Long-term concerns linger on safety of Mitomycin-C
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
"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
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
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
"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
"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.
But the question of whether there will be delayed toxicity remains
"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
"But because it is so efficacious in that indication, it makes
more sense to use mitomycin-C therapeutically rather than prophylactically,"