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A 7-year-old, 4.5 kg, neutered male domestic shorthair cat was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of bilateral blepharospasm of 1-day duration. The cat had been diagnosed 1 mo previously with bilateral idiopathic anterior uveitis and chorioretinitis causing partial retinal detachment. A systemic work-up including general physical and neurological examination, systolic blood pressure, complete blood (cell) count (CBC), serum biochemistry, urinalysis, FeLV/FIV antigen testing, Toxoplasma gondii and Bartonella henselae antibody titers, were completed at that time and no underlying systemic etiology was discovered for the ocular lesions. Treatment was initiated empirically with oral azithromycin (Zithromax; Pfizer Canada, Kirkland, Quebec), 5 mg/kg, q12h and topical prednisolone acetate 1% (Sandoz Prednisolone; Sandoz Canada, Boucherville, Quebec), q6h while awaiting the serology results.
The cat was re-evaluated 2 wk after initial diagnosis, at which time the anterior uveitis appeared controlled and the retinal detachments were resolving. Therapy was continued with plans to re-evaluate in 2 wk. At the 2-week re-evaluation, both eyes had moderate blepharospasm. General physical examination was normal except for the ocular abnormalities. The menace responses were present bilaterally. Direct and consensual pupillary light reflexes were present in both eyes. The palpebral, and oculocephalic reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 11 and 23 mm/min in the right and left eye, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet; Tiolat, Helsinki, Finland) and were 11 mmHg bilaterally. Results from fluorescein staining (Fluorets, Bausch & Lomb Canada, Markham, Ontario) were positive bilaterally. On direct examination, moderate conjunctival hyperemia and serous ocular discharge were present bilaterally. Biomicroscopic (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) and indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examinations following dilation with 0.5% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario) were completed. The anterior uveitis and chorioretinitis were resolved at that time and the underlying cause was not discovered. A photograph of the cat is provided for your assessment (Figure 1).
Our clinical diagnosis was bilateral ulcerative keratitis. Differential diagnoses for causes of corneal ulceration in the cat include trauma, ectopic cilia, conjunctival foreign body, keratoconjunctivitis sicca, and infection with feline herpesvirus type-1 (FHV-1). Because of the dendritic (branching) nature of the ulcers, the etiology was considered to be FHV-1. Swabs were obtained from the cornea and conjunctiva and the diagnosis was confirmed with a positive polymerase chain reaction (PCR) test for FHV-1.
Feline herpesvirus type-1 infection is specific to felines and the virus is widespread in the cat population worldwide. The initial or primary FHV-1 infection most often occurs in neonatal and young cats and results in upper respiratory tract disease (1,2) (feline viral rhinotracheitis). The predominant ocular manifestations during primary infection are bilateral conjunctivitis with or without corneal ulceration (1). Following primary infection, viral latency is established in the trigeminal ganglion (3). Ocular manifestations of FHV-1 infection in adult cats are primarily the result of reactivation of latent virus (1). Reactivation of latent virus is induced by natural stresses such as change in housing, parturition, and lactation, as well as, iatrogenically following glucocorticoid therapy (4–6). The long duration of topical corticosteroid therapy for anterior uveitis preceded the development of keratitis in this cat, and likely induced the reactivation of latent virus. During this recrudescent stage of the disease signs of upper respiratory tract disease are usually absent and ocular signs predominate (1,2). The spectrum of ocular disease ranges from mild conjunctivitis to variable degrees of keratitis. Linear, branching, or dendritic ulcers are considered pathognomonic for FHV-1 infection (4). Dendritic ulcers may persist for prolonged periods, and may be associated with mild edema and superficial vascularization (1). Small ulcers may coalesce to form larger geographic lesions. Most cats are able to clear the virus from the corneal surface in a few days; however, disease may become chronic in cats that are unable to mount an appropriate immune response. The course of recrudescent disease can last weeks to months and the frequency of recurrence depends on the cat’s immune system status and viral burden (1,4).
Diagnosis of FHV-1 is based on identifying pathognomonic dendritic ulceration, or by laboratory confirmation using virus isolation, immunofluorescent antibody, or PCR from samples taken from the conjunctiva or cornea. Polymerase chain reaction is the most sensitive method of detecting FHV-1 in ocular tissues and the most often used (7,8). Clinically normal cats, however, may shed the virus and viral DNA can be found in ocular tissues of normal cats (8). Therefore, a positive test result should always be evaluated in light of the history and clinical signs of the cat.
Treatment of FHV-1 corneal ulceration involves the use of antiviral therapy and antibiotic prophylaxis to reduce the chance of bacterial infection of the ulcer. Antiviral agents generally act to inhibit viral replication and are virostatic. They are only effective when the virus is replicating and are therefore not useful during periods of viral latency. The most commonly used topical antiviral ophthalmic formulations are idoxuridine and trifluridine. Trifluridine is commercially available as a 1% solution (Viroptic, Glaxo Smith Kline, Mississauga, Ontario) and Idoxuridine is available as a 0.1% generic topical solution or can be compounded as a 0.1% solution or 0.5% ointment for ocular use. These should be used a minimum of 4 times daily and it is recommended that antiviral agents be continued for 14 d after resolution of clinical signs. Newer antiviral agents that are receiving attention in human medicine include gancyclovir, cidofovir, and famciclovir. These agents have good antiviral activity versus FHV-1 in vitro and clinical trials are ongoing to study them in vivo. L-lysine is an amino acid that reduces in vitro replication of FHV-1 (9). Oral administration of L-lysine is reported to lessen the severity of clinical signs of primary FHV-1 infection, reduce viral shedding in latently infected cats following natural stressors, and increase the intervals between episodes of recurrence (10,11). L-lysine supplementation is recommended at a dose of 500 mg twice daily in adults and 250 mg twice daily in kittens. L-lysine supplementation is a useful adjunctive therapy in the treatment of acute disease as well as a long-term therapy in cats with frequent recurrences or chronic signs.
Treatment was initiated in this cat with a topical idoxuridine 0.1% q6h to reduce viral load, as well as bacitracin zinc/neomycin sulphate/polymyxin B sulfate ointment (BNP; Vetcom, Upton, Quebec), q6h for antibacterial prophylaxis for the ulcers. Oral L-lysine (Enisly-F; Vetoquinol, Lavaltrie, Quebec), 500 mg PO, q12h was also used to reduce viral replication. Topical prednisolone acetate 1% was also discontinued. The corneal ulcers gradually resolved over the next 6 wk. Upon resolution, the topical antiviral was continued for an additional 2 wk and L-lysine was continued indefinitely. There has been no recurrence of the corneal disease or the uveitis for 2 y.
Prognosis for cats with FHV-1 ocular disease is guarded to good. In most cats the primary and recrudescent infections are self-limiting and cause mild clinical signs. However, some cats suffer from chronic ongoing disease or frequent recurrence. Keratitis may result in corneal scarring and secondary bacterial infection of corneal ulcers can lead to more severe clinical disease. Vaccination does not protect against infection, shedding of the virus, or development of latency. It may, however, reduce the severity of clinical signs in cats challenged with FHV-1 (1).
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