Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?

Spandau, Ulrich; Tomic, Zoran; Ewald, Uwe; Larsson, Eva; Åkerblom, Hanna; Holmström, Gerd

doi:10.1111/j.1755-3768.2011.02351.x

Cited by 45 publications

(40 citation statements)

References 34 publications

(45 reference statements)

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“…Vannak közlések arra nézve, hogy négyes stá-diumban, ahol sajnos a parciális retinaleválás része az agresszív ROP-nak, szemlencsét megtartó vitrectomia látásmentő beavatkozás lehet. Az anti-VEGF-kezelés hatékonyságának alátámasztása további kutatást igényel [17]. Egyéb potenciális terápiás lehetőségek közül a ROP 1. fázisában alkalmazott IGF-1-IGFBP3 komplex (inzulinszerű növekedési faktor -inzulinszerű növeke-dési faktor kötő fehérje komplex 3) szubsztitúció már svéd kutatók által indított klinikai II.…”

Section: A Rop Kezeléseunclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

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A retinopathia prematurorum, a bronchopulmonalis dysplasia, az intraventricularis haemorrhagia és a periventricularis leukomalacia a koraszülöttek legfontosabb krónikus utóbetegségei, amelyek alapvetően befolyásolják a gyermekek életminőségét. Mivel Magyarországon a koraszülés gyakorisága az elmúlt években nem csökkent, és a kialakult kórképek nehezen kezelhetők, a megelőzés jelentősége óriási. Kockázatifaktor-elemzések bebizonyították, hogy mindegyik kórkép multifaktoriális, a számos közös kóroki tényező közül a fejlődő szervek angiogenesise az egyik legfontosabb. A koraszülés következtében számos stresszhatás miatt károsodhat az érfejlődés. A megszületés után, a méhen belüli élethez viszonyítva, a relatív hyperoxia és a csökkenő vascularis növekedési faktorok szintje érsérü-lést, akár vascularis apoptózist okozhat. Mindezek következtében, a folyamat későbbi fázisában, a hypoxia által indukált gének aktiválódnak, óriási mértékű és kóros neovascularisatio, krónikus szervkárosodás alakul ki. A normális angiogenesis megtartása és a reaktív neovascularisatio gátlása a koraszülöttek jobb életminőségét eredményezheti. Orv. Hetil., 2013, 154, 1498-1511 Kulcsszavak: retinopathia prematurorum, bronchopulmonalis dysplasia, intraventricularis haemorrhagia, periventricularis leukomalacia Chronic morbidities of premature newbornsThe most important chronic morbidities of premature newborns, deeply infl uencing quality of life, are retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage and periventricular leukomalacia. Since the rate of premature birth has not decreased in recent years in Hungary, and treatments of these end stage disorders are extremely diffi cult, prevention gains tremendous signifi cance. Effective prevention is based on detailed knowledge of the pathophysiological mechanisms of these special diseases having multifactorial nature sharing several common risk factors, and one is the pathological angiogenesis. This sensitive system is affected by several stress situations which are the consequences of prematurity leading to abnormal vascular growth. After birth, relative hyperoxia, compared to intrauterine life, and decreasing concentrations of vascular growth factors result in vascular injury, moreover, may cause vessel apoptosis. The consequence of this phenomenon is the activation of hypoxia responsible genes resulting in robust pathological neovascularization and organ damage during the later phase. Saving normal angiogenesis and inhibiting reactive neovascularization may lead to better quality of life in these premature infants. Orv. Hetil., 2013, 154, 1498-1511 Keywords: retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia (Beérkezett: 2013. augusztus 6.; elfogadva: 2013. augusztus 22.) A szerkesztőség felkérésére készült közlemény. Rövidítések ANGPT-2 = angiopoetin-2; β-ARs = béta-adrenerg receptorok; BPD = bronchopulmonalis dysplasia; CP = cerebral palsy; ELBW = (extremely low birthweight) extrém kis születés...

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Section: A Rop Kezeléseunclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

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“…Spandau et al [19] found that after IVI of bevacizumab, vascularization of the retina was completed in the 65th week. Menke et al [20] reported that after IVI of ranibizumab, vascularization of the retina was completed between the 3rd and 6th months without recurrence.…”

Section: Discussionmentioning

confidence: 99%

The Process of Retinal Vascularization after Anti-VEGF Treatment in Retinopathy of Prematurity: A Comparison Study between Ranibizumab and Bevacizumab

Sukgen

Çömez²,

Koçluk³

et al. 2016

Ophthalmologica

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Purpose: To compare the effects on the process of retinal vascularization of intravitreal ranibizumab (IVR) and intravitreal bevacizumab (IVB) in the treatment of severe retinopathy of prematurity. Methods: The present study is a bi-centered retrospective study. While 44 eyes of 22 patients in group 1 were applied 0.625 mg bevacizumab, 46 eyes of 23 patients in group 2 were applied 0.25 mg ranibizumab. Retinal vascularization was evaluated clinically. Results: The mean time for completion of vascularization was found to be postmenstrual 55.93 ± 4.13 weeks in group 1 and 56.30 ± 4.30 weeks in group 2. There were signiﬁcant differences in the recurrence prevalence between the two groups. The prevalence of recurrence was found to be significantly higher in the ranibizumab group than in the bevacizumab group (p = 0.023). Conclusions: The study showed that after IVR or IVB treatment, vascularization could be completed with delay; there were no differences in this delay time between the ranibizumab and bevacizumab groups. Besides, avascular areas may remain in the peripheral retina, and additional treatment may be necessary after IVB or IVR treatment. When the treatment was applied as monotherapy, more recurrence was observed in the ranibizumab group.

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“…27 Ever since the introduction of bevacizumab as a therapeutic choice, its possible toxicity to the retina has been an issue of great concern and object of intense research. 28,29 Clinical and histological studies testing the effect of bevacizumab on rabbit retinal tissue have failed to show tissue toxicity. 21,30 Nevertheless, most safety studies published to date have evaluated the effect of bevacizumab in adult animals, rather than assessing its safety profile in the developing retina.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

Miguel

Matsuda

Portes

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS.Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared.RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls.CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (Invest Ophthalmol Vis Sci. 2012;53:7904-7911)

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Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?

Cited by 45 publications

References 34 publications

Chronic morbidities of premature newborns

Chronic morbidities of premature newborns

The Process of Retinal Vascularization after Anti-VEGF Treatment in Retinopathy of Prematurity: A Comparison Study between Ranibizumab and Bevacizumab

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

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