Canis ISSN: 2398-2942

Keratitis

Contributor(s): Dennis E Brooks, David L Williams, Natasha Mitchell

Introduction

  • Common condition, variable in presentation: ulcerative/non-ulcerative, vascular/avascular, inflammatory/non-inflammatory, traumatic/non-traumatic.
  • Cause: secondary vascularization of avascular cornea in response to insult, with or without surface ulceration. Further secondary changes possible, eg pigmentation, edema, alteration in corneal contour, fibrosis, calcium and lipid deposition.
  • Signs: corneal opacity, ocular discharge, red eye.
  • Diagnosis: examination (gross, ophthalmoscopic, slit lamp biomicroscopy), fluorescein staining, Schirmer tear test.
  • Treatment: topical antibiotics, anti-inflammatories, artificial tears, surgical support for cornea.
  • Prognosis: many progress to corneal perforation or blinding opacity, so important to diagnose and treat correctly.

Pathogenesis

Etiology

  • Trauma: more common in brachycephalic/exophthalmic dogs, but occurs in any breed. Foreign bodies more common in working dogs.
  • Infection: may be primary or may complicate trauma. May progress to stromal melting → emergency. Stromal abscessation.
  • Precorneal tear film dysfunction: lagophthalmos → exposure keratitis, KCS = deficiency of aqueous tear layers; qualitative tear deficiency (lipid and/or mucus deficiency).
  • Immune mediated: chronic superficial keratitis Chronic superficial keratitis (CSK).
  • Systemic disease: canine viral hepatitis Canine adenovirus type 1 disease (adenovirus), delayed type hypersensitivity response → corneal edema; canine distemper → KCS.
  • Neurological:
    • Neurotrophic keratitis.
    • Lack of sensory (V) innervation → punctate keratitis → may progress to ulceration/edema.
    • Neuroparalytic keratitis.
    • Facial nerve paralysis → loss of eyelid movement.
  • Chemical injury: acid, alkali, other noxious substances.

Pathophysiology

  • Classified according to etiology, depth and appearance. Broad division into non-ulcerative keratitis (epithelium intact) and ulcerative keratitis (epithelium damaged).
  • Superficial keratitis involves epithelium and anterior stroma, vascularization from conjunctival vessels (looks like 'trees'). If conjunctiva also involved, called keratoconjunctivitis.
  • Deep keratitis involves deep stroma +/- Descemet's membrane/endothelium, vascularization arises from ciliary plexus at limbus (looks like 'hedges').
  • Reflex anterior uveitis Reflex uveitis may develop. Signs may include aqueous flare, hypopyon, keratic precipitates and miosis. The vessels of the tissues supplying nutrition to the healthy cornea (conjunctiva and iris) become more leaky when keratitis is present.
  • Stromal malacia arises due to collagenolysis; melting ulcers have an indistinct border, with loss of corneal contour and a gelatinous appearance.
  • Corneal edema may develop due to reduced function of the corneal endothelium or because of loss of integrity of the epithelium, and appears as blue or white areas.
  • Corneal fibrosis occurs in a healing cornea and can remain as a scar; it appears as gray irregular areas within the anterior stroma.
  • Corneal melanosis or pigmentation occurs with chronicity, when melanocytes that are normally present at the limbus migrate through vascularization to corneal epithelium or anterior stroma; it appears as dark patches with indistinct borders.
  • Stromal cell infiltration occurs when white blood cells migrate into the cornea in response to a chemotactic stimular, involving primarily neutrophils but other inflammatory cells can be present including eosinophils; it appears as yellow/cream/green areas within the corneal stroma and may or may not indicate infection.
  • Lipid or mineral deposition in the anterior stroma may arise due to dystrophy or degeneration; it appears as focal crystalline white areas.
  • 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.
  • Secondary bacterial invasion usually gram-positive (Staph/Strep), some gram-negative (Pseudomonas,E. coli,Bacillus).
  • Deep ulcers (>half stromal thickness):
    • 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 Descemetocoele), 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.
  • Pigmentary keratitis: usually associated with chronic keratitis, pigment produced in epithelium, anterior stroma and migrates from perilimbal melanocytes, may be secondary to corneal vascularization. Impairs vision when becomes central.
  • Chronic superficial keratitis (CSK): immune mediated (cell-mediated immunity to corneal/conjunctival antigems - ultraviolet radiation may alter immunogenicity of antigens) vascular lesion appears at temporal limbus and invades cornea, pigmentation follows vascularization. May also affect nictitating membrane. Epithelium remains intact.
  • For further information about diagnosis and treatment see specific diseases:

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Tolar E L, Hendrix D V H, Rohrbach B W, Plummer C E, Brooks D E & Gelatt K N (2006) Evaluation of clinical characterisitics and bacterial isolates in dogs with bacterial keratitis: 97 cases (1993-2003). JAVMA 228 (1), 80-85 PubMed.


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