Oral propranolol versus placebo for retinopathy of prematurity: a pilot, randomised, double-blind prospective study

Makhoul, Imad R.; Peleg, Ofra; Miller, Benjamin; Bar‐Oz, Benjamin; Kochavi, Orna; Mechoulam, Hadas; Mezer, Eedy; Ulanovsky, Irena; Smolkin, Tatiana; Yahalom, Claudia; Khoury, Asaad; Lorber, Avraham; Nir, Amiram; Blazer, Shraga

doi:10.1136/archdischild-2013-303951

Cited by 39 publications

(43 citation statements)

References 4 publications

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“…Two clinical trials demonstrated that oral propranolol administered to preterm newborns with a precocious phase of ROP is effective in counteracting the progression of the disease (11,12) but not sufficiently safe. In fact, when propranolol was administered to newborns with very low gestational age and comorbidity (sepsis, surgical interventions requiring general anesthesia) the risk of severe adverse effects (primarily hypotension and bradycardia sometimes unresponsive to catecholamines) was too high, even when dosage was reduced from Articles the initial dose of 2 mg/kg/d to 1 mg/kg/d (11).…”

Section: Discussionmentioning

confidence: 99%

“…Following these observations, two independent prospective pilot trials have demonstrated that oral propranolol administered to preterm newborns suffering from a precocious phase of ROP is effective in counteracting the progression of the disease (11,12), even though not sufficiently safe (11). The ability of propranolol to cross the cornea and reach the periocular tissues in rabbits (13) or the retina of Padrini et al…”

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confidence: 99%

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Pharmacokinetics and local safety profile of propranolol eye drops in rabbits

et al. 2014

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Background: Oral propranolol, a nonselective β-blocker, is able to reduce the progression of retinopathy of prematurity in newborns, but it appeared unsafe. This study aimed to find, in rabbits, a propranolol eye drop concentration able to induce lower plasma but higher retinal concentrations than those obtained after oral administration. Methods: Male New Zealand white rabbits were treated with oral propranolol (0.25 mg/kg/6 h) for 5 d, and propranolol concentrations were measured after 1, 2, 3, and 6 h in plasma, aqueous humor, vitreous humor, and retina. These concentrations were compared with those obtained after the administration of one drop of 25 μl of propranolol 0.1% prepared in saline, applied every 6 h to both eyes for 5 d. A Draize eye test and histological analyses were performed to assess eye drop tolerability. results: The administration of eye drops produced retinal concentrations similar to, but plasma concentrations significantly lower than, those measured after oral administration. The local tolerability profile was excellent. conclusion: Propranolol eye drops are able to ensure high retinal and low plasma concentrations of propranolol, and this finding opens the perspective of possible topical treatment with propranolol in newborns with retinopathy of prematurity.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Pharmacokinetics and local safety profile of propranolol eye drops in rabbits

et al. 2014

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“…The bicenter trial (NCT01238471) carried out in Haifa and Jerusalem, Israel [18] , randomized 20 infants with a gestational age of 24-28 weeks at birth with stage 2 or more ROP (zone II) or stage 1 ROP (zone I) to oral propranolol (starting dose: 0.5 mg/kg/day, divided in 3 doses, incrementally increased to 1.5 mg/kg/day) or placebo until hospital discharge, full retinal vascularization, or ROP intervention by laser treatment or bevacizumab injection (on average 16 ± 7 days). The short study report does not provide sufficient methodological details to reliably assess the risk of bias.…”

Section: Pilot Randomized Controlled Trials With Published Resultsmentioning

confidence: 99%

“…who.int/trialsearch/) that collects updated trial registration data sets provided by national or supranational registries and the US National Library of Medicine (http:// www.ncbi.nlm.nih.gov/pubmed) using the terms 'propranolol' and 'retinopathy of prematurity' in October 2014, and identified two completed randomized controlled trials that have published results [18,19] as well as two ongoing trials.…”

Section: Oral Propranolol In Infants With Rop: Randomized Controlled mentioning

confidence: 99%

Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?

Bührer

Bassler

2015

Neonatology

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“…Importantly, recent studies have demonstrated that angiogenesis can be controlled by the adrenergic system through its regulation of pro-angiogenic factors [200,201]. Two small pilot, randomized controlled trials investigating oral proponalol (β-adrenergic inhibitor) in preterm infants with ROP, have shown a non-significant reduction of ROP requiring intervention by laser treatment or bevacizumab injection of similar magnitude [202,203]. However, large interventional studies are needed to determine the clinical benefit-risk ratio, since the administration of β-AR inhibitors might be associated with serious adverse effects (e.g.…”

Section: Biochemical and Molecular Pathwaysmentioning

confidence: 99%

Selection Strategy of In Vivo Models for Ophthalmic Drug Development in Diabetic Retinopathy

Geert¹,

Tjing-Tjing²

2016

J Mol Genet Med

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Diabetic Retinopathy (DR) is the most common microvascular complication of diabetes and is one of the leading causes of visual impairment worldwide. DR is a chronic eye disease that eventually can result in legal blindness due to the evolution towards the major vision-threatening disorders diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR). Current treatments with steroids, anti-VEGF compounds or retinal laser photocoagulation have shown a significant improvement in visual acuity in the advanced stage of the disease. However, main concerns are possible side effects and/or the relatively large number of clinical non-responders. A better understanding of the biological and molecular pathways not only in DR patients but also in the preclinical in vivo models would aid the development of novel and more efficient (personalized) therapeutic approaches for DR. This review aims to describe the pathways in a selection of diabetic, non-diabetic and surrogate rodent models of pathogenic neovascularization, vascular permeability, inflammation and neurodegeneration. None of these models can mimic the entire human pathophysiological progression but they all exhibit joint pathophysiological features with human DR pathogenesis. These combined features make these models very relevant in gaining a better understanding of the disease etiology and eventually improved strategies for drug screening. Through highlighting the most important biochemical and molecular pathways that these animal models have in common with DR patients, selection of the most suitable model for mechanistic studies and drug screening can be facilitated.

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Oral propranolol versus placebo for retinopathy of prematurity: a pilot, randomised, double-blind prospective study

Cited by 39 publications

References 4 publications

Pharmacokinetics and local safety profile of propranolol eye drops in rabbits

Pharmacokinetics and local safety profile of propranolol eye drops in rabbits

Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?

Selection Strategy of In Vivo Models for Ophthalmic Drug Development in Diabetic Retinopathy

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