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Compendium June 2011 (Vol 33, No 6)

Equine Recurrent Uveitis: Treatment

by Amanda Curling, DVM

    CETEST This course is approved for 3.0 CE credits

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    Abstract

    Equine recurrent uveitis has traditionally been treated with medical management to reduce ocular inflammation and control pain during a single episode. Newer management methods include surgical options such as cyclosporine implantation and vitrectomy. These methods were developed not only to control inflammation but also to eliminate the underlying cause of uveitis in order to prevent recurrence.

    Click here for the companion article, “Equine Recurrent Uveitis: Classification, Etiology, and Pathogenesis.”

    Medical Management

    Treatment of equine recurrent uveitis is aimed at reducing ocular inflammation to control pain, minimizing production and release of inflammatory mediators, blocking immunologic mechanisms to reestablish the blood–ocular barrier, and limiting recurrence to prevent further intraocular damage. Because vision loss is a common long-term manifestation of equine recurrent uveitis, initial therapy must be aggressive.1 Therapy should be directed at the etiologic cause, whether a primary ophthalmic disease or secondary to a systemic problem. Nonspecific therapy (TABLE 1) should include mydriatic cycloplegics, such as topical 1% atropine, which dilates the pupil, decreases the pain of ciliary muscle spasms, and reduces inflammation, decreasing synechiae formation. As the iris is repositioned, vascular fenestrations are narrowed, decreasing the leakage of protein and inflammatory cells into the anterior chamber.1 The dosage frequency depends on the response of the iris to mydriasis; once the pupil is dilated, 1% atropine should be used only as needed to maintain dilation of the pupil (once-daily topical dosing is usually sufficient until inflammation has subsided). If 1% atropine is not effective, 3% atropine can be used; however, patients should be monitored for signs of colic because administration of high doses of atropine can cause decreased intestinal motility, potentially leading to ileus, gas distention, or cecal or large colon impaction. If dilation cannot be achieved with atropine alone, 10% phenylephrine hydrochloride can be used in combination with atropine.

    Table 1. Common Topical Medications

    Medication

    Dosage

    Mydriatics

         Atropine HCl 1%

         Phenylephrine HCl 10%

    q6–48h

    q6–12h

    Steroids

         Prednisolone acetate

         Dexamethasone HCl

    q1–6h

    q1–6h

    NSAIDs

         Flurbiprofen

         Diclofenac

    q1–6h

    q1–6h

    Topical corticosteroids are most commonly used to suppress inflammation. Prednisolone acetate has the best corneal penetration; dexamethasone HCl is the next best option.2 Application frequency (ranging from twice daily to eight times daily) depends on the severity of the uveitis and should be tapered slowly once clinical signs have resolved. Adverse effects of topical steroids include potentiation of infectious agents and collagenase enzymes. Application of topical steroids when corneal ulceration is present may result in corneal melting and perforation or delayed epithelialization and healing of ulcers. Subconjunctival injection can provide a therapeutic intraocular level of corticosteroid, especially if application frequency is not conducive to owner compliance. Topical NSAIDs such as flurbiprofen and diclofenac can be used with fewer adverse effects and less concern when an ulcer is present; however, they can also delay epithelialization and are not as effective as corticosteroids in reducing intraocular inflammation.2

    Systemic therapy is the most effective method of managing equine recurrent uveitis.2 Intravenous flunixin meglumine is reportedly the most effective NSAID.2 Phenylbutazone, aspirin, and ketoprofen may also be used according to the situation.2 Systemic dexamethasone or prednisolone is highly effective for reducing inflammation; however, the adverse effects of steroids in horses may outweigh the benefits. Systemic steroids are reserved for severe cases that are unresponsive to NSAIDs or for cases involving corneal ulceration.

    Topical, intravitreal, or systemic antimicrobials are indicated when uveitis is due to bacterial infection. When possible, the antimicrobial should be chosen according to sensitivity patterns of bacteria. Tetracycline or doxycycline is generally not indicated to treat horses with leptospirosis because systemic administration of these drugs does not result in therapeutic levels in the eyes. Systemically administered enrofloxacin (7.5 mg/kg IV q24h) has achieved intraocular therapeutic levels against Leptospira interrogans serovar pomona; therefore, this drug should be considered if uveitis has been documented to be associated with leptospiral infection.3 Medical management of uveitis should be continued for several weeks or even months after remission of clinical signs because rapid tapering of topical or systemic antiinflammatories frequently leads to flare-ups of uveitis.

    Vaccination against leptospirosis (multivalent inactivated strands of L. interrogans serovars bratislava, canicola, hardjo, icterohaemorrhagiae, and pomona as well as Leptospira kirschneri serovar grippotyphosa, all of which are labeled for use in swine and cattle only) in horses with nontraumatic uveitis was shown to significantly increase the time to first recurrence after the second vaccination; however, there was no effect on future recurrences after the second vaccination.4 Vaccination also failed to slow the progression of uveitis and seemed to speed progression in the vaccinated group versus the control group. Comparison of antibody titers in vaccinated horses versus unvaccinated horses demonstrated no difference. Therefore, the use of vaccination as an adjunct therapy for equine recurrent uveitis is not supported at this time.4

    Surgical Management

    Newer therapies aimed at preventing recurrence of equine recurrent uveitis and providing long-term control of the disease include implantation of a cyclosporine A–releasing device and pars plana vitrectomy. Cyclosporine A is an immunosuppressant that focuses on cell-mediated immune responses and has some effect on humoral immunity. Cyclosporine’s exact mechanism of action is not fully known, but the drug is known to inhibit T-cell responsiveness and block the release of interleukin (IL)-2 and T-cell growth factor.5 Because high numbers of T cells and IL-2 have been found in eyes with equine recurrent uveitis, cyclosporine A may be ideal in preventing T-cell activation and uveitis recurrences.6

    Key Facts

    • Systemic antimicrobials can be administered for leptospiral-induced uveitis. The distribution of tetracyclines to the eye has been shown to be below the therapeutic level; however, enrofloxacin can achieve a therapeutic level against Leptospira interrogans serovar pomona within the eye.
    • No vaccine exists for leptospiral-induced uveitis in horses. Vaccination of horses using swine- or bovine-labeled vaccine is not recommended.
    • Implantation of a cyclosporine-releasing device has been shown to decrease the recurrence of uveitis, decrease the severity and length of episodes, and increase the response to topical medications in patients with recurrent episodes by suppressing immunity and blocking inflammatory cytokines.
    • Vitrectomy can clear inflammatory debris from within the vitreous to improve vision and decrease inflammatory mediators that may perpetuate episodes of equine recurrent uveitis.

    Cyclosporine A may be applied topically; however, it is hydrophobic and does not penetrate the cornea well. Therefore, it does not obtain a therapeutic concentration within the eye. A device containing cyclosporine A was evaluated for intravitreal implantation in horses after it demonstrated a sustained drug level in the ocular tissue of rabbits with experimentally induced uveitis.7,8 In experimentally and naturally affected horses, intravitreal cyclosporine A decreased the severity and duration of clinical signs, cellular infiltrate, and T cell numbers and significantly decreased IL-2 and interferon-γ.6 The cyclosporine A device, which is designed to release 4 μg/d for up to 5 years, (1) limited the recurrence of uveitis in most horses and (2) decreased the severity of recurrence and length of active inflammation and increased the response to topical medications in the other horses; however, complications associated with intravitreal placement included glaucoma, cataract formation, and retinal detachment, leading to vision loss.9

    Because of the risk of such serious complications when the vitreous cavity is entered, a biodegradable cyclosporine A implant was manufactured for placement in the deep scleral lamella of horses with uveitis. The deep sclera lamella is situated under the sclera but above the choroid and allows cyclosporine A to be delivered to the choroid without surgical entry into the vitreous cavity. This technique provided sustained delivery of cyclosporine A to the deep sclera-suprachoroidal space and achieved a high intraocular level of drug, resulting in significant reduction of postoperative uveitis flare-ups and rates of vision loss.10 No toxicoses or severe complications were associated with the implant itself. However, the selection of appropriate candidates to receive cyclosporine A implants is important for long-term success. For example, irreversible changes due to chronic uveitis eventually result in vision loss and decreased success of the implantation device.11 Candidates should be in the quiescent phase of the disease to help prevent severe inflammation after surgery.10

    Vitrectomy has been evaluated for removing immune mediators, antigens, and inflammatory debris within the vitreous, possibly reducing the recurrence of equine recurrent uveitis.12 Vitrectomy does not completely remove all the vitreous; therefore, interaction between the uvea and vitreous is not completely eliminated. However, reduced interaction between the uvea and vitreous seems to be sufficient in halting the recurrence of episodes.12 Other reports claim that the goal of vitrectomy is not to eliminate inflammatory episodes, but to clear the vitreal opacities to improve vision.13 This is the main goal in humans and is typically achieved in more than half of cases, although anterior uveitis is a common complication after vitrectomy in human patients with posterior uveitis.13

    The goal in equine patients is first to halt progressive globe destruction and recurrence of pain. Vision is usually stabilized secondarily. Vitrectomy has been performed in Europe for almost 2 decades, and most European studies report a decrease in vision over time, coupled with a decrease or cessation of uveitis attacks.14,15 Vision loss was primarily due to progressive cataract formation, especially in patients that had lens damage before surgery; however, this rate was low. In the United States, vitrectomy is still fairly new, and only a few ophthalmologists perform it. Results in the United States seem to be less favorable than those in Europe, but this could be due to the use of different instrumentation, leading to more complications, such as intraocular hemorrhage and cataract formation.16 Affected horses in Europe tend to be Warmbloods with posterior uveitis, whereas affected horses in the United States tend to be Appaloosas and Quarter horses with panuveitis.16 Posterior uveitis may respond to vitrectomy better than panuveitis. In addition, US and European horses have different leptospiral organisms. L. interrogans serovar pomona predominates in the United States, whereas uveitis caused by L. kirschneri serovar grippotyphosa  is more common in Europe.16

    The Future

    Further research is needed to fully understand the following regarding equine recurrent uveitis: (1) what predisposes certain horses to it, (2) the role of autoantigens and immune mechanisms in inflammation and the immune response, and (3) the role of infectious agents. Research is being conducted to further determine the genetic predisposition to recurrent uveitis in certain equine breeds. The results may allow genetic selection of unaffected individuals, thereby improving the breed and decreasing the prevalence of equine recurrent uveitis. Research is also being conducted on the role of leptospires in equine recurrent uveitis, the use of leptospirosis vaccines in horses, and newer immunosuppressive therapies. Because severe recurrent uveitis leads to vision loss and, often, euthanasia, this disease results in large economic losses worldwide. Continued research should lead to a better understanding of equine recurrent uveitis, improved therapies, and reduced vision loss in horses.

    Downloadable PDF

    1. Schwink KL. Equine uveitis. Vet Clin North Am Equine Pract 1992;8(3):557-574.

    2. Gilger BC, Michau TM. Equine recurrent uveitis: new methods of management. Vet Clin North Am Equine Pract 2004;20(2):417-427.

    3. Divers TJ, Irby NL, Mohammed HO, et al. Ocular penetration of intravenously administered enrofloxacin in the horse. Equine Vet J 2008;40(2):167-170.

    4. Rohrbach BW, Ward DA, Hendrix DVH, et al. Effect of vaccination against leptospirosis on the frequency, days to recurrence and progression of disease in horses with equine recurrent uveitis. Vet Ophthalmol 2005;8(3):171-179.

    5. Plumb DC. Veterinary Drug Handbook. 5th ed. Ames, IA: Blackwell Publishing; 2005:206-207.

    6. Gilger BC, Malok E, Stewart T, et al. Effect of an intravitreal cyclosporine implant on experimental uveitis in horses. Vet Immunol Immunopathol 2000;76(3-4):239-355.

    7. Enyedi LA, Pearson PA, Ashton P, Jaffe GJ. An intravitreal device providing sustained release of cyclosporine and dexamethasone. Curr Eye Res 1996;15(5):549-557.

    8. Pearson PA, Jaffe GJ, Martin DF, et al. Evaluation of a delivery system providing long-term release of cyclosporine. Arch Ophthalmol 1996;114(3):311-317.

    9. Gilger BC, Wilkie DA, Davidson MG, Allen JB. Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis. Am J Vet Res 2001;62(12):1892-1896.

    10. Gilger BC, Salmon JH, Wilkie DA, et al. A novel biodegradable deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci 2006;47(6):2596-2605.

    11. Gilger BC, Malok E, Stewart T, et al. Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A. Vet Ophthalmol 2000;3(2-3):105-110.

    12. Fruhauf B, Ohnesorge B, Deegen E, Boeve M. Surgical management of equine recurrent uveitis with single port pars plana vitrectomy. Vet Ophthalmol 1998;1(2-3):137-151.

    13. Scott RA, Haynes RJ, Orr GM, et al. Vitreous surgery in the management of chronic endogenous posterior uveitis. Eye 2003;17:221-227.

    14. Gerhards H, Wollanke B, Brem S. Vitrectomy as a diagnostic and therapeutic approach for equine recurrent uveitis. Proc AAEP 1999:89-93.

    15. Winterberg A, Gerhards H. Langzeitergebnisse der pars plana vitroktomie bei equiner rezidivierender uveitis. Pferdeheilkunde 1997;13(4):377-383.

    16. Brooks D. Core vitrectomy for treatment of equine recurrent uveitis: 23 cases. Proc ACVO 2001:52.

    References »

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