Level 3 [lacking direct] evidence
Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor first approved for treatment of diabetic macular edema (DME) in July 2014 after several large trials showed it was superior to laser photocoagulation in patients with reduced visual acuity. It is an intravitreal injection administered every 4 weeks for the first 5 injections, and then every 8 weeks for at least 20 weeks.
Before the introduction of VEGF inhibitors, laser photocoagulation was the standard of care for treatment of DME with or without preserved visual acuity. In a randomized clinical trial, aflibercept was compared with either laser photocoagulation or observation to determine whether aflibercept has the same benefit in patients with DME and preserved visual acuity as in patients with reduced visual acuity.1
The study included 702 adults with type 1 or type 2 diabetes, with only one eye with center-involved macular edema. There were 3 treatment groups: laser photocoagulation, aflibercept injections, and observation. However, some patients in each group received aflibercept injections. Sixteen percent of patients in the aflibercept group had a decrease in visual acuity of 1 line or more at 2 years compared with 17% of patients receiving laser photocoagulation and 19% of those in the observation group.
At the end of the trial period, all 3 groups had a mean vision of 20/20, and the mean changes in visual acuity were not statistically significant. Aflibercept was associated with a higher frequency of increased intraocular pressure compared with observation, whereas laser photocoagulation was not. The clinical significance of this is unclear.
Cost is a critical consideration when deciding among therapies with similar efficacy. Each aflibercept injection costs around $1850, with total baseline treatment cost in the United States of about $416,250 compared with $120,000 for patients having laser photocoagulation. In addition, 80 of the 236 eyes in the observation group received at least 1 aflibercept injection, with a median of 9 injections over 2 years ($16,650). The bottom line is that for diabetic patients with preserved visual acuity, the benefit of receiving aflibercept or photocoagulation, even in patients with diabetic macular edema, is limited. Given the cost associated with this, most patients will just see their money slipping away, rather than experience benefit from the expensive and invasive treatment. More data are needed to determine whether aflibercept makes a difference in the preservation of vision in patients with DME.
1. Baker CW, Glassman AR, Beaulieu WT, et al. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. JAMA. 2019;321(19):1880-1894.