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.

Pathogenesis

Etiology

• Trauma:
  • Blunt, penetrating or perforating.
  • Thermal/chemical burns Eye: chemical burns.
  • Cat scratch.
  • Foreign body.
  • Entropion Entropion.
  • Distichiasis Distichiasis.
• Collagenases.
• Epithelial basement dystrophy (causing SCCED).
• Abnormalities of corneal lubrication:
  • Keratoconjunctivitis sicca Keratoconjunctivitis sicca.
  • Exophthalmos.
  • Proptosis Proptosis / prolapse orbit / globe.
  • Macropalpebral fissure Macropalpebral fissure.
• Infectious causes are limited to herpesvirus. Bacteria and fungi can invade the stroma after the epithelium has been disturbed, but are not the initiating cause of the ulcer.

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).

• 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  (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

Treatment

Outcomes