The Singapore 5–FU Study: A Prospective Randomized Masked Trial of Intra–Operative 5–Fluorouracil vs Placebo– Effect on Long–Term Pressure Control and Glaucoma Progression

Abstract

Abstract: : Purpose: To determine the effects of a single 5–minute application of intra–operative 5–fluorouracil (5–FU) during glaucoma filtration surgery on intraocular pressure (IOP) lowering and field and optic disc progression in an Asian population. Methods:A prospective, randomized, masked trial of intra–operative 5–FU (50mg/ml) vs. placebo in trabeculectomy was carried out in Asian patients with primary glaucoma. Trabeculectomy was performed using a standard technique and subjects randomly assigned to intra–operative augmentation with 5–FU under the conjunctiva or placebo. The two primary outcomes of the trial were based on the Moorfields 5–FU Study criteria i.e. post–operative IOP and progressive loss of visual fields and optic disc neuro–retinal rim. Three critical levels of IOP were used to define three types of ‘IOP Failure’: post–operative IOP of >14mm Hg, > 17mm Hg, and >21mmHg, on two consecutive visits (ignoring day–1). Modified CNTGS criteria were used to determine visual field progression. Loss of optic disc neuro–retinal rim was determined only after agreement by 2 masked observers of stereo disc photographs, comparing baseline with each visit. Results: Mean follow–up was 54.0 ± 15.1 months. Failure defined as IOP > 14mm Hg as above occurred in 83/115 in the 5FU group and 101/120 in the placebo group. The failure rate was significantly lower in 5FU compared to placebo (RR=0.69, 95% CI: (0.52,0.93), p=0.014). Similar results were obtained for failure defined as IOP > 17mm Hg: 57 failed in the 5FU group and 73 in the placebo group (RR= 0.72, 95% CI:(0.51,1.02), p=0.064). Progressive loss of visual fields or disc neuro–retinal rim (progression) occurred in 14/111 in the 5–FU group and 21/115 in the placebo group (9 subjects were excluded due to protocol violations). The Cox relative risk regression analysis leads to an estimated RR of 0.67 (95% CI:(0.34,1.31), p=0.239) for the 5–FU group. There were no significant differences in blebitis, endophthalmitis, hypotony, cataract, or other adverse events. Conclusions: Intra–operative 5–FU significantly improves the long–term IOP lowering effect of glaucoma surgery, without any significant increase in complications in an Asian population.

Keywords: wound healing • clinical (human) or epidemiologic studies: outcomes/complications • optic disc