Stiles J, Coster M. Use of an ophthalmic formulation of megestrol acetate for the treatment of eosinophilic keratitis in cats. Vet Ophthalmol. 2016;19 (Suppl 1):86-90.
Eosinophilic keratitis (EK), also called proliferative keratitis, is a relatively common feline eye disorder of unknown etiopathogenesis. Feline herpesvirus-1 (FHV-1) was associated with this condition in one study that identified this virus in the corneas of cats with EK using a polymerase chain reaction (PCR) assay. However, many cats with EK do not have a history or clinical signs that would be associated with FHV-1 infection. It is also possible that the inflammation associated with EK could lead to recrudescence of latent FHV-1 infection. Given that a single eye is usually initially affected by EK, it is easy to assume that EK might be associated with FHV-1, but the condition can progress to both eyes. Ultraviolet light may be a trigger for the development of EK.
In EK there is generally conjunctival hyperemia, corneal neovascularization, and a visible cellular corneal stromal cellular infiltrate that eventually develops into a whitish, proliferative plaque that often starts at the dorsolateral limbus or near the medial canthus. Tearing, whitish mucoid ocular discharge, and blepharospasm usually accompany EK, and over time the cat is likely to become progressively more uncomfortable. Diagnosis of EK is accomplished through cytology of corneal or conjunctival samples taken with a cytobrush or small blunt collection device such as a spatula. In EK, cytological samples will contain eosinophils, mast cells, neutrophils, lymphocytes, plasma cells, and occasionally, histiocytes.
Anti-inflammatory drugs, either systemic or topical, are the mainstay of treatment for EK. Topical glucocorticoids, such as prednisolone acetate 1% or dexamethasone 0.1% are frequently used, but may result in recrudescence of FHV-1 if present. Successful use of topical 1.5% cyclosporine has also been reported, as well as combination therapy with a topical nonsteroidal anti-inflammatory and 0.2% cyclosporine ointment. Concurrent treatment of the eye with a topical antiviral medication, if available, may be prudent when topical glucocorticoids or cyclosporine are used, given the potential for recrudescence of FHV-1 in feline patients. Eosinophilic keratitis can become chronic, and require extended ongoing treatment, sometimes lifelong.
Some cats with EK have been treated very succesfully with oral megestrol acetate, a potent progestogen with glucocorticoid-like activity. However, the side effects of using this drug systemically may outweigh the benefits as they are serious and may include diabetes mellitus, adrenal suppression, weight gain, mammary hyperplasia or neoplasia, and behavior changes.
In this prospective study of 17 client-owned cats with EK in one or both eyes, these investigators evaluated treatment with a topical ophthalmic formulation of megestrol acetate, hypothesizing that the topical megestrol acetate would resolve the EK lesions with no systemic adverse effects. Cats recruited into the study had EK confirmed by cytology, did not have signs of active FHV-1-associated disease, and had not experienced recent prior treatment with topical or systemic antiviral or anti-inflammatory drugs including megestrol acetate. Sixteen of the cats were mixed breed domestic shorthair or longhair, and one cat was a Persian; they ranged in age from 3 to 17 years, with a mean age of 7.3 years.
The topical medication, prepared by a compounding pharmacist, consisted of 0.5% megestrol acetate in an aqueous base. This was first tested on seven healthy cats without ocular disease to verify that the medication itself did not cause ocular irritation. In the 17 study patients with EK, the topical megestrol acetate 0.5% preparation was given at one drop in the affected eye(s) every 8-12 hours, depending on the severity of the lesions. The cats’ owners were advised to monitor their pets at home for signs of ocular irritation or potential systemic side effects such as polyuria or polydipsia, weight gain, or depression. The patients also had clinical ophthalmologic examinations every 2-4 weeks after starting treatment, and serum glucose measurements were performed at the first or second clinical re-examination appointment. No adrenal function testing was performed.
The majority of the patients (15/17; 88%) had a positive response to treatment; their eosinophilic plaques either diminished in size or resolved, the corneal neovascularization regressed, and any previously noted fluorescein-positive areas on their corneas resolved. Six of the 15 cats considered successfully treated (35%) had complete resolution of the lesions by the first clinical re-examination, while another eight demonstrated improvement but not complete resolution. The eight cats who had only partial resolution by the first clinical re-examination progressed to complete resolution within six weeks. The other cat (1/15) improved gradually and achieved complete resolution at 3 months. The two cats (2/17; 12%) who did not improve, one after 3 weeks, and the other after 3 months, were dropped from the study and had their therapy changed.
Ten of the 17 cats had serum glucose levels evaluated at various points during the study, and all were within the reference range except for one cat who had pre-existing diabetes mellitus. This diabetic cat did not experiencing worsening of its diabetes regulation while receiving the topical megestrol acetate. Tapering of the frequency of daily treatment was based on the severity of initial disease and clinical response in each patient. None of the cats developed clinical signs consistent with chronic-active FHV-1 during the course of treatment, even when this was prolonged. Six of the 17 cats had positive fluorescein uptake at their initial examination, and all such lesions went on to heal while the patients were receiving the topical megestrol acetate. The use of topical ophthalmic 0.5% megestrol acetate in aqueous solution is a viable option for treating feline EK, and is unlikely to cause significant systemic side effects; nonetheless, monitoring of patients receiving this therapy for potential systemic adverse effects is prudent. [PJS]
Dean E, Meunier V. Feline eosinophilic keratoconjunctivitis: a retrospective study of 45 cases. J Feline Med Surg 2013;15:661-6.