Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants

Abstract

Limited evidence of low-to-moderate quality suggests that prophylactic administration of oral beta-blockers might reduce progression towards stage 3 ROP and decrease the need for anti-VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long-term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta-blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long-term functional outcomes. We would encourage researchers to conduct large, well-designed trials to confirm or refute the role of beta-blockers for prevention and treatment of ROP in preterm infants. Trials should report on long-term visual impairment. Researchers should consider dose-finding studies of systemic beta-blockers and topical administration of beta-blockers, in order to optimise drug delivery and minimise adverse events.

Clinical Efficacy and Safety of Propranolol in the Prevention and Treatment of Retinopathy of Prematurity: A Meta-Analysis of Randomized Controlled Trials

“…Compared with previous systematic reviews ( 31 , 32 ), our study has some advantages. First, this study conducted a comprehensive search, including English databases, such as PubMed, Cochrane Library, EMBASE, and Web of Science, and Chinese databases, such as CNKI, CBM, VIP, and WanFang.…”

Propranolol Attenuates Proangiogenic Activity of Mononuclear Phagocytes: Implication in Choroidal Neovascularization

“…9,62 Activation of b-ARs in human choroidal endothelial cells using the agonist isoproterenol, increases the expression of growth factors and promotes vascular proliferation. 63 Conversely, propranolol effectively improves outcome in a model of oxygen-induced retinopathy, 64 and selective b2-AR inhibition blocks retinal 65,66 and choroidal vasoproliferation. 9 However, in the choroid the effects of propranolol have only been demonstrated in vitro in noninflammatory conditions.…”

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

“…Based on these preclinical studies, the efficacy and the safety of a treatment with propranolol, administered during the proliferative phase, was tested in human preterm newborns with ROP in a series of pilot clinical trials (Filippi et al, 2013;Makhoul et al, 2013;Bancalari et al, 2016;Korkmaz et al, 2017;Sanghvi et al, 2017;Sun et al, 2018;Ozturk and Korkmaz, 2019). Three recent meta-analyses demonstrated that oral administration of propranolol to newborns with ROP slows down the progression of retinal neovascularization and reduces the indication for laser photocoagulation or anti-VEGF drugs (Kaempfen et al, 2018;Stritzke al., 2019;Kong et al, 2021). However, treatment with propranolol aroused safety concerns because its systemic administration was responsible of life-threatening events in instable preterm infants (Filippi et al, 2013).…”

“…This is the reason why a new trial with propranolol 0.4% eye micro-drops is planned (EudraCT number 2021-000131-31). The realistic objective of the treatment with propranolol is to obtain a reduction of ROP progression of about 60%, as is at the moment described by recent metaanalyses that have evaluated the few and small trials until now concluded (Kaempfen et al, 2018;Strizke al., 2019;Kong et al, 2021) and in line with the efficacy observed in the treatment of IHs (Léauté-Labrèze et al, 2015).…”