Equine Recurrent Uveitis: Introduction - The Merck Veterinary Manual

Equine Recurrent Uveitis: Introduction
(Periodic ophthalmia, Moon blindness, Equine uveitis)

Equine recurrent uveitis is one of the most common ocular diseases in horses, classically characterized by episodes of active inflammation followed by varying periods of quiescence. During the so-called quiescent periods, low-grade, subclinical inflammation may continue in at least some individuals. Regardless of the specific course, the inflammatory events eventually lead to secondary changes. It is these adverse secondary complications that make this syndrome the most common cause of blindness in horses worldwide.

Etiology and Pathogenesis:

Equine recurrent uveitis is an immune-mediated disease with many potential initiating causes. The common denominator is damage to the uveal tract, which may be initiated by trauma (both penetrating and blunt) or systemic disease. Specific conditions or agents implicated in the pathogenesis include leptospirosis, brucellosis, strangles ( Streptococcus equi infection), onchocerciasis, equine influenza, tooth root abscess, and hoof abscess. The most widely investigated of these are the Leptospira spp , in particular L interrogans serovar pomona , although other serogroups have been implicated. As active uveitis often does not occur for months, or even years, after the systemic disease, the exact relationship between leptospirosis and equine recurrent uveitis remains obscure. Although onchocerciasis is less common due to the routine use of ivermectin, equine recurrent uveitis is thought to be stimulated by dead or dying microfilaria that have aberrantly migrated to the eye. Therefore, active episodes of uveitis can be seen following normal worming.

Even though the immunologic basis for the recurrent nature of uveitis has been extensively studied, detailed understanding of the factors involved remains elusive. Sequestration of organisms, antigen, or antibody-antigen complexes within the anterior uvea has been advanced as an explanation for the chronicity of the ocular inflammation long after the initiating cause has resolved. Additionally, T lymphocytes have been found to be the predominant inflammatory cell type in clinical cases; their presence suggests a cytokine-driven, immune-mediated inflammatory response. The mechanisms by which this response is activated (or deactivated) remain unknown.

Clinical Findings and Lesions:

Recurrent equine uveitis

The clinical signs associated with equine recurrent uveitis include both acute signs of active inflammation and chronic secondary side effects. Damage to the uveal tract leads to the release of inflammatory mediators such as leukotrienes, prostaglandins, and histamines, which in turn causes increased permeability of anterior uveal vessels, breakdown of the blood-aqueous barrier, iris sphincter spasm, and ciliary body muscle spasm. The compromise of the blood-aqueous barrier allows for leakage of protein, fibrin, and cells into the aqueous. These responses account for the classic signs of acute uveitis: blepharospasm, epiphora, episcleral injection, corneal edema, aqueous flare, fibrin clots in the anterior chamber, and miosis. Often, the anterior segment signs restrict the visibility of the posterior segment. If visible, posterior segment signs of an acute episode may include an inflammatory cell infiltrate involving the retina and/or choroid, focal or diffuse retinal separation, retinal hemorrhage, and a hazy appearance to the vitreous secondary to infiltration by inflammatory or red blood cells. One or both eyes may be affected. When bilateral, it is not unusual for one eye to be more severely inflamed.

Corneal scarring, iridal fibrosis, blunting of the corpora nigra, posterior synechia, glaucoma, cataracts, and pigment clumping of the nontapetal fundus (retinal degeneration) are all signs consistent with chronic equine recurrent uveitis. The importance of careful fundoscopy as a part of prepurchase or soundness examinations cannot be overstated. Horses with chronic uveitis can have few or no anterior segment signs but may manifest equine recurrent uveitis by retinal degeneration. Such horses usually have normal or near-normal pupillary light responses and may not exhibit overt signs of visual compromise until late in the disease course. However, any horse with significant retinal degeneration must be suspected of having equine recurrent uveitis and therefore also regarded as a likely candidate for future vision compromise.

Diagnosis:

Onchocerca cervicalis microfilariae

While the diagnosis is based on the presence of characteristic clinical signs, an attempt should be made to identify the underlying cause. Because an acute episode of uveitis can be the first sign of systemic disease, a thorough physical examination should always be performed in addition to the ophthalmic examination. A CBC and serum chemistry panel are often included as part of the minimum database. Specific tests may aid in finding an underlying cause of the initial episode of uveitis. Serologic testing for Leptospira spp is frequently advocated, although a recent study did not find a correlation between serology for Leptospira spp and leptospiral antibodies or organisms in the aqueous humor of horses with equine recurrent uveitis. Serologic testing for Brucella may be done, but the marked reduction of brucellosis from cattle has probably lessened its role as a causative agent. Conjunctival biopsies from the lateral aspect of the bulbar conjunctiva may be examined for Onchocerca microfilaria, but results must be interpreted with caution as horses without equine recurrent uveitis may also exhibit these microfilaria. Paracentesis of either the anterior chamber or the vitreous cavity offers the possibility of identifying a causative agent; however, the procedure may cause severe intraocular damage, especially if attempted in a conscious patient.

Treatment, Prevention, and Control:

Therapy is initiated as soon as possible once signs of the acute phase are recognized. If a specific underlying cause can be identified, it should be addressed as part of the initial treatment protocol. In addition to dealing with the causative agent, or in instances where no specific cause is found, aggressive therapy with both topical and systemic anti-inflammatory medications is started to minimize the damage associated with intraocular inflammation. Both steroidal and nonsteroidal topical medications are commonly used. Prednisolone acetate (steroid, 1% suspension), dexamethasone (steroid, 0.1% suspension or ointment), flurbiprofen (nonsteroidal, 0.03% solution), and diclofenac (nonsteroidal, 0.1% solution) have all been successfully used. When selecting a topically applied steroid, either prednisolone or dexamethasone are preferred to hydrocortisone, which penetrates the cornea poorly and is not sufficiently potent to be an effective medication for anterior uveitis. Frequency of application depends on severity of the inflammation, but administration 4-6 times a day is common. As the signs resolve, the frequency can be slowly reduced. It is recommended that therapy be continued for 1 mo after the signs of acute inflammation have resolved. Topical atropine (1% solution or ointment) benefits patients with acute anterior uveitis by paralyzing the iris sphincter and ciliary body musculature. These effects reduce the likelihood of posterior synechia formation and markedly decrease the pain associated with ciliary body muscle spasm. Atropine is applied topically bid-tid until the pupil is widely dilated. The frequency can then be reduced to sid or once every other day as needed to maintain mydriasis. Although such a dosage schedule is well tolerated in most horses, gut motility should be monitored, as topically applied atropine can potentially lead to ileus.

Flunixin meglumine administered systemically, and particularly when given IV, may be the single most effective treatment of acute anterior uveitis in horses. The usual initial IV dose is 1.1 mg/kg, administered at the time of diagnosis. This is followed by a 5- to 7-day course at a dosage of 0.25-1.1 mg/kg, bid, PO. Because of the potential for GI and renal problems with the longterm use of flunixin meglumine, it is common to switch to oral phenylbutazone (2-4 mg/kg, sid-bid) after the initial treatment period. Alternatively, some horses respond better to aspirin (25 mg/kg, sid-bid, PO) after flunixin meglumine. Systemic steroids, specifically prednisolone (100-300 mg/day) and dexamethasone (5-10 mg/day) have also been successfully used to treat acute uveitis episodes, but their longterm use has been associated with laminitis. As the severity of the clinical signs lessens, the dosage and frequency of oral anti-inflammatory medications can be tapered over the 2- to 3-mo treatment period. If frequent topical medication is not feasible, subconjunctival injections of triamcinolone (10-40 mg), methylprednisolone acetate (10-40 mg), or betamethasone (5-15 mg) can supply therapeutic intraocular anti-inflammatory levels. However, these should be used with caution as they cannot be easily removed once injected and can have devastating consequences should an infectious component be present or a corneal ulcer develop. Except in instances when bacterial infection is present, systemic antibiotics are not indicated.

Historically, horses with frequent recurrences or chronic, low-grade uveitis were managed medically with daily (or every other day) doses of oral phenylbutazone or aspirin. Although most horses tolerate this regimen well, these medications can have adverse GI and hematologic side effects and the need for daily administration can lead to adherence problems. In addition, these regimens frequently do not eliminate recurrence. Recently, in an attempt to address the problems of medical management alone, 2 surgical procedures have been developed. Core vitrectomy removes virtually all of the vitreous through an incision ~1 cm posterior to the dorsolateral aspect of the limbus. The vitreous is then replaced with either saline or balanced salt solution. The theorized benefit of this procedure is that T lymphocytes and/or organisms in the vitreous significantly contribute to the chronic inflammation of equine recurrent uveitis. By removing these elements, the frequency and severity of the inflammatory events can be minimized. Although the core vitrectomy procedure has been successful in achieving this goal, postoperative formation of cataracts has led to significant vision compromise in ~50% of patients. An alternative procedure has recently been introduced— suprachoroidal cyclosporine implant. In this procedure, a cyclosporine A disk ~5 mm in diameter is implanted under a scleral flap created ~8 mm posterior to the dorsolateral aspect of the limbus. Although this procedure is still regarded as experimental, early results have been encouraging.

Good husbandry practices such as effective fly control, frequent bedding changes, routine worming and vaccinations, minimizing contact with cattle or wildlife, draining stagnant ponds or restricting access to swampy pastures, and maximizing nutrition have all been advocated as means to reduce the effects of equine recurrent uveitis. While such measures provide overall benefits for individual horses, the extent to which they impact the clinical course of equine recurrent uveitis is debatable.