Mitomycin-C (MMC)  is an antibiotic that has been used in the medical field for a number of decades. It has been used as an anti-cancer drug because it can stop the proliferation or growth of certain types of cells such as those seen in tumours, and also those cells in the eye which produce scarring or haze. MMC has been used in the eye since the 1980s to prevent scarring after many types of surgical procedures, such as glaucoma filtration and pterygium surgeries. The use of MMC for treatment and prevention of corneal haze is a relatively new potential indication for this medication.

There is little controversy in the use of MMC for the treatment of eyes with corneal haze after surgery, as this is the only technique to date that works. However, there is some concern about using this powerful drug in virgin eyes. Recent research has reduced the time the drug is used from the 2 minutes used in damaged eyes to 12 seconds in virgin, non-operated eyes. There are studies out to 8 years now with MMC for 2 minutes and there seems to be no damage so far. (August 2005)  I tend to use MMC for 10 seconds when I am lasering above 90 microns into the cornea. Read the MMC consent form for some more information on the use of this drug.

Update Nov 2009 ATLANTA — Topical mitomycin C has been used for 10 years in corneal refractive surgery with no major complications, a speaker said here, but there is no consensus on its use, which he said should be customized.

Marcelo V. Netto, MD, speaking at the Refractive Surgery Subspecialty Day preceding the American Academy of Ophthalmology meeting, made recommendations for using MMC in patients with high risk of developing postoperative corneal haze.

For prophylactic use in virgin corneas, a concentration of 0.02% should be used with exposure time of 12 seconds. For prophylactic use after previous corneal procedures, a concentration of 0.02% should be used with an exposure time of 1 minute. For therapeutic purposes in patients with previous corneal haze, a concentration of 0.02% should be used with an exposure time of 2 minutes.

Below is an article from Eurotimes November 2002 about the use of MMC in refractive surgery.

Long-term concerns linger on safety of Mitomycin-C (2002)

By Cheryl Guttman

PHILADELPHIA - Good results with mitomycin-C in the treatment of haze after corneal refractive procedures has prompted some surgeons to use the drug for haze prophylaxis - but the risk-benefit ratio remains a contentious issue.

Randy J. Epstein MD and Florentino Palmon MD debated the pros and cons of prophylactic mitomycin-C use at a session of the annual meeting of the ASCRS.
Dr Epstein discussed different scenarios for prophylactic use of mitomycin-C. In cases of complicated LASIK flaps, particularly central buttonholes, he and his colleagues consider transepithelial PTK/PRK with prophylactic mitomycin-C the best approach for proceeding with refractive surgery.

Procedure timing

"There is probably little debate in the refractive surgery community about the acceptability of mitomycin-C prophylaxis in that situation. Rather, the real issue probably centres around the question of what represents the best timing for performing that procedure," Dr Epstein said.
He co-authored a landmark paper published in the journal Ophthalmology in 2000 describing the successful use of mitomycin-C for the treatment of visually disabling haze after PRK or RK.

At his practice, Dr Epstein waits two to four weeks to allow healing. He then applies mitomycin-C to the cornea with a concentration of 0.02% for two minutes followed promptly by copious irrigation.
An alternative advocated by some is to perform the procedure on the same day in order to lessen any psychological impact on the patient.

Dr Epstein suggested the appropriateness of using mitomycin-C prophylactically is likely to be more controversial when performing myopic PRK or LASEK in eyes which are poor LASIK candidates because of thin corneas or large pupils.
He noted he uses mitomycin-C routinely when treating eyes with greater than -7.0 D of myopia after obtaining informed consent from the patient.

Dr Epstein acknowledged there are potential downsides for using mitomycin-C but pointed out that most of the significant complications associated with mitomycin-C have developed under other circumstances of treatment.

"Scleral melting has occurred with the use of mitomycin-C in pterygium surgery. The development of endothelial decompensation in eyes treated with mitomycin-C has always been in the setting where there is some potential for intraocular entry like filtering.

"There are a few refractive surgery reports of corneal melts associated with mitomycin-C use, but to our knowledge those have occurred mostly with prolonged administration using topical drops and we vigorously oppose that technique," Dr Epstein said.
He added he is unaware of any reports of significant complications using mitomycin-C as he and his colleagues have described.

However, they have undertaken a prospective clinical trial to address various questions raised about an adverse impact on the cornea.
"With some patients now up to three years out from their surgery, I am pleased to say we have so far seen no evidence of any adverse endothelial effects.

"Obviously we need to follow these patients in the long term and we look forward to defining an appropriate benefit-risk ratio for mitomycin-C," Dr Epstein stated.
Dr Palmon concurred that some of the most significant complications reported in association with mitomycin-C are derived from reports involving eyes undergoing pterygium surgery, particularly if the epithelium was not intact.

Delayed toxicity

But the question of whether there will be delayed toxicity remains unanswered.
"Mitomycin-C affects DNA in the same way as beta-irradiation does, and looking back at the radiation literature we see that problems with corneal and scleral flap melts did not develop for 15 to 20 years after treatment.
"So, only time will reveal the long-term safety of mitomycin-C in refractive surgery," Dr Palmon said.

Dr Palmon's concerns about potential late complications were echoed by panel members Eric Donnenfeld MD, Jonathan Rubinstein MD and Dimitri Azar MD.
Dr Rubinstein noted that he has begun to see superior stem cell problems in eyes that are 10 to 12 years after a glaucoma filtering surgery procedure with adjunctive mitomycin-C.

"These patients are just beginning to show up with significant conjunctivalisation of the superior cornea and I think we will have to wait to see if there are going to be long-term complications secondary to stem cell effects," he said.
Dr Azar, Associate Professor of Ophthalmology, Harvard Medical School, Boston, US remarked that treatment of haze with mitomycin-C is entirely justifiable.
"But because it is so efficacious in that indication, it makes more sense to use mitomycin-C therapeutically rather than prophylactically," he added