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

– α2-macroglobulin = protease inhibitor that entraps

both main classes of proteases

– α1-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

Hypopyon

Fibrin

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

DON’T!

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

“Dixie” Stacy

2

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”

Grid Keratotomy for superficial ulcers only! 20 gauge needle.

Not for cats!!

“Scratchers”

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 (Lugol’s iodide, TCA, phenol)

Superficial keratectomy

Tarsorrhaphies and TE Flaps

Corneal Foreign Bodies

Day 7

Day 1

FB

Penetrating Keratoplasty (PK)

Deep corneal ulcers

Descemetoceles

Endothelial dystrophy

PK in a dog for endothelial dystrophy