Dataset Information

Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?

ABSTRACT: Treatment of retinopathy of prematurity (ROP) is currently evolving. Novel therapeutic options are emerging that have the potential to complement existing therapies and improve treatment outcomes. However, any new therapeutic option must be thoroughly evaluated before existing (and successful) treatment paradigms can be amended. This is particularly so when switching from locally effective therapies like photoablative laser therapy to systemic pharmacological treatments, which may have hitherto unknown widespread side effects. This review compiles the current knowledge of where and when the two most advanced pharmacological treatment options for ROP, insulin-like growth factor-1 supplementation and anti-vascular endothelial growth factor treatment, may have their place in future therapy regimens for ROP. The requirement for clinical studies is emphasized: these are needed to address safety considerations before any of these interventions can achieve the status of standard clinical care in the very vulnerable population of ROP infants.

SUBMITTER: Stahl A

PROVIDER: S-EPMC4197141 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?

Stahl Andreas A Hellstrom Ann A Smith Lois E H LE

Neonatology 20141005 3

Treatment of retinopathy of prematurity (ROP) is currently evolving. Novel therapeutic options are emerging that have the potential to complement existing therapies and improve treatment outcomes. However, any new therapeutic option must be thoroughly evaluated before existing (and successful) treatment paradigms can be amended. This is particularly so when switching from locally effective therapies like photoablative laser therapy to systemic pharmacological treatments, which may have hitherto ...[more]

PMID: 25300950

Similar Datasets

Project description:ImportanceAnti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified.ObjectiveTo determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment.Design, setting, and participantsThis multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation.ExposuresAnti-VEGF therapy vs laser photocoagulation.Main outcomes and measuresNew receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening.ResultsAmong 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10).Conclusions and relevanceAnti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.

Project description:OBJECTIVE:To determine the effects of oxygen fluctuations on pigment epithelial-derived factor (PEDF) and vascular endothelial growth factor (VEGF)/PEDF ratios in a relevant rat model of retinopathy of prematurity (ROP). METHODS:The expression of retinal PEDF mRNA and of VEGF and PEDF protein were determined using real-time polymerase chain reaction or enzyme-linked immunosorbent assays at different postnatal day ages for rat pups raised in room air (RA) or in a rat model mimicking ROP. Statistical outcomes were determined with factorial analyses of variance. Mean VEGF and PEDF protein levels were determined at different ages for rats in the ROP model and for RA-raised rats, and the ratio of VEGF/PEDF protein versus age was plotted. At postnatal day (P) 14, inner retinal plexus vascularization had extended to the ora serrata in pups raised in RA. In the ROP model, avascular retina persisted at P14 and intravitreous neovascularization developed at P18. Therefore, VEGF and PEDF expression was determined in the ROP model and in RA-raised rat pups at P14 and P18. RESULTS:Older age was associated with increased PEDF mRNA (p<0.001), PEDF protein (p=0.005), and VEGF protein (p=0.005), and VEGF protein (p<0.0001). Exposure to fluctuations of oxygen in the 50/10 oxygen-induced retinopathy model compared to RA was associated with increased PEDF mRNA (p=0.0185), PEDF protein (p<0.0001), or VEGF protein (p<0.0001). The VEGF/PEDF ratio favored angiogenic inhibition (<1.0) before but not on P14, when avascular retina persisted in the ROP model but not in RA. The VEGF/PEDF ratio favored angiogenesis (>1.0) at P14 and P 18 when intravitreous neovascularization occurred in the ROP model. CONCLUSIONS:Increased expression levels of VEGF and PEDF are associated with older postnatal day age or with exposure to fluctuations in oxygen in the 50/10 oxygen-induced retinopathy model compared to RA. PEDF protein more closely associates with avascular retinal features and neovascularization than does VEGF protein or the VEGF/PEDF in the ROP model. Although PEDF has been proposed as a potential treatment in ROP, interventional studies using PEDF in an ROP model to potentially reduce intravitreous neovascularization are required to determine timing, efficacy, and dose of PEDF.

Project description:OBJECTIVE:To investigate the relationship between vascular endothelial growth factor (VEGF) gene polymorphisms and Retinopathy of prematurity (ROP) development in preterm infants of China Han ethnic population. METHODS:VEGF gene promoter polymorphisms (-165C/T and -141A/C) were studied in 54 neonates with ROP but not requiring treatment (regressive ROP group), 48 neonates with ROP that requires cryotherapy/photocoagulation (severe ROP group), and in a control group of 62 preterm infants without ROP. Genotyping for VEGF gene promoter was performed by polymerase chain reaction (PCR) and gene sequencing. RESULTS:In this study, -165C/T genotype was found to be associated with severe ROP (P=0.012<0.05), but not with regressive ROP. For the dominant genetic model, subjects carrying the -165T allele had a decreased risk of ROP compared to those non-carrying the -165C allele in both regressive ROP regressive group and severe ROP group, and especially in severe ROP group (in regressive ROP group: OR=2.069, 95% CI=0.986-4.340; in severe ROP group: OR=3.677, 95% CI=1.339-10.099). For the allelic model, comparing the A allele to the C allele, the -165C/T site also showed a decreased risk of ROP in both regressive ROP group and severe ROP group (in regressive ROP group: OR=2.395, 95% CI=1.112-5.157; in severe ROP group: OR=4.258, 95% CI=1.518-11.945). In -141A/C genotypes and alleles were found not to be associated with severe ROP or regressive ROP. Linkage disequilibrium analysis revealed -165C/T and -141A/C were a strong linkage disequilibrium, and haplotype analysis revealed that T-165C-141 haplotype was associated with resistance to severe ROP but C-165A-141 haplotype was associated with risk to severe ROP. No statistically significant differences were observed in regressive ROP group. CONCLUSION:VEGF -165C/T SNP is associated with ROP especial in severe ROP. VEGF -141A/C SNP is not associated with ROP. T-165C-141 and C-165A-141 haplotypes may have a role in severe ROP.

Dataset Information

Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?

Publications

Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets