{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:07:50Z","timestamp":1790064470311,"version":"4.0.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder unique to preterm infants with extremely low birth weight, ranking as the top cause of preventable childhood blindness. Retinal hypoxia, excessive secretion of vascular endothelial growth factor (VEGF) and dysregulation of insulin-like growth factor-1 (IGF-1) constitute the core pathogenic cascades of ROP. As competitive antagonists of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -adrenergic receptors (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -AR), beta-blockers suppress the HIF-1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \/VEGF and PI3K\/Akt\/VEGF signaling axes to inhibit pathological retinal neovascularization, while exerting auxiliary anti-inflammatory, anti-oxidative stress and retinal neuroprotective effects. Derived from the mature clinical application of propranolol in infantile hemangioma (IH), preclinical and clinical trials of beta-blockers for the prevention of ROP progression and for ROP treatment have expanded rapidly over the past decade, with two administration routes available: oral systemic delivery and topical ocular micro-drops. Oral propranolol possesses solid anti-angiogenic preclinical evidence, yet its clinical promotion is restricted by severe systemic adverse reactions including bradycardia, hypoglycemia and apnea. The 0.2% propranolol eye micro-drops carry minimal systemic exposure risk and deliver comparable efficacy to oral formulations for Stage 2\u20133 ROP, but long-term visual and neurodevelopmental follow-up data remain absent. Critically, all existing clinical evidence is limited by small sample sizes, single-center designs and inconsistent dosing protocols; large-scale, multicenter, long-term follow-up Phase III randomized controlled trials are still lacking. At present, beta-blockers cannot replace laser photocoagulation or intravitreal anti-VEGF injection as the routine standard treatment for ROP. They are only regarded as experimental early intervention candidates pending further high-level clinical validation.\n                  <\/jats:p>","DOI":"10.3389\/fped.2026.1953347","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:54:41Z","timestamp":1790063681000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Research progress on the use of beta-blockers in the progression prevention, and treatment of retinopathy of prematurity"],"prefix":"10.3389","volume":"14","author":[{"given":"Shuanghong","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital Affiliated with Zhengzhou University","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital Affiliated with Zhengzhou University","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.2147\/OPTH.S519292","article-title":"Retinopathy of prematurity (ROP): an overview of biomarkers in various samples for prediction, diagnosis, and prognosis","volume":"19","author":"Huang","year":"2025","journal-title":"Clin Ophthalmol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3390\/biomedicines13020400","article-title":"Retinopathy of prematurity and MicroRNAs","volume":"13","author":"Albanese","year":"2025","journal-title":"Biomedicines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/OPTH.S496737","article-title":"Safety and efficacy of combination therapy with anti-vascular endothelial growth factor and laser for retinopathy of prematurity: a systematic review and meta-analysis","volume":"19","author":"Alamoudi","year":"2025","journal-title":"Clin Ophthalmol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s40001-024-02206-7","article-title":"Effect and factors associated with reactivation after intravitreal conbercept or aflibercept in retinopathy of prematurity","volume":"30","author":"Huang","year":"2025","journal-title":"Eur J Med Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"8567912","DOI":"10.1155\/2018\/8567912","article-title":"Current evidence for the prevention of endophthalmitis in anti-VEGF intravitreal injections","volume":"2018","author":"Lau","year":"2018","journal-title":"J Ophthalmol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1186\/s12887-025-05707-4","article-title":"Impact of congenital heart disease on clinical outcomes of oral propranolol therapy for infantile hemangiomas: a propensity score-matched analysis","volume":"25","author":"Yu","year":"2025","journal-title":"BMC Pediatr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.2147\/DDDT.S383101","article-title":"Progress and challenges of anti-VEGF agents and their sustained-release strategies for retinal angiogenesis","volume":"16","author":"Xu","year":"2022","journal-title":"Drug Des Devel Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e219","DOI":"10.1002\/hsr2.219","article-title":"How to prevent ROP in preterm infants in Indonesia?","volume":"4","author":"Siswanto","year":"2021","journal-title":"Health Sci Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40348-023-00163-5","article-title":"Retinopathy of prematurity: from oxygen management to molecular manipulation","volume":"10","author":"Woods","year":"2023","journal-title":"Mol Cell Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.3389\/fimmu.2017.01868","article-title":"Abnormal complement activation and inflammation in the pathogenesis of retinopathy of prematurity","volume":"8","author":"Rathi","year":"2017","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1159\/000330174","article-title":"Understanding retinopathy of prematurity: update on pathogenesis","volume":"100","author":"Rivera","year":"2011","journal-title":"Neonatology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1080\/08820530902800314","article-title":"Retinopathy of prematurity: current concepts in molecular pathogenesis","volume":"24","author":"Heidary","year":"2009","journal-title":"Semin Ophthalmol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"230","DOI":"10.31365\/issn.2595-1769.v21i4p230-232","article-title":"Hemangioma infantil: 17 casos tratados com propranolol","volume":"21","author":"Haddad","year":"2026","journal-title":"Rev Ped SOPERJ"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e979699","DOI":"10.4161\/19381980.2014.979699","article-title":"Mechanisms of propranolol action in infantile hemangioma","volume":"6","author":"Kum","year":"2014","journal-title":"Derm Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3892\/etm.2013.1159","article-title":"Induction of apoptosis in infantile hemangioma endothelial cells by propranolol","volume":"6","author":"Tu","year":"2013","journal-title":"Exp Ther Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1007\/s43440-025-00762-1","article-title":"Early plasma changes of HIF-1 alpha, matrix metalloproteinases-2 and -9, and tissue inhibitor of matrix metalloproteinase-1 in patients with infantile hemangiomas treated with propranolol","volume":"77","author":"Kowalska","year":"2025","journal-title":"Pharmacol Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"835771","DOI":"10.3389\/fphar.2022.835771","article-title":"Decoupling oxygen tension from retinal vascularization as a new perspective for management of retinopathy of prematurity. New opportunities from \u03b2-adrenoceptors","volume":"13","author":"Filippi","year":"2022","journal-title":"Front Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2792","DOI":"10.1016\/j.bbrc.2018.08.041","article-title":"Propranolol increases vascular permeability through pericyte apoptosis and exacerbates oxygen-induced retinopathy","volume":"503","author":"Yun","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s00210-012-0828-x","article-title":"Beta3-adrenergic receptors modulate vascular endothelial growth factor release in response to hypoxia through the nitric oxide pathway in mouse retinal explants","volume":"386","author":"Dal Monte","year":"2013","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/bcp.14196","article-title":"The effectiveness and safety of topical \u03b2-receptor blocker in treating superficial infantile haemangiomas: a meta-analysis including 20 studies","volume":"86","author":"Lin","year":"2020","journal-title":"Br J Clin Pharmacol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1159\/000510029","article-title":"The efficacy and safety of topical \u03b2-blockers in treating infantile hemangiomas: a meta-analysis including 11 randomized controlled trials","volume":"237","author":"Wang","year":"2021","journal-title":"Dermatology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e15016","DOI":"10.1111\/dth.15016","article-title":"Topical beta-blockers in dermatologic therapy","volume":"34","author":"Filoni","year":"2021","journal-title":"Dermatol Ther"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1515901","DOI":"10.3389\/fphar.2024.1515901","article-title":"Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review","volume":"15","author":"Huang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.3390\/ijms24054698","article-title":"\u03b2-adrenoreceptors as therapeutic targets for ocular tumors and other eye diseases-historical aspects and nowadays understanding","volume":"24","author":"B\u00f6hm","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"552","DOI":"10.18240\/ijo.2020.04.04","article-title":"Beta-adrenergic agonist protects retinal pigment epithelium against hydroxycholoroquine toxicity via cAMP-PKA signal pathway","volume":"13","author":"Zhang","year":"2020","journal-title":"Int J Ophthalmol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.1038\/s41598-021-83552-y","article-title":"Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes","volume":"11","author":"Kim","year":"2021","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.18535\/jmscr\/v10i10.23","article-title":"Prophylactic propranalol in prevention of retinopathy of prematurity in premature neonates","volume":"10","author":"Mansuri","year":"2022","journal-title":"J Med Sci Clin Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1167\/iovs.16-20204","article-title":"\u03b22-adrenergic receptor antagonism attenuates CNV through inhibition of VEGF and IL-6 expression","volume":"58","author":"Lavine","year":"2017","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1617797","DOI":"10.3389\/fendo.2025.1617797","article-title":"A new perspective on protecting the blood-retinal barrier against injury in diabetic retinopathy: mitophagy","volume":"16","author":"Li","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"11232","DOI":"10.1038\/s41598-025-95055-1","article-title":"Association of the ADRB2 rs1042714 variant with retinopathy of prematurity highlights the importance of the renin-angiotensin-aldosterone system","volume":"15","author":"Chmielarz-Czarnoci\u0144ska","year":"2025","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1167\/iovs.65.10.34","article-title":"Agonism of \u03b23-adrenoceptors inhibits pathological retinal angiogenesis in the model of oxygen-induced retinopathy","volume":"65","author":"Melecchi","year":"2024","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.3390\/cells14141107","article-title":"The long-standing problem of proliferative retinopathies: current understanding and critical cues","volume":"14","author":"Cammalleri","year":"2025","journal-title":"Cells"},{"key":"B33","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/35085068","article-title":"Transcriptional regulation by the phosphorylation-dependent factor CREB","volume":"2","author":"Mayr","year":"2001","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e12340","DOI":"10.14814\/phy2.12340","article-title":"Pathological hypertrophy reverses \u03b22-adrenergic receptor-induced angiogenesis in mouse heart","volume":"3","author":"Xu","year":"2015","journal-title":"Physiol Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3390\/nu15061340","article-title":"Naringenin attenuates isoprenaline-induced cardiac hypertrophy by suppressing oxidative stress through the AMPK\/NOX2\/MAPK signaling pathway","volume":"15","author":"Li","year":"2023","journal-title":"Nutrients"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7061","DOI":"10.1167\/iovs.13-12883","article-title":"Involvement of Nox2 NADPH oxidase in retinal neovascularization","volume":"54","author":"Chan","year":"2013","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"190","DOI":"10.31083\/j.fbl2905190","article-title":"Physiological and pathophysiological relevance of nitric oxide synthases (NOS) in retinal blood vessels","volume":"29","author":"Gericke","year":"2024","journal-title":"Front Biosci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"395","DOI":"10.3389\/fncel.2017.00395","article-title":"The beta adrenergic receptor blocker propranolol counteracts retinal dysfunction in a mouse model of oxygen induced retinopathy: restoring the balance between apoptosis and autophagy","volume":"11","author":"Cammalleri","year":"2017","journal-title":"Front Cell Neurosci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1322783","DOI":"10.3389\/fped.2024.1322783","article-title":"Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression","volume":"12","author":"Pascarella","year":"2024","journal-title":"Front Pediatr"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1408605","DOI":"10.3389\/fphys.2024.1408605","article-title":"A promising case of preclinical-clinical translation: \u03b2-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity","volume":"15","author":"Cammalleri","year":"2024","journal-title":"Front Physiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1038\/s41390-022-02211-8","article-title":"Propranolol ameliorates retinopathy of prematurity in mice by downregulating HIF-1\u03b1 via the PI3K\/Akt\/ERK pathway","volume":"93","author":"Su","year":"2023","journal-title":"Pediatr Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1167\/iovs.10-5536","article-title":"Role of the adrenergic system in a mouse model of oxygen-induced retinopathy: antiangiogenic effects of \u03b2-adrenoreceptor blockade","volume":"52","author":"Ristori","year":"2011","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/archdischild-2013-303951","article-title":"Oral propranolol versus placebo for retinopathy of prematurity: a pilot, randomised, double-blind prospective study","volume":"98","author":"Makhoul","year":"2013","journal-title":"Arch Dis Child"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.18502\/wjpn.v2i1.2810","article-title":"Evaluation of the oral propranolol effect on retinopathy of prematurity: randomized clinical trial","volume":"2","author":"Mirjalili","year":"2020","journal-title":"World J Peri Neonatol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"631673","DOI":"10.3389\/fped.2021.631673","article-title":"Clinical efficacy and safety of propranolol in the prevention and treatment of retinopathy of prematurity: a meta-analysis of randomized controlled trials","volume":"9","author":"Kong","year":"2021","journal-title":"Front Pediatr"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/s41372-019-0503-x","article-title":"Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis","volume":"39","author":"Stritzke","year":"2019","journal-title":"J Perinatol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s40272-024-00647-5","article-title":"Comparison of different doses of oral and ocular propranolol for retinopathy of prematurity: a network meta-analysis","volume":"26","author":"Ortiz-Seller","year":"2024","journal-title":"Paediatr Drugs"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e00399","DOI":"10.1002\/prp2.399","article-title":"Propranolol pharmacokinetics in infants treated for infantile hemangiomas requiring systemic therapy: modeling and dosing regimen recommendations","volume":"6","author":"Del Frari","year":"2018","journal-title":"Pharmacol Res Perspect"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e021749","DOI":"10.1136\/bmjopen-2018-021749","article-title":"Oral propranolol for prevention of threshold retinopathy of prematurity (ROPROP): protocol of a randomised controlled trial","volume":"8","author":"B\u00fchrer","year":"2018","journal-title":"BMJ Open"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1080\/14740338.2020.1826927","article-title":"A safety review of drugs used for the treatment of retinopathy of prematurity","volume":"19","author":"Filippi","year":"2020","journal-title":"Expert Opin Drug Saf"},{"key":"B51","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1089\/jop.2020.0092","article-title":"Ocular versus oral propranolol for prevention and\/or treatment of oxygen-induced retinopathy in a rat model","volume":"37","author":"Qadri","year":"2021","journal-title":"J Ocul Pharmacol Ther"},{"key":"B52","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/pr.2016.230","article-title":"Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial","volume":"81","author":"Filippi","year":"2017","journal-title":"Pediatr Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3389\/fped.2019.00180","article-title":"Propranolol 0.2% eye micro-drops for retinopathy of prematurity: a prospective phase IIB study","volume":"7","author":"Filippi","year":"2019","journal-title":"Front Pediatr"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/j.jpeds.2013.07.049","article-title":"Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives","volume":"163","author":"Filippi","year":"2013","journal-title":"J Pediatr"},{"key":"B55","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1186\/s12886-025-04572-0","article-title":"Prevalence and associated factors of retinopathy of prematurity in sub-Saharan Africa: a systematic review and meta-analysis","volume":"25","author":"Ismail","year":"2025","journal-title":"BMC Ophthalmol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1186\/s12886-025-04527-5","article-title":"Prevalence of retinopathy of prematurity in African preterm infants and evaluation of the accuracy of the WINROP predictive algorithm: an observational clinical study","volume":"25","author":"Amouzou","year":"2025","journal-title":"BMC Ophthalmol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.7196\/SAMJ.2025.v115i5.2936","article-title":"The prevalence, risk factors and outcomes of retinopathy of prematurity at a tertiary care centre in South Africa","volume":"115","author":"Germishuys","year":"2025","journal-title":"S Afr Med J"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1953347\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:54:41Z","timestamp":1790063681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1953347\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":57,"alternative-id":["10.3389\/fped.2026.1953347"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1953347","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1953347"}}