Preclinical studies provide insight into risks and benefits of MMC

New Orleans-Topical application of mitomycin-C (MMC) is more effective for preventing corneal haze after PRK than it is for treating existing haze, but further studies are needed to establish the long-term corneal safety of this strongly cytostatic agent, said Marcelo V. Netto, MD, at the refractive surgery subspecialty day meeting.

"Studies of the effects of MMC on the cornea began almost 15 years ago, but corneal application in human eyes was only first reported 4 years ago. While its use prophylactically to prevent corneal haze after PRK is becoming very popular, it is still very controversial," said Dr. Netto, who is on staff at the Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH.

To further examine the efficacy, safety, and mechanism of action of MMC in haze prevention and treatment, Dr. Netto and colleagues undertook a series of animal and in vitro studies. They performed PRK to correct -9 D of myopia in all animals. To study haze prophylaxis, one group of animals was divided to receive intraoperative application of MMC 0.02% for 2 minutes while controls were treated with BSS. A second group of rabbits had PRK alone and when haze developed 4 days later, they underwent epithelial scraping with application of MMC or BSS.

Follow-up evaluations were performed after 1 hour, 4 hours, 24 hours, and 4 weeks, and showed that MMC used as an adjunct to PRK minimized haze formation but did not eliminate it. In the treatment study, however, MMC-treated eyes still manifested significant residual haze.

While our in vitro studies show that MMC is able to induce myofibroblast apoptosis, relatively few cells die, and the most important cellular effect of MMC is to block fibroblast replication, Dr. Netto explained.

From the perspective of safety, no statistically significant differences were seen between BSS- and MMC-treated eyes in measures of endothelial toxicity. However, MMC was associated with significant keratocyte depletion.

"We are hoping to see late repopulation with further follow-up, but it is also possible that the depletion will be permanent and might lead to corneal melting or ectasia," Dr. Netto said.