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Treatment of Infectious Disease of the Eye

By Nick Whelan, BVSc, MVSc, MACVSc, DACVCP, DACVO, Animal Eye Clinic of Waterloo Region, Cambridge, Ontario, Canada

Feline Herpesvirus Keratitis and Conjunctivitis:

Systemic antiviral drugs to treat feline ocular herpesvirus are needed only in circumstances when topical antiviral therapy is not effective. Famciclovir (the prodrug of penciclovir) at 15–30 mg/kg, PO, bid-tid for 10–14 days (or empirically at 31.25 mg/kitten or small cat, or 62.5 mg/cat, bid for 2 wk) is the drug of choice for treatment and longterm management. Acyclovir has also been used at 200 mg, PO, bid-tid, although repeated dosing can cause systemic toxicity and is not recommended as first-line treatment. Previously, lifelong oral l-lysine (250–500 mg/day) was recommended to help prevent or reduce the severity of recurrent feline herpesvirus infections. However, recent work has shown that oral L-lysine can actually exacerbate feline herpesvirus infections. Recombinant human α-interferon (5–25 U/day, PO and topically) has also been recommended and may work by inhibiting replication of herpesvirus and enhancing macrophage activation and lymphocyte-mediated cytotoxicity.

Feline Chlamydial Conjunctivitis:

Feline conjunctivitis caused by Chlamydia felis (see Chlamydial Conjunctivitis) that is nonresponsive to topical tetracycline therapy can be treated with oral doxycycline (10 mg/kg/day, or 5 mg/kg, bid). To avoid esophageal strictures, animals should be treated with 3–5 mL of oral fluid after dosing to ensure the tablets pass into the stomach. All cats in the household should be treated for at least 4 wk, or for 2 wk after clinical signs have resolved. To avoid issues associated with tetracycline use in pregnant queens or young cats, systemic macrolides such as erythromycin (15–25 mg/kg, PO, bid, or 10–15 mg/kg, PO, tid for 3–4 wk) or azithromycin (10–15 mg/kg/day, PO, for 3–5 days then twice weekly for 3 wk) are also effective. Alternatively, potentiated amoxicillin (12.5–25 mg/kg, bid for 3 wk) can be used. If signs recur after treatment ceases, therapy should be continued for an additional 4–5 wk.

Feline Toxoplasmosis:

Many cases of feline anterior uveitis with increasing Toxoplasma gondii titers, as shown by serology and anterior chamber centesis, remain undiagnosed. Chorioretinitis is often the most common presentation. Treatment is clindamycin at 8–17 mg/kg, PO, tid, or 10–12.5 mg/kg, PO, bid for 3–4 wk, in association with topical corticosteroids (0.5%–1% prednisolone acetate or 0.01% dexamethasone alcohol tid-qid) and topical atropine for mydriasis. Adverse effects of clindamycin include anorexia, vomiting, and diarrhea, mainly at the higher doses. Other systemic antibiotics less frequently used include the synergistic combination of sulfonamides (sulfadiazine, sulfamethazine, sulfamerazine, 100 mg/kg/day, PO) and pyrimethamine (2 mg/kg/day, PO) for 1–2 wk. Adverse effects include gastric upsets and bone marrow suppression. Frequent hematologic monitoring is recommended if therapy is to last >2 wk.

Feline and Canine Rickettsial Infection:

Anterior and posterior uveitis and chorioretinitis secondary to infection with Ehrlichia or Rickettsia spp (see Rickettsial Diseases) is common. Tetracyclines (doxycycline at 5–10 mg/kg, once to twice daily for dogs, and 10 mg/kg, bid, for cats, for 14–21 days) are the drugs of choice and have excellent intraocular penetration. In a dog from an area associated with rickettsial disease, it is rational to empirically treat uveitis with doxycycline pending serology. Enrofloxacin (3 mg/kg, PO, bid for 7 days) can also be used, although care should be taken not to exceed the dosage associated with retinal toxicity in cats (>5 mg/kg/day). Chloramphenicol is not recommended, because it directly interferes with heme and bone marrow synthesis. Appropriate topical and systemic NSAID therapy is also recommended to control ocular inflammation. When the intraocular inflammation is severe or there is a serous retinal detachment, short-term (2–7 days) corticosteroids (0.25–0.5 mg/kg, PO, once to twice daily) may be used concurrently 24–48 hr after the start of oral antibiotic therapy. Animals can regain some vision after reattachment of the retina; the amount depends on the duration of the detachment and degree of inflammation.

Canine and Feline Ocular Mycoses:

Dogs and cats diagnosed with ocular mycoses require systemic treatment. Along with systemic antifungals, topical and systemic anti-inflammatories and topical mydriatics/cycloplegics are needed to control the secondary and potentially blinding intraocular inflammation.

Blastomycosis (see Blastomycosis) is more common in dogs than cats. Up to 40% have ocular signs, usually anterior uveitis. Treatment options include parenteral amphotericin B deoxycholate or PO or IV triazoles. In dogs, itraconazole is used at 5 mg/kg, PO, bid for 5 days, then continued at 5 mg/kg/day, PO, for a minimum of 60 days or 1 mo after all signs of the disease have resolved. Adverse effects include anorexia, which is associated with liver toxicity. Cats can be treated with 10 mg/kg/day or 5 mg/kg, bid; however, there are few published cases of successful treatment in cats. Ketoconazole may also be used to treat blastomycosis, but because the onset of effect is so slow, other triazoles should be used initially. Amphotericin B deoxycholate is also effective but is nephrotoxic. The dosage (dogs: 0.5 mg/kg, IV; cats: 0.25 mg/kg, IV) is given three times weekly until the animal becomes azotemic or a cumulative dose of 4–6 mg/kg in dogs or 4 mg/kg in cats is reached. Amphotericin B lipid complex used at the same or a slightly higher dosage is less nephrotoxic.

The predominant lesion of histoplasmosis (see Histoplasmosis) is granulomatous choroiditis, but anterior uveitis, retinal detachment, and optic neuritis can be present. Treatment options are itraconazole (10 mg/kg, PO) or fluconazole (2.5–5 mg/kg, PO) once to twice daily for 4–6 mo, or amphotericin B deoxycholate (0.25–0.5 mg/kg, IV, every 48 hr) until a cumulative dose of 5–10 mg/kg (dogs) or 4–8 mg/kg (cats) is reached. Because of its lipophilic nature and ability to cross the blood-ocular barriers, fluconazole is recommended for use in ocular disease, although animals have also had complete resolution when treated with the more hydrophilic triazole itraconazole.

Ocular signs are present in 15% of cryptococcosis (see Cryptococcosis) cases and are more common in cats than in dogs. Treatment can be with amphotericin B deoxycholate (0.1–0.5 mg/kg, IV, three times per wk) alone or in combination with flucytosine (30–75 mg/kg, bid-qid for up to 9 mo). Ketoconazole, itraconazole, and fluconazole are also effective. In cats, ketoconazole is administered PO at either 5–10 mg/kg, bid, or 10–20 mg/kg/day for 6–10 mo. If toxicity occurs, the dosage can be changed to 50 mg/kg/cat, PO, every other day. In dogs, dosages are either 5–15 mg/kg, PO, bid, or 30 mg/kg/day, PO, for 6–10 mo. Systemic absorption from the GI tract is significantly enhanced by food. Adverse effects of ketoconazole include anorexia, diarrhea, vomiting, and increased liver enzymes. Because of poor CNS penetration, ketoconazole is not recommended for use as the sole agent in ocular cryptococcosis. Itraconazole (cats: 5–10 mg/kg, PO, bid, or 20 mg/kg/day, PO) is less likely to cause adverse effects than ketoconazole, and its GI tract bioavailability is enhanced by fatty food. Like ketoconazole, its hydrophilic nature leads to poor distribution into the CNS, but it has been successful in treating CNS and ocular cryptococcosis. Adverse effects are mainly associated with the GI tract (anorexia and vomiting), but liver disease can also develop. Liver enzymes (ALT) should be monitored every 2 wk for the first month of treatment and monthly thereafter. Fluconazole is more lipophilic and has better bioavailability than itraconazole. It also penetrates the CNS better (60%–80% of serum levels) and causes fewer adverse effects than itraconazole. The dosage for cats and dogs is 5–15 mg/kg, PO, once to twice daily for 6–10 mo.

Ocular coccidioidomycosis (see Coccidioidomycosis) is more common in dogs than in cats. Ocular involvement requires systemic treatment with ketoconazole (dogs: 15–20 mg/kg, PO, bid; cats: 15–20 mg/kg, PO, once to twice daily), although there is poor CNS and ocular penetration. Ketoconazole can be toxic in cats, so itraconazole (5–10 mg/kg/day, PO) would be a safer choice. Treatment is for 3–6 mo or longer, and relapses are common. Amphotericin B deoxycholate can also be used (0.4–0.5 mg/kg, IV, every 48–72 hr) until a cumulative dose of 8–11 mg/kg is reached.

Over the past 10 yr, a number of newer triazoles (voriconazole, ravuconazole [both fluconazole derivatives], and posaconazole [an itraconazole derivative]) with broader spectrum of activity against systemic mycoses (including those resistant to other azoles) have become available. Information on their clinical usage is limited and mostly published as pharmacokinetic studies or individual case reports. Doses have been extrapolated from their use and preclinical toxicology trials in people, and using these doses must be done carefully. Because posaconazole is primarily metabolized in most species by glucuronidation, care needs to be taken with the dose and duration, especially in cats. Voriconazole is predominantly hepatically metabolized, and in toxicology trials, chronic usage at 12 mg/kg for 6–12 months caused hepatotoxicosis. Very limited information is available on the use of ravuconazole in dogs and cats. The current literature should be reviewed before using any of these compounds.

Infectious Keratoconjunctivitis:

Treatment of infectious keratoconjunctivitis (see Infectious Keratoconjunctivitis) associated with Moraxella bovis in cattle is improved with use of systemic antibiotics. Oxytetracycline and florfenicol are the two most commonly used. Two doses of parenteral long-acting oxytetracycline (20 mg/kg, IM or SC) 48–72 hr apart is effective, although care should be taken using tetracyclines in endemic anaplasmosis areas. Florfenicol, at a single dose of 40 mg/kg, SC, or two doses of 20 mg/kg, IM, 48 hr apart, is also effective. The organism is also sensitive to trimethoprim-sulfonamide (15–30 mg/kg, IM or IV, once to twice daily) or a single SC dose of tilmicosin (5–10 mg/kg), ceftiofur (6.6 mg/kg), or tulathromycin (2.5 mg/kg). M bovis is resistant to systemic macrolides, lincosamides, and often penicillins.

Chlamydial keratoconjunctivitis in sheep and goats and nonchlamydial keratoconjunctivitis caused by Mycoplasma spp in goats can be treated with systemic antibiotics in addition to topical therapy. These include oxytetracycline (6–11 mg/kg, IV or IM), florfenicol (20 mg/kg, IM or SC), tylosin (10 mg/kg, IM), erythromycin base (2.2–15 mg/kg, IM, once to twice daily), or tilmicosin (10 mg/kg, IM). Most animals are treated with a single dose because of management issues involved in treating flock outbreaks.

Penetrating Trauma:

All penetrating wounds of the eye should be considered infected, and animals should be treated promptly with systemic broad-spectrum bactericidal antibiotics. For dogs and cats, oral amoxicillin-clavulanic acid (10–20 mg/kg, bid) is appropriate. When feasible, culture and sensitivity and cytology performed on anterior chamber centesis samples best guide appropriate antibiotic selection. Treatment should continue for a minimum of 14–21 days. In horses, the combination of systemic penicillin G procaine (22,000–44,000 U/kg, IM, bid) and gentamicin (6.6 mg/kg/day, IM or IV) is an appropriate choice.

In all cases, intensive systemic NSAIDs (flunixin 0.5–1 mg/kg, IV or PO, once to twice daily; ketoprofen 1.1–2.2 mg/kg/day, PO or IV) are warranted to control the severe inflammation usually associated with these injuries. Because treatment duration in these cases extends beyond label recommendations of 5 days, an appropriate H2-blocker (ranitidine, famotidine) or proton pump inhibitor (omeprazole) should be used prophylactically to prevent gastric ulceration. When inflammation is also associated with leakage of lens material into the anterior chamber, the only treatment to control the inflammation is removal of the lens.