Mitomycin C, when used in accordance with the approved guidelines, can be beneficial but can cause haze with long exposures and higher concentrations.
Mitomycin C when used in accordance with the approved guidelines can be beneficial but can cause haze with long exposures and higher concentrations.
By Lynda Charters; Reviewed by Randy J. Epstein, MD
Chicago-Therapeutic mitomycin C (MMC) with a 2-minute exposure can prevent corneal haze when treating complicated LASIK flaps and other forms of surface pathology. MMC can be used for late enhancements, but the risk of development of haze remains.
“Prophylactic use of MMC is safe and effective for preventing haze in high-risk PRK patients, but we do not recommend that MMC be used routinely in every PRK patient,” said Randy J. Epstein, MD, professor of medicine, Cornea Service, Department of Ophthalmology, Rush University Medical Center, Chicago.
MMC has had a colorful history in ophthalmology, according to Dr. Epstein. The initial basic science work with the drug showed good results, although there was a lot of concern regarding the potential for toxicity.
“The morphologic appearance of these patients was reminiscent of those described by Joseph Frucht-Pery for corneal dysplasia,” Dr. Epstein pointed out and reported that patients presented with 2 to 3+ reticular haze following PRK.
Additional laser alone and debridement alone were once the accepted treatments, but the haze recurred. MMC drops were ineffective. Debridement of the haze with intraoperative MMC without PTK was tried to avoid a refractive "surprise." In the first patient treated with MMC for haze after RK, at the 2-year follow-up evaluation, the patient had central subepithelial fibrosis. He underwent complicated phaco with a vitrectomy and the cornea did not decompensate. After a 10-year follow-up there has been no evidence of endothelial toxicity.
MMC is a chemotherapeutic agent that cross-links DNA and generates free radicals. The mechanism of action of the drug, summarized by Steve Wilson, MD, from the Cleveland Clinic (personal discussion, Sept. 2014), is that MMC causes increased normal apoptosis of keratocytes and inhibits myofibroblastic proliferation.
The potential effect of MMC on keratocytes is of particular concern. However, recent studies by Rajan et al. and Teus et al. have concluded that the initial decrease in the number of keratocytes does not persist and MMC actually optimizes keratocytic repopulation, Dr. Epstein explained.
Important results were obtained from a series of studies of MMC for use as prophylaxis against haze during PRK. The first large randomized study by Carones et al. found that eyes at risk for development of haze actually did not do so when MMC was used prophylactically compared with 63% of the control eyes in which haze did develop. This result was confirmed by subsequent studies.
MMC also came to the rescue in early LASIK cases with flap complications (button holes and partial flaps) that developed in from 5% to 8% of patients. To treat these patients, MMC was applied during PTK performed with an excimer laser laser to scrape the epithelium during a 50-µm ablation.
Because MMC decreases the normal wound-healing response, Dr. Epstein advised reducing the degree of the planned correction to avoid hyperopia. During this treatment, MMC is put into a contact lens case with a corneal light shield (Merocel, Medtronic). After the excess MMC is removed the light shield is then applied to the stromal bed after PRK or PTK is performed. The 0.02% MMC is applied for 12 seconds for prophylaxis and 2 minutes for therapeutic indications.
The surgical area is irrigated with balanced salt solution after the light shield is removed.
“Excellent postoperative uncorrected and best-corrected visual acuity levels were achieved after PTK and fairly good refractive outcomes as well. No patients had haze after a mean follow-up of 6 months,” he noted, but recommended that treatment of flap complications be delayed until the topography has stabilized and the patient has been consulted.
MMC toxicity has been reported in most cases with scleral application and during corneal use when guidelines for established application have not been followed. Most complications have occurred when higher concentrations of MMC, 0.03% to 0.05% were used. The drug has no proven use in treatment of interface complications.
MMC is an “excellent” indication during PRK after PK and sees use of MMC as essential when performing PRK after RK, Dr. Epstein noted. Regarding using MMC for PRK enhancement over LASIK flaps, there remains a risk of development of haze.
The drug can be used to treat Salzmann’s nodular degeneration, Dr. Epstein noted.
He also cited a study by Robert Maloney, MD, which found substantial induced myopia with debridement alone. However, when MMC is applied the clinical scenario can be aggravated.
“Consideration of the refractive factors is very important,” Dr. Epstein said.
MMC can also be used therapeutically to treat corneal dystrophies including Avellino and Reis-Buckler corneal dystrophies and for patients with traumatic amputation of flaps with and without PRK.
Dr. Epstein cited what he described as a desperate case of recurrent Avellino dystrophy in which the outcome was successful with intrastromal application of MMC with PTK.
“However, this is generally not recommended,” he said.
Some cosmetic indications have included the use of MMC. One notable example is cosmetic eye whitening performed in South Korea. Initially the patients had excellent outcomes with no complications; however, a later study showed that the outcomes were not good and the Korean government later forbade the surgical procedure.
Dr. Epstein and colleagues have used MMC for 17 years without development of significant complications, no delayed re-epithelialization, irritation, and no significant impact on the epithelium.
“We believe that the lack of toxicity with our published technique results from our adherence to published guidelines for the use of MMC,” he said. “We use 0.25% for 12 seconds prophylactically and 2 minutes therapeutically and we apply it only to the central cornea.”
Randy J. Epstein, MD
This article was adapted from Dr. Epstein’s presentation at Refractive Subspecialty Day during the 2014 meeting of the American Academy of Ophthalmology. His co-authors were Parag A. Majmudar, MD, and Rachel H. Epstein, MD (both also from the Department of Ophthalmology, Rush University Medical Center. Dr. Epstein has received lecture fees from Alcon Laboratories, but has no conflict of interest with any product mentioned in this report.