Efficacy of Oral Propranolol on the Treatment of Retinopathy of Prematurity

Hosseini, Mina; Gharehbaghi, Manizheh Mostafa; Bagheri, Masood; Yeganehdoost, Sadollah; Milani, Amir Eftekhari; Niyousha, Mohamad Reza

doi:10.34172/cjmb.2022.10

Cited by 4 publications

(2 citation statements)

References 25 publications

(38 reference statements)

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“…Based on these promising preclinical results, a series of clinical trials have been carried out testing oral propranolol in very low birth weight extremely premature newborns with ROP. Propranolol was administered, at newborns at stage 2 ROP, at doses up to 2 mg/Kg/day, the dose used for infantile hemangioma ( 98 – 106 ). As demonstrated in four recent meta-analyses, treatment with oral propranolol minimizes the progression of the disease reducing the need for anti-VEGF administration and laser ( 107 – 110 ).…”

Section: Propranolol In Humans With Retinopathy Of Prematuritymentioning

confidence: 99%

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Pascarella,

Scaramuzzo,

Pini

et al. 2024

Front. Pediatr.

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Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of β1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.

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Section: Propranolol In Humans With Retinopathy Of Prematuritymentioning

confidence: 99%

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Pascarella,

Scaramuzzo,

Pini

et al. 2024

Front. Pediatr.

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“…Supplemental oxygen demand and lower gestational age (GA) and birth weight (BW) are among the major risk factors for the occurrence and progression of ROP. 2 In the proliferative phase of ROP, overactivation of the vascular endothelial growth factor (VEGF) and other proangiogenic factors induced by the avascular retina causes abnormal neovascularization and subsequent problems, which in turn can lead to vitreous hemorrhage and finally tractional retinal detachment. 3 Hence, VEGF, acting as a pivotal mediator for the normal development of retinal vasculature, might be considered the major biomarker for ROP pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Clinical Outcomes of Intravitreal Bevacizumab and Aflibercept in Type 1 Prethreshold Retinopathy of Prematurity in Posterior Zone Ii

Milani

Bagheri

Niyousha

et al. 2022

Journal of Current Ophthalmology

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Purpose: To evaluate the efficacy and safety of intravitreal injection (IVI) of bevacizumab (IVB) versus aflibercept (IVA) in premature infants with type 1 prethreshold retinopathy of prematurity (ROP) in the posterior Zone II. Methods: The study was a multicenter, historical cohort of premature newborns diagnosed with type 1 prethreshold ROP in the posterior Zone II, treated with IVB or IVA. Demographic features, complications, and treatment outcomes were then compared between the two groups. Results: Seventy-six patients received aflibercept (the IVA group), and 210 received bevacizumab (the IVB group). The two groups were not significantly different in terms of postmenstrual age (PMA) at the time of ROP diagnosis and other known risk factors for ROP development and progression. All eyes in both the groups responded to IVI; however, recurrence was observed in four eyes (1.9%) in the IVB group and 12 (15.8%) in the IVA group (P = 0.001). Recurrence occurred 9.1 ± 0.83 (5–12) and 15.5 ± 0.98 (12–18) weeks after primary treatment in the IVB and IVA groups, respectively (P = 0.000). In the IVA group, retinal vascularization was completed in 38.18 ± 6.5 weeks (21–48) after IVI, and it happened in 23.86 ± 9.3 weeks (13–60) in the IVB group (P = 0.009). Furthermore, vascularization reached the peripheral retina in 73.25 ± 6.5 (56–84) and 58.75 ± 8.8 (45–93) weeks, PMA in the IVA and IVB groups, respectively (P = 0.03). No acute postoperative complications were observed in the treated eyes in either group. Conclusion: This study shows that both IVA and IVB are effective and well tolerated for the management of type 1 prethreshold ROP in the posterior Zone II; however, IVA needs a significantly longer time for vascularization completion and has a higher recurrence rate compared with IVB.

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Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis

Ortiz-Seller,

Martorell,

Roselló

et al. 2024

Pediatr Drugs

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Objective The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints. Methods Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose–response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI). Results Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2–3; S23) of ROP progression compared with its administration at earlier stages (stages 0–1; S01). OR values for oral propranolol 1.5 and 2 mg/kg/day given at S23 were 0.13 (95% CrI 0.04–0.37) and 0.16 (95% CrI 0.04–0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02–2.96) and 0.78 (95% CrI 0.14–4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09–1.00) versus an S01 OR of 0.64 (95% CrI 0.21–2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5–2 mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose–response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5 mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02–0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05–0.93) and laser (OR 0.16; 95% CrI 0.02–1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5–1.0 mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5 mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5 mg/kg/day and the highest risk difference for oral propranolol 2.0 mg/kg/day (0.06; 95% CI −0.01 to 0.13). Conclusion A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the paucity and quality of the available studies. ...

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Efficacy of Oral Propranolol on the Treatment of Retinopathy of Prematurity

Cited by 4 publications

References 25 publications

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Comparison of Clinical Outcomes of Intravitreal Bevacizumab and Aflibercept in Type 1 Prethreshold Retinopathy of Prematurity in Posterior Zone Ii

Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis

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