The cornea is made up of three layers:  the epithelium (outer layer), the stroma (middle layer) and the endothelium (innermost layer). The epithelium serves as a protective barrier and prevents irritants and infectious agents (bacterial and fungal organisms) from entering the deeper layers of the cornea and the eye. This epithelial layer lies on top of a thin membrane that helps to anchor or attach the epithelium to the underlying stroma.

A corneal ulcer develops when there is a break in the outer epithelium. Following a superficial injury to the surface of the cornea, the epithelial cells adjacent to the wound expand themselves and migrate toward the defect in an attempt to repair and seal injury. In a normal eye, complete healing of an uncomplicated, superficial corneal ulcer can occur in 7 to 14 days time. When a corneal ulcer does not heal normally and persists beyond the expected period of time for recovery, it is regarded as refractory or indolent.  

Causes of Refractory Corneal Ulcers

In some instances the healing process of a corneal ulcer can be complicated or prolonged.  

"External" factors or other ocular disorders that can contribute to prolonged healing of a corneal ulcer include:

  • physical abnormalities such as entropion, eyelash disorders, the presence of a foreign body, eyelid tumors, and trauma from rubbing
  • Keratoconjunctivitis sicca (KCS)
  • presence of infection
  • nerve damage affecting the eye

"Internal" abnormalities or other factors that can lead to delayed healing or non-healing of a corneal include:  

  • Corneal edema
  • Corneal endothelial degeneration
  • Aging
  • Systemic diseases that affect tissue healing including Cushing's Syndrome
  • Systemic medications that can affect general healing including corticosteroids
  • Basement membrane disorder - this is an abnormality in the thin membrane that serves to anchor the epithelium to the underlying stroma.  This is typically seen in dogs and is most common in the Boxer breed.  Corneal ulcers that fail to heal due to this cause are generally regarded as "indolent."
Diagnosing a Refractory or Indolent Corneal Ulcer

A corneal ulcer is diagnosed during an eye examination.  The defect may be detected by visual inspection, but it requires the application of special stains to definitely determine the presence, size and the extent of the ulceration.  Veterinary ophthalmologists also use equipment (slit lamp biomicroscope) to further magnify and inspect the tissues during an examination.  

Indolent corneal ulcers can have a characteristic quality of developing "lipping" of epithelium around the wound, in which the cells that have proliferated to repair the defect stack up at the edges but don't adhere to the underlying tissue.  When examined further, these cells strip away easily with a cotton swab (which does not occur in a normal eye).

If an underlying cause for the ulceration or concurrent medical problem is identified, then those issues should be addressed to faciliate healing of the corneal ulceration.  In addition, it is necessary to prevent or treat infection and pain, prevent self-trauma, and promote healing of the tissue.

In the case of indolent corneal ulcers, debridement of the wound (to remove dead epithelial cells and to freshen up the wound edges) is generally performed.  In addition, other procedures may be recommended to address the abnormality in the basement membrane.  A keratotomy or a surgical keratectomy may be recommended to encourage the epithelium to adhere to the underlying stroma.

  • Grid or Punctate Keratotomy

A keratotomy can generally be done in the awake patient using a topical anesthetic to numb the eye.  In this procedure, the abnormal basement membrane is disrupted using a surgical needle, creating "channels" for the epithelial cells to migrate into and adhere.

In some instances, a therapeutic soft contact lens may be placed on the cornea to serve as a bandage.

  • Keratectomy

This is a procedure done under general anesthesia.  The abnormal basement membrane and associated diseased tissue is surgically debrided, peeling them away from the cornea much like the layers of an onion.

A contact lens or a temporary third eyelid flap may be placed over the eye to aid with the healing of the tissues postoperatively. 

After either procedure, patients may appear slightly more uncomfortable for a few days and medical treatment of the corneal ulcer is continued until healing is determined to be complete.  Although these procedures stimulate the healing of an indolent ulcer, patience is required, as it can take up to 2 to 6 weeks for healing to occur.