Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial)

Sanghvi, K P; Kabra, Nandkishor S; Padhi, Phalguni; Singh, Umesh Kumar; Dash, Swarup Kumar; Avasthi, Bhupendra S

doi:10.1136/archdischild-2016-311548

Cited by 23 publications

(23 citation statements)

References 18 publications

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“… 20 Intravenous propranolol has been associated with arrhythmias. 21 Intraocular anti-VEGF has been associated with systemic inhibition of VEGF for up to 8 weeks after a single injection. 22 The effects of systemic VEGF inhibition on other developing vascular beds such as the lungs are unknown.…”

Section: Discussionmentioning

confidence: 99%

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity

Shaw

Calzi

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeLow levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR).MethodsPostnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA).ResultsWith Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins.ConclusionsArg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.

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Section: Discussionmentioning

confidence: 99%

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity

Shaw

Calzi

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Further, recent studies demonstrate a possible deleterious refractive outcome of topical propranolol therapy, highlighting the importance of continued study [102]. Conversely, a recent meta-analysis including clinical trial and study data for 461 infants, demonstrated efficacy of oral propranolol for ROP prevention in preterm infants demonstrating a decreased relative risk of severe ROP disease (not complete ROP prevention), supporting prior PreROP trial data [103,104]. However the authors do note that additional well-powered, multinational, randomized control trials reporting on long-term outcomes are needed.…”

Section: Beta Blockersmentioning

confidence: 72%

Current evidence and outcomes for retinopathy of prematurity prevention: insight into novel maternal and placental contributions

Carroll

Owen

2020

Exploration of Medicine

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Retinopathy of prematurity (ROP) is a blinding morbidity of preterm infants, which represents a significant clinical problem, accounting for up to 40% of all childhood blindness. ROP displays a range of severity, though even mild disease may result in life-long visual impairment. This is complicated by the fact that our current treatments have significant ocular and potentially systemic effects. Therefore, disease prevention is desperately needed to mitigate the life-long deleterious effects of ROP for preterm infants. Although ROP demonstrates a delayed onset of retinal disease following preterm birth, representing a potential window for prevention, we have been unable to sufficiently alter the natural disease course and meaningfully prevent ROP. Prevention therapeutics requires knowledge of early ROP molecular changes and risk, occurring prior to clinical retinal disease. While we still have an incomplete understanding of these disease mechanisms, emerging data integrating contributions of maternal/placental pathobiology with ROP are poised to inform novel approaches to prevention. Herein, we review the molecular basis for current prevention strategies and the clinical outcomes of these interventions. We also discuss how insights into early ROP pathophysiology may be gained by a better understanding of maternal and placental factors playing a role in preterm birth.

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“…There was a trend toward a lower incidence of ROP (56.8 vs. 68.6%) and less use of laser therapy in the group treated with propranolol, which did not reach statistical significance. 60 After evaluating the incidence of ROP in the propranolol versus the control group, the incidence of stage 1 retinopathy was the same in both groups (27.4%), suggesting that the prophylactic administration of propranolol was not effective in preventing the development of retinopathy. However, a decrease in the incidence of retinopathy was demonstrated in prethreshold stages (stage 2 or stage 3 without plus disease), as shown in other studies.…”

Section: β-Adrenergic Blockers: Propranololmentioning

confidence: 89%

“…During the last 6-year, five studies 48, [57][58][59][60] have been published with the use of oral propranolol as a treatment or prophylaxis and two studies using propranolol drops of ROP. 61,62 One of the first publications by Filippi et al 57 in 2013 evaluated the safety and effectiveness of oral propranolol in 52 preterm infants with ROP.…”

Section: β-Adrenergic Blockers: Propranololmentioning

confidence: 99%

“…However, in children with stage 2 ROP, treatment with propranolol significantly reduced the need for laser therapy. 59 The other study, which was done in India, 60 enrolled 109 infants under 32 weeks; 55 of them received prophylactic oral propranolol and 54 were controls. The group with propranolol initiated after the first postnatal week (day 8) at a dose of 1 mg/kg/day until a corrected GA of 37 weeks or until retinal vascularization was completed.…”

Section: β-Adrenergic Blockers: Propranololmentioning

confidence: 99%

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Update in the Treatment of Retinopathy of Prematurity

Bancalari

Schade

2020

Am J Perinatol

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Retinopathy of prematurity (ROP) is an alteration in the development of the immature retina vascularization that frequently occurs in premature infants and is one of the leading causes of childhood blindness worldwide. In threshold stage retinopathy, laser photocoagulation is the standard treatment, particularly in those located in zone II. However, this therapy destroys parts of the retina and can lead to significant eye complications later in life. For this reason, in the last few years, antivascular endothelial growth factor agents are being used as monotherapy or as coadjuvant with laser, especially in retinopathy located in zone I. More recently, the administration of oral propranolol has been used as prevention and/or treatment of prethreshold retinopathy with encouraging results. This review provides an overview of the current evidence on newer treatment strategies for ROP. Key Points

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Prophylactic propranolol for prevention of ROP and visual outcome at 1 year (PreROP trial)

Abstract: CTRI/2013/11/004131.

Cited by 23 publications

References 18 publications

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity

Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity

Current evidence and outcomes for retinopathy of prematurity prevention: insight into novel maternal and placental contributions

Update in the Treatment of Retinopathy of Prematurity

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