Equine recurrent uveitis (ERU) is an important ophthalmic condition, with a reported prevalence of 2%–25% worldwide. The classic form of ERU is characterized by episodes of active intraocular inflammation followed by variable quiescent periods. However, some horses experience insidious ERU, in which subclinical ocular inflammation persists without obvious signs of discomfort. With chronicity, the inflammatory bouts cause secondary ocular changes such as cataracts, lens luxation, glaucoma, phthisis bulbi, and retinal degeneration. As a result, ERU is the most common cause of blindness in horses in the world.
Etiology and Pathogenesis of Equine Recurrent Uveitis
Equine recurrent uveitis is an autoimmune syndrome that ensues after an initial episode of acute uveitis. Although not every horse with a single bout of uveitis will develop ERU, horses that have experienced acute uveitis are at risk of developing ERU for several years after the primary episode. Although numerous bacterial, viral, protozoan, parasitic, and noninfectious causes, including ocular trauma, have been linked to the initiation of ERU, the pathophysiology of ERU is complex and multifactorial. Of the infectious causes investigated, Leptospira spp, especially L interrogans serogroup Pomona, have been most studied with regard to their role in the initiation of ERU. The precise mechanisms by which Leptospira spp initiate ERU remain unknown, but it is likely that loss of ocular immune tolerance, cross-reaction between Leptospira organisms and self-antigen, and intra- and intermolecular epitope spreading all play a critical role.
There is no gender or age predisposition for ERU. However, Appaloosas, Warmbloods, and draft breeds are overrepresented among horses diagnosed with ERU, which suggests a heritable component. Genes of the major histocompatibility complex (MHC) have been most widely investigated and likely play a role in susceptibility to ERU and/or to leptospirosis as an inciting trigger for ERU. The prevalence of ERU varies with geographic region, with higher rates reported in tropical and temperate climates than in arid, dry climates, an observation that may be partially attributable to differences in persistence of pathogenic Leptospira spp within the environment. Thus, the underlying cause of the primary uveitis, genetic composition of the horse, and environmental factors are all integral to the development of ERU.
Clinical Findings and Lesions of Equine Recurrent Uveitis
Clinical findings associated with equine recurrent uveitis include acute signs of active inflammation as well as chronic secondary complications. Changes in ocular immunity allow leukocytes to invade the uvea and release proinflammatory cytokines such as prostaglandins and leukotrienes. These inflammatory mediators cause increased vascular permeability within the uvea, breakdown of the blood-ocular barrier, iris sphincter muscle spasm, decreased aqueous humor production, and ciliary body muscle spasm. These changes are responsible for the classic signs of acute uveitis: epiphora, blepharospasm, corneal edema, episcleral congestion, aqueous flare and cell, and fibrin in the anterior chamber. These anterior segment signs often reduce visualization of the posterior segment. Active posterior segment inflammation can result in vitreous haze secondary to cellular infiltrate, fibrinous traction bands, focal or diffuse retinal detachment, or chorioretinitis.
Courtesy of UC Davis Veterinary Ophthalmology Service.
Courtesy of UC Davis Veterinary Ophthalmology Service.
Chronic sequelae of ERU include:
corneal scarring
iridial fibrosis
corpora nigra atrophy
posterior synechia
cataract
lens dislocation
glaucoma
phthisis bulbi
chorioretinal scarring
ERU can be unilateral or bilateral and can affect the eyes asymmetrically.
Horses with primary ocular disease, especially corneal disease, experience many clinical signs typical of ERU, especially epiphora, blepharospasm, miosis, and corneal edema. It is critical to differentiate primary corneal disease from ERU considering the marked differences in treatment. A complete ophthalmic examination and fluorescein stain are essential. A thorough ophthalmic examination, including fundoscopy, is also critical during prepurchase or soundness examinations. Horses with chronic ERU may exhibit subtle or no anterior segment signs but have significant retinal degeneration and thus potential for vision compromise.
Diagnosis of Equine Recurrent Uveitis
Complete examination of both eyes
Tonometry
Fluorescein stain
Diagnosis of equine recurrent uveitis is based on characteristic clinical signs combined with a history of recurrent or persistent episodes of uveitis. A thorough ophthalmic examination of the anterior and posterior segment is critical to observing signs consistent with ERU and to excluding other primary ocular diseases. Tonometry should be performed in all cases to exclude glaucoma and document hypotony that is common with ERU. Application of fluorescein stain is important to assess corneal epithelial integrity and exclude reflex uveitis from ulcerative keratitis.
In cases of acute uveitis, a physical examination is performed to exclude systemic disease. A CBC and serum biochemistry panel are often warranted as part of the minimum database. Specific tests may assist in determining the underlying cause of a primary bout of uveitis. Serologic testing for Leptospira spp may confirm exposure to this common risk factor but is not helpful in determining treatment. Anterior chamber or vitreous cavity paracentesis may help identify a causative organism, but this procedure may cause severe intraocular damage and is not recommended.
Treatment, Prevention, and Control of Equine Recurrent Uveitis
Topical steroids and systemic nonsteroidal anti-inflammatories are used in conjunction to decrease inflammation.
Topical atropine is used as an adjunctive treatment to reduce intraocular pain and cause mydriasis.
A suprachoroidal implant or vitrectomy can be performed in visual patients to reduce the uveitic episodes.
Enucleation should be performed for blind, painful eyes.
The primary goals of therapy for equine recurrent uveitis are to reduce inflammation, relieve discomfort, and prevent vision loss. If possible, the specific underlying cause should be diagnosed and addressed as part of the initial treatment regimen. Regardless of whether the underlying cause is identified, aggressive treatment with systemic and topical anti-inflammatory medications is initiated immediately to minimize damage from intraocular inflammation. Flunixin meglumine administered systemically (especially IV) is critical to the initial management of acute uveitis in horses. The typical initial IV dosage is 1.1 mg/kg, administered at the time of diagnosis, followed by a 5- to 7-day course at a dosage of 0.5–1.1 mg/kg, PO, twice daily. As inflammation resolves, the dosage can be reduced to 0.25–0.5 mg/kg once daily or every other day throughout a 1- to 3-mo treatment period.
Because of the potential for renal toxicity, serum creatinine is intermittently monitored if flunixin meglumine is used for >1 month. Horses treated with flunixin meglumine should also be observed for signs of GI ulceration, and concurrent prophylactic administration of omeprazole (2 mg/kg/day, PO) may be indicated. If flunixin meglumine is not tolerated, phenylbutazone (2–4 mg/kg, PO, once to twice daily) or aspirin (10–25 mg/kg, PO, once to twice daily) can be used alternatively, but neither is as potent or effective. 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, hematologic, or renal effects, and these regimens frequently do not eliminate recurrence.
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. Except in cases when bacterial infection is present, systemic antibiotics are not indicated.
Topical steroidal medications, including dexamethasone (0.1% suspension or ointment) and prednisolone acetate (1% suspension), are very effective at decreasing inflammation. Topical acetate and suspension preparations of steroids are designed to penetrate the cornea and achieve adequate uveal concentrations and are thus preferred to sodium phosphate formulations. Topical hydrocortisone should be avoided, because it lacks adequate corneal penetration and is not sufficiently potent to treat anterior uveitis.
A fluorescein stain is warranted before initiation of topical steroids, because these medications are contraindicated with corneal ulceration and/or infection. Topical nonsteroidal medications include flurbiprofen (0.03% solution) and diclofenac (0.1% solution); they are less potent than topical steroids but offer a wider safety margin in cases of concurrent corneal disease. Frequency of administration depends on inflammation severity; initially, administration may be 4–6 times daily. With improvement in clinical signs, frequency of administration of topical steroidal or nonsteroidal medications can be gradually decreased. However, therapy should continue for 1 mo after complete resolution of active inflammation.
Topical atropine (1% solution or ointment) causes mydriasis (which decreases the likelihood of posterior synechia formation) and cycloplegia (which decreases pain associated with ciliary body muscle spasm) and stabilizes the blood-aqueous barrier. Atropine is applied topically 2–3 times daily until the pupil is widely dilated; the frequency can then be adjusted to maintain mydriasis. Because atropine decreases GI motility, horses treated with topical atropine should be monitored for signs of ileus.
If frequent topical medication is not possible, subconjunctival injections of triamcinolone acetamide (1–2 mg) provide adequate intraocular anti-inflammatory concentrations for 7–10 days and are less likely to cause abscess or granuloma formation than other steroids, including methylprednisolone acetate (10–40 mg). However, all subconjunctival steroids should be used with caution, because they cannot be easily removed once injected and can have devastating consequences if an infectious component is present or a corneal ulcer develops.
Two surgical procedures are commonly used in longterm management. A suprachoroidal cyclosporine implant is a sustained-release medication device that provides therapeutic concentrations of cyclosporine A, an immunosuppressive T-cell inhibitor, for ~3 years after implantation. During 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. Horses with implants have markedly fewer uveitic episodes than they did before surgery, and this device results in effective longterm control of ERU.
Courtesy of UC Davis Veterinary Ophthalmology Service.
Core vitrectomy removes virtually all of the vitreous through an incision posterior to the dorsolateral aspect of the limbus. The vitreous is then replaced with either balanced salt solution or saline. The theorized benefit of this procedure is that organisms, especially Leptospira spp, and/or inflammatory cells in the vitreous significantly contribute to the chronic inflammation of ERU. By removing these factors, the frequency and severity of uveitic episodes are minimized. Enucleation should be recommended in eyes that are blind or painful from ERU.
Good husbandry practices to manage ERU ensure proper health maintenance, prevent ocular trauma, and reduce environmental triggers. Specific management recommendations include routine deworming and vaccinations, proper nutrition and dental care, a quality fly mask, minimizing contact with cattle or wildlife, draining stagnant ponds or restricting access to swampy pastures, effective fly control, and frequent bedding changes. Although such measures benefit individual horses, the extent to which they impact the clinical course of ERU has not been evaluated.
Key Points
Equine recurrent uveitis is a common condition that can result in blindness and ocular pain.
Prompt diagnosis combined with medical then surgical management are typically necessary to maintain vision and ocular comfort.
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