Fluocinolone acetonide (FA) intravitreal inserts are the first pharmacologic treatment for diabetic macular edema (DME) that can be administered by an outpatient injection. They are a nonbiodegradable cylindrical tubes measuring 3.5 mm × 0.37 mm that are loaded with FA but do not require a surgical operation for implantation. Instead, the device is inserted into the vitreous cavity through a 25-gauge needle in an outpatient clinic.
The authors of this study report results from two parallel, double-masked Phase 3 studies that assessed the safety and efficacy of intravitreal inserts. The studies randomized 953 patients with persistent diabetic macular edema (DME) to either a low- (0.2 μg/day) or high- (0.5 μg/day) dose fluocinolone acetonide vitreous insert or to sham injection. Based on retreatment criteria, additional study drug or sham injections could be given after one year.
They found that at two years follow-up, mean BCVA improved significantly in the low- and high-dose insert groups compared with sham (P = 0.002), with the risk-to-benefit ratio being superior for the low-dose insert. The percentage of patients whose BCVA improved by 15 letters or more after two years was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). They observed significantly more improvement in foveal thickness in both insert groups at all time points compared with sham. Furthermore, a greater percentage of patients were given repeated laser treatments in the sham group than in the insert groups.
The authors write that the biggest drawback for the FA inserts is an increased risk of incisional glaucoma surgery over a two-year period, estimated at 3.7 percent in this report. Considering the substantial benefit provided by low-dose inserts, they say patients and physicians will have to make a judgment as to whether this risk is acceptable. Although the need for frequent injections may be reduced after use of an FA insert, it is prudent for patients to be seen initially every four to six weeks to measure IOP.
The most common drug-related serious adverse event in study eyes was cataract surgery, which was listed as an adverse event in 41.1 percent of the low-dose group, 50.9 percent of the high-dose group, and 7.0 percent of the sham group; this constituted 74.9 percent, 84.5 percent, and 23.1 percent, respectively, of the patients in each of the groups that had not undergone cataract surgery in the study eye at baseline.
The authors conclude that this study validates a new platform for sustained drug delivery to the retina. However, the U.S. Food and Drug Administration requested an additional year of data before considering approval for this drug delivery system.