History

An 11-year-old spayed female mixed-breed dog was presented to Gulf Coast Animal Eye Clinic with the chief complaint of mild blepharospasm, intensifying conjunctival hyperemia, and corneal cloudiness of 3 weeks’ duration. Ophthalmic examination included fluorescein stain, tonometry, slit-lamp biomicroscopy, and fundoscopy, which revealed mild blepharospasm and mild to moderate conjunctival hyperemia OD. The cornea was fluorescein negative but had pink and cream-colored consolidated infiltrates at 11-o’clock (largest in density), 1-o’clock, and 4-o’clock positions with perilimbal vessels extending toward the infiltrative lesions with moderate to severe generalized edema (Figure 1). It was difficult to view intraocular structures and retinal detail due to the significant corneal opacification. The left eye had no significant findings.

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Clinical photograph of an 11-year-old spayed female mixed-breed dog with a corneal lesion upon initial presentation to Gulf Coast Animal Eye Clinic.

Citation: Journal of the American Veterinary Medical Association 262, 4; 10.2460/javma.23.10.0548

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Diagnostic Findings and Interpretation

Differential diagnoses considered on initial examination included infectious corneal stromal abscessation, neoplasia (specifically lymphoma), and immune-mediated/inflammatory disease. Based upon ophthalmic examination findings, the patient was presumptively diagnosed with nonulcerative keratitis, more specifically multifocal corneal stromal abscessation with a suspected infectious component. Medical management of the right eye was initiated, including ulcer mix (compounded gentamicin, N-acetylcysteine, and artificial tears), ophthalmic solution (q 6 h, OD), 1% voriconazole ophthalmic solution (q 6 h, OD), 0.3% ofloxacin ophthalmic solution (q 6 h, OD), 5% mefoxin ophthalmic solution (q 6 h, OD), 25 mg of carprofen (q 12 h, PO), and 100 mg of doxycycline (q 12 h, PO). The patient was maintained on this medication regimen for 1 month. While the patient had minimal blepharospasm, the corneal infiltrate, significant vascularization and severe corneal edema continued to worsen.

Treatment and Outcome

With poor response to initial medical management, a keratectomy was subsequently performed 1 month after initial presentation. A circular region of cornea 10 mm in diameter was outlined with a biopsy punch and excised with a No. 69 Beaver blade and corneal section scissors. The majority of stromal infiltrate that included both consolidated nodules and a milky intrastromal liquid infiltrate in the axial region was removed (Figure 2). Multifocal areas of infiltrate/incomplete excision were noted nasally and dorsotemporally. Once 50% corneal thickness was removed, a swab for culture was taken in the region of excision. Due to depth, it was decided to forgo trying to excise these areas completely. Histopathology and culture/sensitivity were performed. Samples were sent out to the Specialty Vetpath and Ocular Microbiology Laboratory of Animal Eye Consultants of Iowa to have histopathology and culture/sensitivity performed, respectively. Histopathologically (Figure 3), the corneal stromal infiltrate was characterized by lipid-laden histiocytes surrounding deposits of granular to specular/radial amphophilic material with small clefts (lipid) in a background of lymphoplasmacytic inflammation and neovascularization. The stroma between edges of xanthogranulomatous infiltrate had moderate edema with scattered lipid-laden macrophages and rare neutrophils. Culture and sensitivity results yielded no growth. The differential diagnosis and treatment plan was changed after the histopathologic diagnosis and culture/sensitivity results returned.

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Clinical photograph (2 days before operation, 27 days after initial presentation) of progression of the corneal lesion, seeming to form a liquefied, cream-colored infiltrate in the axial region.

Citation: Journal of the American Veterinary Medical Association 262, 4; 10.2460/javma.23.10.0548

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Photomicrograph of the corneal biopsy. Central deposits of granular to spicular, basophilic material are present with clear clefts (asterisk) surrounded by foamy macrophages and more peripheral lymphoplasmacytic and neovascular infiltrate. H&E stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 262, 4; 10.2460/javma.23.10.0548

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Following surgical intervention, the medication regimen included equine serum (q 6 h, OD), ulcer mix ophthalmic solution (q 6 h, OD), 1% voriconazole ophthalmic solution (q 6 h, OD), 0.3% ofloxacin ophthalmic solution (q 6 h, OD), 5% mefoxin ophthalmic solution (q 6 h, OD), 25 mg of carprofen (q 12 h, PO), 100 mg of gabapentin (q 12 h, PO), and 100 mg of doxycycline (q 12 h, PO). At 5 days postoperatively, the cornea still contained the multifocal areas of cream and pink infiltrate that had not been excised, and the lesions were well vascularized by peripheral vessels. The corneal surface had re-epithelialized, and there was no evidence of infiltrative lesions in the axial cornea. At approximately 2 weeks postoperatively, the cornea had multifocal remnants of the infiltrates with vessels that were less perfused. There was now fibrosis and edema axially. The previous medication regimen was discontinued. Instead, 0.2% tacrolimus ophthalmic ointment (q 8 h, OD) and 0.05% difluprednate ophthalmic emulsion (q 8 h, OD) were prescribed to reduce the localized immune response, decrease inflammation, and prevent fibroblastic formation. Approximately 3 weeks postoperatively, ophthalmic examination revealed generalized corneal fibrosis with poorly perfused vascularization. There was a focal area of midstromal infiltrate at the ventral edge of the keratectomy site. One month postoperatively, the cornea had axial fibrosis with perilimbal vessels and no signs of stromal infiltrate. The tacrolimus was decreased to every 12 hours, OD, and a taper was begun on the difluprednate (q 12 h, OD, for 1 week, then q 48 h until recheck). Approximately 2 months postoperatively, the cornea had few faint vessels with faint fibrosis and multifocal areas of superficial pigment. No signs of the pink and cream corneal infiltrate were present. The fundus was able to be visualized and appeared normal. At the time of writing, the patient is being managed on the 0.2% tacrolimus ointment (q 12 h, OD). At approximately 9 months postoperatively, there was faint perilimbal fibrosis, central pigmentation, and multiple faint, scattered vessels. These findings are expected following corneal surgery, and there were no indications of lesion recurrence. The last examination was performed 1 year postoperatively (Figure 4), and there were no ophthalmic changes noted. The patient was comfortable and visual with good corneal clarity.

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Clinical photograph of an 11-year-old spayed female mixed-breed dog 1 year postoperatively with resolution of the corneal lesion.

Citation: Journal of the American Veterinary Medical Association 262, 4; 10.2460/javma.23.10.0548

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Comments

Xanthogranulomatous disease has been previously described in dogs and cats and encompasses a few distinct clinical diseases, including ocular surface xanthogranulomas and intraocular xanthogranulomatous endophthalmitis.^1-4 The published articles further characterize the histopathologic appearance as well as potential risk factors, including hyperlipidemia in Miniature Schnauzers.² It is noted that ocular surface granuloma disease is refractive to medical management, and while surgical excision has been conducted in some of the cases, adjunctive cryotherapy, conjunctival grafts, or intralesional triamcinolone injections were also performed as part of the treatment to limit recurrence.¹ Additionally, xanthogranulomatous disease has been described in the human literature.⁵ It refers to a group of 4 different clinical syndromes: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. These clinical syndromes encapsulate a large range of systemic involvement, and patients present with a range of symptoms depending on what region of the body is affected (ie, orbit, periorbital area, trunk, or extremities), but they all present with progressively enlarging, yellowish lesions that share the histopathologic characteristics of foamy histiocytes and Touton-type giant cells. Treatment and prognoses depend upon the characteristic of each clinical syndrome.

It is important to have a complete list of differential diagnoses when trying to treat any disease process. Regarding nonulcerative keratitis, it is imperative to recognize the underlying etiology and treat appropriately to avoid further damage to not only the cornea, but potentially the intraocular structures as well. The case described by the authors aids in forming a more complete differential diagnoses list for nonulcerative keratitis. Differentials for pink and cream-colored corneal stromal infiltrate should include stromal infectious abscessation, lymphoma, corneal dystrophy, corneal degeneration, and xanthogranulomatous keratitis. Furthermore, xanthogranulomatous keratitis should be at the top of the differential diagnoses list if the patient is nonpainful, as the aforementioned corneal diseases typically cause pain by negatively impacting the corneal nerves, the uveal tract musculature, or a combination thereof. It is key to recognize xanthogranulomatous keratitis early and initiate treatment to prevent extension of corneal lesions, which may lead to significant corneal opacity and visual impairment. This case demonstrated that accurate histopathological diagnosis and surgical excision followed by adjunctive medical therapy may be successful in treating the immune-mediated/inflammatory disease described. Thus, after a lesion is excised, the medications should target reduction of the local immune response, inflammation, and fibrosis. Surgical intervention and medical treatment can be a viable option for preventing recurrence of xanthogranulomatous keratitis and thus maintaining functional vision.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have nothing to disclose.