Research progress on the use of beta-blockers in the progression prevention, and treatment of retinopathy of prematurity

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder unique to preterm infants with extremely low birth weight, ranking as the top cause of preventable childhood blindness. Retinal hypoxia, excessive secretion of vascular endothelial growth factor (VEGF) and dysregulation of insulin-like growth factor-1 (IGF-1) constitute the core pathogenic cascades of ROP. As competitive antagonists of β -adrenergic receptors ( β -AR), beta-blockers suppress the HIF-1 α /VEGF and PI3K/Akt/VEGF signaling axes to inhibit pathological retinal neovascularization, while exerting auxiliary anti-inflammatory, anti-oxidative stress and retinal neuroprotective effects. Derived from the mature clinical application of propranolol in infantile hemangioma (IH), preclinical and clinical trials of beta-blockers for the prevention of ROP progression and for ROP treatment have expanded rapidly over the past decade, with two administration routes available: oral systemic delivery and topical ocular micro-drops. Oral propranolol possesses solid anti-angiogenic preclinical evidence, yet its clinical promotion is restricted by severe systemic adverse reactions including bradycardia, hypoglycemia and apnea. The 0.2% propranolol eye micro-drops carry minimal systemic exposure risk and deliver comparable efficacy to oral formulations for Stage 2–3 ROP, but long-term visual and neurodevelopmental follow-up data remain absent. Critically, all existing clinical evidence is limited by small sample sizes, single-center designs and inconsistent dosing protocols; large-scale, multicenter, long-term follow-up Phase III randomized controlled trials are still lacking. At present, beta-blockers cannot replace laser photocoagulation or intravitreal anti-VEGF injection as the routine standard treatment for ROP. They are only regarded as experimental early intervention candidates pending further high-level clinical validation.