What to Do When Ulcers Won't Heal: Management of Superficial, Chronic Corneal Epithelial Defects in Dogs
School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USA
The most common causes of erosions/ulcers seen on an emergency basis are secondary to foreign bodies and trauma. Other causes of corneal problems are adnexal disease or poor conformation leading to exposure or mechanical injury to the cornea, both quantitative and qualitative tear film abnormalities, corneal edema leading to bullous keratopathy, abnormalities in globe position leading to lagophthalmia and facial nerve paralysis causing lagophthalmia. Appropriate management of corneal disease includes a thorough ophthalmic exam to ensure that lid function is normal, tear function is normal, and that no other ocular abnormalities are present which could contribute to the formation or persistence of a corneal erosion.
The most important aspect of treatment is to determine and correct the underlying cause, if present. Many superficial erosions caused by trauma will heal rapidly and uneventfully, however, if there is an underlying cause (such as KCS, entropion, etc) then the erosion will not heal without addressing that underlying cause. Treatment of superficial erosions (urgent non-emergencies) includes debridement if epithelial lipping (see section on SCCED below), and topical antibiotics prophylactically. A broad spectrum antibiotic such as neomycin/polymyxin/gramicidin is suitable with a BID to TID frequency for a non-infected erosion. It is important not to over-treat the erosion and impair wound healing. Consider atropine only if secondary uveitis present, however, it is often not necessary. Remember, atropine is contraindicated with concurrent KCS as it will further lower tear production and delay wound healing. E-collars are recommended.
Spontaneous Chronic Corneal Epithelial Defects
Spontaneous chronic corneal epithelial defects (SCCEDs) in dogs are chronic erosions with no apparently underlying cause that fail to resolve through normal epithelial wound healing. Various names have been applied to this condition, including boxer erosions, indolent erosions or ulcers, canine recurrent erosions, recurrent epithelial erosions, persistent corneal erosions, refractory corneal ulcers, nonhealing erosions, and idiopathic persistent corneal erosions. The typical clinical appearance of a SCCED is that of a superficial, noninfected erosion surrounded by a sheet of nonadherent or loose epithelium. The epithelium sometimes appears thickened, and fluorescein stain often leaks beneath the abnormal, nonattached epithelium. Left untreated or if improperly treated, these erosions can persist for weeks to months and sometimes for even over a year. These erosions usually occur in middle-aged dogs (i.e., 7 to 9 years) and in all breeds of dogs, although Boxers are often overrepresented.
A spontaneous, chronic, corneal epithelial defect should be suspected in any middle-aged dog with a nonhealing corneal erosion (i.e., an uncomplicated erosion that has not healed within 1 to 2 weeks). Careful examination must be performed to eliminate any possible underlying causes for delayed wound healing, such as mechanical trauma from lid abnormalities (e.g., lid mass, entropion, lagophthalmos) or foreign bodies, infection, tear film abnormalities, exposure (e.g., conformational, neurogenic, secondary to globe abnormalities such as exophthalmos or buphthalmos), or corneal edema causing secondary bullous keratopathy. If any underlying causes are found, addressing those issues generally results in resolution of the corneal erosion.
Diagnosis is also aided by the typical clinical appearance. A rim of loose epithelium around the erosion is characteristic in SCCEDs. The erosion is highlighted by diffuse staining with fluorescein, and a less intense ring of fluorescein staining surrounds the defect. The lesion is superficial, with no loss of stromal substance. Any corneal edema is confined to the area of the erosion. Diffuse stromal edema implies that endothelial disease, with secondary corneal edema and bullous keratopathy, is the more likely underlying cause of the erosion. The amount of blepharospasm, epiphora, and corneal vascularization varies tremendously. A central corneal lesion may commonly exist weeks to months without any vascular response at all. Peripheral lesions are more likely to vascularize.
Multiple treatment modalities have been recommended for the management of SCCEDs. It is important to remember that because SCCEDs are by definition nonseptic, frequent application of antibiotics is not necessary and may delay corneal wound healing. Topical antibiotics are administered prophylactically only, and application is needed only q 12 to 8 hours. Changing antibiotics seldom results in healing, unless the animal is suffering a toxic response to the antibiotic. After all the procedures described below, animals should be maintained on antibiotics until epithelial closure occurs. It is also important to communicate to the owners that these erosions often require multiple treatments and often recur in one or both eyes. For dogs with multiple recurrences, sometimes limiting access to bushes and tall dry grass decreases the frequency of recurrences, as superficial trauma likely initiates SCCEDs.
Epithelial debridement has long been a mainstay of therapy for SCCEDs. After application of a topical anesthetic, dry, sterile, cotton-tipped applicators are used to gently remove the loose epithelium, starting in the center of the erosion and working outward in a radial motion. Normal corneal epithelium is very firmly attached to the underlying stroma and is not easily removed with a cotton-tipped applicator, so debridement is continued until all loose epithelium is removed (without fear of unnecessary removal of normal epithelium). Often, a much larger area of epithelium is removed than originally indicated by fluorescein staining. Combining the outcomes of the various studies in the literature results in an overall success rate of approximately 50%.
Another therapy for SCCEDs involves making either small punctures or linear scratches in the superficial stroma, which likely creates channels for epithelial cells to penetrate the abnormal superficial stromal hyalinized zone noted on histopathology of these samples. Various names have been given to these procedures, including punctate keratotomy, anterior stromal puncture, multiple punctate keratotomy, multifocal superficial punctate keratotomy, and grid keratotomy. To perform an anterior stromal puncture, a 25-gauge needle is clamped in a hemostat so that the tip of the needle is barely exposed. This allows the hemostat to be used as a handle and controls the depth of the puncture. Alternatively, a commercially available anterior stromal puncture needle can be used. After application of topical anesthesia and debridement of loose epithelium, multiple small punctures are made 0.5 to 1 mm apart across the surface of the exposed stroma and extending 1 mm into the normal, surrounding attached epithelium. To perform a grid keratotomy, small lines are made in a crosshatched pattern extending from normal cornea across the epithelial defect. Combining the outcomes in the various studies in the literature results in a success rate of approximately 80%. A contact lens or third eyelid flap may also be used after these procedures; one study found that 100% (n = 12) of eyes healed after treatment with grid keratotomy followed by a third eyelid flap.
A more invasive procedure for the treatment of SCCEDs is superficial keratectomy. This procedure, unlike the two described above, requires general anesthesia and is best performed under an operating microscope. As a result, veterinary ophthalmologists generally perform this procedure. To perform a superficial keratectomy, the loose epithelium may or may not be debrided. If it is not debrided, careful examination of the cornea must be done to ensure that the entire area of nonadherent epithelium is removed with the keratectomy. The area is either outlined with a corneal trephine of appropriate size or with a 64 Beaver blade, and then it is undermined with a corneal dissector. The flap of cornea, usually 150 to 200 µm thick, is then removed, and any attachments are trimmed as necessary. Following the keratectomy, either a contact lens or third eyelid flap may be placed. Superficial keratectomy probably works by completely removing the abnormal superficial zone of stroma, allowing epithelial adhesion. The success rate with this surgery has been reported to be 100%. Although this procedure results in rapid healing, it is often not recommended as an initial therapy because of the need for referral, its higher cost, the risks inherent with general anesthesia, and the increased likelihood of corneal scarring.
Erosions Due to Bullous Keratopathy
Bullous keratopathy is typically due to endothelial degeneration. Endothelial degeneration may be due to old age, dystrophies, or some previous insult that decreased the number of endothelial cells (uveitis, glaucoma). In this process, stromal edema leads to alterations in epithelial attachment, and small bulla (epithelial water blisters) form. These small bulla easily rupture, leading to corneal erosions that do not heal easily. Corneal erosions due to edema are often multifocal, and the associated edema is more generalized and more severe than the mild edema associated with epithelial loss alone. Differentiating a long-standing SCCED from bullous keratopathy can sometimes be difficult, but erosions due to bullous keratopathy have an even more protracted course of healing.
Medical therapy of bullous keratopathy is often unrewarding. Topical hypertonics may provide palliative therapy for epithelial edema. Hypertonic agents increase the tonicity of the tear film, which draws excess fluid from the epithelium. Topical hypertonics, however, have no significant effect on stromal edema. The most commonly used hypertonic is 5% sodium chloride drops or ointments. Ointments used 4 times daily appear to have the best efficacy in canine patients with bullous keratopathy. If erosions are present, topical broad-spectrum antibiotics should be used as described for SCCEDs. Contact lenses may relieve pain and discomfort as well as protect corneal epithelium from mechanical trauma. Contact lenses can be left in place for two weeks, and an Elizabethan collar should be placed to facilitate retention.
Surgical therapy provides the most definitive treatment of bullous keratopathy. Goals of therapy are pain relief and visual recovery, if possible. In veterinary medicine, pain relief is often the only easily obtainable goal. Thermal cautery is an easy and practical surgical option for painful bullous keratopathy, but usually requires referral. In this process, the anterior stroma is denatured by heat. This destroys the basement membrane, which is abnormal in bullous keratopathy, along with altering the anterior stroma. Thermal cautery creates a light subepithelial scar that is a barrier to fluid flux. This barrier prevents the formation of bulla, and allows the epithelium to re-attach. Excessive scar formation will often result in decreased vision, but the animals are usually comfortable. If scar formation is minimal, vision can be retained, but owners should be warned that vision may decrease after surgery. The procedure is performed with the animal under general anesthesia using disposable hand-held thermal cautery to make small, superficial burns across the affected area after epithelial debridement. Several hundred burns may have to be placed. In cases of degeneration or dystrophy, often the entire cornea is treated to prevent future problems because the edema typically continues to progress. A blunt tipped diathermy probe on its lowest setting may also be used. A contact lens should be placed, and broad-spectrum topical antibiotics used. Mydriatics should be used if the patient appears painful and if tear production is normal. After the cornea is epithelialized, topical corticosteroids may be used to decrease scar formation. Skill with microsurgical techniques and a familiarity with working under magnification (preferentially an operating microscope) are required, and therefore, referral to an ophthalmologist is recommended.
Anterior stromal puncture (ASP) has been advocated in human patients with bullous keratopathy as a means to improve their comfort while awaiting penetrating keratoplasty (the definitive treatment for humans). The punctures penetrate the abnormal basement membrane and anterior stroma, allowing focal epithelial adhesions to occur. One advantage of this procedure is that it can usually be performed in conscious animals using topical anesthesia, which can be an important consideration in elderly patients with endothelial degeneration. ASP also causes less scarring than thermal cautery, but may not be as effective long term as it does not significantly alter the anterior stroma.
A thin conjunctival flap may also be placed over the cornea in cases of painful bullous keratopathy. Generally thermal cautery is preferred, as there is a better chance of retaining vision, however, a thin, partial flap may result in decreased edema and retention of vision. Again, this procedure usually requires referral to a veterinary ophthalmologist.