Cytologic Diagnosis and Review of Feline Eosinophilic Keratitis

Suzanna Mackey; Laurence D. Mackey; Kenneth S. Latimer, DVM, PhD, DACVP; Ursula Dietrich, DVM, DACVO, DECVO; Phillip Anthony Moore, DVM, DACVO; Heather L. Tarpley, DVM

Class of 2005 (S. Mackey, L. Mackey), Department of Pathology (Latimer, Tarpley), Department of Ophthalmology (P.A. Moore, U. Dietrich), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

Introduction

Feline eosinophilic keratitis (FEK) is an ocular disease that affects cats and horses. Details concerning the presentation of this disease process in horses have been reviewed previously. In cats, this disease appears in animals from 1 to 14 years of age with the average age of occurrence of <4 years of age.⁴ Castrated males are over represented in most studies.^6-8 FEK commonly occurs in both domestic short hair and the domestic long hair cats. However, this disease also is seen in specific breeds of cats including the Persian, Siamese, Himalayan and Russian Blue.^6-9 In FEK, disease begins with corneal deposition of material that does not cause erosion of the epithelium. Corneal deposits are affixed to the surface of the epithelium and may be removed for cytologic analysis by gentle scraping.

Etiology

A typical medical history of FEK includes chronic ocular irritation that may have been associated with corneal ulceration months previously to the onset of disease. The precise etiology of FEK is currently unknown. It has been hypothesized that FEK may be an immune-mediated disease or a response to certain allergic stimuli with the variable appearance of peripheral eosinophilia. Organisms have not been identified via culture of biopsy material or following the application of special stains to histologic sections. Other hypotheses have suggested a link between herpesvirus infection and chronic eosinophilic keratitis as well as between FEK and feline eosinophilic granuloma complex. Although these associations have not been proven, veterinary ophthalmologists generally concur that feline herpesvirus-1 (FHV-1) may be the cause of FEK because polymerase chain reaction analysis has been positive for FHV-1 for the majority (76.3 %) of corneal scrapings from cats with this disease.^5,6 Currently, the prevailing theory suggests that the feline herpesvirus acts as an eliciting antigen causing the development of FEK or that viral infection predisposes the cornea to cellular infiltration with eosinophils.

Clinical Signs

Feline eosinophilic keratitis typically presents as a white to pink plaque that affects a variable portion of the cornea (Fig. 1). The most common location of the initial lesion is at the temporal limbus, while the second most common site of development occurs at the nasal limbus.⁴ Lesions may progress to involve multiple quadrants of the eye. In addition, FEK may eventually become a bilateral condition, if left untreated.⁵ Grossly, the corneal plaque has the appearance of a thick white deposit of material that has a gritty consistency⁵ and can easily be removed by scraping. The appearance and consistency of this white plaque is pathognomonic for the FEK. Furthermore, these white plaques also can occur on the temporal bulbar conjunctiva. Eosinophilic conjunctivitis has been described as a possible variant of eosinophilic keratitis and is characterized by eosinophil and mast cell infiltration of the bulbar or palpebral conjunctival tissue.^1,12 Clinically, severe conjunctivitis and chemosis are observed and in some cases the conjunctiva has a granular, cobblestone appearance (Fig. 2). Superficial keratitis may or may not be present.

Figure 1. Gross appearance of feline eosinophilic keratitis as white plaques that partially cover portions of the cornea. Neovascularization also is present (image courtesy of Dr. U. Dietrich).	Figure 2. Gross appearance of eosinophilic conjunctivitis. The bulbar conjunctiva is thickened, light pink, and extends onto the cornea from the lateral limbus (image courtesy of Dr. U. Dietrich).

The presence of corneal edema is a common clinical finding as well as superficial vascularization, conjunctivitis, mucoid discharge, blepharospasm, and prolapse of the nictitans. Mucoid to mucopurulent discharge is a consistent finding with FEK. Immunoflourescent antibody staining and PCR analysis of ocular material from cats with FEK have documented concurrent FHV-1 infection in 33% and 76% of cats, respectively.^5,10

Cytologic and Histologic Examination in the Diagnosis of FEK

Diagnosis of FEK is largely based on the presence of the typical corneal lesion(s) and cytologic examination. Microscopic examination of corneal scrapings usually contains an increased number of eosinophils, a few neutrophils, noncornified squamous epithelial cells, mast cells, and lymphocytes (Fig. 3). Other cytologic findings include detritus and free eosinophilic granules (Fig. 4).

Figure 3. Corneal scraping of a cat with eosinophilic keratitis. Cells present include four angular corneal epithelial cells, two eosinophils with dull red granules, a neutrophil, and a partially degranulated mast cell. Two disrupted neutrophils also are present (Wright stain).	Figure 4. Corneal scraping of a cat with eosinophilic keratitis. Corneal epithelial cells, a partially degranulated mast cell, and an intact eosinophil are present. A disrupted eosinophil also is present and brown-red, rod-shaped eosinophil granules are scattered throughout the background of the smear (Wright stain).

Deeper scrapings of the cornea may contain a predominance of plasma cells and lymphocytes admixed with fewer mast cells, eosinophils, and macrophages.⁴ Currently, a debate exists among veterinary ophthalmologists whether a deeper corneal scraping that lacks many eosinophils should be classified as FEK or some other form of proliferative keratitis.³ Histopathologic evaluation of the plaques reveals a chronic to granulomatous inflammatory response that is characterized by infiltration of plasma cells and lymphocytes admixed with fewer mast cells, macrophages, and variable numbers of eosinophils.⁵

Treatment

Once the diagnosis of FEK has been made, prompt and consistent treatment should be instituted. Because FEK is a progressive disease process, it can spread to cover the entire cornea and potentially cause blindness. Prompt and persistent treatment, therefore, will provide the best resolution of disease.

FEK was initially treated as a neoplastic process and the plaques were surgically removed from the cornea. Once the lesion reepithelialized, it was treated with topical and subconjunctival corticosteroid administration. However, the lesion often would return once medication was discontinued. Further understanding of this disease revealed histologic similarities with eosinophilic granuloma complex. FEK was treated in a similar fashion using megesterol acetate at a dosage of 5 mg PO daily for 5 days. The dosage was then decreased to 5mg every other day for three doses, and ultimately 5 mg weekly for maintenance.^2,6 Potential adverse reactions of megesterol acetate administration include polyphagia, behavioral changes, hair loss, diabetes mellitus, mammary hyperplasia, and neoplasia. Therefore, some clinicians propose to reserve the use of megasterol acetate to cases of FEK that are refractory to other treatment options such as topical dexamethasone 0.1% ophthalmic solution, prednisolone acetate 1% solution, or cyclosporine.^6,11 Corticosteroids initially are administered two to four times daily as an anti-inflammatory treatment regimen. The frequency of treatment is reduced to once daily and then to once every other day over a two to three month time period. Corticosteroid therapy must be maintained continuously to control FEK.

Since the underlying problem is thought to be a latent herpesvirus infection, some clinicians feared that the use of steroids could lead to recrudescence of the viral infection. Topical antiviral administration may be a benefit to manage herpesvirus infection, but studies to support this regimen in the resolution of FEK have not been reported.

Topical cyclosporine (0.5% ointment, 1-2% solution) is an alternative treatment to the use of topical corticosteroids. Cyclosporine solution is applied two to three times daily initially, with a reduction in the frequency of drug administration as long as the lesion is effectively controlled. Once again, the objective of cyclosporine treatment is to control lesion progression rather than trying to effect a cure. In any event, treatment for FEK must be continuously maintained at to the lowest effective drug dosage to prevent lesion progression.

References

1. Allgoewer I, Schaffer EH, Stockhaus C, et al: Feline eosinophilic keratitis. Vet Ophthalmol 4:69-74, 2001.

2. Glaze MB, Gelatt KN: Feline ophthalmology. In: Gelatt KN (ed): Veterinary Opthalmology, 3rd ed. Philadelphia, PA, Lippincott Williams & Wilkins, 1999, pp. 997-1052.

3. Hacker D: Eosinophilic Keratitis. Animal eye specialists. 1998. www.animal-eye-specialists.com/ek.html, website visited site on 04-18-05

4. Ketring KL: Feline Herpesvirus I & II. Eosinophilic keratitis. Proc Western Veterinary Conf, Las Vegas, NV, 2004, Small animal section.

5. Martin C: Ophthalmic Disease in Veterinary Medicine, 1st ed. Manson Publishing, United Kingdom, 2005, pp. 258-259.

6. Moore PA: Feline Corneal Disease. Clinical Techniques in Small Animal Practice (in press, 2005).

7. Morgan,RV, Abrams KL, Kern TJ: Feline eosinophilic keratitis: A retrospective study of 54 cases (1989-1994). Prog Vet Comp Ophthal 6:131-134, 1996.

8. Paulsen ME, Lavach JD, Severin GA, et al: Feline eosinophilic keratitis: A review of 15 clinical cases. J Am Animal Hosp Assoc 23:63-69, 1987.

9. Prasse KW, Winston SM: Cytology and histopathology of feline eosinophilic keratitis. Vet Comp Ophthal 6:74-81, 1996.

10. Zigler M: Eosinophilic Keratitis. Eyevet Consulting Services, 2001. www.eyevet.info/eosinker.html, website visited 04-18-05.

11. Sapienza JS: Corneal diseases of dogs and cats. WSAVA Congress, 2002. www.vin.com/proceedings, website visited on 04-18-05.

12. Pentlarge VW: Eosinophilic conjunctivitis in five cats. J Am Animal Hosp Assoc 27:2128, 1991 (abstract).

Acknowledgement

"Two Cats" by Karen Fincannon is from the Cat Paintings section of her website Art Works by Karen Fincannon and is used with permission.

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