Trabeculectomy Analysis: Fewer Adverse Blebs With Mitomycin-C Than 5-Fluorouracil

Trabeculectomy. Close-up of suturing the eye of a patient after a trabeculectomy, an operation to reduce pressure in the eye caused by glaucoma. The eye is held open by a metal retractor and a needle & forceps are seen stitching the thread. Glaucoma is caused by fluid build up in the eyeball. A trabeculectomy creates an alternative outlet for this fluid, thus reducing pressure. The mucous membrane covering the front of the eyeball (the conjunctiva) is opened and a half thickness of the white of the eye (the sclera) is cut and folded forward. A connection is made into the front chamber of the eye to act as a fluid outlet. The flap is sutured shut & conjunctiva replaced.
Norwich trabeculectomy study: mitomycin-C led to fewer cystic blebs than 5-fluorouracil, and prior conjunctival incision increased overall risk.

Patients undergoing a glaucoma filtration surgery had better outcomes and fewer adverse blebs when they were managed with mitomycin-C (MMC) than with 5-fluorouracil (5-FU), according to data published in Acta Ophthalmologica.

Antimetabolites are a common adjunct therapy to trabeculectomy. They are employed to inhibit postprocedural fibrosis; however, there is concern from glaucoma surgeons that wound healing modulators may bring about blebs that are thin or leaky. This unease expanded upon introduction of MMC, a stronger drug than 5-FU. A follow-up analysis of the Norwich Trabeculectomy Study cohort takes an in-depth look at these 2 medications and overall risks for cystic blebs after 24±2 months.

Original participants, mean age 69±11 years, were recruited from a single center in the UK. The research included 631 eyes of 507 patients (mean age 69±11 years) who underwent filtration surgery between 1998 and 2008. Diagnoses ranged from primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG), along with ocular hypertension and other glaucoma types. Participants were administered 5-FU at a concentration of 25 mg/ml perioperatively, or MMC at 0.2 mg/ml or 0.4 mg/ml. Of the total sample, 75 cases did not involve an antimetabolite or were part of a trial for a novel medication. The adjunctive drug was administered with soaked sponge to the posterior subconjunctival space — most 5-FU doses for 5 minutes, and MMC for 3 minutes.  

Less than 18% of total cases developed dysfunctional blebs. Of 257 eyes undergoing the procedure with 5-FU, 24% developed blebs that were cystic or partially cystic; and for 299 eyes receiving MMC, 12% experienced unfavorable blebs (P =.002 univariate, P =.000 multivariate analyses.) “Specifically, MMC produced blebs that had 3–7 times the odds of having a favorable morphology,” the study explains. Investigators suggest that although the drugs work similarly, differences may have resulted from 5-FU having less perfusion through the subconjunctiva, directed to a smaller region with more concentrated dispersion, possibly causing the tissue to thin.

Second, risk for unfavorable outcome was calculated, with 2 factors showing statistical significance — history of prior surgery with conjunctival incision (OR =0.28, P =.02), and care provided by a private rather than National Health Service (NHS) clinic (OR =0.30, P =.02). Existing literature describes conjunctival priming, with excessive post-trabeculectomy inflammatory reaction. Scarring may also produce blebs with areas of various pressure, and the ocular tissues that overlap sites of higher pressure could thin.

At the NHS, 429 procedures were performed, compared with 127 at private centers. Despite near-identical protocols in private and public settings, the private clinics did not have Fellows operate, and difficult or complex surgeries were likely performed by the experienced consultant surgeon. The antimetabolite selected may also have affected this data point.

An element of subjectivity involved clinical judgment in the choice of specific adjunctive, potentially limiting this investigation, along with a bleb classification system determined by the researchers, not established systems such as the Moorfields Bleb Grading System. Further, the population included predominantly British Caucasian adults. The analysis notes correlation does not prove causation. 

Because many risks exist, it recommends patients with a prior conjunctival incision have “particularly careful postoperative management in an attempt to avoid the development of future cystic bleb formation.”


Al-Mugheiry TS, Clark A, Broadway DC. The Norwich trabeculectomy study: risk factor analysis for the development of adverse, thin cystic blebsACTA Ophthalmol. Published online May 30, 2022. doi:10.1111/aos.15193