AUTHOR=Filippi Luca , Cavallaro Giacomo , Berti Elettra , Padrini Letizia , Araimo Gabriella , Regiroli Giulia , Raffaeli Genny , Bozzetti Valentina , Tagliabue Paolo , Tomasini Barbara , Mori Annalisa , Buonocore Giuseppe , Agosti Massimo , Bossi Angela , Chirico Gaetano , Aversa Salvatore , Fortunato Pina , Osnaghi Silvia , Cavallotti Barbara , Suzani Martina , Vanni Maurizio , Borsari Giulia , Donati Simone , Nascimbeni Giuseppe , Nardo Daniel , Piermarocchi Stefano , la Marca Giancarlo , Forni Giulia , Milani Silvano , Cortinovis Ivan , Calvani Maura , Bagnoli Paola , Dal Monte Massimo , Calvani Anna Maria , Pugi Alessandra , Villamor Eduardo , Donzelli Gianpaolo , Mosca Fabio 

TITLE=Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 7 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2019.00180

DOI=10.3389/fped.2019.00180

ISSN=2296-2360

ABSTRACT=Background. Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well tolerated, but not sufficiently effective. 
Methods. A multicenter open-label trial was conducted to assess safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters and propranolol plasma levels were monitored. 
Results. Ninety-eight newborns were enrolled. The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297-0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment.
Conclusion. Propranolol 0.2% eye micro-drops reduced ROP progression and were well tolerated. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that β-adrenoreceptor blockade is useful only during the proliferative phase. Further randomised placebo-controlled trials are required to confirm current results.