Keeping the Windshield Clean!

Corneal Ulceration: Diagnosis and Aggressive Treatment

University of Florida

Different ulcer types/depths

Making the diagnosis of a corneal ulcer is critical for the welfare of the patient. It is the difference between sight and blindness, or a small scar and a large scar. Assume ulcers will get worse! Treat aggressively.

The dog cornea is 0.55 mm thick centrally and 0.65 mm thick peripherally. The cat cornea is about 0.58 mm thick centrally and peripherally. The superficial cornea is most sensitive. The tear film gives a smooth optical surface. Most of the stroma is collagen. The endothelium contains a pump.

The corneal stroma is 90% of the corneal thickness.

parallel bundles of collagen fibrils keratocytes and GAGs.

Corneal sensitivity is reduced

brachycephalic dog and cat breeds diabetic dogs: 28% lower STT; 37% lower corneal sensation; 58% shorter TFBUT

not related to degree of control or duration

Nerves

Corneal epithelium is a barrier against bacteria. In simple traumatic corneal injuries in which a small amount of epithelium is removed, healing is rapid.

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

In infected ulcers, tear proteases digest stromal collagen to cause a descemetocele, and iris prolapse (within 24 hrs). Proteases (MMP and NE) are produced by keratocytes, tear film PMNs and microbes.

Melting

??

Corneal degeneration due to proteases is referred to as "melting". Ulcers in which proteases are active have a grayish-gelatinous appearance Distinguish melting from corneal edema. Topical corticosteroids increase tear protease activity. MMP-9 increased in dog ulcers

Melting and necrosis

A corneal ulcer is a lesion in which the corneal epithelium and a variable amount of corneal stroma have been lost. Cobalt blue filters aid diagnosis.

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 of the initial cause, all ulcers are associated with some iridocyclitis. The uveitis may be severe with the potential to progress to endophthalmitis.

Hypopyon

Ulcers can be classified by Etiology

A. 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, Viral C. KCS D. Bullous Keratopathy - Cats E. Neurotrophic corneal insensitivity F. Neuroparalytic - CN7 paralysis

Diagnosis of Corneal Ulceration a. Clinical signs of ulceration: 1) Pain and blepharospasm 2) Tearing 3) Purulent ocular discharge 4) Miosis due to uveitis 5) Corneal edema/vascularization

b. Culture c. Schirmer tear test d. Cytology e. Fluorescein stain

Descemetoceles do not stain

Initial therapy for an ulcer depends on whether:

the ulcer is infected the ulcer is superficial or deep the ulcer is melting UVEITIS IS FOUND WITH EVERY ULCER!

The primary objective of current treatment strategies for infectious keratitis is to sterilize the ulcer as rapidly as possible with topically administered 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 with anticollagenase activity. Treat Uveitis Topical atropine: cycloplegia/mydriasis Topical NSAIDs?????

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

Antibiotics commonly used in ulcers:

bacitracin, neomycin, polymyxin erythromycin Tobramycin Fusidic acid chloramphenicol: static gentamicin* ciprofloxacin*** cefazolin (55 mg/ml)***

Antibiotics are Toxins

Effects of in vitro antibiotics on dog corneal epithelial cells:
chloramphenicol < tobramycin < neopolygram < gentamicin < cefazolin < ciprofloxacin
(Hendrix AJVR 62:1664-1669, 2001)

Horses: Increasing resistance of Streptococcus to gentamicin, and Pseudomonas to gentamicin and tobramycin.
Pseudomonas: 20% resistant to gentamicin and tobramycin in 92-98 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: Serum

inhibition 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 of antiproteases Treatment reduces MMP by ~80% after 4-7 days.

Antiproteases
Inhibition of MMP-2 & MMP-9 is most important in dogs, cats and horses The significance of the serine proteases is under investigation Serum

2-macroglobulin = protease inhibitor that entraps both main classes of proteases 1-PI (serine protease inhibitor )

Combining antibiotic therapy with MMP inhibitors can speed corneal healing as MMP play an important role in corneal ulceration and stromal liquefaction.

Every animal with a corneal ulcer has anterior uveitis

Fibrin

Hypopyon

Topical NSAIDS for ophthalmic use

Flurbiprofen (Ocufen) Suprofen (Profenal) Diclofenac (Voltaren)
Can be used to decrease signs of uveitis in the presence of a corneal ulcer BUT DONT!

Superficial Ulcers with Minimal Corneal Tissue Loss Triple antibiotic or tobramycin QID 1% atropine SID or BID till pupil is dilated- May not send home. Serum QID recheck the next day to evaluate for melting

Eyes with ulcers should show reduced fluorescein uptake and the eye be less painful in 24-48 hours, unless...

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

Healing of a corneal ulcer will be observed as a 360 clearing of the cornea, beginning at the limbus. If the cornea is healing, the stimulus for the uveitis should be reduced
the pupil will stay dilated easier The frequency of atropine therapy can be reduced.

Ulcers with Melting or Keratomalacia: Therapy

Ulcers infected or sterile Very aggressive medical and/or surgical therapy Tobramycin, gentamicin or cefazolin q2h Natamycin if + for hyphae q4h Atropine q4h till dilated Serum and EDTA q1h Systemic NSAIDS BID Keratectomy and CF

PMNs are stimulated by epithelial cell cytokines to release serine and matrix metalloproteases to cause melting.
Topical Serum is very beneficial for melting ulcers. It inhibits serine proteases and MMPs. Topical EDTA (0.17%) and acetylcysteine (5%) inhibit MMPs. Ilomostat Topical 0.1% doxycycline

Combined antibiotic/protease inhibitor therapy might improve clinical results. Ulceration often continues due to the continued presence of tear proteases in spite of ulcer sterilization with effective antibiotic treatment.

SURGICAL TREATMENT OF ULCERS

Conjunctival flap autografts are used for the clinical management of: deep and large corneal ulcers stromal abscesses descemetoceles perforated corneal ulcers with and without iris prolapse.
Tarsorrhaphies and TE flaps

Deep Ulcers, Descemetoceles and IP

Types of conjunctival flaps (CF)

CF surgery requires general anesthesia. Pedicle flaps allow monitoring of the anterior chamber
Leave in place for 4-6 wks. Most CFs require a temporary tarsorrhaphy.

Conjunctival flap/Tarsorrhaphy

DESCEMETOCELES
14 microns!!

Look at the flash??

??

Amnion Membrane Transplants

2
Dixie Stacy

Iris Prolapse
a) Emergency b) Systemic antibiotics c) General anesthesia and surgical repair of cornea d) Topical antibiotic solutions, not ointments. Topical atropine e) Reposition or amputate protruding iris; suture cornea (7-0 suture); reform AC with LRS f) CF if needed

CORNEAL LACERATIONS

Management depends on depth of laceration. Superficial lacerations (stain with FL). Treat as simple ulcer topical antibiotics and atropine Deep, non-perforating lacerations. Topical antibiotics, serum and atropine Less than 1/2 thickness: CF or treat as ulcer More than 1/2 thickness: suture cornea

Herpes keratitis
Cats Dendritic ulcers of the cornea and conjunctiva

Topical acyclovir or idoxuridine QID Oral lysine 500 mg BID Viralys Vet Oral interferon: 300 U/day

Geographic herpes ulcer

REFRACTORY SUPERFICIAL CORNEAL EROSIONS

"Indolent Ulcer or "Boxer Ulcer" Middle to old age, increased incidence in females Breed 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 of the basal corneal epithelial cells. The basal corneal epithelium may not be producing normal basement membrane. A hyaline membrane forms on the ulcer.

Other Rule-outs for Nonhealing ulcers

KCS ectopic cilia foreign bodies entropion infection

Ectopic Cilia

Treatment of boxer ulcers

Remove abnormal epithelium by debridement with topical anesthesia and cotton-tipped applicator may need numerous debridements

the lip

Scratchers

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

MULTIPLE PUNCTATE KERATOTOMY

Pokers 20 g bent needle

scars

Needle guard or bend the tip

Medical treatment of boxer ulcers

Topical antibiotic solutions. Do not use gentamicin or ciprofloxacin!! No steroids!! Topical 1% atropine as needed Topical hyperosmotics (5% NaCl)

Use Elizabethan collars to help prevent self trauma Adequan (100 mg/ml) for topical use:
50 mg/ml in PVA artificial tears (Tears Naturale)

Growth factors in serum may be beneficial in persistent erosions. EGF?? Hylashield (Hylan) topically Soft contacts and collagen shields Chemical cautery (Lugols iodide, TCA, phenol) Superficial keratectomy Tarsorrhaphies and TE Flaps

Corneal Foreign Bodies

FB Day 7 Day 1

Penetrating Keratoplasty (PK)

Deep corneal ulcers Descemetoceles Endothelial dystrophy

PK in a dog for endothelial dystrophy