John Moss, DVM, has treated many animals, mostly dogs, suffering from corneal ulcers during his 30-plus years of practice. But part of what prompted him to consider new treatment solutions was something both simple and personal–he developed an indolent ulcer himself.
“It really, really hurt,” says Moss, owner of Brandywine Valley Veterinary Hospital in Coatesville, Pa. “I think these dogs suffer the same way. I’ve always been aggressive on treating corneal ulcers, but now I don’t hesitate to be even more aggressive.”
In searching for ways to accelerate healing, Moss began adding a cross-linked hyaluronan wound healant to his treatment protocol, a step he first tried in late 2009 with a boxer with a stubborn recurring ulcer. Within days, the treatment worked where months of traditional antibiotics and other treatments had failed, Moss says. Now, “I use it as my first-line treatment with most corneal ulcers, especially in boxers,” he says.
The new-generation corneal wound healants accelerate healing time, cutting it to as little as 48 hours, while also alleviating pain and reducing the risk of scarring, says Heidi Lobprise, DVM, Dipl. AVDC, senior technical manager at Virbac Corporation in Fort Worth, Texas. Virbac is introducing Remend Corneal Repair Drops, with advanced technology that produces a unique cross-linked hyaluronan to support the natural tissue repair process.
Hyaluronic acid (HA) is a glucosaminoglycan (GAG) that is naturally found in connective, neural and epithelial tissues, including synovial fluid and cartilage. As part of the extracellular matrix (ECM), it is known to assist in cell proliferation and migration–the very cellular tasks that are necessary to repair corneal tissue damaged by ulcers.
As a simple compound, HA degrades so rapidly that it is not usable in medications, Lobprise says. But when the modified substance is cross-linked to form the drops, it becomes more stable, allowing it to remain in place long enough to help support the body’s own natural repair.
Cross-linked hyaluronan has been used for topical wound treatment for some time, but veterinary ophthalmic uses were not explored until recently.
However, in a study published in 2010 in “Veterinary Ophthalmology,” researchers at the University of Utah looked at the efficacy of chemically modified and cross-linked hyaluronan (CMHA-SX) in treating abrasion corneal ulcers in rabbits. The wounds treated with CMHA-SX healed within 48 hours, and also exhibited better epithelial and stromal organization than the untreated control cornea.
“In addition to the standard use of antibiotics, if we can provide hyaluranon drops in a stabilized form via these corneal repair drops, not only does it keep the cornea better hydrated, but it also helps the body with its own wound care,” Lobprise says. “Basically, it works with the body to help it heal itself faster.”
To understand where the cross-linked hyaluronan healant is indicated in treatment, it helps to review the standard of care for corneal ulcers and how such wounds heal.
Corneal ulcers, usually caused by trauma, detergent burns or infections, are far more common than other corneal diseases, including congenital conditions such as cysts and conditions such as corneal dystrophy. They are not only painful, but if not aggressively treated, can progress to the stage that the eye could be lost, Moss says. Typically, they are more common in canines than cats–about five-to-one in Moss’s practice.
After a clinical diagnosis, the first step in treating a corneal ulcer traditionally is to determine the depth of the ulcer. The most commonly used method is to administer a fluorescein stain, which allows the clinician to see how deep into the cornea the injury has progressed.
Superficial cases usually can be treated with antibiotic drops, which provide moisture to the eyes while also minimizing chance of infection. Pain medications may also be administered to keep the patient comfortable and to keep dogs from pawing at or disturbing the eye while it is attempting to heal, Moss says.
Repair of the defect begins when epithelial cells start moving to the defect within one hour of the injury. Basal cells touching the defect stretch up to nine times their typical width, allowing adjacent cells to migrate over until cells have completely covered the epithelial defect. After 24 hours, basal cells will begin replicating to fill the defect in, from bottom to top.
Injuries that have progressed into the deeper stroma, however, are much more complicated, Lobprise says. Any damage or swelling of the deeper stroma elicits a strong immune response from the body, and white blood cells are required to help heal the defect. In such cases, the repaired collagen is irregular, leading to corneal scarring, impaired light passage, and, in severe or untreated cases, the loss of sight.
With deep or complicated ulcers, it may be best to consult with or refer the case to a local ophthalmologist, Lobprise recommends. If the defect extends through the stroma to Descemet’s membrane and the final one cell thickness of the endothelium, surgical protection of the site with a conjunctival or lid flap is often necessary.
Even with some poorly healing superficial ulcers (indolent ulcers) with inadequate reorganization of the anterior epithelium and connection to the stroma, gentle curettage of the diseased tissue may have to be done carefully to help stimulate full healing. Contact lenses may be used in conjunction with medication to help protect the layers as they heal.
To prevent superficial ulcers from reaching this point, and to help them heal faster, a cross-linked hyaluronan healant should be considered as a first-line treatment for acute, trauma-induced, non-infected corneal ulcers of dogs and cats, Lobprise says.
Moss says that in the last year he and the other doctors in his practice have changed their protocol to include it in most cases, usually simultaneously with antibiotic drops.
“The body needs to be very aggressive in trying to cover this defect as quickly as possible,” Lobprise says, “to help prevent the deeper problems and even corneal perforation. These can be critical cases, and it is important to try to provide the optimal supportive care possible for our patients, and Remend Corneal Repair Drops can help veterinarians do that.”
This Education Series article was underwritten by Virbac Corporation in Fort Worth, Texas.