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Prophylactic mitomycin with laser treatment may prevent haze but also may delay healing

Application of MMC in conjunction with PRK can be used in every case, but should it be?

Issue: April 25, 2019

ByMark Kontos, MD

ByDouglas A. Katsev, MD

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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a joint society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.

Despite the popularity of LASIK, PRK is still commonly done. Two concerns with PRK are epithelial healing and corneal haze. The use of mitomycin C with PRK is becoming more common, but it is not without risks.

This month, Douglas Katsev, MD, and Mark Kontos, MD, discuss how they use MMC with PRK surgery. We hope you enjoy the discussion.

Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor

PRK with mitomycin C delays healing

I do not use mitomycin C in all PRK cases. Yes, there are indications for use of MMC to prevent haze in certain cases, for example, the high myope who needs high amounts of correction or the patient with underlying disease that would lend to scar formation. These are patients whom I would treat with MMC with PRK as prophylaxis.

But MMC is a powerful alkylating agent whose long-term effects have not been determined. Studies are few and far between to say definitively what dose and duration are ideal for which patient. Its use as a prophylactic to prevent haze in PRK cases is off label, with dose and duration dictated by physician preference and personal experience.

The American Academy of Ophthalmology training materials suggest a “very low dose,” 0.01% or 0.02%, applied to the operative site for between 12 seconds and 2 minutes, and cite delayed healing, persistent epithelial defects and corneal scarring as potential risks. Some clinicians are using an even lower concentration of 0.002%.

Notwithstanding the lack of study data, and the conflicting data and norms, my concern in particular has to do with the longer healing time of the epithelium in a process that already takes too long for return of vision. The reason LASIK is preferred over PRK is because patients experience less pain and shorter healing time. Anything that delays healing is not good for my practice, and in my practice, when I began using mitomycin in all PRK patients, I saw more recurrent erosions late and a delay in healing time.

It is debatable whether the addition of MMC affects epithelial cell loss or has a negative effect on corneal nerve regeneration after PRK. Either way, any effect or resolution of effect may not be detectable for months.

These issues must be addressed more often now as PRK “touch-ups” are performed in patients who have undergone previous corneal surgery such as LASIK or implantation of a premium IOL.

In short, I feel MMC is a must when performing PRK in high myopes, but I avoid it in patients whom I believe have less chance for developing haze.

A long-term study looking at recurrent erosion, healing time and haze formation would be a great project for a busy refractive laser practice that has fellows to keep accurate data and would finally turn feelings and experiences into data.

• References:
• American Academy of Ophthalmology. Mitomycin C for haze prophylaxis. https://eyewiki.aao.org/Mitomycin_C_for_Haze_Prophylaxis#cite_note-14.
• American Academy of Ophthalmology. Refractive management/intervention. Mitomycin C for haze prophylaxis (risk vs. benefits). file:///C:/Users/pnale/Downloads/Refractive-1.pdf.
• Coelho LM, et al. Int Ophthalmol. 2018;doi:10.1007/s10792-017-0817-7.
• Kaiserman I, et al. Cornea. 2017;doi:10.1097/ICO.0000000000001231.
• Medeiros CS, et al. J Refract Surg. 2018;doi:10.3928/1081597X-20181112-01.

• For more information:
• Douglas Katsev, MD, can be reached at email: katsev@aol.com.

Disclosure: Katsev reports no relevant financial disclosures.

PRK with mitomycin C prevents haze, scarring

We use mitomycin C in all of our patients who receive surface laser treatment of any kind. The 0.02% concentration has been used for more than 20 years, every day, in refractive surgery, and in our practice for many years.

We have found that it is extremely helpful in preventing haze in all patients, high myopes or low myopes. Patients with higher degrees of correction are more likely to potentially develop an issue, but sometimes it is hard to predict who might develop haze or scarring after PRK. Even patients with low degrees of cylinder can be at risk.

In our practice, we apply the 0.02% concentration for 15 seconds. It is my feeling that the low exposure time and low dose is essentially harmless to the corneal epithelium and nerve plexus, but it is critical to the reduction and formation of collagen haze after excimer laser treatment.

Especially for patients who are being re-treated with PRK after LASIK, it is critical that they receive MMC; otherwise, scarring will develop and can be severe. Regarding corneal erosion, to my knowledge, there are no studies that show low-dose short-duration MMC increases the likelihood of corneal erosion or reduces corneal healing when used on the center of the cornea. Gambato and colleagues’ paper in Cornea in 2011 showed in a long-term study no measurable ill effects from MMC use in PRK. Just this last December in the Journal of Refractive Surgery, an article by Medeiros showed no effect from MMC in corneal nerve regeneration after PRK at 1 month. There are concerns when MMC is placed on the sclera or the limbus in patients with corneal defects, but when applied properly and used only on the central cornea, there is no evidence to suggest that it retards healing in any way. In our experience over the years, there is no evidence to suggest late, long-term sequelae or recurrent erosion syndrome. We just don’t see it.

In my opinion, MMC with PRK is safe, effective and simple to apply. It has a track record for treating or preventing other ocular pathology, and should not be considered new and untried. MMC is used to prevent fibrosis of trabeculectomies and to prevent recurring pterygium. Its application varies depending on the clinical situation. If corneal scarring is being treated, not prevented, then each clinician may have a personal “recipe” that may involve longer exposure time or greater concentration of drug.

The only real issues we have with MMC are availability and cost. We as physicians have no control over the cost or availability. If the cost increases prohibitively, that could change the landscape dramatically, but for now, it is pretty much a benign, simple treatment to prevent a significant issue.

• References:
• Gambato C, et al. Cornea. 2011;doi:10.1097/ICO.0b013e31820123c8.
• Medeiros CS, et al. J Refract Surg. 2018;doi:10.3928/1081597X-20181112-01.
• Teus MA, et al. Surv Ophthalmol. 2009;doi:10.1016/j.survophthal.2009.04.002.

• For more information:
• Mark Kontos, MD, can be reached at email: mark.kontosempireeye.com.

Disclosure: Kontos reports no relevant financial disclosures.