MMC pearls

At a glance ...

• MMC application after pterygium head excision has been linked to central corneal endothelial cell loss
• This can be prevented by applying the agent before head excision
• Endothelial cell loss in the periphery of the cornea after MMC application during pterygium surgery still requires further study
Source: Rahamim Avisar, M.D.

Recurrent pterygium before and after injection of MMC in the office to facilitate regression prior to surgery
Source: Steven Safran, M.D.

To avoid endothelial cell loss after pterygium surgery, apply mitomycin C before excision of the pterygium head.
That’s what researchers from Rabin Medical Center, Petah Tikva, Israel, have concluded, noting that no endothelial cell loss was found when such tactics were employed.
In contrast, when MMC was applied after excision of the pterygium head, significant endothelial cell loss was documented.
“When MMC was applied before excision of the head, such that it did not come into contact with the corneal surface, there was no endothelial loss,” according to Rahamim Avisar, M.D., Rabin Medical Center. The study was published online in August 2009 in the journal Cornea.
Researchers only analyzed endothelial cell loss in the central cornea, however. Peripheral endothelial cell loss would require further study.

The biggest loser

Dr. Avisar looked at 40 patients who underwent pterygium surgery with the bare sclera technique retrospectively. MMC 0.02% was applied to 16 patients before pterygium head excision and 24 patients after excision.
“Endothelial images were acquired at the center of the cornea with a specular microscope before surgery and at 3 intervals during follow-up,” Dr. Avisar reported.
Mean pre-op endothelial cell count in the post-excision MMC application group was 2,254 +/–128 cells per square millimeter. This group lost 21.25% of endothelial cells per square millimeter at 1 week, 24.26% at 1 month, and 21.05% at 3 months. The loss was statistically significant compared to baseline at all follow-up points.
In the group in which MMC was applied before pterygium head excision, mean pre-op cell count was 2,352 +/–118 cells per square millimeter, and no endothelial cell loss was documented at any time point. Dr. Avisar speculated as to why the results were more favorable for this group.
“Because the underlying corneal epithelium is removed together with the pterygium head, post–excision MMC treatment is applied directly on the bare sclera,” Dr. Avisar noted. “From there, the drug might easily diffuse to the cornea and into the anterior chamber, affecting the endothelial cells.”
Dr. Avisar explained that MMC binds to DNA, inhibiting its synthesis. “Because MMC is not cell cycle specific, rapidly dividing cells are preferentially sensitive to its effects,” Dr. Avisar noted. “The mechanism underlying mitomycin-induced apoptosis in cultured corneal endothelial cells has recently been reported.”
This shouldn’t scare ophthalmologists away from using MMC because of its treatment applications as long as proper usage is considered. “The intraoperative application of MMC has become an established part of several ophthalmic procedures, including glaucoma filtering surgery, pterygium surgery, and removal of conjunctival and corneal intraepithelial neoplasia,” Dr. Avisar noted. “When applied during pterygium surgery, MMC treatment has been found to effectively prevent recurrence.”
This study suggests the timing of MMC application is important, while previous research has focused on dosing. “Most studies so far have used single-dose applications at concentrations of 0.01%–0.04% for durations of 3–5 minutes,” Dr. Avisar noted. “Its antimitotic effect depends on both the dose and the length of application.”
Remember, alternatives to MMC are out there. “Corneal endothelial loss in pterygium surgery with MMC is another reason for switching from MMC to limbal-conjunctival autograft,” Dr. Avisar noted.
John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va., further noted that even “properly” timing MMC application won’t be the silver bullet to end all challenges with MMC usage.
“MMC usage is clearly a highly variable procedure,” Dr. Sheppard said. “There’s no real standard for treating pterygium pre-, intra-, or post-operatively with MMC.”
That’s partly because the amount of MMC that percolates to the anterior chamber varies depending on where it is applied, Dr. Sheppard said.
“Sometimes you might need a higher dose of mitomycin C to prevent recurrence,” Dr. Sheppard said. Thus, where MMC is applied and how long it is applied for are factors that influence decision making about MMC usage. No application advice, therefore, can be universally accepted, he said.
“We all use different concentrations and duration of exposure,” Dr. Sheppard said. “It’s difficult to characterize any one method as best.”
Dr. Sheppard is an advocate of using MMC in almost all pterygium cases. “Corneal edema is just not a big problem,” he said.

Editors’ note: Dr. Avisar has no financial interests related to this study. Dr. Sheppard has no financial interests related to his comments.

Contact information

Avisar: avi-sar@hotmail.com
Sheppard: 757-622-2200, docshep@hotmail.com