The equine corneal noninfectious ulcerative keratitis (Proceedings)

1. Introduction

     a. Corneal disease is a common presenting complaint

     b. Non-specific signs

          i. Epiphora, blepharospasm, blepharoedema

     c. Appearance alteration

          i. Cornea "looks" funny

     d. Devastating sequelae

          i. Vision loss

          ii. Globe loss

2. Clinical Anatomy Review

     a. Major refractive structure of the eye due to the large refractive index change at the air / cornea interface

     b. Healthy corneal thickness: central = 780 μm, slight increase at periphery

     c. Corneal histology

          i. Trilaminar tear film:

               1) Lipid: sebaceous glands (tarsal / meibomian), decreases evaporation

               2) Aqueous: thickest, lacrimal gland, nictitans gland

               3) Mucin: conjunctival goblet cells, "adheres" film to epithelium, BUT test

          ii. Epithelium: lipophilic, stratified squamous 10-12 layers; anchored by hemidesmosomes to basement membrane, fibrils penetrate BM ending in anchoring plaques in anterior stroma; prevents microbial invasion, limits tear film uptake

          iii. Stroma: 90% of thickness which is 75-80% water with specifically arranged collagen fibers and chondroitin, dermatin, and keratan sulfates GAGs (glycosaminoglycans) forming the proteoglycan matrix

          iv. Descemet's membrane: basement membrane of the endothelium, thicker with age (continued secretion)

          v. Endothelium: single layer of interdigitating hexagonal cells, forms physical barrier between aqueous and cornea; efficient pumping mechanism keeping solutes and water out of cornea

3. Clinical Physiology Review

     a. Innervation: highly sensitive; CN V ophthalmic branch with ciliary nn branches entering mid-stroma at limbus; radiate to superficial cornea forming anterior stromal and subepithelial plexi

     b. Microflora: normal gram-positive bacteria and fungal organisms with some gram-negative

4. Corneal Wound Healing

     a. Epithelium: basal cell mitotic rate of 10-15% per day, entire epithelium replaced in 7 days typically; cells migrate rapidly (hours) to injury edge, mitosis beginning at 24-36 hours

     b. Stroma: healing definitely more complex; PMN and monocyte infiltration within hours of injury; keratocytes transform, proliferate, and synthesize collagen and ECM GAGs; remodeling over months to years restores tensile strength and degrees of transparency

     c. Endothelium: response is significantly reduced; layer incapable of mitosis; replacement by enlargement and migration of adjacent cell

     d. Sequelae: pigmentation, edema, vascularization

5. Noninfectious Ulcerative Keratitis

     a. Superficial / uncomplicated ulcerative keratitis:

          i. Definition: uncomplicated superficial corneal ulcer lacking any cellular infiltration with a duration of less than 7 days

          ii. Prevalence: common – environment, large globe, flight nature

          iii. Clinical Presentation:

               1) Common: significant pain (extensive sensory innervations), epiphora, blepharoedema, blepharospasm, conjunctival hyperemia

               2) Possible: mild edema

               3) Fluorescein positive obvious

               4) No cellular infiltration (cream to yellow lesion opacification

               5) No neovascularization

               6) Possible: mild anterior uveitis (flare, miosis, hypotony)

          iv. DDX:

               1) Adnexal abnormalities (ex: ectopic cilia, distichia, cicatricial)

               2) Herpesvirus keratitis

               3) Non-healing (indolent) ulcer

               4) Conjunctival foreign bodies

               5) Possibility of underlying infection

          v. Pathogenesis: trauma which includes both exogenous (horse + hay, trailer, barn, fence) and endogenous (ex: entropion, trichiasis)

          vi. TX:

               1) Topical prophylactic antibiotic (TID, not a "big gun")

                    • TAB, chloramphenicol, erythromycin, oxytetracycline (anti-MMP)

               2) Systemic NSAID (flunixin meglumine)

               3) Mydriatic / cycloplegic (atropine)(q 24 -48 hrs)

          vii. Prognosis: Favorable provided initiating cause eliminated, simple epithelial healing should be complete in 5-7 days; if fails to heal, no longer superficial / uncomplicated

     b. Traumatic corneal wounds / corneal foreign bodies

          i. Definition: corneal lesion secondary to known external blunt or penetrating cause (ie: whip, hay, retained foreign body) encompassing superficial to full thickness (including iris prolapse) lacerations

          ii. Prevalence: common – environment, large globe, flight nature

               1) One study (1984)

                    • 46.5% blunt – risk of severe posterior segment damage

                    • 23.3% sharp – risk of severe corneal damage

                    • 30.2% unknown

          iii. Clinical Presentation:

               1) Common: significant pain (extensive sensory innervations), epiphora, blepharoedema, blepharospasm, conjunctival hyperemia (may be severe)

               2) Enophthalmos

               3) Possible: mild to severe edema

               4) Fluorescein: typically positive, may be negative depending on lesion; utilize Seidel's test

               5) Foreign body may be indentified (fornix, associated with nictitans)

               6) Full thickness: may be sealed with fibrin or iris

               7) Possible: degree of anterior uveitis variable(flare, miosis, hypotony, hyphenate, hypopyon)

               8) Posterior segment may be involved (vitreal hemorrhage, cataract, retinal detachment)

          iv. DDX:

               1) Primary = corneal ulcer

               2) For iris prolapse (foreign body, sequestrum, neoplasia, descemetoceles, anterior synechia); greater degree of uveitis with partial / full lacerations

          v. Pathogenesis: environmental foreign bodies, blunt or penetrating injury

          vi. Medical TX:

               1) Superficial foreign bodies: attempt safe removal

                    • Sedation, auriculopalpebral and frontal nn blocks, topical anesthesia

                    • Cotton-tipped applicator, Kimura spatula, 25 or 27 gauge needle

                    • Cytology, bacterial / fungal culture

                    • Implement tx as for superficial ulcerative keratitis

               2) Deep or full-thickness wound or foreign body

                    • Minimal manipulation

                    • Institute if sx not practical or possible

                    • Goals: pain management, control intraocular and surface inflammation, prevent/eliminate surface and intraocular infection

                    • If possible, cytology, bacterial / fungal culture

                    • Topical AB (fluoroqinolone, aminoglycoside) q 2-4 hrs

                    • Systemic AB

                    • Topical and oral antifungal possibly indicated pending location

                    • Topical atropine q 6-8 hrs

                    • Systemic NSAIDs (flunixin meglumine)

                    • Omeprazole / Gastrogard

                    • Subpalpebral lavage system

          vii. Surgical TX:

               1) Indications: irregular lesion, large lesion, ≥1/3 stromal depth

               2) Options: primary suture, conjunctival graft, amnion, autogenous corneal graft, combination of above

               3) Shipping: Systemic NSAIDs, atropine, eye cup

          viii. Prognosis:

               1) Foreign bodies: Favorable for superficial / anterior stromal

               2) Lacerations:

                    • Poor - cross the limbus, associated with keratomalacia / hyphema ≥ 15 mm in length, lens luxation, lens capsule rupture, long duration

                    • Favorable – quick repair, not associated with posterior segment damage, aggressive medical management

                    • Corneoscleral rupture – enucleation

               3) Iris prolapse:

                    • Corneal trauma – guarded for vision; globe retention more favorable

                    • Descemetocele rupture – guarded for vision; less favorable for globe retention

     c. Nonhealing ulcerative keratitis

          i. Definition: refractory to healing in the absence of a persistent underlying cause

          ii. Ages 2-38 yrs reported; mean = 12-13 yrs

          iii. No gender, no breed predilection

          iv. Prevalence: numerous reports in literature, less common than superficial ulcerative keratitis and infectious ulcerative presentations

          v. Clinical Presentation:

               1) 2.5 – 8 weeks duration

               2) Variable discomfort not correlating to disease duration

               3) Limited to epithelium and lacking infection / mechanical trauma

               4) Mild superficial edema not associated with cellular infiltration

               5) Fluorescein: positive with classic migration of stain under nonadherent epithelial edges

               6) Neovascularization: present in about 50% of cases not correlating to disease duration

               7) Mild reflex anterior uveitis may be present (miosis, aqueous flare)

          vi. DDX:

               1) Eyelid abnormalities (entropion, ectopic cilia, trichiasis, cicatricial)

               2) Infectious ulcerative keratitis

               3) Pre-existing corneal disease (endothelial degeneration, dystrophy, bullous keratopathy)

               4) Tear film abnormalities (quantitative, qualitative)

          vii. Pathogenesis:

               1) Basement membrane discontinuity

               2) Presence of a superficial stromal hyaline membrane

               3) Extracellular and anterior stromal abnormalities inhibit adhesion complex formations?

          viii. Medical TX:

               1) Corneal cytology

               2) Superficial ulcerative keratitis treatment

          ix. Surgical TX:

               1) Corneal cytology (+/- culture?)

               2) Epithelial debridement

               3) Auriculopalpebral nn block, topical anesthesia

               4) Cotton-tipped applicator debridement

               5) Diamond Burr Keratotomy, grid keratotomy

               6) Placement of contact lens

               7) Perform with caution in fungal regions

          x. Prognosis:

               1) Favorable: 2-3 weeks for healing

     d. Eosinophilic keratoconjunctivitis

          i. Definition: Eosinophilic inflammatory response often to allergic, environmental, parastic stimuli

          ii. Prevalence:

               1) Rare (literature), uncommon (practice)

               2) Arabian, Quarter, Thoroughbred

               3) Younger (1-5 yrs)

          iii. Clinical Presentation:

               1) Variable non-specific signs (blepharospasm, blepharoedema, conjunctival hyperemia, epiphora)

               2) Variable pain

               3) Caseous mucoid discharge

               4) Whitish necrotic plaques often associated with ulceration

               5) Start lateral, extend axial

          iv. DDX:

               1) Confirmed with corneal cytology = abundant eosinophils accompanied by fewer mast cells, plasma cells, neutrophils, and lymphocytes

               2) Infectious ulcerative keratitis

                    • Bacterial, fungal, parasitic (Onchocerca cervicalis), viral (EHV-2)

               3) Neoplasia (OSCC, mastocytoma)

               4) Fibrosis

               5) Lipid / calcium deposition

          v. Pathogenesis:

1) Remains unknown

2) Possible allergic or parasitic response

3) Fomites, environmental allergens, improper management, seasonal

4) Immune system?

          vi. TX:

               1) Goal: treat underlying immune component

               2) Topical corticosteroid:

                    • Prednisolone acetate 1% 0.1 ml TID / QID, taper

                    • NeoPolyDexamethasone 0.1% ¼ inch strip TID / QID, taper

                    • Secondary infection while on steroid not common

               3) Topical NSAIDs:

                    • Reported to increase severity of disease

                    • NSAID-induced potentiation of inflammation medicated by leukotriene B4 which is a major regulator of eosinophilic disease in the horse

               4) Systemic NSAIDs (analgesia)

               5) Systemic corticosteroids

               6) Mast cell stabilizers: Olopatadine, 0.1 ml TID / QID

               7) Topical cyclosporine?

          vii. Prognosis:

               1) Overall fair to good, but requires long-term treatment

               2) Possible recurrence

     e. Tear deficiencies

          i. Definition: a decrease and/or alteration of aqueous, mucin, and/or lipid tear film layers resulting in qualitative or quantitative changes to the trilaminar structure

          ii. Prevalence:

               1) Much less common than in the canine

               2) Uncommon (literature and practice)

               3) Thoroughbred, Quarter Horse, German Warmbloods, Shetland Pony

          iii. Clinical Presentation:

               1) Common – conjunctivitis, blepharospasm, mucopurulent discharge, lackluster and hazy corneal appearance

               2) Variable superficial neovascularization, pigmentation, +/- ulceration

               3) Recurring ulcers or ulcers with delayed healing

               4) Other clinical signs due to etiology (deviation of muzzle, ear droop, anisocoria, facial swelling)

               5) STT I (measures basal and reflex tears) decreased from normal of 13-25 mm wetting / one minute

          iv. DDX: Conditions damaging periocular innervation (trigeminal – sensory; facial – motor); conditions damaging lacrimal tissue

          v. Pathogenesis: Congenital or acquired eyelid defects, inflammatory (eosinophilic), toxins (locoweed), mandibular ramus / stylohyoid bone fractures causing neurologic dysfunction

          vi. Medical TX:

               1) Tear replacement / stimulant medications – hyaluronate

               2) Lacrimostimulants – (topical cyclosporine, tacrolimus) increase tear production by suppressing inflammatory response attacking gland and improving conjunctival mucin stores

               3) Pilocarpine – direct neurologic stimulation to gland, applied topically (0.125%, 0.25%, 4.0%) produces mixed results

               4) Treat underlying condition

               5) Topical / systemic NSAIDs if indicated

          vii. Surgical TX:

               1) One reported PDT (1981) – bilateral sx may impair digestive capabilities

               2) Temporary or permanent tarsorrhaphies – esp. facial nn damage

               3) Enucleation

          viii. Prognosis:

               1) Traumatic fractures – good

               2) Inflammatory dacryoadenitis – poor long term

     f. Sequestrum

          i. Definition: Focal corneal necrosis often associated with chronic superficial irritation and no evidence of infection

          ii. Prevalence: Rare / Europe

          iii. Clinical Presentation:

               1) Blepharospasm

               2) Duration weeks to months

               3) Epiphora

          iv. DDX:

               1) Non-healing ulcerative keratitis

               2) Infectious ulcerative keratitis

               3) Traumatic / foreign body / iris prolapse

          v. Pathogenesis: unknown

          vi. Medical TX: see superficial ulcerative keratitis

          vii. Surgical TX: superficial keratectomies –

          viii. Prognosis: resolution w/out recurrence for surgical; no resolution with medical

6. Summary / Questions