Equine infectious ulcerative keratitis uveitis (Proceedings)

Introduction

     o Moon Blindness, Periodic Ophthalmia

     o Most common cause of blindness in horses

          • 2-5% of US horses

     o Recurrent episodes of intraocular inflammation separated by quiescence

     o What causes ERU?

          • Genetic

          • Environment

          • Cause of initial uveitis

     o Etiology debatable, but agreement that a dysregulated ocular immune response causes the disease

          • Positive corticosteroid effects

          • Inflammatory recurrences

          • Lack of antibiotic tx success

     o Unilateral vs bilateral disease

          • May be either

          • Recurrences may be either

          • If 2+ years pass without disease in second eye, vastly reduced chance of developing disease

Uveitis Classification: any cause of blood-ocular barrier breakdown

     o Primary: any etiology causing inflammation

          • Trauma: blunt vs penetrating

          • Infectious

               √ Bacterial: Brucella, Borrelia burgdorferi, Leptospira, Rhodococcus equi, Streptococcus

               √ Viral: EHV-1, EHV-2, Equine influenza, EVA, Parainfluenza type 3

               √ Parasitic: Onchocerca, Strongylus, Toxoplasma

          • Miscellaneous: endotoxemia, neoplasia, septicemia, tooth root abscess

     o Equine Recurrent Uveitis

          • Two or more episodes observed

          • Two+ years w/out an episode diminishes risk

          • Labeled: active / acute, quiescent, or end-stage

          • Three clinical syndromes

               √ Classic

                    • Most common

                    • Inflammation of iris, ciliary body, and choroid and adjacent cornea, anterior chamber, lens, vitreous, retina

                    • Attacks become more frequent / more severe

                    • Sequelae include blindness, phthisis bulbi, cataract, synechia

               √ Insidious

                    • Low grade inflammation not outwardly painful

                    • Gradual destructive effect

                    • Draft and appaloosa breeds

               √ Posterior

                    • Vitreous, retina, choroid and some anterior segment associated inflammation

                    • Blindness, vitreal cloudiness, retinal detachments

                    • Warmbloods, Europeans, draft breeds

Clinical Appearance

     o No gender preference

     o Variable clinical signs

     o Over half of cases present before 12 years of age

     o Anterior Segment

          • Pain

          • Epiphora

          • Blepharospasm

          • Miosis*

               √ Unless dilated or synechia present

          • Hypotony

               √ IOP = 5 – 15 mmHg

          • Aqueous flare

          • Iris color change

               √ Dull, rubeosis

          • Corneal edema

          • Deep, short perilimbal vessels common

          • Fluorescein dye test – negative uptake

          • Calcific band keratopathy w/chronic disease

          • Uncommon – corneal cellular infiltrates, extensive neovascularization

     o Posterior Segment

          • Difficult to assess – anterior segment inflammation

          • Vitritis (debris, murky, "glow")

          • Vitreal liquefaction / floaters / traction bands

          • Fundus obscured

Chronic End Stage Disease

     o Posterior synechia, capsular pigment, focal / diffuse cataracts

     o Lens luxation / subluxation

     o Secondary glaucoma

     o Retinal Detachment

     o Chorioretinal scarring (peripapillary region)

          • Non-tapetal area: small, circular focal depigmentation with central hyperpigmentation

          • Wing-shaped hypopigmentation nasal and temporal to disc = Butterfly Lesion

DDX / Diagnostics

     o Dx determined by characteristic clinical signs and historical clinical bouts

     o DDX

          • Corneal diseases (ulcer, abscess, foreign body, neoplasia, immune-mediated, viral)

          • Non-ERUveitis

          • Glaucoma

     o Diagnostic tests:

          • CBC/Profile

          • Leptospiral serology: questionable value / tests previous exposure

          • Aqueous humor / serum leptospiral serology more helpful

               √ Microagglutination titers (MAT)

               √ Positive C value: aqueous MAT value / serum MAT value

                    • Suggests intraocular production of antibodies against the organism

          • Equine leukocyte antigen (ELA) typing: may help determine genetic susceptibility

          • Fecal

          • Lyme and EVA titer / Western blot analysis

Leptospira

     o Linked to spontaneous ERU around the world

     o Initial report linking leptospirosis to ERU in 1940 in Germany

     o Abundant research generated since then

     o Precise pathogenesis of disease (induction, role of organism in uveitis) remains poorly understood

          • 1985 – UF detected AB specific to L. interrogans

          • 1985 – Argentina demonstrated antigentic relationship between cornea and Leptospira, suggesting molecular mimicry

Appaloosa Horses

     o Significantly higher risk: 8.3 times higher than other breeds combined

     o Clinically distinct from classic ERU cases

     o Often insidious course without bouts of pain

     o Age of onset variable

     o Secondary complications / sequelae biggest problem

     o Bilateral – 80% of cases

     o Glaucoma affected 21%

     o Sequelae: posterior synechia, iris color change, cataracts, luxation/subluxation, vitritis, retinal detachments, phthisis bulbi, blindness

     o Coat color pattern: significant finding

          • Light base coats with focal darker spots**

               √ Leopard pattern

          • Dark base coats with light rump blanket least likely affected

     o Equine MHC may play a factor in susceptibility

Medical Treatment

     o Two main goals

          • Reduce inflammation: corticosteroids and NSAIDs

          • Reduce discomfort: mydriatic- cycloplegic

     o Medication categories

          • Topical steroids

               √ Prednisolone acetate 1%

                    • Indication – potent anti-inflammatory with excellent penetration

                    • Dose – q 1 to 6 hours

                    • Risk – predisposes to corneal fungal infection

               √ Dexamethasone 0.5-1.0%

                    • Indication – potent anti-inflammatory with excellent penetration

                    • Dose – q 1 to 6 hours

                    • Risk – predisposes to corneal fungal infection

          • Topical NSAIDs

               √ Flurbiprofen 0.03% / Diclofenac 0.1%

                    • Indication – anti-inflammatory with good penetration

                    • Dose – q 1 to 6 hours

                    • Risk – decreases corneal epithelialization

          • Mydriatic – cycloplegic

               √ Atropine 1%

                    • Indication – cycloplegic / mydriatic (minimize synechia / pain relief)

                    • Dose – q 6 to 24 hours

                    • Risk – may predispose to colic by decreasing gut motility

               √ Phenylephrine 10%

                    • Indication – use combined with atropine; not great in horse but may provide some added help (alpha agonist)

          • Systemic anti-inflammatory medications

               √ Flunixin meglumine

                    • Indication – potent ocular anti-inflammatory

                    • Dose – 0.5 mg/kg PO, IV, IM x 5 days, then 0.25 mg / kg

                    • Risk – long term use may predispose to gastric / renal toxicity

               √ Phenylbutazone

                    • Indication – anti-inflammatory

                    • Dose – 4.4 mg/kg PO, IV

                    • Risk- long term use may predispose to gastric / renal toxicity

               √ Dexamethasone (Azium)

                    • Indication – potent anti-inflammatory

                    • Dose – 5-20 mg / day PO or 2.5 – 5.0 mg/day IM

                    • Risk – frequent side effects, laminitis formation so use with caution and as a last resort, taper off dose, alter management (decrease confinement, stress, starches while increasing forage and access to paddocks / pastures)

               √ Prednisone

                    • Indication – potent anti-inflammatory

                    • Dose – 100-300 mg / day PO, IM

                    • Risk - see dexamethasone

          • Subconjunctival injection

               √ Trimacinolone

                    • Indication – potent anti-inflammatory, 7-10 day duration of action

                    • Dose – 1-2 mg

                    • Risk – severe predisposition for bacterial or fungal keratitis; cannot remove once administered

          • Intravitreal antibiotic

               √ Gentocin – 4 mg

          • Systemic antibiotic?

               √ Doxycycline - 12 mg/kg PO BID for one month

               √ Enrofloxacin - 7.5 mg/kg PO QD for one month

Surgical Treatment

     o Suprachoroidal cyclosporine sustained-release implants

          • Constant therapeutic drug delivery to affected tissues

          • By-passes some of blood-ocular barriers

          • Reduces / eliminates need for regular tx by owner

          • Release rates well below toxic drug levels

          • Patient convenience

          • Blocks transcription of IL-2 production and the responsiveness of the T-

     o Rapamycin injection

Prognosis

     o See chronic end-stage disease

     o Corneal ulcers

     o Pthisis bulbi

     o Enucleation

     o Poor for sight: 50-60% of ERU cases in studies experienced blindness in one or two eyes

     o Appaloosas that were seropositive for Leptospirosis had the worst visual prognosis