing Inc

CASE REPORT

Keratoconjunctivitis associated with

Toxoplasma gondii

in a dog

Robert L. Swinger,* Karl A. Schmidt, Jr.* and Richard R. Dubielzig†

*

Animal Eye Specialty Clinic, 20290 NW 2nd Avenue, Miami, FL 33169, USA;

†

Department of Pathobiological Science, University of Madison-Wisconsin, School of Veterinary Medicine, Madison, Wisconsin, USA

Abstract

A 12-year-old Pug presented with a 3-mm corneal mass OD. The dog was currently being treated for keratoconjunctivitis sicca (KCS) and pigmentary keratitis OU. A superficial keratectomy followed by cryotherapy was performed OD. A histopathologic diagnosis of epithelial dysplasia and suppurative keratitis was made and the lesion resolved. Two months later, a yellow/tan conjunctival mass, diffuse chemosis and conjunctival thickening was discovered OD. Necrotizing conjunctivitis with protozoal parasites was diagnosed with histopathology. Complete blood count and a serum biochemistry panel were normal.

Neospora caninum

and

Toxoplasma gondii

titers were negative. The conjunctivitis resolved after a 6-week course of oral clindamycin. Two months later, the patient presented with a similar conjunctival mass OS.

Toxoplasma gondii

was confirmed as the etiologic agent with immunohistochemical staining. Repeat

T. gondii

titers were negative. Oral clindamycin was re-instituted. The corneal biopsy was re-reviewed and protozoal organisms were discovered. Three months later, a recurrence was suspected and oral ponazuril was initiated for 28 days. There has been no evidence of recurrence since this treatment. Ocular toxoplasmosis is rare in the dog but reports have included episcleritis, scleritis, retinitis, anterior uveitis, ciliary epithelium hyperplasia, optic neuritis and polymyositis. To our knowledge, this is the first confirmed report of toxoplasmosis causing only corneal and conjunctival disease in the dog. We hypothesize that these localized lesions may be associated with topical immunomodulating therapy for KCS. Toxoplasmosis should be considered as a differential for canine conjunctivitis and corneal disease and has the potential to manifest in one or both eyes.

Key Words:

conjunctivitis, dog, keratoconjunctivitis, keratitis, ponazuril,

Toxoplasma gondii

Address communications to:

R. L. Swinger

Tel.: +305 652 0448Fax: +305 652 0425e-mail: swingermiamieye@bellsouth.net

HISTORY

A 12-year old, female-spayed Chinese Pug presented fora corneal mass OD that developed over the prior week.For the past 6 years the dog had been treated for kerato-conjunctivitis sicca (KCS) and severe pigmentary keratitiswith cyclosporinee (Optimmune

®

0.2% ophthalmic ointment,Schering-Plough Animal Health Corporation, Summit, NJ)or tacrolimus 0.03% (Skip’s Pharmacy, Boca Raton, FL)and neomycin/polymycin/dexamethasone (neopolydex)(Fougera & Company, Melville, New York, NY) topicalophthalmic ointments. The current medical protocol consistedof tacrolimus 0.03% and neopolydex ointments in botheyes (OU) q8h. The dog was routinely examined every 3–4 months. There were no other known medical conditions.

There was one other geriatric Pug in the household beingtreated for KCS. Both dogs were housedogs that wereexercised on a lead several times a day. The owner traveledwith both dogs throughout Florida.

INITIAL CLINICAL FINDINGS

Excluding ocular disease, vital parameters and physicalexamination were unremarkable. Menace responses anddazzle reflexes were present OU. Direct and consensualpupillary light reflexes were present OU. Schirmer tear test(Schering Plough Animal Health, Union, NJ) were normalOU (18 mm/min OD, 25 mm/min OS). Intraocular pressures(IOP) were normal OU (17 mmHg OD, 16 mmHg OS)with applanation tonometry (Tonopen-XL, Mentor O & O,

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Inc.) following topical anesthesia (proparacaine hydrochloride0.5% ophthalmic solution, Bausch & Lomb, Inc., Tampa,FL). Neither cornea retained fluorescein dye (ContacareOphthalmics & Diagnostics, Gujarat, India). Dense, non-ulcerative, corneal pigmentation affecting 90% of the cornealsurface OU and a 3-mm, raised, vascular, pink, axial cornealmass OD were diagnosed following slit-lamp evaluation.Indirect ophthalmoscopy OU was limited due to cornealdisease but appeared normal.

Based on the breed, clinical exam, and history, the causeof pigmentary keratitis is most likely due to a combinationof brachycephalic syndrome and KCSN.

1

Neoplasia

2,3

or apapilloma

2

lesion was deemed the most likely cause of thecorneal mass.

INITIAL TREATMENT AND RATIONALE

Under the assumption the lesion was most likely neoplasticin origin, a superficial keratectomy was performed undergeneral anesthesia. Cryosurgery of the surgical bed andsurrounding corneal tissue was performed by completingtwo freeze cycles (nitrous oxide; rapid freeze-slow thaw, 20 seach). A temporary tarsorrhaphy was placed laterally to limitcorneal exposure and expedite healing. The patient wasdischarged on gentamicin sulfate 0.3% ophthalmic solution(Pacific Pharma, Irvine, CA) OD q8h, neopolydex ointment OSq8h, and tacrolimus 0.3% ointment OU q8h. An Elizabethancollar was dispensed to help prevent self-induced trauma.

On histopathology the mass consisted of focally disorganized,irregularly hyperplastic, pigmented corneal epithelium. Theepithelial cells exhibited features of atypia: loss of definedcellular borders, increased nuclear size, stippled chromatin,and prominent nucleoli. In less affected areas of the epithelium,there was inter- and intracellular edema and exocytosis ofneutrophils. The corneal stroma subtending the epitheliumwas severely infiltrated by a mixed population of inflammatorycells, primarily neutrophils and scattered macrophages,plasma cells, and lymphocytes. This lesion was initiallydiagnosed as corneal epithelial dysplasia and suppurativekeratitis with the recommendation to monitor closely as thesechanges in the corneal epithelium may progress to squamouscell carcinoma.

PROGRESS REPORT

Three weeks following surgery, the lateral tarsorrhaphy wasremoved and the patient showed no signs of ocular discomfort.Fluorescein corneal dye was not retained by either cornea.Mild conjunctival hyperemia, dense diffuse pigmentary keratitiswith associated corneal vascularization, and a 3-mm white,axial, anterior stromal opacity consistent with fibrosis wasdiagnosed OD. Intraocular exam could not be performeddue to extensive corneal disease. The original medicationprotocol for KCS was re-instituted at this time.

Seven weeks after surgery the patient presented withmoderate, diffuse conjunctival hyperemia and chemosis OD.

A 10-mm yellow/tan movable perilimbal conjunctival masswas present from the 2–5 o’clock position (Fig. 1). The masswas excised by sharp excision following topical anesthesiaand submitted for histopathology. Topical therapy includedneomycin/polymyxin B sulfates/gramicidin ophthalmicsolution (Neocidin, Bausch & Lomb, Inc.) OD q8h, neopo-lydex ointment OS q8h, and tacrolimus 0.3% ointment OUq8h.

On histopathology the conjunctival mass was partiallyepithelialized and subtended by loose connective tissue withextensive tissue necrosis, lymphoplasmacytic and suppurativeinflammatory infiltrate, and dilated blood vessels. In severalareas, seemingly within endothelial cells, there were aggregatedclusters of protozoal parasites, leading to the diagnosis ofnecrotizing conjunctivitis with protozoal parasites. Either

Toxoplasma gondii

or

Neospora caninum

were probable butcould not be confirmed by histopathologic evaluationwithout immunohistochemical staining (Fig. 2). At this time,clindamycin (Ohm Laboratories, Inc., North Brunswick,NJ) 10 mg/kg PO q12h was initiated in addition to topicalmedications. Complete blood count (CBC) and serumbiochemistry profile were normal and titers (IgG and IgM)for

N. caninum

and

T. gondii

were negative (Antech Diagnostics,Lake Success, NY).

After 6 weeks of clindamycin treatment, STT haddecreased (15 mm/min OD, 25 mm/min OS) and moderateconjunctival hyperemia with no evidence of a conjunctivalmass was present OD. Repeat CBC and titers for

N. caninum

and

T. gondii

were unchanged. The neopolygram ophthalmicsolution and clindamycin were discontinued and flurbipro-fen 0.03% ophthalmic solution (Pacific Pharma) OD q8hwas initiated as a topical anti-inflammatory agent. Theconjunctival hyperemia OD resolved after 6 weeks and theoriginal medication protocol for KCS was re-instituted.

Twenty weeks following initial presentation, the dogreturned with a 5-mm yellow/tan conjunctival mass andassociated moderate conjunctival hyperemia OS. STT werenormal OU (19 mm/min OD, 21 mm/min OS). Followingtopical anesthesia, the mass was excised by sharp excisionand submitted for histopathology.

Toxoplasma gondii

titers(IgG and IgM) were negative. Clindamycin was re-institutedand continued for 10 weeks. The neopolydex ointment wasreplaced with neopolygram and flurbiprofen 0.03% solutionsOS q8h.

Histopathology of the conjunctival mass OS was very similarto the conjunctival mass OD (Fig. 3). Immunohistochemicalstaining was positive for

T. gondii

antigens (Fig. 4). At thistime, the initial corneal biopsy OD was re-reviewed andprotozoal organisms were discovered.

Forty weeks following initial presentation, the dog hadmoderate conjunctival hyperemia and thickening with adeveloping conjunctival nodule OS. The current treatmentprotocol was neopolydex and tacrolimus 0.03% ointmentsOU q8h. Ponazuril (Marquis

®

, Bayer HealthCare LLC,Shawnee Mission, KS) 20 mg/kg PO q24h was initiatedand continued for 28 days in addition to topical therapy.

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At the last examination (6 months after completing pona-zuril treatment), there was no evidence of toxoplasmosis OUand both pigmentary keratitis and KCS OU were stable.

DISCUSSION

Toxoplasmosis is considered one of the most commonparasitic infections worldwide.

4–6

This disease is caused by theobligate intracellular protozoal organism,

Toxoplasma gondii

,and the sexual form is found in the definitive feline host.

4–6

The parasite undergoes normal coccidian development inthe cat’s intestine leading to the shedding of oocysts, whichare extremely resistant to environmental influences.

7

The

ingested sporozoites (found in oocysts) and/or bradyzoites(found in tissue cysts) develop into tachyzoites, which aredisseminated throughout the vascular system to varioustarget organs, including the central nervous system, skeletalmuscles, visceral organs, and eye.

6

These tachyzoites multiplyintracellularly and form cysts of bradyzoites in soft tissue.Generally, the cysts remain dormant, the disease remainsnon-clinical and the animal becomes a chronic carrier ofdisease.

8–10

Young dogs and cats, including those that contractthe organism

in utero

, often develop severe and/or fatalsystemic disease.

8

Adult animals may show a variety of clinical

Figure 1. Photograph OD 7 weeks following superficial keratectomy and cryosurgery for a corneal mass. Note the dorsomedial 10 mm yellow/tan perilimbal bulbar conjunctival mass and associated diffuse conjunctival chemosis and hyperemia. Additionally, dense pigmentary keratitis affects the entire corneal surface.

Figure 2. Photomicrographs of the conjunctival biopsy from the mass shown in Figure 1. There is extensive tissue edema, lymphoplasmacytic and suppurative inflammatory infiltrate, and dilated blood vessels. Clusters of T. gondii tachyzoites are noted by the arrow.

Figure 3. Photomicrographs of the conjunctival biopsy from the mass OS. These findings are similar to those in Figure 2. In this sample, T. gondii organisms are seen within the epithelium and subepithelial inflammatory infiltrate (noted by the arrow).

Figure 4. Immunohistochemical staining of the conjunctival biopsy in Figure 3. Toxoplasma gondii antigens are labeled red.

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signs, including lethargy, anorexia, pneumonia, fever, hepatitis,gastrointestinal, hyperesthesia from myositis, and neuro-logic abnormalities resulting from central nervous systeminfection.

8,9,11

Cats classically develop initial lesions in thechoroid and may present with anterior uveitis.

9,11–14

Oculartoxoplasmosis is rare in dogs but reports have includedepiscleritis, scleritis, retinitis, anterior uveitis, optic neuritis,ciliary epithelium hyperplasia and polymyositis.

5,8,15–18

It is unclear why some animals develop clinical toxoplasmosisand others do not; however, a variety of immunosuppressivestates may be associated with either primary or recurrentinfections. It is presumed that clinical disease is generallythe result of a defect in systemic or local immunity to theorganism.

7

A proper cell-mediated immune response isnecessary to control

T. gondii

infection and provide protectiveimmunity.

7,19

Our patient had been treated with topicalanti-inflammatory and immune-modulating drugs for KCSand pigmentary keratitis. Glucocorticoids markedly reduceleukocyte recruitment and migration into inflamed areas byinhibiting the ability of inflammatory cells to elaboratechemotactic mediators.

20

Tacrolimus is an immune-modulatingdrug that has been demonstrated to suppress cell-mediatedreactions through T-lymphocyte inhibition in animals.

20

Increased susceptibility to infection may result from immuno-suppression. We hypothesize that this case of

T. gondii

localizedin the extraocular tissues is associated with aggressive topicalanti-inflammatory therapy required to control the underlyingKCS condition.

Unfortunately, most systemic drugs commonly used totreat

T. gondii

are protozoal-static and suppress only thetachyzoite stage of the organism.

7

Having limited to noeffect on the tissue cyst stage, it is often difficult to eliminate

T. gondii

from the host and thus prevent recurrence of disease.

7

Clindamycin is the drug of choice for treating toxoplasmosisin dogs and cats.

5,7,17

The recommended protocol is generally10–20 mg/kg PO q12h for 4 weeks.

5,21

Due to recurrence,we opted to increase to a 10-week course of therapy duringthe second treatment. Other drugs reported to be effectiveagainst

T. gondii

include pyrimethamine/sulfonamide com-binations

5,7

and doxycycline.

22

Ponazuril (Marquis

®

) is an anticoccidial compoundcommonly used to treat equine protozoal myeloencephalitis(EPM) due to its cidal activity against

Sarcocystis neurona.

23,24

Although not approved for dogs and cats, it has been foundto be safe and efficacious in horses

23

and effective in preventingand treating toxoplasmosis in mice.

25

Based on our clinicalfindings and the apparent resolution of disease followingtreatment, ponazuril may be an effective treatment againstcanine toxoplasmosis and should be further investigated as asafe and effective treatment for this disease in dogs.

The diagnosis of

T. gondii

in this case was made throughhistopathologic identification and confirmed with immuno-histochemical staining. While serologic testing is available(ELISA, IFA, PCR), it is difficult to differentiate past andcurrent infections and paired serum samples taken 2–4 weeksapart are often necessary for meaningful interpretation.

7

Multiple serum samples were submitted in this case and allwere negative. We believe that this local disease was notsignificant enough to generate a substantial humoral immuneresponse.

To our knowledge, this is the first confirmed report oftoxoplasmosis causing only corneal and conjunctival diseasein the dog. We hypothesize that these localized lesions maybe associated with topical immunomodulating therapy forKCS. Toxoplasmosis should be considered a differential formasses occurring in the conjunctiva and cornea and has thepotential to manifest in one or OU. Ponazuril may be aneffective treatment for toxoplasmosis in the dog.

ACKNOWLEDGMENTS

The authors thank Animal Eye Specialty Clinics of SouthFlorida, Susan M. Carastro, DVM, MS, DACVO, and CarmenColitz, DVM, PhD, DACVO for their support and reviewof this case report.

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