Contributors: Dennis E Brooks, David L Williams, Natasha Mitchell

 Species: Canine   |   Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

  • Important ocular disease characterized by loss of corneal epithelium plus variable amounts of stroma.
  • Cause: complex; trauma, collagenase activity and bacterial/viral infections should be considered.
  • Mycotic infection is more common in dogs than cats in the USA.
  • Diagnosis: relatively straightforward; use of fluorescein is strongly advised.
  • Treatment: remove causative agent(s) and create an environment suitable for healing.
  • Prognosis: corneal rupture is a possibility in cases of deep ulceration.

Presenting Signs

  • Very variable, but typically present with ocular pain (blepharospasm and epiphora).
  • Any or all of: vascularization, pigmentation, ulceration, ocular discharge (serous, mucopurulent), pain, 'red eye', lipid or calcium deposition.
  • May be acute or chronic.
  • History of trauma.

Age Predisposition

  • There is no age predisposition.

Breed Predisposition

  • Ulcers may occur secondary to other corneal diseases that have a breed disposition and a genetic basis. Examples include corneal epithelial dystrophy in the boxer dog, and endothelial dystrophy in the Boston Terrier Boston Terrier Cornea: endothelial dystrophy.

Spontaneous chronic corenal epithelial defect (SCCED) (syn. indolent ulcer)

Cost Considerations

  • Deep ulcers that require microsurgical intervention can be expensive.
  • Small corneal erosions (superficial ulcers) can heal quickly with few expenses needed.
  • The underlying cause will need treatment, eg correction of entropion or removal of an eyelid mass.

Pathogenesis

Etiology

Predisposing Factors

General

  • Brachycephalic breeds:
    • Macropalpebral fissure.
    • Lagophthalmos.
    • Entropion.
    • Qualitative or quantitative tear film deficiency.

Specific

  • KCS.
  • Qualitative tear film deficiency.
  • Trauma.
  • CN VII paralysis.
  • CN V paralysis.
  • Eyelid mass.
  • Foreign body.
  • Trichiasis - entropion, ectopic cilium or distichiasis.
  • Canine herpesvirus Canine herpesvirus.

Pathophysiology

  • Rapid progression of superficial ulcers to corneal rupture (melting ulcers) may occur following liberation of proteolytic collagenase enzymes from invading microorganisms, white blood cells or keratocytes, which cause rapid collagenolysis and loss of corneal structure.
  • Spontaneous chronic corneal epithelial defects (synonym indolent ulcers) are non-healing superficial ulcers which involve loss of the epithelium but there is no loss of corneal stroma.
  • Canine corneal anatomy:
    • Non-keratinized stratified squamous epithelium, including trilaminar precorneal tear film (lipid, aqueous and mucous phases) with basement membrane (analogous to primate Bowman's membrane).
    • Stroma, composed of type 1 collagen arranged in lamellae, precisely orientated, in relatively dehydrated glycosaminoglycan ground substance - both important for transparency.
    • Elastic Descemet's membrane, secreted by endothelium.
    • Monolayered endothelium, site of Na/K-ATPase-dependent pump, responsible for regulating water content of stroma.
  • Superficial ulcers - 3 types:
    • Uncomplicated: rapid healing by epithelial sliding and mitosis (conjunctival sliding/mitosis/metaplasia if all corneal epithelium damaged). Pluripotential limbal stem cells are source of dividing cells.
    • Progressive: underlying cause must be identified. Eyelids (agenesis, entropion, distichiasis, trichiasis, inflammation, neoplasia, ectopic cilia), nasal folds (trichiasis), precorneal tear film.
    • Refractory: basement membrane abnormality, specific condition (SCCED).
Secondary opportunistic bacterial invasion usually gram-positive (Staph/Strep), some gram-negative(Pseudomonas, E. coli, Bacillus).
  • Deep ulcers (>half stromal thickness) - 2 types:
    • Non-progressive - as for superficial uncomplicated ulcers, healing takes longer because stromal regeneration necessary, scar persists, possibly results in a corneal facet (irregularity in corneal surface).
    • Progressive - may erode through stroma to elastic Descemet's membrane, which bulges forwards because of intraocular pressure (then called Descemetocele), perforation a common sequela. Deep ulcers usually associated with uveitis via axon reflex. Gram-negative infection (especially Pseudomonas) produces proteases which, with endogenous collagenases (serine and matrix metalloproteinases) from keratocytes and neutrophils, produce rapid stromal breakdown (liquefaction or 'melting') emergency intensive treatment necessary.
  • Initial corneal injury → allows bacteria to adhere to ocular surface.
  • Within minutes leucocytes also enter tear film.
  • Bacteria, polymorphs or corneal keratocytes release proteases → liquefaction of corneal stroma and rapid progression of some ulcers.
  • Most severe cases are termed 'melting ulcers'.
  • If stroma overlying Descement's membrane is removed → descemetocele Fracture in Descemets membrane Basset Hound female 7 years (the exposed membrane then bulges forwards as a result of intraocular pressure).
    Descemetoceles do not stain with fluorescein at the base of the ulcer, although the 'walls' of the ulcer are typically positive for fluorescein uptake.
  • Boxer/Corgi (and may other breeds) - epithelial basement dystrophy (SCCED) may be underlying cause of indolent ulcers. Failure of epithelium to anchor to basement membrane prevents re-epithelialization of cornea.

Timecourse

  • In the case of superficial ulcers, the entire cornea can re-epithelialize rapidly in 4-7 days, although further healing process continue for longer.
  • Melting ulcers can progress over a matter of hours.

Diagnosis

Presenting Problems

  • Ocular pain (blepharospasm).
  • Red eye.
  • Ocular discharge.
  • Cloudy eye.

Client History

  • Ocular discharge.
  • Cloudy eye.
  • Blephrospasm.
  • Epiphora.
  • Nictitans protrusion.
  • Trauma.

Clinical Signs

  • Ocular discharge.
  • Ocular pain (blepharospasm, photophobia).
  • Indolent ulcers have an epithelial lip.
  • Deep ulcers appear as a crater-like defect.
  • Corneal edema.
  • Direct visualization of ulceration.
  • Variable degree of corneal vascularization depending on chronicity. No vascularization with acute corneal ulcer.
  • Hypopyon occasionally, due to reflex uveitis.

Diagnostic Investigation

Other

  • Schirmer tear test Schirmer tear test:
    • To rule out KCS as an underlying cause.
  • Fluorescein staining:
    • Fluorescein stain Fluorescein test if ulceration present - denuded stroma stains green with fluorescein, staining accentuated by UV light (Woods lamp).
      Multi-dose vials can become contaminated with Pseudomonas - use strips or single-dose vials.Descemet's membrane doesn't stain.Aqueous stains bright yellow-green with fluorescein if a hole is present to cause an aqueous leak , useful for detecting perforation.
    • Rose Bengal stains devitalized epithelium (KCS) and mucin layer defects but painful on instillation.
      Assess tear production (Schirmer tear test Schirmer tear test ) before adding fluid to eye.

Bacteriology

  • Always take swabs for culture before applying topical anesthesia/vital stains.

Cytopathology

  • Corneoconjunctival scrapings are useful.
  • Taken from the edges of the ulcer.
  • Can direct appropriate treatment, eg antibiotic active against Gram negative bacteria if present.

Ultrasonography

  • Corneal opacity is variable with ulcerative keratitis, and is usually due to corneal edema. It can hinder intraocular examination, in which case ocular ultrasound Ultrasonography: eye can provide useful information, eg lens capsule rupture in the case of a corneal penetration injury.

Histopathology Findings

  • Epithelial cells undergo mitosis and migration to heal a superficial ulcer.
  • Stromal ulcers heal by fibrovascular infiltration.
  • Deep ulcers tend to scar.

Differential Diagnosis

Treatment

Initial Symptomatic Treatment

  • Remove causative agent.
  • Topical antibiotics are used to treat all corneal ulcers.
  • Atropine Atropine SID-BID to reduce concurrent reflex uveitis Uveitis. Contraindications include ocular hypertension and KCS.
  • Anti-collagnease agents to prevent corneal melting, eg serum/plasma, acetylcysteine Acetylcysteine or EDTA Calcium disodium edetate (CaEDTA).
  • Prevent self-trauma by physical restraints, eg Elizabethan collar.
  • Topical non-steroidal drugs (eye therapeutics) may reduce pain but can delay healing and have been associated with progression of infected ulcers, and therefore could only be used in non-infected ulcers, and even then with much caution.
Corticosteroids, topically or systemically, must be avoided as they can cause melting and potentiate infection.

Standard Treatment

  • Antibiotic preparations TID-QID treat infection in cases of bacterial involvement based on results of bacteriology.

Surgical treatment

  • Improve blood supply to affected region and provde tectonic support to the cornea using a conjunctival pedicle Conjunctival graft for deeper ulcers.
  • Replacement of prolapsed iris tissue and corneal suturing (if feasible - otherwise application of a pedicle flap) if corneal rupture has occurred (as for corneal and scleral lacerations/perforations).
  • Contact lens application Contact lens: application may be appropriate for more superficial ulcers unless infection or melting is present.
  • Anticollagenases, serum/plasma, acetylcysteine, EDTA to prevent corneal 'melting'.
  • Direct corneal suturing Cornea: suturing is only appropriate for cornea lacerations.  
  • Third eyelid flaps Third eyelid flap have a limited role in the treatment of deep ulcers.
    Third eyelid flaps are not advised in the treatment of rapidly progressing ulcers, infected ulcers or those which are greater in depth than one half of the corneal thickness.
  • SCCED only are treated with debridement alone, or debridement with a keratotomy such as a grid or punctate keratotomy, or a diamond burr keratotomy Cornea: debridement and grid keratotomy.

Monitoring

  • Re-examine within 3 days to ensure healing is occurring, or the next day in the case of a deep or melting ulcer. SCCED can take 10 days to fully re-epithelialize.
  • Topical atropine Atropine can reduce tear production so needs to be avoided if there is pre-existing KCS.
  • Increase in uveitis signs is associated with poor corneal healing.

Subsequent Management

Treatment

  • Refractory ulcers (SCCED only) may require surgical removal (debridement) of non-adherent epithelium prior to performing a grid or punctate keratectomy Cornea: superficial keratectomy.
  • Application of a membrane flap Third eyelid flap or a contact lens Contact lens: application may be used in conjunction with this treatment regime.
  • Superficial keratectomy Cornea: superficial keratectomy to improve corneal transparency can be carried out 8-9 months after corneal repair to remove areas where there is considerable scarring, but there is a risk of repeated scarring if the underlying cause isn't identified, eg corneal pigmentation associated with brachycephalic syndrome.
    Topical corticosteroids should only be used once epithelialization has occurred - check using fluorescein. Topical ciclosporin Ciclosporin is a good alternative.

Monitoring

  • Regular checks twice weekly until ulcer healed.

Outcomes

Prognosis

  • Deep ulcers may epithelialize leaving a corneal defect (facet).

Expected Response to Treatment

  • Rapid healing of superficial ulcers.
  • Corneal clarity and vision.
  • Absence of pain.

Reasons for Treatment Failure

  • Failure to correctly identify and eliminate the underlying cause:
    • Untreated bacterial infection.
    • Continued trauma.
    • Untreated KCS or uveitis.
  • Severe corneal scarring.
  • Topical or systemic steroid use with an ulcer can cause melting.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Kern T J (1990) Ulcerative keratitis. Vet Clin North Am Small Anim Pract 20 (3), 643-666 PubMed.

Other sources of information

  • Gelatt K N (ed) (1999) Veterinary Ophthalmology.3rd edn. Lippincott, Williams & Wilkins. ISBN 0683300768.

Other Sources of Information