The Role of Anti-vascular Endothelial Growth Factor (anti-VEGF) in Retinopathy of Prematurity (ROP)

Abstract Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, with a higher burden in middle-income countries, such as India. Traditional treatment with cryotherapy and laser photocoagulation has evolved with the introduction of intravitreal anti-vascular endothelial growth factor (VEGF) agents. These agents promote regression of neovascularization, preserve peripheral retina, and reduce adverse sequelae of laser, though concerns remain regarding recurrence, systemic safety, and long-term follow-up. A narrative review of landmark clinical trials, pharmacological properties, and real-world evidence was undertaken to compare efficacy, safety, and indications of different anti-VEGF agents in ROP alongside emerging data on biosimilars. Key parameters assessed included regression rates, recurrence, visual outcomes, systemic absorption, refractive status, and safety profiles. Bevacizumab demonstrated superiority over laser for Zone I disease in BEAT-ROP, with longer half-life but higher systemic exposure. Ranibizumab showed comparable efficacy with earlier reactivation allowing timely supplemental laser, with long-term follow-up from RAINBOW showing reduced myopia versus laser. Aflibercept demonstrated non-inferiority trends but remains less widely used in India due to cost. Biosimilars have shown promising efficacy and safety with favourable cost-effectiveness. Anti-VEGFs are particularly valuable in aggressive ROP, Zone I disease, cases unsuitable for laser, and as adjuncts in surgery. Limitations include persistent peripheral avascular retina, recurrence risk, and the ‘crunch’ phenomenon. Anti-VEGF therapy has revolutionized ROP management, offering vision salvage and reduced myopia compared to laser. However, it has not supplanted laser as the gold standard due to concerns of long-term recurrence, systemic effects, and follow-up challenges. Future directions include dose refinement, standardized protocols, and combination strategies to enhance vascular maturation and safety.