Equine recurrent uveitis (Proceedings)

Equine Recurrent Uveitis (ERU) is the most common cause of equine blindness and it has an estimated yearly cost to the equine community of 100 to 250 million dollars. The prevalence of equine uveitis has been estimated to be anywhere from 8 to 25% in the general equine population. Overt costs accrue from medications for treatment and veterinary care. Indirect losses result from poor performance, disruption of training, missed competitions and loss of use. Euthanasia for practical and economic reasons is not uncommon. A clear understanding of the disease and client education is of paramount importance to support the well being of the patient.

Uveitis can also be divided into two separate syndromes Classic ERU and Insidious ERU, which is the form most commonly found in Appaloosas. Cases of classic ERU are characterized by intense bouts of intraocular inflammation followed by periods of clinical quiescence. Research has shown however, that even in the absence of overt inflammation intraocular damage is ongoing. The insidious form of uveitis does not show overt painful episodes of inflammation. Subtle signs of low grade chronic intraocular inflammation often go unnoticed until the disease is far progressed. Uveitis in the horse is considered recurrent if more than two episodes have been observed to occur. After a single episode of inflammation the risk of recurrent episodes is decreased after two or more years of a disease free state.

Anatomy of ERU:

The anterior uvea consists of the iris and the ciliary body, while the posterior uvea is made up of the choroid. The choroid is the major blood supply to the retina in the horse and this structure lies between the sclera and the retina. In total, the uveal tract contains the majority of the blood supply to the eye and maintenance of ocular health depends upon maintenance of a barrier between the vascular system and the internal ocular environment via the blood ocular barrier. The blood ocular barrier prevents the migration of large molecules into the intraocular environment and maintains the eye's immune-privileged status.

Ocular Pathology & ERU:

All cases of uveitis result from damage to the uveal tract causing the release of inflammatory mediators, prostaglandins, leukotrienes and histamines. Inflammation of the uveal tissues manifests as vascular congestion. Dilation of scleral and conjunctival blood vessels appears as a "ciliary flush" that gives an inflamed eye its red appearance. Inflammatory mediators cause the ciliary and iris sphincter muscles to spasm and cause discomfort. Additionally, inflammatory mediators cause increased vascular permeability and breakdown of the blood aqueous barrier which leads to the leakage of protein, fibrin and cells into the aqueous humor. These inflammatory responses cause the common clinical signs of uveitis, including blepharospasm, increased lacrimation, aqueous flare, hypopyon, fibrin accumulation and miosis.

Uveitis also frequently causes inflammation of the eyelids, conjunctiva, cornea, lens, retina, and optic nerve can be observed. Blepharospasm, increased serous to mucopurulent discharge, chemosis and conjunctival hyperemia are typical in cases of ERU. Corneal cloudiness or edema is commonly seen. Edema results from inflammatory damage to the corneal endothelial cells in contact with the aqueous humor. Normally, the metabolic pump mechanism within the endothelial cells draws water out of the corneal stroma and replaces it into the aqueous humor; this function is diminished in the inflamed eye. In addition to edema, 360 degrees of neovascularization of the corneal stromal tissue occurs after several days of inflammation.

Aqueous flare, the cloudy appearance of floating particles with in the anterior chamber, is a hallmark of ERU. The accumulation of non-cellular exudate causes the disfunction of the ciliary body resulting in a reduction in aqueous humor production giving the hypotonia that is found in uveitic eyes. Hypopyon, can be observed with the settling of inflammatory cells into the ventral aspect of the anterior chamber and intraocular bleeding occur in severe cases.

The iris spincter and ciliary body muscles are affected by the inflammatory mediators in uveitis, causing ciliary body and spincter muscles to spasm resulting in marked miosis. The iris can also take on a dull appearance with mottled pigmentation and hyperemia. Chronic cases of ERU can exhibit atrophy of the granular irides (corpra nigra) and hyperpigmentation of the iris tissue.

Early lens opacities in uveitis consist of inflammatory exudate adhering to the lens capsule. Areas of pigment can develop on the lens surface from pigment migration from the iris or from posterior synechia of the iris to the lens. With changes in aqueous humor composition, the metabolism of the lens is compromised, and lens transparency is reduced resulting in cataract development. In chronic cases of ERU the inflammation can cause the premature degeneration or detachment of lens zonules resulting in anterior or posterior lens luxation.

Inflammation of the posterior uvea is accompanied by the infiltration of inflammatory cells into the normally acellular vitreous body. The inflammatory infiltrate can give the vitreous body a distinct yellow color.With chronicity, migration of cells into the vitreous can result in fibrous strands of aggregated inflammatory cells and inflammatory products(vitreal traction bands). Vitreal liquefaction occurs and strands of inflammatory debris may appear to "wave" in the liquid vitreous with globe movement. Vitreal degeneration and vitreal traction bands that physically pull on the retina contribute to the potential for retinal detachement in ERU.

Fundic examination in ERU horses can show peripapillary chorioretinal scaring, such as winged shaped area of retinal depigmentation (butterfly lesions) or multiple circular focal areas of depigmentation (target lesions). Evidence of retinal degeneration can also present as changes in reflectivity or color of the retinal tissues. Inflammatory episodes can cause changes in choroidal blood flow causing retinal cellular hypoxia. The influx of infiltrates and exudates from the choroidal vasculature into the subretinal space results in retinal detachments. Severe choroidal inflammation can cause disruption in blood flow to the optic nerve resulting in optic nerve damage. Additionally, inflammatory cell accumulation within the aqueous outflow channels can result in the development of glaucoma.

Etiology of ERU:

A single cause of ERU has yet to be elucidated. Many infectious agents have been implicated, particulary Leptospirosis. Leptospira organisms have been shown to persist in the eyes of horses with ERU, but the organism's role in the development of recurrent disease has not been clearly identified. Molecular mimicry between leptospiral DNA and proteins of the equine cornea and lens, supports an autoimmune component. Disruption of the blood ocular barrier allows for the activation of host immune responses with the expected production of antibodies to foreign antigens and the inappropriate production of antibodies to self antigens. The pathogenesis of ERU has clearly been shown to be immune-mediated with a T-helper cell type response. The genetic makeup of an individual horse may also play a role in determining its susceptibility to leptospirosis and its ability to initiate ERU.

Breed Predisposition /Appaloosa Horses:

Research has shown thatAppaloosa horses are 8.3 times more likely to develop uveitis than other breeds. Additionally, Appaloosa horses that are seropositive for Leptospira interrogans serovar pomona have more severe signs of disease and close to a 100% occurrence of blindness. Appaloosa horses also tend to suffer from the insidious form of the uveitis without overt episodes of inflammation. The pathogenesis of the disease in the Appaloosa horse may be completely distinct from the classic form that is seen in other breeds. Definitive information as to the age of onset and the duration of the syndrome is hard to define in that the signs of disease are often not noticed by owners until the disease is far progressed. Coat color of affected horses tends to be the lighter patterns with focal dark spots. Dark colored Appaloosas with a blanket tend not to develop the disease as commonly. Interestingly, a large portion of Appaloosas that are affected with uveitis also show signs of obstructive airway disease. Uveitis in the Appaloosa horse likely has a genetic basis and specific genetic markers have been identified in affected horses.

Treatment & Management of ERU:

The goals of uveitis therapy include preserving vision, minimizing ocular damage and providing comfort. Diagnostic testing for specific infectious causes is warranted. Serologic screening for bacterial and viral agents, particularly testing for seroreactivity to Leptospiral interrogans serovars, is recommended based upon physical examination, complete blood count and serum biochemistry findings. If a specific inciting cause can be found specific treatment is indicated in addition of treatment of the intraocular inflammation.

Vaccination with multivalent vaccines or administering multiple vaccines at once has been clinically associated with a recurrence of ocular inflammation. Generally, spacing vaccinations a week apart and limiting the use of unnecessary vaccines based on geographic location and animal use is recommended. Concurrent treatment with systemic or topical anti-inflammatories has been supported by some authors. A recent report looked at the efficacy of vaccinating horses against pathogenic leptospiral serovars and the data did not support the use of leptospiral vaccinations in horses. Although vaccinated horses had a significant increase in the days to recurrence of inflammation, vaccination failed to slow the progression of the disease, and more vaccinated horses experienced progression of the disease than those in the control group.

Oral and topical anti-inflammatories are the mainstay of ERU management. The clinical impression has been that flunixin meglumine has better ocular anti-inflammatory effects than phenylbutazone. Topical steroids combined with antibiotics are very helpful in the treatment of acute cases, however their long term use is associated with an increase in bacterial and fungal keratitis. The use of topical non-steroidals is recommended for long term therapy if necessary.

Treatment of ERU can be extremely frustrating and sometimes impossible due to the intractable nature of some horses. The development of the cyclosporine implant provides an alternative to consistent topical management. Candidates for implant placement must have no other systemic illnesses, good vision and no cataracts. Horses with ERU must also be well controlled with conventional medical treatments. Initial research estimates that the implant can be effective for up to four years.