Feline keratitis and conjunctivitis (Proceedings)

Conjunctivitis is probably the most common ocular disease of cats, and is often infectious is origin. The most common viral cause of conjunctivitis is cats is FHV-1, but Reovirus and Calicivirus conjunctivitis are reported. Other infectious causes include Chlamydophila, Mycoplasma, systemic salmonellosis, and other less common non-infectious causes such as allergic and hypersensitivity reactions, tear film disorders and eosinophilic conjunctivitis.

Acute herpes virus keratoconjunctivitis is usually a bilateral ocular disease with systemic signs (upper respiratory signs, fever, lethargy). It is a very common cause of neonatal ophthalmia and is supposedly the only infectious, upper respiratory disease causing keratitis (ulcerative or interstitial). Two forms of ulcerative keratitis are usually seen: dendritic ulcers and geographic ulcers. The diagnosis can be obtained by various tests, however each has their potential pitfalls. The IFA test is a low yield test; if comes back positive it probably is. There is a high number of "false negatives". False positives are seen when an animal's cornea is stained with fluorescein prior to doing scraping. PCR testing (looking for amplified viral DNA) can be performed, but false negatives are common as laboratory processing is important in obtaining a definitive diagnosis. Conjunctival scrapings or biopsies can be put into laboratory specific transport media. The most common diagnostic test of the past was antibody titers, but it is felt by most to be useless, as most cats are naturally exposed or vaccinated with FVRCP. Virus isolation is considered the "gold standard", but it is expensive and only useful when special media can be immediately inoculated. Acute disease usually runs its course in immune competent animals within 14 days. The presence of dendritic ulcerations is considered pathognomonic for FHV-1 infection. Screening for FeLV/FIV in FHV-1 infected cats is recommended as immunosuppression is a common underlying cause of this disease in cats. Systemic symptoms of FHV-1 infection are treated with supportive care.

The initial therapy for ocular symptoms include supportive care and treatment with topical broad spectrum antimicrobials. Other therapies may include the application of Betadine solution (not the scrub) diluted in saline 1:10 (1% final concentration) several times daily, oral Interferon 30-100 (up to 1000) IU PO daily one week on, one week off. When disease is progressive, severe, and corneal or conjunctival ulcerations are present, topical and/or oral antivirals are indicated.

Various topical antiviral medications are available. The most commonly prescribed topical antivirals in cats include trifluridine, idoxuridine, vidarabine and cidofovir. Trifluridine, idoxuridine, and vidarabine need to be administered 6-8 times daily until effect and then slowly tapered thereafter, treating one week beyond resolution of clinical symptoms. Trifluridine is the only topical antiviral that is commercially available (Viroptic). Studies have shown this to be a very effective antiviral in cats, but is often associated with local irritation. Idoxuridine 1% can be obtained from compounding pharmacies and is usually well tolerated by cats. Cidofovir 0.5% is also available through compounding pharmacies and is the only topical BID antiviral, which makes it very appealing to clients (and their pets). In my experience, topical cidofovir is irritating to cats after 6 weeks or more of continuous treatment. Other topical antivirals available include a 3% compounded vidarabine (vira-A) and is well tolerated, but may be less effective at controlling the virus in cats.

Oral antivirals should be used with caution in cats. The only oral antiviral I currently recommend for cats is famcyclovir because high doses appear to be extremely well tolerated in cats. 125 and 250 mg tablets are available. Dose is 30mg/kg (anecdotal) to 90mg/kg (therapeutic -Maggs et al) PO BID-TID. Acyclovir 200mg PO BID-TID was previously recommended for cats, but most agree now this is not enough to maintain a therapeutic and tolerated dose. Consider ANY other oral antiviral (ie. Valacyclovir) to be hepato/nephro/myelo toxic and potentially lethal to cats!

L-lysine, an amino acid supplement, comes in 500 mg -1000mg tablets for humans which can used for cats. Various other veterinary specific flavored formulations are available as pastes/gels, powders, or Lysine can be compounded into flavored liquids by most compounding pharmacies. Currently I prescribe 250mg/day PO BID for cats <10# and 500 mg/cat PO BID for cats >10# in cases where recrudescence is common. Work at Purdue University showed that l-lysine therapy early in course of disease reduces duration of illness, viral shedding, and incidence of recrudescence. Various other studies are available in the veterinary literature. Lysine may work by binding arginine, an essential amino acid for FHV-1 replication.

Many and often the most severe cases of FHV-1 related disease seen at our clinics have a history of oral and/or topical use of steroidal medications that were prescribed for conjunctivitis. Both topical and/or systemic corticosteroids in the face of disease have been shown to increase viral shedding, the incidence of corneal sequestration (a surgical disease), and development of stromal keratitis (often a painful disease). Recurrent herpes viral conjunctivitis/keratitis and development of acute bullous keratopathy is often associated with immunosuppression and use of oral steroids (for diseases such as IBD, skin disease, etc). The point being: DO NOT USE TOPICAL CORTICOSTEROIDS IN CATS, ESPECIALLY IF FHV-1 IS SUSPECTED.

Nonulcerative causes of keratoconjunctivitis include Mycoplasma felis, Chlamydophila psittici, feline Calicivirus and Bartonella henselae). Mycoplasma is felt by some not be a primary infection and is only seen in association with FHV-1. This disease can start unilateral and become bilateral with time. There may or may not be an associated respiratory disease. Keratitis is not common. A "diphtheritic membrane" on the conjunctival surface is supposedly pathognomonic. Clinical signs of Chlamydia psittaci infection include conjunctival hyperemia and chemosis in one or both eyes often with formation of conjunctival follicles. Intracytoplasmic inclusion bodies may be found during the first 2-9 days after the onset of clinical signs, so conjunctival scrapings during initial outbreaks can be diagnostic. Polymerase chain reaction is available and appears more sensitive for detecting Chlamydophila infections. Treatment consists of topical tetracycline, chloramphenicol or erythromycin 4 times a day for 14 days. If Chlamydophila is present within a cattery, it may be necessary to treat all adult cats with 5 mg/kg doxycyline twice a day for 30 days to eliminate carriers since it is highly contagious and recovery from this infection does not necessarily translate to long-term protective immunity.

Reovirus and calicivirus conjunctivitis are also reported in the literature but clinical prevalence is not well documented. Reovirus infection may cause a serous ocular discharge associated with conjunctivitis, but appear to be of no long-term significance. Therapy is symptomatic as listed above. Calicivirus has been associated with the upper respiratory disease/conjunctivitis complex in cats, but some studies have shown that calici virus infection only rarely causes conjunctivitis in cats.

Recrudescent herpes virus disease is a very common clinical entity. 80% of cats infected with FHV-1 will be latently infected, and 45% will have spontaneous recurrences of clinical disease (and potential viral shedding). Stress (boarding, traveling) and immunosuppression (iatrogenic use of corticosteroids, other diseases, or FeLV/FIV), may cause acute recrudescence and clinical disease. Since the virus lays dormant in sensory nerve ganglia (trigeminal ganglia with distribution to the conjunctiva and cornea), recrudescence usually results in localized disease which may be unilateral or bilateral. Therapy is the same as for acute disease. DO NOT USE TOPICAL CORTICOSTEROIDS! In an attempt to mitigate severity of recurrent episodes, some will treat with l-lysine or topical antivirals prior to an anticipated stressful event.

Non-infectious causes for feline conjunctivitis include eosinophilic conjunctivitis, allergic conjunctivitis, hypersensitivity reaction and tear film disorders. All other infectious causes and treatments for viral infections should be performed before considering topical anti-inflammatories for these diseases in cats.

Corneal sequestrum is a unique clinical disease of cats and most often seen in the Asiatic breeds such as Persians, Himalayans, and the Burmese. There is light amber to dark black axial pigmentation of the corneal surface (localized necrosis of the epithelium and anterior stroma), which may progressively extend deep into the corneal stroma. This disease may be painful and elicit significant squinting, increased tearing, and often brown ocular discharge. Diffuse keratitis is often present as the disease progresses. It is thought that frictional irritation ("dry eye", entropion, exposure keratitis) is contributory. In research settings, inoculation with FHV-1 followed by topical and/or systemic corticosteroids resulted in sequestrum formation, as well as interstitial (stromal) keratitis (IOVS 30:1758-1768, 1989). Medical treatment can include treatment with broad spectrum topical lubricant antimicrobials to prevent infection, as the eye may slough the diseased cornea naturally. Corneal perforation is a risk with medical management alone. Surgical treatment options include superficial keratectomy and other supportive surgery (third eyelid flap, conjunctival graft, partial thickness keratoplasty, BioSIST) and medical therapy (antibiotics, antivirals). Since the disease may progress to affect the full thickness of the cornea, and involves often chronic and painful non-healing ulcers, surgical treatment options seem most appropriate in these cases.

Eosinophilic keratoconjunctivitis may be a bilateral disorder with no other history of eye disease consistent with FHV-1, or present unilaterally (occasionally bilateral) with a history consistent with previous FHV-1 infection. With the former presentation, it is usually young mature to middle aged cats (3-8 years). It is not necessarily a symmetric presentation. White to grey "plaques" appear on the corneal surface and over raised areas of lateral or nasal limbal neovascularization. It may or may not be painful and appears to be fairly seasonal in occurrence with summer months more common. Diagnosis is obtained via scrapings and cytology which show eosinophils, eosinophilic granules and occasional mast cells. This disease presentation often responds well to topical and/or systemic corticosteroids. When patients present with a history of previous FHV-1, topical steroids must be used with caution. These patients may have other prior signs (keratitis, dendritic ulcers, conjunctivitis, sequestra, symblepharon) and may respond well to topical/systemic steroids, or the eye may worsten (so monitor them closely). Systemic and topical antivirals are indicated when obvious ulcers are present and may be iniated prior to the use of topical steroids for safety. Systemic steroids in lieu of topical steroids in conjunction with antivirals may also be initiated in some refractory cases. Megestrol acetate 2.5-5mg mg per day for first 7-10 days, followed by weaning to a final dose sometimes as low as 1.25 mg every other week can be attempted,when topical therapy is not possible due to owner or patient compliance. Owners must be warned of the risks of diabetes mellitus and mammary gland hyperplasia with the use of Megestrol acetate and bloodwork must be submitted prior to the initiation of this medication.

Stromal keratitis patients often present with blepharospasm, the appearance of corneal edema (corneal infiltrates) and neovascularization. Often there is a history of conjunctivitis that was treated with topical or oral steroids. This condition is thought to represent a hypersensitivity to stromal viral antigens. Therefore, antiviral therapy alone or along with JUDICIOUS use of topical steroids can help control this painful condition. I will usually start topical antivirals alone. If disease progression is seen, I will add in oral antivirals. If the disease continues to progress, I may increase the dose of oral antivirals or initiate topical steroids, always warning clients of the potential for worsening the disease.

Symblepharon is a term that describes "adhesions" that occur between the conjunctiva, either to itself or to the cornea. It may involve the bulbar, palpebral or third eyelid conjunctiva. It will often result in a lack of palpebral/bulbar cul-de-sacs due to scarring and may appear as a membrane covering the entire corneal surface. It is often seen secondary to early FHV-1 infections and/or neonatal ophthalmia and tends to affect young cats in first few months of life. It is the most common cause of chronic epiphora in young cats due to the nasolacrimal duct system scarring over. If the cat is visual and comfortable without restriction to movement of the third eyelid, no therapy is necessary. If the cat is visually impaired, surgical excision of these membranes from the cornea, and/or manual break down of these adhesions can be attempted to reconstruct the conjunctival the cul-de-sacs. Concurrent antiviral therapy until the corneal and conjunctiva is healed is recommended. Recurrence of these adhesions is common and surgery often frustrating in severe cases.

Keratoconjunctivitis sicca is not commonly recognized in cats, and if often misdiagnosed given tear production in cats is normally lower than it is in dogs. Schirmer Tear Tests in cats can also be difficult to interpret because the sympathetic nervous system can cause STT values to be very low in normal cats. The diagnosis can made based on both low STT (commonly 5 or less) and other clinical signs such as a lackluster (dull appearing) cornea, a horizontal axial band of exposure keratitis, and often superficial corneal neovascularization. The heavy blood vessel in-growth, scarring and pigmentation seen in dogs is not common in cats with KCS. Some feel that FHV-1 infection is the initiating cause of KCS in most cats and is not immune mediated as it is in dogs. Therefore, therapy involving the use of cyclosporine-A may not be effective and must be used with caution as it may cause herpes recrudescence. Topical or systemic pilocarpine seems to do little good (as in dogs). Supportive lubrication works well and is recommended in all affected cats with conjunctivitis. Newer products that contain preservative free sodium hyaluronate are well tolerated and seem to make these patients more comfortable.

Anterior uveitis

A report in AJVR (60:932-936,1999) indicates that some cats with chronic anterior uveitis have FHV-1 antigen in aqueous humor as well as intraocular production of antibody against FHV-1. These results may indicate that some previously diagnosed "idiopathic uveitis" cases may have FHV-1 as an underlying cause. Systemic therapy with antivirals and judicious use of topical steroids may be useful in treating these previously frustrating cases.

Recurrent erosions (AKA "Indolent ulcers")

Most veterinary ophthalmologists believe that all "superficial erosion complex" cases in cats are a form of FHV-1 infection and not necessarily a degenerative disease of the cornea that often accompanies middle age and specific breeds as in the canine. Some ophthalmologists treat these with topical anti-virals and antibiotics, following gentle cotton swab debridement and/or treatments with dilute betadine. Topical bandage contact lenses or topical nalbuphine may also help improve patient comfort without delaying healing. A study in cats demonstrated that linear grid keratotomies in cats increased the rate of development of sequestra, and is therefore contraindicated.

References

Willis AM. Feline Leukemia Virus and Feline Immunodeficiency Virus. Vet Clinics of North America: Small Animal Practice: 30 (5) 971-986

Stiles J. Feline Herpesvirus. Vet Clinics of North America: Small Animal Practice: 30 (5) 1001-1014

Ramsey T. Feline Chlamydia and Calicivirus Infections. Vet Clinics of North America: Small Animal Practice: 30 (5) 1015-1028

LaCroix NC, van der Woerdt A, Olivero DK. Nonhealing corneal uilcers in cats: 29 cases (1991-1999). J Am Vet Med Assoc 2001;218:733-735

Morgan RV. Feline corneal sequestration: A retrospective study of 42 cases (1987-1991). J Am Anim Hosp Assoc 1994;30:24-28.