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Corneal Ulceration - Small Animal Hospital - University of Florida

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Keeping the Windshield Clean!<strong>Corneal</strong> <strong>Ulceration</strong>: Diagnosisand Aggressive Treatment<strong>University</strong> <strong>of</strong> <strong>Florida</strong>


Different ulcer types/depths


• Making the diagnosis <strong>of</strong> a corneal ulcer iscritical for the welfare <strong>of</strong> the patient.• It is the difference between sight andblindness, or a small scar and a large scar.• Assume ulcers will get worse!• Treat aggressively.


• The dog cornea is 0.55mm thick centrally and0.65 mm thickperipherally.• The cat cornea is about0.58 mm thick centrallyand peripherally.• The superficial cornea ismost sensitive.• The tear film gives asmooth optical surface.• Most <strong>of</strong> the stroma iscollagen.• The endotheliumcontains a pump.


• The corneal stroma is 90% <strong>of</strong> the corneal thickness.– parallel bundles <strong>of</strong> collagen fibrils– keratocytes and GAGs.• <strong>Corneal</strong> sensitivity is reduced– brachycephalic dog and cat breeds– diabetic dogs: 28% lower STT; 37% lower corneal sensation;58% shorter TFBUT• not related to degree <strong>of</strong> control or durationNerves


<strong>Corneal</strong> epithelium is a barrier against bacteria.In simple traumatic corneal injuries in which a smallamount <strong>of</strong> epithelium is removed, healing is rapid.


• If the ulcer becomes infected or the epithelium isunable to attach to the stroma, healing is delayed,and progression to a deep stromal ulcer mayoccur.• WBCs can help too much!! NE and MMPs.


• In infected ulcers, tear proteases digeststromal collagen to cause a descemetocele,and iris prolapse (within 24 hrs).• Proteases (MMP and NE) are produced bykeratocytes, tear film PMNs and microbes.“Melting”??


• <strong>Corneal</strong> degeneration due toproteases is referred to as"melting".• Ulcers in which proteases areactive have a grayish-gelatinousappearance• Distinguish melting fromcorneal edema.• Topical corticosteroids increasetear protease activity.• MMP-9 increased in dog ulcersMelting and necrosis


• A corneal ulcer is a lesionin which the cornealepithelium and a variableamount <strong>of</strong> corneal stromahave been lost.• Cobalt blue filters aiddiagnosis.


• Ulcers can be classified by depth:– a. Superficial ulceration• Epithelial erosions/abrasions• Recurrent "Boxer Ulcers“• Early herpes ulcers in cats– b. Deep stromal ulcers• Melting ulcers• Geographic herpes ulcers in cats– c. Descemetoceles (about to rupture)– d. Perforating ulcers (Iris prolapse)


• Regardless <strong>of</strong> the initial cause, all ulcers areassociated with some iridocyclitis.• The uveitis may be severe with the potentialto progress to endophthalmitis.Hypopyon


Ulcers can be classified byEtiologyA. Mechanical disruption:• Trauma• Foreign bodies• Exposure (anesthesia, CN7 paralysis)• Entropion and trichiasis• Eyelash disease- distichiasis, ectopic cilia• “Boxer” ulcers and nonadherence


B. Infectious: Bacterial, Mycotic, ViralC. KCSD. Bullous Keratopathy - CatsE. Neurotrophic – corneal insensitivityF. Neuroparalytic - CN7paralysis


Diagnosis <strong>of</strong> <strong>Corneal</strong> <strong>Ulceration</strong>a. Clinical signs <strong>of</strong> ulceration:1) Pain and blepharospasm2) Tearing3) Purulent ocular discharge4) Miosis due to uveitis5) <strong>Corneal</strong> edema/vascularization


. Culturec. Schirmer tear testd. Cytologye. Fluorescein stain


Descemetoceles do not stain


• Initial therapy for anulcer depends onwhether:– the ulcer is infected– the ulcer is superficial ordeep– the ulcer is melting– UVEITIS IS FOUNDWITH EVERY ULCER!


The primary objective <strong>of</strong> current treatmentstrategies for infectious keratitis is to sterilize theulcer as rapidly as possible with topicallyadministered antibiotics.Kill everything !!Ulcers can degenerate even if sterile!Sterility does not guarantee healing!!


MEDICAL TREATMENT OF ULCERS• Treat etiology: eg KCS, entropion, infection• Broad-spectrum topical antibiotics– culture and sensitivity tests can guide selection.• Reduce tear protease activity:EDTA, Serum, Acetylcysteine– Serum contains an alpha-2 macroglobulin withanticollagenase activity.• Treat Uveitis– Topical atropine: cycloplegia/mydriasis– Topical NSAIDs?????


No steroids with ulcers. They really do not help!!


• Antibiotics commonly used inulcers:– bacitracin, neomycin, polymyxin– erythromycin– Tobramycin– Fusidic acid– chloramphenicol: static– gentamicin*– cipr<strong>of</strong>loxacin***– cefazolin (55 mg/ml)***


Antibiotics are ToxinsEffects <strong>of</strong> in vitro antibiotics on dog corneal epithelial cells:chloramphenicol < tobramycin < neopolygram < gentamicin< cefazolin < cipr<strong>of</strong>loxacin(Hendrix AJVR 62:1664-1669, 2001)


• Horses: Increasing resistance <strong>of</strong> Streptococcus togentamicin, and Pseudomonas to gentamicin andtobramycin.– Pseudomonas: 20% resistant to gentamicin and tobramycin in92-98 and 55% resistant at present.– Ciloxan is still good for Pseudomonas.• No pattern like this seen in dogs.


• “Melting”: gray, mucoid,gelatinous cornea– autogenous serum: Seruminhibition lasts 8 days!!• Alpha 2 macroglobulins• NE and MMP inhibition– 0.17% ETDA (MMP)– 5% acetylcysteine (MMP)• RB positive– topical 0.025% doxycycline(MMP)• Combinations <strong>of</strong> antiproteases• Treatment reduces MMP by ~80%after 4-7 days.


Antiproteases• Inhibition <strong>of</strong> MMP-2 & MMP-9 is most importantin dogs, cats and horses• The significance <strong>of</strong> the serine proteases is underinvestigation• Serum– α2-macroglobulin = protease inhibitor that entrapsboth main classes <strong>of</strong> proteases– α1-PI (serine protease inhibitor )


Combining antibiotic therapy with MMPinhibitors can speed corneal healing as MMP playan important role in corneal ulceration andstromal liquefaction.


Every animal with a corneal ulcerhas anterior uveitisFibrinHypopyon


• Topical NSAIDS for ophthalmicuse– Flurbipr<strong>of</strong>en (Ocufen)– Supr<strong>of</strong>en (Pr<strong>of</strong>enal)– Dicl<strong>of</strong>enac (Voltaren)– Can be used to decrease signs <strong>of</strong> uveitisin the presence <strong>of</strong> a corneal ulcer BUTDON’T!


• Superficial Ulcers withMinimal <strong>Corneal</strong> Tissue Loss– Triple antibiotic ortobramycin QID– 1% atropine SID or BIDtill pupil is dilated- Maynot send home.– Serum QID– recheck the next day toevaluate for “melting”


• Eyes with ulcers should show reducedfluorescein uptake and the eye be lesspainful in 24-48 hours, unless……...


Melting ulcers should show an increase instromal rigidity in the first 24 hours. If not,surgery is indicated as corneal rupture ispossible.


• Healing <strong>of</strong> a corneal ulcerwill be observed as a 360°clearing <strong>of</strong> the cornea,beginning at the limbus.• If the cornea is healing,the stimulus for theuveitis should be reduced– the pupil will stay dilatedeasier– The frequency <strong>of</strong> atropinetherapy can be reduced.


Ulcers with Melting orKeratomalacia: Therapy– Ulcers infected or sterile– Very aggressive medicaland/or surgical therapy– Tobramycin, gentamicin orcefazolin q2h– Natamycin if + for hyphaeq4h– Atropine q4h till dilated– Serum and EDTA q1h– Systemic NSAIDS BID– Keratectomy and CF


• PMNs are stimulated byepithelial cell cytokines torelease serine and matrixmetalloproteases to cause“melting”.– Topical Serum is verybeneficial for melting ulcers.It inhibits serine proteasesand MMPs.– Topical EDTA (0.17%) andacetylcysteine (5%) inhibitMMPs.– Ilomostat– Topical 0.1% doxycycline


• Combinedantibiotic/proteaseinhibitor therapy mightimprove clinical results.• <strong>Ulceration</strong> <strong>of</strong>ten continuesdue to the continuedpresence <strong>of</strong> tear proteasesin spite <strong>of</strong> ulcersterilization with effectiveantibiotic treatment.


SURGICAL TREATMENT OF ULCERS• Conjunctival flap autografts areused for the clinical management<strong>of</strong>:– deep and large corneal ulcers– stromal abscesses– descemetoceles– perforated corneal ulcers withand without iris prolapse.• Tarsorrhaphies and TE flaps


Deep Ulcers, Descemetocelesand IP


Types <strong>of</strong> conjunctival flaps (CF)• CF surgery requiresgeneral anesthesia.• Pedicle flaps allowmonitoring <strong>of</strong> the anteriorchamber– Leave in place for 4-6 wks.– Most CFs require atemporary tarsorrhaphy.


Conjunctivalflap/Tarsorrhaphy


• DESCEMETOCELES– 14 microns!!


Look at the flash??


Amnion Membrane Transplants2“Dixie” Stacy


Iris Prolapsea) Emergencyb) Systemic antibioticsc) General anesthesia andsurgical repair <strong>of</strong> cornead) Topical antibiotic solutions,not ointments. Topicalatropinee) Reposition or amputateprotruding iris; suture cornea(7-0 suture); reform AC withLRSf) CF if needed


CORNEAL LACERATIONS• Management depends on depth<strong>of</strong> laceration.• Superficial lacerations (stainwith FL). Treat as simple ulcer -topical antibiotics and atropine• Deep, non-perforatinglacerations. Topical antibiotics,serum and atropine– Less than 1/2 thickness: CFor treat as ulcer– More than 1/2 thickness:suture cornea


Herpes keratitis• Cats• Dendritic ulcers <strong>of</strong> thecornea and conjunctiva• Topical acyclovir oridoxuridine QID• Oral lysine 500 mg BID– Viralys Vet• Oral interferon: 300 U/day


Geographic herpes ulcer


REFRACTORY SUPERFICIALCORNEAL EROSIONS"Indolent Ulcer” or"Boxer Ulcer"Middle to old age, increasedincidence in femalesBreed predilection: Boxer,Corgi, Pekes, Lhasa Apso


Clinical Signs:• Superficial corneal erosion with epithelial "lips"(Epithelium rolled up and back at edges)• Chronic blepharospasm, epiphora, and photophobia• Lesions usually unilateral• Fluorescein diffuses under epithelium


The cause is a defect in the hemidesmosomes<strong>of</strong> the basal corneal epithelial cells.The basal corneal epithelium may not beproducing normal basement membrane. Ahyaline membrane forms on the ulcer.


Other Rule-outs forNonhealing ulcers• KCS• ectopic cilia• foreign bodies• entropion• infection


Ectopic Cilia


Treatment <strong>of</strong> “boxer ulcers”• Remove abnormal epitheliumby debridement with topicalanesthesia and cotton-tippedapplicator• may need numerousdebridements“the lip”


“Scratchers”Grid Keratotomy for superficial ulcers only! 20 gauge needle.Not for cats!!


MULTIPLE PUNCTATE KERATOTOMY“Pokers”20 g bent needlescars


Needle guardor bend the tip


Medical treatment <strong>of</strong> “boxer ulcers”• Topical antibiotic solutions.– Do not use gentamicin orcipr<strong>of</strong>loxacin!!– No steroids!!• Topical 1% atropine as needed• Topical hyperosmotics (5%NaCl)


• Use Elizabethan collars to help prevent selftrauma• Adequan (100 mg/ml) for topical use:– 50 mg/ml in PVA artificial tears (Tears Naturale)• Growth factors in serum may be beneficial inpersistent erosions. EGF??• Hylashield (Hylan) topically• S<strong>of</strong>t contacts and collagen shields• Chemical cautery (Lugol’s iodide, TCA,phenol)• Superficial keratectomy• Tarsorrhaphies and TE Flaps


<strong>Corneal</strong> Foreign Bodies


FBDay 7Day 1


Penetrating Keratoplasty (PK)• Deep corneal ulcers• Descemetoceles• Endothelial dystrophy


PK in a dog for endothelial dystrophy

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