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Novel drug delivery method reduces postoperative bleb needling
Hyaluronic acid gel releases 5-fluorouracil into the eye, offering sustained action to inhibit scarring after trabeculectomy.
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Sustained delivery of an antifibrotic agent significantly reduced scar tissue formation and the number of needling procedures needed to restore bleb function after trabeculectomy, according to a study.
The new treatment involves subconjunctival injection of a combined formulation of 5-fluorouracil (5-FU) and hyaluronic acid (HA) gel. The HA provides steady, prolonged release of 5-FU into the eye over a period of several days rather than a few hours, the study authors said.
“The study subjects who were randomized to receive the new treatment had an improved postoperative outcome,” Tina Tzee Ling Wong, BSc(Hons), MBBS, FRCOphth, FRCS(Ed), PhD(Lond), the senior study author, said in an email interview with Ocular Surgery News. “With this novel treatment, we observed a dramatically lower rate for repeat needling. … In addition, because these patients require fewer interventions, their risk of ocular infection and side effects is significantly reduced.”
Tina Tzee Ling Wong
The study was published in Ophthalmology.
Patients and parameters
The prospective, randomized, controlled clinical trial included 49 patients who had undergone trabeculectomy and were scheduled for bleb needling. One eye of each patient was randomized to undergo needling with the HA and 5-FU combination (25 patients) or subconjunctival injection of 5-FU alone (24 patients).
Mean patient age was 65.9 years in the 5-FU group and 68.2 years in the combination treatment group.
Baseline IOP was 21.4 mm Hg in the 5-FU group and 20.1 mm Hg in the combination group. Mean number of glaucoma medications was 0.8 in the 5-FU group and 0.2 in the combination group; the between-group difference was statistically significant (P = .04).
A grade of HA equivalent to Healon 5 (Abbott Medical Optics) was used in the formulation. A simple vortex technique was used to mix 0.2 mL of 2.3% HA with 0.2 mL of a 50 mg/mL concentration of 5-FU. The resulting 0.2-mL solution, containing a 5-mg dose of 5-FU, was preloaded into a 1-mL syringe.
Patients in the control group underwent injection of 0.1 mL of 5-FU solution (50 mg/mL).
A 27-gauge needle attached to the syringe was used to perform bleb needling before injection.
The primary outcome measure was the percentage of patients with IOP of 15 mm Hg or less with no medication at 3 months. Secondary outcome measures included the need for additional bleb needling and changes in bleb morphology.
Decreased IOP, improved VA
Study results at 3 months showed that IOP decreased from baseline by 5.9 mm Hg in the combination treatment group and 6 mm Hg in the 5-FU group. Both decreases were statistically significant (P < .001); the between-group difference was not significant.
Repeated needling was required in 50% of the 5-FU group and 12% of the combination group; the between-group difference was statistically significant (P = .004).
Complete success, defined as IOP lower than 15 mm Hg with no pressure-lowering medications, was 48% in the combination group and 33% in the 5-FU group.
Qualified success, or IOP lower than 15 mm Hg with mediations, was 8% in both groups.
Mean number of medications at 3 months was 0.2 in the combination treatment group and 0.4 in the 5-FU group.
Mean logMAR distance visual acuity was 0.29 in the combination group and 0.19 in the 5-FU group.
Both groups had similar rates of reported adverse events, bleb vascularity and bleb morphology.
Further development
Wong and colleagues from the School of Materials Science and Engineering, Nanyang Technological University, in Singapore are exploring the use of a single application of the sustained-release formulation at the time of trabeculectomy to reduce or eliminate postoperative bleb needling. Following the promising results of the pilot study, the team is now developing a more sophisticated HA nano-based formulation that will significantly extend the sustained drug delivery effect to several weeks rather than a few days with the current formulation, Wong said.
“Because the acute and most active stage of wound healing occurs in the first 12 to 16 weeks after surgery, we ideally need a sustained time release of the anti-scarring drug that can be administered as a single injection and provide the right amount of drug to continually suppress the scarring response for that crucial time frame,” she said. “That way, we won’t have to keep injecting patients with top-ups, often on a fortnightly or even weekly basis, which is not only inconvenient for the patient but greatly increases the risk of complications with each additional injection.” – by Matt Hasson