Indolent Ulcers

Indolent ulcers frequently occur in dogs and are the most common canine eye disorder seen by the UVS Ophthalmology service. They are also referred to as spontaneous chronic corneal epithelial defects (SCCEDs), persistent corneal erosions, non-healing ulcers and Boxer ulcers. While indolent ulcers are certainly non-healing, not all non-healing ulcers are indolent ulcers. Underlying ophthalmic diseases and infection can also prevent ulcers from healing. Therefore, a thorough ophthalmic exam to exclude other diseases that cause persistent ulcers, such as keratoconjunctivitis sicca, distichia, entropion, ectopic cilia, eyelid masses, lagophthalmos (inability to properly blink the eyelids) and ocular foreign bodies is essential before making a diagnosis of an indolent ulcer. Boxers and Corgis are especially predisposed to indolent ulcers, but they can occur in any breed of dog.

Pathophysiology

Indolent ulcers are most likely caused by trauma, but the exact insult is often never known. The inability of the ulcer to properly heal is due to a number of changes that can be observed on histopathology. These factors are believed to be age-related. The corneal epithelium appears dysplastic and is either unattached or poorly attached to the underlying stroma. A hyalinized aceullar zone is often present in the superficial stroma, and this is the issue that grid keratotomies specifically target. Indolent ulcers are also known to have an abnormal surrounding nerve plexus and mild to moderate suppurative or lymphoplasmacytic inflammation. Unlike melting corneal ulcers, increased levels of matrix metalloproteinases (the corneal enzymes that cause the “melting”) are not present in indolent ulcers, and this is likely why serum is not an effective treatment for them.

Diagnosis

Indolent ulcers have several unique attributes that can be identified on exam. By definition, they are always superficial. If an ulcer appears to involve the corneal stroma or you can see a divot on the cornea, then it is either not an indolent ulcer or it is an indolent ulcer that has become infected and should now be classified as an infected ulcer. In addition, indolent ulcers occur in middle-aged and older dogs with the average age being eight to nine years old. They can occur in dogs as young as 5 years old, though that is uncommon. An indolent ulcer in a dog less than five years old is rare, and other differentials should be strongly considered in that instance. Finally, indolent ulcers typically have a ring of loose corneal epithelium that fluorescein stain can seep under, creating a diffuse stain uptake pattern or a “halo” of stain around the ulcer. As mentioned previously, a thorough ophthalmic exam to exclude other causes of non-healing ulcers is essential.

Indolent ulcers have several unique attributes that can be identified on exam. By definition, they are always superficial. If an ulcer appears to involve the corneal stroma or you can see a divot on the cornea, then it is either not an indolent ulcer or it is an indolent ulcer that has become infected and should now be classified as an infected ulcer. In addition, indolent ulcers occur in middle-aged and older dogs with the average age being eight to nine years old. They can occur in dogs as young as 5 years old, though that is uncommon. An indolent ulcer in a dog less than five years old is rare, and other differentials should be strongly considered in that instance. Finally, indolent ulcers typically have a ring of loose corneal epithelium that fluorescein stain can seep under, creating a diffuse stain uptake pattern or a “halo” of stain around the ulcer. As mentioned previously, a thorough ophthalmic exam to exclude other causes of non-healing ulcers is essential.

Treatment

Various medical and surgical modalities are used to treat indolent ulcers. The first step is debridement of the loose corneal epithelium with a sterile cotton swab. Generally, normal corneal epithelium cannot be removed with a cotton swab, so any epithelium that is removed is abnormal and considered part of the indolent ulcer. Studies show that cotton swab debridement alone heals an average of 50% of indolent corneal ulcers. When cotton swab debridement is unsuccessful, more aggressive procedures are used.

Diamond burr debridement involves using a dremel-like tool with a spinning bit to debride the ulcer. The exact mechanism for how diamond burrs heal indolent ulcers is unknown, but studies have shown that over 90% of indolent ulcers can heal with this technique.

Grid keratotomies are another essential tool for indolent ulcer management and have an 80% success rate. Superficial scratches are made on the cornea with a 25-gauge needle in a cross-hatch pattern. The scratches should be deep enough that they can be seen, but not so deep that they create deep grooves in the cornea. With noncompliant patients, the last mm of the tip of the needle can be bent 90 degrees with sterile hemostats so that if the needle were to accidentally penetrate the cornea it would avoid lacerating the lens or iris. At our clinic, almost all debridements and grid keratotomies are done using only topical anesthesia with proparacaine and good restraint. Sedation can be useful for clinicians uncomfortable with ophthalmic procedures in conscious patients, but be mindful that it can cause the eye to roll into an unfavorable position. It is not uncommon for a debridement or keratotomy to have to be repeated before an indolent ulcer heals, but it rarely should have to be done more than three times. Placement of a bandage contact lens has been shown in multiple studies to shorten the healing time for indolent ulcers. This may occur due to protection of migrating corneal epithelial cells from the mechanical forces of the eyelids, providing a scaffold for epithelial cells to travel across or increasing contact between the epithelium and underlying stroma. Some studies show an improvement in patient comfort with use of a contact lens.

Less commonly used procedures for indolent ulcers include thermokeratoplasty, application of cyanoacrylate surgical glue to the ulcer and superficial keratectomy. They are rarely used due to the success of the aforementioned procedures. Thermokeratoplasty can be useful for indolent ulcers that are associated with significant corneal edema. Low temperature handheld cautery is used to make numerous punctate superficial burns across the ulcer. The application of excessive heat can cause corneal perforation, so it is best for an ophthalmologist to perform this procedure. The application of cyanoacrylate tissue glue can also be useful in refractory cases, but care has to be taken to avoid gluing the eyelids or third eyelid to the cornea. When none of these modalities work, the last resort option is a superficial keratectomy, or surgical excision of the outermost layer of the corneal ulcer. Keratectomy has a 100% success rate but requires general anesthesia and significant expense compared to the other procedures.

Medically, indolent ulcers should be treated with a topical antibiotic at a frequency of three to four times daily. While a variety of antibiotics can be used, terramycin is our recommendation because it is broad spectrum and has been clinically proven to make indolent ulcers heal faster. This is thought to occur because tetracyclines increase expression of growth factors involved in corneal epithelial cell migration. If terramycin is unavailable, other reasonable options are neopolybac, neopolygram or tobramycin. We do not recommend treating indolent ulcers with topical fluoroquinolones, as those are reserved for infected ulcers. Pain management is also important and can be achieved with oral NSAIDs, tramadol and/or topical atropine. Finally, an e-collar should be worn for the duration of the ulcer. We recommend weekly rechecks until the ulcer has healed. Other medical therapies include artificial tears and topical polysulfated glycosaminoglycans, but these therapies should be used as adjunctive modalities rather than as a substitute for topical antibiotics. Studies have shown that serum is not effective in healing indolent ulcers. Remend has not been shown to specifically heal indolent ulcers, though it may have some benefit as an ocular lubricant.

Pearls and Pitfalls in Indolent Ulcer Management 

1. The management of indolent ulcers and infected ulcers is significantly different. It is critical to identify the type of ulcer being treated.
2. While brachycephalics certainly can develop indolent ulcers, their tendency to also develop infected melting corneal ulcers can complicate their diagnosis and management. Chronic ulcers in brachycephalic dogs, even if indolent, are probably best served by an exam with an ophthalmologist to minimize the chance for development of a melting ulcer and the subsequent risk for corneal perforation.
3. Do not be alarmed if an indolent ulcer seems to be small in diameter initially, but then almost the entire corneal surface area is removed with cotton swab debridement. Remember that it is the depth of the ulcer and not the diameter that is cause for concern, and indolent ulcers should always be superficial. If the ulcer appears to be deeper than superficial, it is likely infected and should be treated as such.
4. Indolent ulcers can be deceiving. At times, they can appear healed and stain negative, but the epithelium still has not adhered. These are cases where the dog had a chronic superficial ulcer; it goes away, but then occurs again soon after. In reality, the ulcer never completely healed. Normal corneal epithelium should not come off with cotton swab debridement, so when in doubt, touch the ulcer with a sterile cotton swab.
5. Do not debride the ulcer more often than every seven days, as that may not give enough time for healing.
6. Taking a sharp object to the cornea can have adverse consequences to the eye. You must be sure that the ulcer is indolent before you attempt a grid keratotomy. Performing a grid keratotomy on an infected corneal ulcer can lead to corneal perforation and loss of the eye.
7. Warn clients that indolent ulcers get their name because they are frustrating to treat and stubborn to heal. The ulcer may need more than one debridement or examination by an ophthalmologist before it heals. Establishing expectations from the first appointment is important in minimizing client frustration.
8. Dogs that get an indolent ulcer in one eye often develop one in the contralateral eye in the future.
9. Other species also can develop indolent or indolent-type ulcers, including horses, cats and rabbits. They can be more frustrating than canine indolent ulcers, but not all treatment modalities used in dogs can be used for other species. For example, cats should never receive a grid keratotomy as that has been shown to cause corneal sequestra. In horses, a grid keratotomy should never be done unless a culture has been done to rule out fungal keratitis.

If you have any questions, please do not hesitate to contact our Ophthalmology service for a consultation. We are happy to help.