Cidofovir shows promise in treatment of FHV-1 conjunctivitis

FORT COLLINS, COLO. — An antiviral drug used to treat humans for certain viral diseases is showing promise in the treatment of eye disorders associated with feline herpesvirus type 1 (FHV-1).

Cynthia Powell, DVM, MS, associate professor in ophthalmology at Colorado State University in Fort Collins, Colo., recently completed a study that examined the effectiveness of cidofovir as a treatment option for conjunctivitis caused by FHV-1.

Cidofovir is a parenteral antiviral agent used primarily to treat symptoms of cytomegalovirus (CMV) retinitis in humans with acquired immune deficiency syndrome (AIDS).

Powell read of studies in rabbits using an eye drop solution containing cidofovir .5%-1% to successfully treat conjunctivitis caused by adenovirus or herpes. Then a colleague told Powell that she had obtained positive results using the same treatment in cats that were suffering from keratitis associated with FHV-1.

"She suggested that this would be a good subject for a study at a research institution," Powell states.

Powell, a diplomate of the American College of Veterinary Ophthalmologists (ACVO) worked with Michael Lappin, DVM, PhD, professor in small animal medicine at Colorado State University to develop protocols for the research.

The study was supported by the Morris Animal Foundation and completed in October 2005.

FHV-1 conjunctivitis

FHV-1 is the causative agent behind feline viral rhinotracheitis and associated eye disorders. Because the virus is highly contagious, FHV-1 infections are common in catteries and in households that have more than one cat.

The initial infection is generally seen in younger or adolescent cats. It is characterized by upper respiratory symptoms, oral ulcers, hyperemia and redness of the conjunctiva, serous or mucopurulent discharge from one or both eyes and, in some cases, corneal ulcers.

Following recovery from the initial episode, most cats — up to 80 percent — may become latently infected with FHV-1. The virus may lie dormant indefinitely or it may flare up when the cat is stressed. Stressors may be physiologic, such as illness, estrus or pregnancy, or lactation, or from external causes such as disruption of the cat's household or normal routine, surgery or systemic illness, or corticosteroid therapy.

Symptoms of recurrent FHV-1 conjunctivitis may appear intermittently, or the cat may display chronic symptoms that do not resolve with treatment or time. Unlike the initial infection, usually only one eye is affected. Respiratory symptoms are not present in most chronic cases.

Limitations of current options

Treatments of chronic FHV-1 infections are usually focused on providing symptomatic relief through the use of ointments and artificial tears. If corneal ulcers are present, antibiotics may also be used to prevent secondary bacterial infections of the eye. But neither of these general approaches has any effect on the specific viral causes underlying the infection.

Effective antiviral treatments in recurrent instances of chronic FHV-1 conjunctivitis are a challenge due, in part, to the number of doses normally required to reach a therapeutic level. The very short half-life of these agents in the ocular tissues necessitates as many as five or six applications daily to be effective.

But an even larger problem results from the inherently irritating nature of these medications.

"Pretty quickly, cats will either hide to avoid receiving another painful treatment or they will hurt the person who is trying to apply the medication," Powell says. "Either way, it's a treatment failure."

Powell's study involved 12 cats, each 6 months old. The cats were carefully examined and certified to be free of pathogens prior to testing.

The research sought to identify the amount of virus present in the infected animals and document any difference in those animals treated with cidofovir.

"Was there a difference? Yes, there was," Powell tells DVM Newsmagazine. "We looked for the viral DNA and quantified it, counting the actual virus particles present. There were significantly fewer virus numbers in the treated cats than in the cats treated with placebo."

The second objective of the study was aimed at discovering whether the use of cidofovir had any effect on the duration and severity of the FHV-1-related symptoms.

While all cats showed upper respiratory symptoms and conjunctivitis, Powell reports that, in blind studies, there were "...significantly reduced clinical signs and duration of clinical signs in treated cats versus placebo."

No evidence of toxicity related to cidofovir was discovered during the study. Blood and urine testing on the cats conducted before and after treatment revealed no compromises in liver or kidney functions.

The cats involved recovered quickly and, at the conclusion of the study, were adopted out.

Next steps

Powell says that her next goal is to conduct broader clinical trials on cats with naturally occurring FHV-1. If those results are similar to those documented in this study, the next step would be to work at making cidofovir available for veterinary use.

In contrast to topical treatment options, other investigators continue to evaluate new systemic treatments for FHV-1-related infections. Famcyclovir is one antiviral agents being tested. Anecdotal reports of its use have been promising, with no adverse effects noted so far. However, completed investigations into its effectiveness and potential toxicity are needed before this drug can be officially recommended.