Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.
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ABSTRACT:
SUBMITTER: Sankar MJ
PROVIDER: S-EPMC6491066 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP.A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic.Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P?=?0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P?=?0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P?=?0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P?=?0.12).This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.
| S-EPMC5789737 | biostudies-literature
Project description:PurposeVascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk.MethodsPublished literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included.ResultsBy pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population.DiscussionThis meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation.
| S-EPMC4250490 | biostudies-literature
Project description: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.
| S-EPMC4197141 | biostudies-literature
Project description:This is a phase 3, randomized, double-blind, placebo-controlled multi-center study evaluating the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia (FN) in patients with newly diagnosed, locally-advanced or metastatic colorectal cancer receiving first-line treatment with bevacizumab and either 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) or 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI).
This study will also investigate the effect of adding pegfilgrastim to bevacizumab and either FOLFOX or FOLFIRI by evaluating overall survival, progression-free survival, and overall response rate in each arm at regular intervals over a maximum of 60 months follow-up.
| 2073020 | ecrin-mdr-crc
Project description:Diabetes is a major cause of visual impairment among working-age adults in the United States. The proliferative form of diabetic retinopathy is associated with severe vision loss (acuity <5/200). The standard treatment in proliferative diabetic retinopathy (PDR) is panretinal photocoagulation (PRP), which is effective but has established side effects such as peripheral visual-field constraints. Vascular endothelial growth factor (VEGF) is thought to drive the process of vascular proliferation. Drugs targeting VEGF (anti-VEGF) have been studied extensively in diabetic macular edema (DME), and results have shown that diabetic retinopathy regresses with anti-VEGF treatment. Recent studies show that anti-VEGF is not inferior to PRP for PDR while treatment is maintained, though recurrence rate when anti-VEGF treatment is stopped is unclear. In vitreous hemorrhage where PRP cannot be performed, use of anti-VEGF medications can treat underlying PDR and delay or reduce need for vitrectomy. Limitations of anti-VEGF treatment, however, require careful patient selection and monitoring. This review discusses recent clinical trials and guidelines for anti-VEGF use in PDR.
| S-EPMC6113746 | biostudies-literature
Project description:ObjectiveTo investigate refractive error development in preterm children with severe retinopathy of prematurity (ROP) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and laser photocoagulation.MethodsSelection criteria were comparative studies that compared the refractive errors in children, birthweights ≤1500 grams and gestational ages ≤30 weeks, and treatments for Type I ROP with intravitreal bevacizumab (IVB) versus laser photocoagulation. Studies were identified using PubMed, Google Scholar, and published reviews. Meta-analyses were performed on the post-treatment outcomes of spherical equivalent (SEQ), cylindrical power, and prevalence of high myopia. Longitudinal development of refractive error in IVB, or in laser-treated children, or in normal full-term children was visually summarized.ResultsTwo randomized controlled trials and 5 non-randomized studies, including a total of 272 eyes treated by IVB and 247 eyes treated by laser, were included in this study. Compared with laser-treated children, IVB-treated children have less myopic refractive error (P<0.001), lower prevalence of high myopia (P<0.05), and less astigmatism (P = 0.02).ConclusionsTreatment with IVB is associated with less myopia and astigmatism than laser treatment for infants with severe ROP. Given the complexity of ROP and the variability of dosing, our review supports close monitoring of refractive error outcomes in children treated with IVB.
| S-EPMC6886775 | biostudies-literature
Project description:Laser photocoagulation is the current gold standard treatment for proliferative retinopathy of prematurity (ROP). However, it permanently reduces the visual field and might induce myopia. Vascular endothelial growth factor (VEGF) inhibitors for the treatment of ROP may enable continuing vascularization of the retina, potentially allowing the preservation of the visual field. However, for their use in infants concern remains. This meta-analysis explores the safety of VEGF inhibitors.The Ovid Interface was used to perform a systematic review of the literature in the databases PubMed, EMBASE and the Cochrane Library.This meta-analysis included 24 original reports (including 1.457 eyes) on VEGF inhibitor treatment for ROP. The trials were solely observational except for one randomized and two case-control studies. We estimated a 6-month risk of retreatment per eye of 2.8%, and a 6-month risk of ocular complication without the need of retreatment of 1.6% per eye. Systemic complications were only reported as isolated incidents.VEGF inhibitors seem to be associated with low recurrence rates and ocular complication rates. They may have the benefit of potentially allowing the preservation of visual field and lower rates of myopia. Due to the lack of data, the risk of systemic side effects cannot be assessed.
| S-EPMC4470662 | biostudies-literature
Project description:BackgroundThe 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.MethodsThis 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.ResultsVEGF 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.ConclusionCirculatory 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.
| S-EPMC5788569 | biostudies-literature
Project description:Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF-A, VEGF-D, placental growth factor (PlGF) and plasminogen activator inhibitor-1 (PAI-1) have tumor angiogenic activity. VEGF-A and PAI-1 levels in the blood may impact the activity of bevacizumab, and VEGF-D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti-VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first-line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti-VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second-line chemotherapy. VEGF-A, VEGF-D, PlGF and PAI-1 levels were measured before starting chemotherapy and were re-assessed every 1-2 months until disease progression. Bevacizumab had reduced benefit as a first-line chemotherapeutant in patients with very low or very high levels of VEGF-A. Bevacizumab increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1. Anti-VEGF drugs offered the greatest benefit to patients with high PAI-1 before first- and second-line chemotherapy. PAI-1 levels were not affected by anti-VEGF drugs. Since ramucirumab increased VEGF-D, it offered less benefit to patients with high VEGF-D in second-line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF-D, without increasing VEGF-D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti-VEGF drugs.
| S-EPMC9667458 | biostudies-literature
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.
| S-EPMC9539731 | biostudies-literature