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«Feline Ophthalmology Alexandra van der Woerdt, DVM, MS, DACVO, DECVO Staff Ophthalmologist Associate Director, Bobst Hospital The Animal Medical ...»

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The 25th Annual

Waltham/OSU Symposium

Small Animal Ophthalmology

October 27—28, 2001

Feline Ophthalmology

________________________________________

Alexandra van der Woerdt, DVM, MS, DACVO, DECVO

Staff Ophthalmologist

Associate Director, Bobst Hospital

The Animal Medical Center

510 East 62nd Street

New York, NY 10021

212-329-8729

212-752-2592 (fax)

sandra.vanderwoerdt@amncy.org

________________________________________

Ophthalmic examination of a feline patient follows the same principles as ophthalmic examination of the canine patient.

A few differences exist between dogs and cats that present the clinician examining a feline patient with a few unique challenges. The menace response is often subtle in cats. Many cats will respond with a subtle movement of the upper eyelid only. Some cats, especially brachycephalic cats, may not respond initially. A few gentle taps on the eyelids prior to repeating the menace gesture will usually solve this problem. Cats have the ability to actively protrude the third eyelid, and prevent visualization of the globe. Limiting restraint to the absolute minimum necessary in combination with avoiding very bright light during the ophthalmic examination will prevent third eyelid protrusion in most cats. If this doesn’t work, it may be necessary to apply topical anesthetic, such as 0.5% proparacaine, to the cornea, and gently push the third eyelid out of the way with a cotton tip applicator. Pupillary light reflexes are usually brisk and complete in cats, limiting visualization of deeper intraocular structures. Decreasing the amount of light used during the examination usually prevents this problem, but 1% tropicamide may be necessary to dilate the pupil for complete examination of the fundus.

Conjunctivitis Conjunctivitis is a common problem in cats and is usually of infectious origin. The most common causes for feline conjunctivitis include infection with Chlamydia psittaci, Mycoplasma felis or feline herpes virus 1 infection. Other infectious causes include salmonella, M. gatae, reovirus and calicivirus. Clinical signs of Chlamydia psittaci infection include conjunctival hyperemia and chemosis in one or both eyes. Formation of conjunctival follicles may be present.

Chlamydia does not affect the cornea. Intracytoplasmic inclusion bodies may be found during the first 2-9 days after the onset of clinical signs. Polymerase chain reaction is more sensitive for detecting Chlamydia infection than culture.

Treatment consists of topical tetracycline, chloramphenicol or erythromycin 3-4 times a day for 10-14 days. Chlamydia infection is seen in cattery situations in which asymptomatic queens carry the infectious agent in the urogenital tract. If chlamydia 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. Non-infectious causes for feline conjunctivitis include eosinophilic conjunctivitis, allergic conjunctivitis, hypersensitivity reaction and tear film disorders.

Feline herpes virus infection Clinical signs Feline herpes virus 1 (FHV-1) infection is a very common infection in cats. FHV-1 is an alpha herpes virus. It has been associated with many ocular diseases in cats including conjunctivitis, keratitis, corneal ulceration, symblepharon formation, chronic epiphora, eosinophilic keratitis, sequestrum formation, keratoconjunctivitis sicca and anterior uveitis.

Primary infection with feline herpes virus manifests itself usually in the respiratory tract and the eyes. FHV-1 replicates in epithelium of nasal mucosa, conjunctiva, tonsil and nasal turbinates. Tissue damage during active infection is due to viral cytolisis.1 Clinical signs include lethargy, fever, sneezing, nasal and ocular discharge, conjunctival hyperemia and chemosis. One or both eyes may be affected. In more severe cases, the corneal epithelium is affected as well leading to corneal ulceration. Dendritic corneal ulcerations represent viral replication within the corneal epithelium. Corneal lesions are most common on days 3 and 12 of the primary infection. Lysis of conjunctival epithelium cells with subsequent virus release is responsible for the corneal lesions seen around day 12 of the primary infection.1 Dendritic ulcers may coalesce to form larger geographic ulcerations. Secondary bacterial infection may lead to deep corneal ulceration or corneal perforation. Iris prolaps and anterior synechiae may form after corneal perforation. Adhesions between third eyelid and the cornea or eyelids may lead to permanent protrusion of the third eyelid. The corneal epithelium may be replaced by conjunctival-like epithelium that contains blood vessels and is not completely transparent. Approximately 80% of cats infected with FHV-1 will become carriers of the virus after the initial infection. The virus has been isolated from trigeminal ganglia, olfactory bulb, optic chiasm, and optic nerve in asymptomatic cats. Extraneural latency in the cornea has also been suggested. Spontaneous shedding occurs in 30% of cats. Recrudescent infections frequently involve the eyes only. Reactivation of the virus in the trigeminal ganglion and axonal transport along the trigeminal nerve to the affected eye is responsible for recrudescent infection. Conjunctivitis with or without keratitis lasting from a few days to several weeks is seen. Epithelial and stromal keratitis with cellular infiltration and edema may be seen in recrudescent infections.





Stromal keratitis is not a direct result of virus infections, but occurs as CD4+ T lymphocytes mount a specific immune response to viral proteins.

Diagnosis of feline herpes virus infection Feline herpes virus infection should be suspected in any young cat with uni-or bilateral conjunctivitis with corneal involvement. The presence of dendritic ulcerations is considered pathognomonic for FHV-1 infection. Dendritic corneal ulcerations may initially involve the epithelium only and are therefore fluorescein negative. Use of Rose Bengal stain will allow visualization of dendritic ulcerations. Especially in recrudescent infections, dendritic ulcers are often absent.

Laboratory methods used in the diagnosis of FHV-1 infection include serum antibody titers by serum neutralization or ELISA, virus isolation, immunofluorescent assay or PCR assay. Diagnosis of FHV-1 infection may be difficult. Serum antibody titers against FHV-1 were found in 97% of normal cats and cats with conjunctivitis in one study, indicating that single or paired FHV-1 antibody titers are not useful in the diagnosis of FHV-1 infection. A significantly higher titer was found in cats without conjunctivitis as compared to cats with conjunctivitis indicating a possible protective action of a high antibody titer. Virus isolation has been used as the gold standard in research situations for many years. Sample handling is difficult and the test takes over a week to perform, making this test of limited use in clinical practice.

Immunofluorescent assay performed on a conjunctival scrape detected only few affected cats in one study. False positive results may occur if the sample is taken from the eye after application of topical fluorescein. Polymerase Chain Reaction assay is a very sensitive method of detecting even limited amounts of DNA. Polymerase chain reaction amplifies small quantities of DNA to detectable amounts. The sensitivity of PCR for FHV-1 diagnosis is superior to other methods. Less than 30 copies of the FHV-1 genome is the detection limit reported for one laboratory.1 PCR was 80% more sensitive than virus isolation in one study evaluating virus shedding in asymptomatic cats. Samples, once collected, should be frozen.

Chances of obtaining a positive result are better when more cellular material is submitted. The sensitivity of nested PCR is even greater than single round PCR, but does increase the possibility of false positive results.

Treatment of feline herpes virus infection Conjunctivitis without ulcerative corneal disease can be treated with topical antibiotic therapy only. The disease is selflimiting and lasts less than 2 weeks in most otherwise healthy cats. Examples of topical antibiotics include tetracycline, chloramphenicol, erythromycin, or gentamicin. Some cats may develop an allergic reaction to the neomycin component of triple antibiotic solution or ointment, making this a less desirable choice in cats. Antiviral medications are indicated in cats with ulcerative corneal disease, or in cats with a compromised immune system. Examples of antiviral medications, in decreasing order of potency include trifluridine, idoxuridine and vidarabine. These drugs work by interfering with DNA synthesis and viral replication. Antiviral medications need to be used frequently in order to be effective. Bacteriologic culture and sensitivity may be indicated in corneal ulcerations with secondary bacterial infections. Ciprofloxacin topically may need to be used in infected corneal ulcers. Systemic antiviral medications are used infrequently in cats because of limited efficacy (Acyclovir) or pronounced toxicity (Valacyclovir). Acyclovir inhibits viral replication by interfering with DNA synthesis. The drug has to be activated by viral-specific thymidine kinase, which makes it non-toxic to normal cells and allows it to be used systemically. The ED50 of acyclovir for treatment of FHV-1 is very high, however this can be lowered by combining acyclovir with interferon. Interferon facilitates incorporation of acyclovir into the viral genome, allowing lower plasma acyclovir levels to be effective against FHV-1 infection. The immune system is important in controlling a FHV-1 infection. L-lysine is an essential amino-acid that has been shown to significantly reduce virus shedding in affected cats and decrease the duration of FHV-1 infection. It suppresses FHV-1 replication by competing with arginine for incorporation into the viral genome. Dose of l-lysine used in various studies varies between 250 mg once a day to 500 mg twice a day over the food. L-lysine appears to be most effective when used early in the course of the disease. Parenteral vaccination with FHV-1 vaccines is not recommended in the treatment of FHV-1 infection. Intranasal and ocular application of modified live FHV-1 vaccine stimulate a mucosal immune response and local antibody production. This may result in some improvement in cats with chronic low-grade FHV-1 conjunctivitis. This should not be done in cats with stromal keratitis.

Recrudescent infections are initiated by a temporary reduction in the immune system allowing the virus to become active again. Stressful situations will often precipitate recrudescent infections. Examples include moving, introduction of a new cat, dog or person into the household, general anesthesia or other systemic diseases. Reducing or preferably eliminating these stressful situations will aid in the recovery of FHV-1 infection.

Complications secondary to feline herpes virus infection Chronic epiphora may persist after the conjunctivitis resolves. Chronic epiphora may be secondary to symblepharon formation in the area of the nasolacrimal punctae, or stricture of the nasolacrimal system. Attempts to irrigate the nasolacrimal system are usually unsuccessful. Symblepharon formation is common after severe infections. Minor adhesions between eyelids and third eyelid or between conjunctiva and cornea can be surgically corrected under general anesthesia. Extensive symblepharon formation is difficult to correct surgically. It is possible to dissect the conjunctiva-like tissue from the cornea and reconstruct a conjunctival fornix, however recurrences are very common making this surgery often unrewarding.

Keratoconjunctivitis Sicca (KCS) is uncommon in cats. The most common etiology in dogs is an immune-mediated destruction of the lacrimal gland. The most common etiology in cats is destruction of the lacrimal gland by FHV-1 infection. The diagnosis of KCS can be difficult in cats. Clinical signs can be subtle and may include blepharospasm, conjunctival hyperemia and mucoid discharge. Biomicroscopic examination of the tear film reveals a thin tear film with a granular appearance. As compared to dogs, clinical signs are always very subtle. The severe corneal changes that may be present in dogs such as vascularization, fibrosis and pigmentation are usually absent in cats. The tear production can be measured using Schirmer Tear Test strips, but the results should be interpreted with caution. A very low value for tear production can be present in normal cats and the results of the STT tests should be interpreted in light of the clinical findings. The phenol read thread tear test has been suggested as an alternative way of evaluating tear production in cats.2 Treatment consists of artificial tear solution 2-4 times a day with artificial tear ointment once or twice a day. Intermittent use of topical antibiotics is occasionally necessary to treat secondary infections. Topical cyclosporine has not been approved for use in cats and its use is not recommended for treatment of KCS in cats.

Eosinophilic keratitis and conjunctivitis Eosinophilic keratitis is an immune-mediated inflammatory disease of the cornea that is characterized by progressive vascularization and cellular infiltration of the cornea.3 It most commonly affects young adult, mixed breed cats. There is often little discomfort present. The disease often starts near the lateral or ventromedial limbus, and may affect one or both eyes. Typical clinical findings include vascularization and infiltration of the perilimbal cornea, presence of gritty, white corneal plaques, inflammation of the adjacent conjunctiva and third eyelid and ocular discharge.3 Eosinophilic keratitis should be suspected in any cat with a relatively pain-free slowly progressive corneal vascularization with white infiltrative plaques in the cornea. The diagnosis can be confirmed by cytologic examination of a corneal scrape specimen using a Kimura spatula. Eosinophils and mast cells are present. Treatment consists of topical corticosteroids such as 1% prednisolone acetate or 1% prednisolone phosphate. These medications are used initially 2-4 times a day until all clinical signs disappear and then slowly discontinued over months. Recurrences are common, especially if medications are discontinued too quickly. Systemic megestrol acetate can be used if ulcerative keratitis is present or if the character of the cat prevents treatment with topical eye medications.



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