Current role of aflibercept in retinopathy of prematurity – A review

The introduction of intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed the management of severe retinopathy of prematurity (ROP) in the zone I/zone II posterior region and aggressive ROP by enabling rapid disease regression while preserving peripheral retinal tissue and improving refractive outcomes compared with laser photocoagulation. Nevertheless, there is a risk of late disease recurrence, which has resulted in interest in longer-acting agents such as aflibercept. Aflibercept is a potent VEGF trap with high binding affinity and prolonged intraocular activity, with the possibility of reducing recurrence compared with other anti-VEGF agents. Early retrospective and prospective studies using 1 mg dose of intravitreal aflibercept have demonstrated high rates of initial regression and favorable refractive outcomes. Subsequently, the pivotal FIREFLEYE and BUTTERFLEYE randomized controlled trials evaluated low-dose aflibercept (0.4 mg) against laser, reporting comparable treatment success but higher recurrence with aflibercept, alongside advantages such as rapid disease regression, preservation of peripheral retina, and lower rates of high myopia. Reactivation following aflibercept generally occurs less frequently and later than with ranibizumab and at a similar or lower rate than bevacizumab; however, persistent avascular retina remains a significant concern, necessitating prolonged surveillance and, when indicated, adjunctive laser treatment. Available systemic safety data are very limited, including pharmacokinetic analyses, but suggest transient systemic exposure without evidence of short-term adverse effects on growth or neurodevelopmental outcomes. The following review focuses on the role of intravitreal aflibercept in ROP.