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Feline Herpetic Keratitis

 

Herpes Virus Infection in the Eye

The feline herpesvirus I (FHV-1) is the causative virus of Feline Viral Rhinotracheitis (FVR), an upper respiratory tract infection, and associated viral eye infections. It has the ability to persist in latent form in the eye making reoccurrence (or recrudescence) of infection common. Eighty percent of cats become carriers following primary infection and vaccinated cats may become chronic carriers without evidence of clinical disease. Recrudescence may be associated with stress, surgery, lactation, corticosteroid therapy, and immunosupression from Feline Leukemia Virus (FeLV) or Feline Immunodeficiency Virus (FIV) infection.

FHV-1 propagates readily in the epithelium of the respiratory tract and the conjunctiva. The course of infection in the conjunctival epithelium is self limiting. Epithelial damage is evident in two days and is most pronounced in seven to ten days post infection. Intranuclear inclusion bodies are readily identified in histologic section of affected tissue, but they are less readily identified on cytological examination of conjunctival scrapings.

Acute FHV-1 infection usually occurs in neonatal and young adult cats. The upper respiratory signs predominate with sneezing and nasal and ocular discharge being most notable. The ocular signs include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. Corneal lesions are much less conspicuous during acute primary FHV-1 infection. Microdendritic lesions may be seen between three and six days after infection. Larger dendrites may be seen around day eleven after a new wave of virus particles are released from degenerating conjunctiva. These lesions are subtle and only occasionally do the dendrites coalesce to form larger geographic lesions. Corneal infection at this stage results in relatively little cytopathic effect, with no inflammatory response. A mild transient superficial vascularization may occur.

It is during this stage that viral latency is established. It is reactivation of latent virus that is responsible for the recrudescent infection seen in older cats. Recrudescent infections generally occur in adult cats that presumably have recovered from primary FHV-1 infection earlier in life. In the adult cat, recrudescent FHV-1 infections may cause conjunctivitis only, or may also cause keratitis. Upper respiratory tract symptoms are usually absent. The conjunctival form generally consists of mild conjunctival hyperemia, and intermittent ocular discharge. The course may be prolonged and often is recurrent. Should corneal involvement occur, dendritic epithelial lesions may be seen using a vital stain such as Rose Bengal. The dendrites often coalesce to form geographic "map like" lesions. Often mild stromal edema and superficial stromal vascularization follow. Stromal involvement in herpetic keratitis is of great concern due to the marked amount of stromal scarring that can occur. This form is characterized by stromal edema, deep vascularization, inflammatory cell infiltrates and ultimately collagen damage and opacification. It is thought that the stromal form of FHV-1 keratitis is not a direct effect of the virus on keratocytes, but an pathologic immune reaction to viral antigen which is mediated by cytotoxic T lymphocytes.

Complications of herpetic keratitis include the development of keratoconjunctivitis sicca (dry eye), symblepharon (conjunctival to corneal adhesions) and corneal sequestration. KCS may occur as a result of lacrimal adenitis or it may be due to ductule obstruction in cats with FHV-1 conjunctivitis. The sicca tends resolve when the inflammation subsides. Symblepharon may occur wherever there is significant damage to the conjunctival epithelium, and as such may occur follow FHV-1 conjunctivitis. Feline sequestrum may occur whenever there is chronic damage or irritation of the corneal stroma, and may follow FHV-1 keratitis.

The diagnosis of FHV-1 ocular infections is based upon the clinical history, the findings on clinical examination and the results of the appropriate diagnostic tests. Corneal dendrites may be very subtle, and it is necessary to use Rose Bengal, a vital stain to detect them. Since full thickness epithelial erosions generally occur only in advanced disease, fluorescein stain may not be helpful. Virus isolation which for many years was the most sensitive means of making a positive diagnosis of feline herpesvirus ocular disease, has for the most part been replaced with the Polymerase Chain Reaction (PCR) test. A commercial virus collection swab is moistened with transport medium and rolled in the conjunctival fornix. The swab is then placed into the transport medium and submitted to the lab.

Conjunctival cytology is not a reliable method of diagnosing FHV-1 ocular disease. Intranuclear inclusion bodies are readily seen in histologic section of affected tissue, they are often not apparent on conjunctival smears. Intracytoplasmic inclusion bodies characteristic of chlamydial infection are more apparent with Giemsa staining of conjunctival smears. Conjunctival cytology is therefore of value in ruling out chlamydial conjunctivitis. It is unusual for chlamydia, mycoplasma or calicivirus ocular infections to cause corneal lesions.

The treatment of acute FHV-1 infection in young cats when upper respiratory involvement is present includes broad spectrum antibiotics given systemically and applied topically. General support may be required in compromised neonates and this may include fluids, heat and the use of a vaporizer. If corneal involvement is present, topical antivirals are prescribed. In the adult cat with recrudescent FHV-1 infection topical antivirals are best used aggressively early in the course of the disease before stromal involvement progresses. Three antiviral medications are available. Idoxuridine (IDU) interferes with viral DNA synthesis by substituting for the essential nucleotide thymidine. IDU is poorly soluble and is virostatic. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. IDU is marketed as Stoxil (Smith Kline & French) and Herplex (Allergan Pharmaceuticals). Adenine Arabinoside inhibits viral DNA polymerase and thus decreases viral DNA synthesis. It is sold as Vira A (Parke Davis) and the 3% ointment is applied five times daily. Triflurothymidine is incorporated into the viral DNA and leads to the synthesis of defective proteins. Sold as Viroptic (Burroughs Wellcome) it is considered the most effective, least toxic and most soluble of the antivirals. It is also the most expensive. Available as a 1% solution, Viroptic is applied every two hours while the animal is awake until the cornea has re-epithelialized, then reduced to every four hours while awake, for two weeks more. Acyclovir is the newest antiviral available for human herpesvirus. It is a tablet given orally and is marketed under the trade name Zovirax (Burroughs Wellcome). Research by Nasisse indicates that triflurothymidine is the most effective against Feline Herpesvirus followed by Idoxuridine then Adenine Arabinoside. Although Acyclovir was most effective against Human herpes simplex virus, it was not effective against Feline Herpesvirus. This may be due to the inability of FHV-1 to induce deoxycytidine kinase.

Other strategies to assist in the treatment of herpetic keratitis reported in the last few years include topically applied interferon, oral administration of l - lysine and oral administration of cimetidine. Interferon is reported to stimulate the local immunity to viral infection. A 20 to 50 IU/ml solution in artificial tear is administered topically twice daily. Orally administered l - lysine has been reported to inhibit herpesvirus growth by competitive inhibition of the uptake of arginine which is required for viral multiplication. It is given to cats at a dosage of 125 mg twice daily. Cimetidine has been shown to generally stimulate cell mediated immunity. It is given at a dosage of 50 mg once daily. Anecdotal reports suggest that maintenance of cats on one or more of these medications during periods of quiescence, will result in a longer period of time before recrudescence of infection occurs, and that when recrudescence occurs, the infection in milder and of shorter duration.

Corticosteroids may be used in the treatment of chronic herpetic stromal keratitis to suppress the potentially scarring immune response if used carefully and in conjunction with an antiviral agent. Steroids are contraindicated if epithelial or conjunctival involvement is still active, because they delay re-epithelialization, prolong virus shedding and may allow conjunctival and corneal epithelial infection to involve the corneal stroma. Alternatively, topical Cyclosporine may be used with caution to reduce the scarring associated with herpesvirus stromal keratitis.