Mitomycin C role remains unclear

February 15, 2012
Lynda Charters

The optimal use of mitomycin C in glaucoma surgery in pediatric patients is still controversial.

Key Points

The role of MMC in glaucoma implant surgery is not yet clear. Drugs such as beva cizumab (Avastin, Genen tech) may have a role in pediatric glaucoma implant surgery. Sharon Freedman, MD, discussed the pros and cons of MMC during Pediatric Subspecialty Day at the annual meeting of the American Academy of Ophthalmology.

"The pediatric glaucomas are a heterogeneous group of disorders," said Dr. Freedman, professor of ophthalmology and chief of the Pediatrics and Strabismus Service, Duke Eye Center, Durham, NC.

Medical therapy is the first option to treat juvenile OAG, secondary open-angle pediatric glaucomas, and children who are at high risk for suspected juvenile OAG.

However, medical therapy is adjunctive for primary congenital glaucoma, angle-closure glaucoma, and other refractory pediatric cases. Angle surgery is an appropriate treatment choice for congenital or infantile glaucoma and also is useful to treat uveitic glaucoma, early-onset aphakic glaucoma, and some cases of juvenile OAG.

"Angle surgery has to be performed in cases in which the anatomy is appropriate, but the surgery is generally safe," she said.

Regarding use of MMC intraoperatively, Dr. Freedman discussed filtration surgery and glaucoma implant surgery.

"These surgeries are performed in refractory cases [in which] angle surgery [has failed] or [those that] are not amenable to angle surgery, such as those with a traumatic closed angle and anterior segment abnormalities," Dr. Freedman said.

Filtration surgery

Children who are candidates for trabeculectomy are those in whom angle surgery has failed or are not amenable to it, who have unscarred superior conjunctiva and will have good follow-up postoperatively and good hygiene. Those patients normally are older children who are phakic, Dr. Freedman explained.

Trabeculectomy previously was a problematic procedure in children before wound modulation was available. Rapid healing and scarring occurred often, as did loss of IOP control.

"The overall success rate was less than 50%," she said.

Dr. Freedman recounted that before the advent of MMC in pediatric glaucoma surgery, wound modulation included the use of topical steroids, beta irradiation to the scleros-tomy site in the United Kingdom, and application of 5-fluorouracil intraoperatively and postoperatively.

MMC is a chemotherapeutic drug that has been shown to prevent cell division, has long-lasting effects in vitro, requires only one application intraoperatively, and showed promising early results in adult patients undergoing trabeculectomy.

"In children, MMC improves the success rate of trabeculectomy, with 65% to 90% of cases reported as successful in published series," she said. "The concentrations and exposure techniques vary.

"However, MMC use has been associated with an increased incidence of hypotony, wound leaks, and postoperative infection," Dr. Freedman said. "Some groups of patients still have poor success rates with increased rates of complications, despite MMC."

A retrospective study of trabeculectomy with MMC in children was conducted that reviewed cases over a decade from 1991 to 2001. The study included 114 children with developmental or congenital glaucoma with a mean age of 58 months.

"The success rate was good-80% at 3 years; however, that decreased to 50% at 5 years," Dr. Freedman said. "Endophthalmitis developed in 5% of patients at a mean of 3 years postoperatively. Other studies have reported even higher rates of infection."

Some modifications of the MMC trabeculectomy have been reported over the years. Peng T. Khaw, MD, PhD, described a fornix-based trabeculectomy technique, in which the incision was created at the limbus in the hope of providing better morphologic results and improved safety. Nischal et al. reported a series of MMC-augmented trabeculectomy in children, using a fornix-based technique. After a mean follow-up of 23 months, with 30 children, the investigators reported success in 87% of patients at the last follow-up visit. The technique, however, uses suture release and bleb needlings that are performed with most young patients under anesthesia. No patients have developed endophthalmitis during the relatively short follow-up period.

"MMC improves the success rates associated with trabeculectomy in children, but the success rates still decline with longer follow-up," Dr. Freedman said. "Success is poor in infants and in those with aphakic eyes, which may have a small therapeutic window for functional filtration surgery. Progressive thinning of the bleb can occur, which might point to a role for aqueous suppression. There are also the risks of long-term leakage and infection. The lifetime risks of MMC exposure are, furthermore, unknown."

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