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Looking for a new treatment for refractive corneal ulcers

Posted February 3, 2012

Many ulcers of the cornea, the front layer of the eye, heal successfully on their own, and the mechanism by which they do so is fascinating – a sheet of healthy corneal cells detaches from an uninjured area and migrates to cover the wound. In order for this type of healing to work, it requires a number of cellular processes to happen simultaneously and in a coordinated fashion, as the corneal epithelial cells (CECs) must grow larger, convert to a migratory form, and detach from their surrounding cells but not from each other in order to fully blanket the ulcer so that it can heal. If you think about it, it’s amazing that the process is successful as often as it is.

Unfortunately, as amazing as the healing processes of the eye can be, they don’t work all the time. Certain dogs experience what are known as refractory (or refractive) corneal ulcers – ulcers which may take up to six months to heal, and for which existing treatments are not consistently effective. Medical treatments for refractory corneal ulcers are cheap but often frustrating, since they require the owner to repeatedly apply a topical medication which may or may not work. There are also surgical options for treating these ulcers; however, those procedures are not only inconsistent but expensive and potentially risky.

That’s why, with the help of the AKC Canine Health Foundation, scientists from Ohio State University set out to investigate the rumor that a simple tetracycline treatment might be an effective way to reduce healing time of refractive corneal ulcers. It’s a drug that has worked for humans with corneal ulcers, but no one had ever prospectively evaluated tetracycline’s effects in dogs.

The researchers compared the healing time of corneal ulcers when dogs were given one of three treatments: cephalexin pills + oxytetracycline cream (the treatment of interest), cephalexin pills + triple antibiotic cream (control), and doxycycline pills + triple antibiotic cream (alternate treatment). What they found was that, as rumor suggested, the oxytetracycline cream significantly increased the speed of wound healing in treated dogs, both compared to the control group and to the alternate treatment. The docycycline treatment also showed a slight improvement in healing speed, but it was not statistically significant when compared to the controls.

This research suggests that tetracycline cream may in fact be a useful addition to the treatment regimen for corneal ulcers. What makes tetracycline so special? Although most people think of tetracycline as just another antibiotic, it also is capable of altering the immune system response in a way that the components of triple antibiotic ointments are not, which may explain why it helps when they don’t.

Interestingly, during the course of their research, the scientists also found that while the size of the ulcer didn’t have a significant effect on healing time, the size of the dog the ulcer was found in did. Corneal ulcers were much more likely to heal quickly in small-breed dogs than they were in medium or large breed dogs. Why? Well, many small breed dogs blink less often, due to the placement of their eyes in their heads. It looks like blinking may disrupt the healing process by tearing or displacing the sheet of healthy cells as it migrates across the eye.

This work was funded by AKC Canine Health Foundation Grant 985-A.

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