Dataset Information

Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.

ABSTRACT:

Background

The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP.

Methods

This study included 52 infants born at <31 wk gestational age (non-ROP n = 33, nonproliferative ROP n = 10, treated for ROP n = 9). VEGF concentrations were analyzed in blood samples collected at birth, at 3 d postnatal age, and then weekly until at least a gestational age of 35 wk.

Results

VEGF concentrations at birth did not differ between groups, independent of later ROP status. In contrast, VEGF serum concentrations were significantly higher at first detection of ROP in infants who were later treated for ROP compared to infants without ROP. At the time of laser therapy, serum VEGF concentrations did not differ between groups.

Conclusion

Circulatory concentrations of VEGF, in infants who later developed severe ROP, were elevated at the time when ROP first was detected but not at the time when current treatment most often occurred. This supports the need for further studies of circulating VEGF in relation to the timing of ROP treatment.

SUBMITTER: Hellgren G

PROVIDER: S-EPMC5788569 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.

Hellgren Gunnel G Löfqvist Chatarina C Hård Anna-Lena AL Hansen-Pupp Ingrid I Gram Magnus M Ley David D Smith Lois E LE Hellström Ann A

Pediatric research 20150915 1-1

<h4>Background</h4>The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP.<h4>Methods</h4>This study included 52 infants born at <31 wk gestational age (non-ROP n = 33, nonproliferative ROP n = 10, treated for ROP ...[more]

PMID: 26372519

Similar Datasets

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.

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:PURPOSE:To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. DESIGN:Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm. PARTICIPANTS:Participants with available plasma samples (N = 436). METHODS:Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES:Changes in the natural log (ln) of plasma VEGF levels. RESULTS:Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were -0.30±0.61 pg/ml, -0.31±0.54 pg/ml, and -0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were -0.01 (-0.12 to +0.10; P = 0.89), -0.31 (-0.44 to -0.18; P < 0.001), and -0.30 (-0.43 to -0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (-0.23 [-0.38 to -0.09]; P < 0.001); the difference between aflibercept and ranibizumab was -0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar. CONCLUSIONS:These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.

Dataset Information

Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.

Background

Methods

Results

Conclusion

Publications

Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets