Non-healing Superficial Corneal Ulcers in Dogs

by Daniel Biros, DVM, DACVO
dbiros@angell.org
617-541-5095
angell.org/eyes

Otherwise known as spontaneous chronic corneal epithelial defects (SCCEDs), these clinical cases often frustrate the clinician because the normal wound-healing process for superficial corneal ulcers is thwarted, and often the affected dogs have prolonged periods of discomfort and in some cases progressive keratitis despite aggressive medical treatment. Other names for this condition include Boxer ulcers, non-healing erosions, persistent corneal erosions, indolent ulcers, or idiopathic persistent corneal erosions. While recognized frequently in Boxers, almost all canine breeds can experience this condition.

Diagnosis is in part directly related to the history of a superficial ulcer with or without corneal neovascularization, conjunctival hyperemia, and irregular or inconsistent patterns of shifting size and shape. On clinical examination there is frequently a discreet superficial ulceration, geographic or multifocal, with loose epithelial wound edges best appreciated after application of fluorescein stain (see photos). Sometimes loose flaps of epithelial sheets or fragments of epithelia from the wound edges are seen freely hanging from the ulcer’s edge, misguided and unsuccessful attempts at wound healing. Most cases are unilateral, but bilateral ulcers may present. Pain in SCCEDs is highly variable and while some dogs have significant blepharospasm, epiphora, and even mild uveitis (as evidenced by miosis with some degree of aqueous flare), other ulcers are found incidentally on physical examination as a corneal opacity initially, later discovered to be an ulcer once the fluorescein stain is applied. Without procedural intervention (described later) the corneal ulcer remains, and secondary inflammatory responses may occur including corneal neovascularization: in severe cases, granulation and necrosis of the cornea may develop.

Etiologies for the condition vary widely. Many believe that while the condition is termed spontaneous there is claim that the condition can be triggered by any physical trauma to the cornea, including but not limited to distichia (which many Boxers have), trichiasis, ectopic cilia, entropion, or other scratches or lacerations from external stimuli (foreign bodies, etc.). While most wounds will heal readily once the inciting cause is removed, SCCEDs linger much longer due to abnormal wound healing and can often create a corneal wound that changes shape and size beyond the initial injury. It is not clear if viral, fungal, and/or bacterial infections play a significant role in the development of SCCEDs, but infectious agents may be present in the early stages of the disease or appear later as opportunists in the ulcerated cornea. By and large, however, SCCEDs are not considered the results of ongoing infection which distinguishes this group of corneal ulcers from others. In SCCEDs, the corneal stroma is rarely lost in these conditions, and cytology and culture of the wound generally is unremarkable for infectious organisms.

With or without the presence of any physical causes for trauma to the corneal surface, these ‘spontaneous’ wounds are known to have an abnormal surface characterized by a broken, inconsistent basement membrane with fibronectin deposition. Other studies claim that the basement membranes appear normal so there is considerable controversy as to the nature of the persistent ulcers. In another study, a specific superficial stromal hyalinized zone suggested that there is chronic inappropriate remodeling of the corneal surface in dogs with SCCEDs. Further, substance P and calcitonin gene-related, peptide-associated nerve fibers were found in increased numbers surrounding the corneal wounds. Whether the presence of these peptides is a reaction to the wounding or associated with the persistence of the ulcer is not clear. Matrix metaloproteinases, or MMPs have also been incriminated in the formation of SCCEDs. Specifically MMP-9 has been found in these chronic wounds, but at much lower levels than in acute corneal injury, making them unlikely to be linked to the chronicity of the wound, but perhaps as more of a result of the injury that is present. Key to the argument of causes of SCCEDs is the role of epithelial migration factors including E-cadherin, beta-catenin, beta-actin, and desmoplakin which do not appear to be expressed in normal canine corneal epithelium. Tetracycline has been proposed as a treatment for SCCEDs since it increases transforming growth factor-beta expression which in turn can increase the production of these epithelial migration factors. Further studies would be necessary to prove these hypotheses. The bottom line with etiology is that the basement membrane of the cornea is damaged and irregular as a result of delayed wound healing. As we will see, the grid keratotomies or diamond burr procedures can significantly aid in the wound healing, likely by removing structural barriers to the epithelial migration and adhesion and allowing some of the inflammatory cells to gain access to the wound site and provide the adhesion factors necessary to repair the wound.

Treatment of SCEDDs (see Table) includes topical medication to promote healing (refrigerated serum, stable for 10-14 days), prevent infection (e.g. terramycin QID), and treat pain (Atropine to effect up to QID). Topical antiinflammatories (both steroids and NSAIDS) should be avoided. If a patient is on cyclosporine topically for dry eye or is found to have concurrent dry eye, the cyclosporine may be used topically alongside the other eye medication. Oral medication including NSAIDS, and in sensitive patients oral narcotics, are also administered as the ulcer heals for pain relief. Procedures that are often integral to wound healing include gentle debridement of all loose and devitalized epithelia at the wound edges, usually accomplished with a soft (sterile) cotton swab with manual restraint and topical anesthesia. This accomplishes a ‘resetting’ of the wound healing and important removal of excessive and unnecessary tissue that is an impediment to recovery. An eyelid speculum can help immobilize the eyelids (including the nictitating membrane) during this procedure and the next. A grid keratotomy or a diamond burring procedure usually follows the thorough debridement to clear the superficial stroma of material thought to be a barrier to healing as discussed above. I perform a grid keratotomy with a 20 gauge needle, a trustworthy technician to hold the animal, and topical anesthesia, usually 2 drops proparicaine administered 5 minutes apart and allowed to work for at least 5 minutes prior to debridement and gridding. Diamond burring is a newer technology available to ophthalmologists and is proving to be equivalent to the grid procedure (see photo). Bandage contact lens placement is an additional aide in the treatment of the most stubborn ulcers. I usually will apply a bandage lens as a secondary effort when the above procedures are not effective. The lens is left in place for up to a week or longer. Invariably, some lenses do not stay in for that long which is a disadvantage to its placement. The lens would be an equivalent of a third eyelid flap or tarsorrhaphy, older methods for corneal protection that are rarely used today. An Elizabethan collar or comfy cone helps reduce the ability of most patients to self traumatize the affected eye during recovery.

Prognosis for SCCEDs is widely variable, but in general favorable with time and medication. Some ulcers heal rapidly with treatment, and others are less rapid to heal, taking weeks or longer. The most important thing for clients to remember is that patience is important as these ulcers can be quite stubborn. Even after healing, ulcers may reappear spontaneously in the same eye or the other eye. Repeat gridding or burring following additional soft swab debridement may be necessary for the most resistant ulcers. Usually after the first treatment the ulcer is rechecked in 5-7 days and medication is adjusted. Rechecks are usually every 1-2 weeks until the ulcer is fully healed. The most sensitive period is usually 1-5 days after the grid keratotomy/burring procedures. Duration of sensitivity may depend on the size of the ulcer, degree of existing keratitis at the time of the procedure, and the use of topical and systemic pain medication.

For more information, please visit www.angell.org/eyes. Dr. Dan Biros may be contacted at dbiros@angell.org. Angell’s ophthalmologists are available for consultation via phone or e-mail (ophthalmology@angell.org) Monday-Friday 9:00am-5:00pm. Evening and early morning appointments are also available. To reach an Angell ophthalmologist by phone or to refer a patient to the Angell Surgery service, please call Sandra Russo at 617 541-5095.