Efficacy and safety of propranolol for the treatment of Retionopathy of Prematurity (ROP): from bench to bedsite

Recently, we have demonstrated in the animal model, the role of β-adrenergic system in the promotion of retinopathy of prematurity (ROP). Systemic propranolol, administered during the proliferative phase, reduces its progression thanks to the down-regulation of proangiogenic factors. A first clinical trial demonstrated that oral propranolol administered to newborns with ROP slows down its progression. However, the life-threatening adverse events advised the exploration of a topical approach.
This strategy was evaluated initially in mice, where propranolol eye-drops confirmed its efficacy in counteracting retinal neovascularization. In rabbits, propranolol 0.1% eye-drops dramatically increased the retina/plasma ratio compared with oral administration, suggesting that it was possible to conciliate ocular efficacy with low plasma levels. The first study, performed in newborns with stage 2 ROP, showed that propranolol 0.1% eye micro-drops were well tolerated, but not sufficiently effective. However, increasing the concentration to 0.2% and anticipating the administration to newborns with stage 1 ROP, ROP progression was significantly reduced with optimal tolerance.