1. Identify and remove the primary cause
2. If an ulcer doesn’t heal in 3 days, something is wrong (1 of 3 things)
3. Recognize when the ulcer is going downhill
4. A brachycephalic dog is not a regular dog
5. All nonhealing ulcers do not equal an indolent ulcer
Corneal diseases are the most common ocular abnormality in small animal practice. We will review signs, classification and treatment. Simple corneal ulcers, nonhealing (indolent) ulcers, infected corneal ulcers, melting corneal ulcers, and other conditions will be reviewed. Deep and/or progressive corneal lesions are the most frustrating of ocular disorders, and mistakes or failure to act aggressively in certain cases can lead to perforation and loss of the eye.
Simple corneal ulcers are the most common type of corneal disease in small animal practice. Simple corneal ulcers are most commonly superficial (involving only the epithelium), acute in onset, and usually painful (exposed nerve endings). Commonly, these ulcers are caused by trauma. These lesions are not associated with significant uveitis, are not infected, and do not have an obvious underlying cause (KCS, a retained foreign body, eyelid abnormality, etc). Simple superficial corneal ulcers will heal in 48 to 72 hours.
GOLDEN RULE 1: Identify and remove the primary cause. The first step in management of corneal ulcers is to eliminate or treat any underlying cause (look for foreign bodies, distichiasis, ectopic cilia, entropion, KCS, etc). The second step is to prevent infection. Topical broad-spectrum antibiotics (i.e., Triple antibiotic, Chloramphenicol, Oxytetracycline) tid-qid +/- atropine (if pupil miotic – then atropine once a day) is the recommended treatment. The third step is to provide pain relief (topical atropine, oral NSAID and Tramadol, topical nalbuphine). Reevaluation should be scheduled in 72 hours.
GOLDEN RULE 2: If an ulcer doesn’t heal in 3 days, something is wrong (1 of 3 things). If the ulcer is still present then it is now complicated and (1) you have missed the underlying cause of the ulcer, (2) it has become infected with bacteria or fungus (complicated corneal ulcer) and/or is melting, or (3) the ulcer is an indolent ulcer.
(1) You have missed the underlying cause
(2) The ulcer has become infected and/or is melting
GOLDEN RULE 3: Recognize when its going downhill. Clinical signs of corneal infection need to be recognized. Stromal loss, cellular infiltrate, malacia, and severe reflex uveitis (hypopion, hyphema, fibrin) are indicators of infection. Corneal ulcers that are associated with stromal loss are most likely infected. Deep and melting corneal ulcers are considered a surgical emergency. Medical therapy may be helpful in slowing some cases of melting, but rarely is enough to stabilize the cornea alone. Aggressive medical therapy alone, with antibiotic choice based on cytology results while cultures are pending, may also be attempted in infected or deep corneal ulcers if less than approximately ½ of the stroma has been lost. These lesions need to be monitored hourly as full thickness loss of the stroma can occur in less than 24 hours. The surgical procedure most commonly used for infected or progressive corneal ulcers is a conjunctival graft. Conjunctival grafts provide tectonic corneal support, fibrovascular tissue to fill corneal defects, and bring blood supply and blood-associated immune components to the lesion. All types of conjunctival grafts consist of thin conjunctival tissue transposed onto the cornea to cover the lesion. The pedicle (or rotational) graft is probably the most useful and versatile conjunctival graft
A descemetocele is a deep corneal lesion in which the corneal epithelium and stroma are completely destroyed leaving a lesion lined only by Descemet’s membrane and corneal endothelium. Descemet’s membrane is an elastic membrane, but it is only 3–12 µm thick and easily ruptured. Once this final barrier is breached, a full-thickness lesion will occur, aqueous humor will be lost, and iris prolapse may occur. Contamination of the anterior chamber also occurs after rupture of Descemet’s membrane, which may lead to endophthalmitis and a much poorer prognosis for saving the eye and vision. Descemetoceles and full-thickness corneal perforations can develop from a progression of deep corneal ulcers or from trauma. If a perforation is present, an assessment of the posterior segment should be attempted to help determine prognosis for vision prior to surgery. Posterior segment examination may be possible in descemetoceles, but it is usually difficult with perforations. In those instances where ophthalmoscopy is not possible, evaluation of consensual pupillary light response (PLR) and dazzle reflexes may provide some information regarding the integrity of the posterior segment of the eye. Presence of a consensual PLR and a dazzle response is a positive clinical sign, but it does not ensure a normal posterior segment. Absence of consensual pupillary light responses and the dazzle reflex indicates a poor prognosis, and alternatives to surgical repair should be considered (i.e., enucleation).
Chronic, infected, or progressive corneal ulcers should have an aerobic bacterial and fungal culture and sensitivity done, and cytology of the cornea should be collected and examined. The cytology will guide immediate antibiotic/antifungal choice. The culture is usually not available in time to make a difference in rapidly progressing ulcers.
A melting corneal ulcer can occur as the result of infection or simply from an in balance of proteinases. A melting corneal ulcer is a descriptive term that describes the collagenolysis and progressive loss of semi-liquefied collagen from the corneal stroma. The collagenolysis develops secondary to enzymes that are released from inflammatory cells (neutrophils) and some bacteria and fungus. This is most commonly seen in Pseudomonas infection, but other types of bacteria or fungi can cause it. These infectious agents produce proteases and collagenases, which break down the corneal stroma. Because corneal stroma does not regenerate, extensive areas of collagenolysis weaken the cornea and lead to perforation. Complete loss of the stroma can occur within 24 hours. Treatment includes antibiotics and collagenase inhibitors such as acetylcysteine and homologous blood serum. Topical oxytetracycline and oral doxycycline are now commonly used and are very effective in binding iron and preventing bacterial protein synthesis. In addition and more importantly, tetracycline inhibits neutrophil-associated collagenolysis. Host tissues are protected from neutrophil-mediated damage by two mechanisms: 1. Neutrophil granule-associated enzymes are secreted in an inactive state; and, 2. Tissues are protected from these enzymes by a potent inhibitor shield. Neutrophils can bypass these protective elements by activating enzymes and by destroying the shield through the synthesis of oxygen radicals. Therefore, tetracyclines may suppress neutrophil-mediated tissue damage by inhibiting their migration and degranulation and, potentially more importantly, by suppressing synthesis of oxygen radicals. However, even in the face of very aggressive medical therapy, surgery is frequently necessary to stabilize a rapidly progressing melt.
GOLDEN RULE 4: A brachycephalic dog is not a normal dog. Brachycephalic dogs have a number of ocular anatomic and physiologic features that predispose them to globe-threatening corneal disease. Surface area, exposure, tear film abnormalities, and decreased corneal sensation can frequently combine to turn a routine corneal ulcer into a ruptured globe. Alterations in routine antibiotic therapy, increased frequency of application, and shorter re-examination times should all be applied to the therapy of corneal ulcers in these dogs.
(3) The ulcer is Indolent
Indolent ulcers (recurrent erosions, Boxer ulcers) are superficial defects of the corneal epithelium that are characterized by nonadherent epithelium forming redundant epithelial ulcer borders. These ulcers do not invade the corneal stroma and are not primarily associated with an infectious agent. The primary etiology may be a basal epithelial or superficial stromal defect that does not allow the normal adherence of the corneal epithelium to the stroma. Surgical therapy for indolent ulcers is the treatment of choice; however, a number of medical therapies, which are used with and without surgery, have been described recently with variable results (e.g., use of fibronectin, epidermal growth factors, and polysulfated glycosaminoglycans). Superficial grid keratotomy (SGK) has been the classic therapy for this disorder. With a grid keratotomy, after application of a topical anesthetic, a 25-gauge needle is used to very lightly scratch the surface of the debrided indolent ulcer. Horizontal and vertical scratches are made to form a grid pattern, with the scratches extending slightly into the normal epithelium. The scratches should be separated by approximately 1 mm. A topical antibiotic is prescribed after surgery and the animal is reevaluated within 5 to 7 days. Topical tetracycline is recommended (Terramycin, oxytetracycline) as it has been shown to be beneficial in these types of ulcers. Concurrent use of soft contact lenses is also beneficial in promoting healing. Eighty percent of dogs will heal within one week following an appropriately performed SGK. Some dogs will require a second procedure.
Corneal debridement with a diamond burr has recently come into more frequent use as a primary therapy or in conjunction with the SGK. In contrast to the SGK, the burr does not break the epithelial basement membrane, but has shown a positive effect in healing indolent ulcers similar to the SGK alone. Because it does not break the basement membrane, its mechanism of action is currently unknown. Advantages to the diamond burr include less scarring and a decreased risk of perforating the cornea. Disadvantages may be an increased incidence of corneal melting following the procedure. A third surgical therapy for indolent ulcers is superficial. Keratectomy: By removing the epithelium and abnormal superficial stroma of the indolent ulcer, the cornea generally heals rapidly. A disadvantage of superficial keratectomy is that general anesthesia is required.
GOLDEN RULE 5: All nonhealing ulcers do not equal an indolent ulcer or “errors of the grid.” Again, SGK has been routinely employed as a treatment option for refractory corneal ulcers in dogs. Superficial grid keratotomy, and now the corneal diamond burr, are employed for superficial ulcers with epithelium basement membrane defects only and are NOT meant for any other corneal ulcerative condition. Unfortunately, these techniques may have devastating ocular consequences when performed incorrectly. The five things that can lead to disaster include (1) applying the technique to the incorrect type of ulcer, (2) inadequate restraint, (3) use of an incorrect needle, and (4) repeat debridement too soon.
(1) Applying the technique to the incorrect type of ulcer. By applying this technique to stromal ulcers, infected ulcers or descemetoceles, infectious agents can be introduced into the deeper layers of the corneal stroma and rupture of the globe can occur. A stromal ulcer or descemetocele should never be touched with a sharp object. Careful debridement of stromal ulcers may be performed by using a sterile cotton tip applicator, but is usually not necessary to the healing process.
The restraint required is dependent on the comfort level of the person performing the procedure and the training of the restrainer. Generally a 25- or 30-gauge needle is used to perform the procedure. The strokes are just firm enough to create a very faint line in the cornea stroma. Applying too much pressure will create deep stromal lesions and significant scarring. Larger needles cause lines that are too deep and large and lead to increased scarring and increased risk of serious damage to the cornea during the procedure. Refractory or indolent ulcers may take two to three weeks to heal, especially in the Boxer. Do not repeat the procedure too soon. Allow the lesion to heal before enlarging it. Wait at least two weeks before repeating.
Finally, anterior stromal or subepithelial degeneration is a condition that can result in nonhealing ulceration and even deep stromal lesions and perforations. Degeneration is usually associated with prior comeal disease and is by lipid (cholesterol) or calcium (characterized crystals deposits) in the anterior corneal stroma. Clinically, this degeneration may resemble subepithelial comeal dystrophy, but unlike dystrophy, it is usually unilateral, is associated with corneal vascularization, causes ulceration, and can lead to significant morbidity. Sloughing of the calcific deposits is a common complication in geriatric dogs. This can lead to significant pain, deep stromal ulceration and rupture of the globe. The age of these dogs frequently poses a serious anesthetic risk, as well, when considering therapy. Mild exposure keratitis or lagophthalmos may contribute to the pathogenesis. Topical EDTA may clear the deposits if they are calcium, and should be used as a trial therapy. Lamellar or superficial keratectomy may be curative for larger painful lesions, but as the keratectomy site heals, the degenerative lesion may return. The corneal diamond burr is an excellent way to remove theses deposits, if a deep stromal ulcer is not present, and can be performed with only topical anesthetic. In addition to EDTA, treatment also includes increasing basal tearing by using topical cyclosporine/tacrolimus, and lubricating the comea with Genteal or Refresh gels.