Feline herpesvirus type-1 (FHV-1) is ubiquitous in the world's cat population. Surveys document that as many as 97% of cats are seropositive for FHV-1. Approximately 80% of cats become latently infected for life as evidenced by the presence of FHV-1 in the trigeminal ganglia, olfactory bulb, optic chiasm and optic nerve. Stressors such as relocation, surgery, pregnancy, lactation, corticosteroid therapy, and immunosuppression associated with feline leukaemia virus (FeLV) or feline immunodeficiency virus (FIV) often precipitate subclinical viral shedding or recrudescent clinical disease.
In domestic cats, primary infection is characterised by diffuse replication of the virus in the epithelium of the upper respiratory tract, conjunctiva and cornea. The virus is cytopathic as it replicates, resulting in epithelial erosions/ulceration and inflammation. Cats may have intermittent episodes of ocular disease, after which they appear clinically normal, or may have chronic clinical signs that do not regress naturally or do not respond to treatment. Owing to herpesvirus-associated neuritis, pain is thought to be more severe than with conjunctivitis or keratitis from other causes.
Conjunctivitis
The typical patient with viral conjunctivitis is a neonatal or adolescent cat with an acute conjunctival-respiratory infection. The conjunctivitis is bilateral and characterised by pronounced hyperaemia and serous discharge that becomes mucopurulent as the disease follows its 10-14-day course. Conjunctival adhesions known as symblepharon frequently occur in very young kittens, resulting in epiphora due to occlusion of the nasolacrimal puncta, reduced eyelid mobility and permanent corneal opacity. Recurrent herpetic conjunctivitis is often unilateral and characterised by intermittent blepharospasm, mild conjunctival hyperaemia and serous discharge, without signs of respiratory infection.
Ulcerative Keratitis
Non-responsive superficial ulceration in any age cat is characteristic of herpesvirus infection. The problem is common, typically affecting adult cats unilaterally and without concurrent upper respiratory signs. Although herpes produces a pathognomonic linear/branching 'dendritic' ulcer reflecting the cytopathic effect of viral replication in the epithelial cells, this early lesion may be overlooked without the use of Rose Bengal stain. Larger 'geographic' erosions, so named for their irregular map-like shape, are more commonly recognised. Epithelial margins are often poorly adherent in these ulcers.
Stromal keratitis is an uncommon herpes-related disorder, mediated by T-lymphocytes directed against viral antigen within the corneal stroma and refractory to treatment. The reaction is characterised by marked stromal oedema and vascularisation, cellular infiltration and fibrosis. The use of corticosteroids in herpes-infected patients has been incriminated in the pathogenesis of stromal keratitis.
Diagnosis of herpetic keratitis is more reliably based on clinical signs and lack of response to conventional therapy than on laboratory confirmation. If laboratory confirmation is attempted, the recommended method is the polymerase chain reaction (PCR) test that identifies viral DNA. A positive PCR result may reflect viral DNA of vaccine origin as well as low levels of latent or persistent FHV-1 DNA that are not contributing to disease. FIV and FeLV should be routinely screened for in herpesvirus suspects.
Although in vitro feline studies suggest the most efficacious topical antiviral is 1% trifluridine, idoxuridine is a less irritating, more economical antiviral that can be formulated by a compounding pharmacist as a 0.1% solution or 0.5% ointment. Topical antivirals are virostatic and inconsistently effective, requiring frequent application (every 2 hours the first day, then five to six times daily). The exception is 0.5% cidofovir solution applied topically twice daily. Long-term topical antiviral use is not recommended due to potential corneal epithelial toxicity. A common side effect of topical antivirals is conjunctival and lid margin irritation. Topically applied dilute 0.5-1% povidone-iodine solution has been used three to four times daily but its extracellular site of action may limit its antiviral effect. Topical viscous lubricants applied several times daily provide a subjectively soothing effect on the ulcerated eye.
An oral antiviral that appears safe in otherwise unresponsive herpetic infections is famciclovir, dosed empirically in adult cats at approximately 32 mg/cat q12h (1/4of a 125-mg tablet) for 10-14 days. Effective antiviral levels are impossible to achieve with oral aciclovir in the cat, but anecdotal success has been claimed with high doses of the drug (100-200 mg q8-12h). Its adverse side effects include bone marrow suppression and nephrotoxicity. Valacyclovir is fatally toxic in cats.
Interferon may shorten the course of the disease by preventing healthy cells from becoming infected. The author currently treats herpesvirus suspects two to four times daily with topical interferon alpha-2b, formulated at a concentration of 3000 IU/ml. Duration of treatment is not limited by epithelial toxicity.
Studies document the in vitro efficacy of L-lysine in reducing viral replication by competing with arginine for incorporation into the viral genome. Lifelong daily oral supplementation (250 mg twice daily in kittens, 500 mg twice daily in adult cats) may reduce the frequency and severity of FHV-1 recurrences. Owners should be instructed to purchase preservative-free formulations in over-the-counter products. Palatable lysine-containing pastes and fish-flavoured powders are available as veterinary formulations.
Topical non-steroidal antiinflammatory agents and ciclosporin reduce inflammation and scarring in studies of herpesvirus in humans, rabbits and mice, but their safety in cats is unknown. Whenever corneal or conjunctival ulceration or other evidence of active cytolysis is present, antiinflammatory medication of any type is ill advised. Glucocorticoids have deleterious effects including increased risk of ulceration, prolonged virus shedding and induction of stromal keratitis, and should not be used. Many of the particularly refractory cases of ocular FHV-1 infection seen in our practice are preceded by the use of topical corticosteroids in patients with conjunctivitis.
Corneal erosions with poorly adherent marginal epithelium should be gently debrided with a cotton-tipped applicator after applying topical anaesthetic. The swab may be moistened with povidone-iodine. Superficial keratotomy is not recommended in the management of refractory ulcers secondary to feline herpesvirus due to the risk of subsequent corneal sequestration.
Corneal Sequestrum
Corneal sequestration is characterised by a brown to black plaque that develops in the central or paracentral feline cornea. The lesion represents coagulation necrosis of the corneal stroma. Although many theories relating to chronic corneal insult have been advanced, the exact aetiology of the disorder is unknown. The mechanism underlying the lesion's bronze to black colour likewise remains a mystery. Retrospective studies indicate an anatomical predisposition to sequestrum formation in brachycephalic breeds of cat and a relationship with herpesvirus infection in non-brachycephalics.
The problem is most often unilateral but can affect both eyes simultaneously. In addition to the characteristic colour change of the affected cornea, clinical signs include varying degrees of ocular discharge and blepharospasm. The epithelium overlying the sequestered tissue is commonly missing but fluorescein retention is usually seen only at the margins of the sequestrum. With time, corneal oedema, adjacent inflammatory cells and vascularisation develop. With luck, a sequestrum may slough spontaneously after several weeks to months.
Topical antibiotic therapy may be used to prevent secondary bacterial infection. Topical corticosteroids are generally contraindicated owing to the state of the epithelium and the possible aetiological link with feline herpesvirus. Topical lubricants symptomatically decrease discomfort by providing a barrier over exposed corneal nerve endings. A German study suggested topical interferon alpha-2b (compounded to 3000 IU/ml) applied two to four times daily speeds resolution of the sequestrum without the need for surgery. In the author's patients, the clinical course is shortened when interferon therapy is initiated early in the sequestrum's development rather than when used in chronically affected eyes. In patients with a stubborn sequestrum, in those with notable discomfort or in cats with progressive vascularisation and scarring, a keratectomy is indicated to remove the sequestrum. A temporary tarsorrhaphy, thin conjunctival graft or lamellar corneal graft reduces the likelihood of recurrence of the sequestrum. The second eye may also develop a sequestrum at a later date, in some cats even years later.
Eosinophilic Keratitis
Eosinophilic keratitis is a progressive, infiltrative corneal disease that usually affects young adult mixed-breed cats. Cell types in affected tissues suggest an immunological aetiology. Herpesvirus infection has been documented concurrently in some patients. Unilateral lesions predominate, with bilateral involvement in only 25-33% of patients. The typical lesion appears as a raised, irregular, white to pink vascularised mass affecting the superior temporal or inferior nasal corneal quadrants. A white, friable exudate customarily adheres to the surface, sometimes organising into a distinct plaque that can also extend over the adjacent bulbar and palpebral conjunctiva. Fluorescein retention is usually negligible.
Diagnosis is based on clinical signs and cytology. Scrapings of the lesion contain eosinophils, mast cells and mixed inflammatory cells; biopsy specimens often include lymphocytes and plasma cells.
Treatment includes topical corticosteroids (1% prednisolone acetate or 0.1% dexamethasone q6h), gradually tapering the frequency as response to therapy occurs. Topical 0.03% tacrolimus solution is effective in some patients. Rapid improvement occurs with concurrent topical corticosteroids and oral megestrol acetate (5 mg daily for 5 days, quickly tapering the dose to avoid endocrinological complications). A topical antiviral should be included in patients infected with herpesvirus. Approximately 60% of patients with eosinophilic keratitis will relapse if therapy is discontinued.
Anterior Uveitis
Whether FHV-1 is a primary cause or a contributing factor to feline uveitis is undetermined. FHV-1 DNA and FHV-1-specific antibodies were detected in the aqueous humour of 15% and 27% of cats with idiopathic anterior uveitis, respectively.