New Trends in Antimetabolite Use

The intraoperative injection of mitomycin C.

By Albert S. Khouri, MD

The use of antimetabolites, particularly mitomycin C (MMC), is standard during glaucoma filtration surgery. In addition to the agent’s classic indications (eg, young patients or previous incisional surgery), evidence suggests that the long-term use of topical glaucoma medications induces a chronic inflammatory state that is detrimental to trabeculectomy’s success. It has therefore become common practice for surgeons to use MMC intraoperatively almost routinely during trabeculectomy. The technique with which the agent is applied, however, varies.


At present, most surgeons soak sponges made of different materials and sizes (cut pieces of a corneal shield or a Weck-Cel spear [Beaver-Visitec International]) with MMC prepared to different concentrations. A disadvantage of this approach is the surgeon’s inability to determine the actual quantity of the drug delivered to the tissues. In one study, it was estimated that the actual dose delivered in a sponge soaked with MMC 0.2 mg/mL varied between 1.9 and 17.3 μg.1 Moreover, the effect of irrigating the site of MMC application with saline is variable. In an in vitro study, irrigation at the site of MMC sponge application influenced the level of the antifibrotic in the superficial scleral layers but had no effect on the deeper layers, where MMC had already diffused.2 A third variable is the size of the sponge. Corneal shields come as discs that are 7, 8, or 10 mm in diameter and are then cut in half.

A downside of sponge application is that it can create a whitish MMC “burn.” The avascular, thin bleb produced is at increased risk of early and delayed leaks as well as of infection. Such localized filtering blebs tend to be functionally limited by encapsulation and sequestration within what is classically described as a “ring of steel” (ie, surrounding Tenon fibrosis). Also, surgeons must use multiple sponges for a more diffuse application, all of which must be carefully collected thereafter.


Multiple investigators have reported success after injecting MMC during bleb revision.3,4 By injecting MMC during trabeculectomy, the ophthalmologist can calculate the exact amount of antimetabolite delivered to the surgical site. The technique also ensures consistency: the same dose is delivered every time to every patient. Another advantage to intraoperative injections is a wide area of application from the subconjunctival dissipation of MMC. Multiple sponges would be required for the same coverage.


First, I prepare the injectable MMC. For most cases, I use 10 or 20 μg. For a 20-μg preparation starting with MMC 0.4 mg/mL, I dilute 0.1 mL of MMC (40 μg) in 0.1 mL of lidocaine (1:1, total volume of 0.2 mL). I then use half of that solution (ie, 0.1 mL of the MMClidocaine [20 μg]) for injection.

After the instillation of topical anesthesia, I perform a small snip incision at the limbus (or elsewhere depending on the type of conjunctival incision; Figure 1). Next, I introduce a blunt 30-gauge cannula 7 to 8 mm from the limbus, where I slowly inject the MMC (Figure 2). I am careful to keep the incision small, because MMC can reflux through the incision to the ocular surface if the original snip incision is generously sized. The conjunctival entry can be compressed with a Weck-Cel spear to prevent any MMC from escaping (Figure 3). The blunt cannula is withdrawn, and the solution can be further spread over a larger surface area using a Weck-Cel spear.

I then complete the conjunctival peritomy. Wet field bipolar cautery can be used for hemostasis, and the surgery is concluded in the usual fashion. I have found the lidocaine to be sufficient for anesthesia in many patients. In others, I will supplement with sub-Tenon lidocaine as needed.


The risks of intraoperative MMC use in trabeculectomy are well known, and they can be severe, even vision threatening (eg, corneal decompensation, scleral thinning, hypotony, increased risk of bleb leaks and infection). At Rutgers University, a review of trabeculectomy cases performed with MMC administered via intraoperative injection versus sponge application (N = 50 eyes, 25 eyes in each group) with 6-month follow-up demonstrated similar IOP efficacy and safety profiles (A.S.K., unpublished data, 2014). Although the injection group had a lower mean IOP overall and a higher proportion of its members achieved an IOP reduction of more than 30% from baseline than the sponge group, the difference did not reach statistical significance. Of note, the injection group needed significantly fewer postoperative interventions (5-fluorouracil and laser suture lysis) than did the sponge group.


The intraoperative injection of MMC during trabeculectomy seems to be safe and effective. This technique allows surgeons to deliver an accurately predetermined dose of MMC over a larger surface area than is readily achievable with traditional sponge application.

Albert S Khouri, MD, is an assistant professor of ophthalmology and program director, ophthalmology residency, at Rutgers-New Jersey Medical School in Newark, New Jersey. He acknowledged no financial interest in the product or company mentioned herein. Dr. Khouri may be reached at (973) 972-2045;

  1. Mehel E, Weber M, Stork L, Pechereau A. A novel method for controlling the quantity of mitomycin-C applied during filtering surgery for glaucoma. J Ocul Pharmacol Ther. 1998;14(6):491-496.
  2. Georgopoulos M, Vass C, Vatanparast Z. Impact of irrigation in a new model for in vitro diffusion of mitomycin-C after episcleral application. Curr Eye Res. 2002;25(4):422-425.
  3. Shetty RK, Wartluft L, Moster MR. Slit-lamp needle revision of failed filtering blebs using high-dose mitomycin C. J Glaucoma. 2005;14(1):52-56.
  4. Maestrini HA, Cronemberger S, Matoso HD, et al. Late needling of flat filtering blebs with adjunctive mitomycin C: efficacy and safety for the corneal endothelium. Ophthalmology. 2011;118(4):755-762.

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