Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy.
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SUBMITTER: Tan JJ
PROVIDER: S-EPMC5523466 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BackgroundRetinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity.MethodsWe conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age.ResultsWe enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P=0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P=0.003) but not for zone II disease (P=0.27).ConclusionsIntravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).
| S-EPMC3119530 | biostudies-literature
Project description:To determine incidence, risk factors, risk period, and characteristics of recurrent retinopathy of prematurity (ROP) treated by intravitreal bevacizumab (IVB) monotherapy.Retrospective case series.Premature infants with type 1 ROP (subdivided into stage 3+ ROP and aggressive posterior ROP [APROP]) in zone I or zone II posterior who received IVB monotherapy and were followed up for at least 65 weeks adjusted age (AA).Retrospective review of infants who demonstrated recurrence of type 1 ROP after IVB monotherapy, including examination of RetCam fundus photographs and fluorescein angiograms.Incidence, risk factors, risk period, and characteristics of recurrent ROP.Intravitreal bevacizumab monotherapy in 241 infants (471 eyes) was reviewed. Recurrence incidence was 8.3% (20/241) for infants and 7.2% (34/471) for eyes. Recurrence risk factors of greatest significance were appearance of neovascularization as APROP (P = 0.006), extended duration of hospitalization (P = 0.01), and lower birth weight (P = 0.024). Recurrence risk period was between approximately 45 and 55 weeks AA (90.0% [18/20] for infants and 94.1% [32/34] for eyes), with mean recurrence of 51.2 weeks AA (±4.6 weeks; range, 45.7-64.9 weeks) and mean interval of 16.2 weeks (±4.4 weeks) between treatments. Recurrence characteristics included plus disease (20/20 infants [100%]) and neovascularization, which appeared at the following sites: stage 3+ ROP with confluent neovascularization recurred both at the advancing edge and at the initial ridge and extraretinal fibrovascular proliferative complex (12/14 infants [85.7%]). However, APROP (6/6 infants [100%]) and stage 3+ ROP with nonconfluent neovascularization (2/14 infants [14.3%]) recurred only at the advancing edge. Also, the anterior extent of retinal vascularization was decreased (mean, 1.76 disc diameters [DD] vs. 4.48 DD), and the rate of retinal vascularization was delayed (mean, 0.11 DD/week vs. 0.23 DD/week) in those with versus without recurrence, respectively. After retreatment with IVB, retinal vascularization proceeded minimally and slowly.Premature children with severe ROP are being treated successfully with IVB monotherapy. However, recurrence is not uncommon, so vigilant follow-up is necessary to ensure timely re-treatment. Knowledge of recurrence incidence, risk factors, risk period, and characteristics allows for tailored clinical management.
| S-EPMC4995132 | biostudies-literature
Project description:PurposeTo evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP).MethodsThis was a retrospective 1:1 matched case-control study. Infants with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups.ResultsFollowing 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (<1500 g: 47 g vs. ≥1500 g: 132 g; P = 0.03).ConclusionIVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment.
| S-EPMC8664189 | biostudies-literature
Project description:This single-centered, retrospective cohort study investigated the timing of involution of retinopathy of prematurity (ROP) and retinal vascularization to zone III after intravitreal bevacizumab (IVB) treatment and its possible impacts on postnatal growth and neurodevelopment. Premature infants with birth weight ≤1500 g, born between 2008 to 2014 and diagnosed with ROP were enrolled. All patients with type 1 ROP underwent IVB as 1st line treatment and were recruited as the study group; those with any stage of ROP except type 1 ROP without treatment served as controls. Neurodevelopmental outcomes were assessed using the Bayley Score of Infant Development (BSID) editions II or III. The study group included 35 eyes from 18 patients; the control group included 86 patients. Twenty-three eyes (65.7%) exhibited ROP regression after a single dose of IVB. The majority of plus sign and extraretinal neovascularization regressed within two weeks. The length of time for retinal vascularization to reach zone III was significantly longer in the treatment group compared with the control (mean post-menstruation age 54.5 vs. 47.0 weeks, p<0.001). Long-term follow-up showed no significant differences in body weight and neurodevelopment between the study and control groups up to the 2-year corrected age.
| S-EPMC6795500 | biostudies-literature
Project description:BackgroundDiabetic retinopathy is a leading cause of visual loss in the working population. Pars plana vitrectomy has become the mainstream treatment option for severe proliferative diabetic retinopathy (PDR) associated with significant vitreous haemorrhage and/or tractional retinal detachment. Despite the advances in surgical equipment, diabetic vitrectomy remains a challenging operation, requiring advanced microsurgical skills, especially in the presence of tractional retinal detachment. Preoperative intravitreal bevacizumab has been widely employed as an adjuvant to ease surgical difficulty and improve postoperative prognosis.Aims: This study aims to assess the effectiveness of preoperative intravitreal bevacizumab in reducing intraoperative complications and improving postoperative outcomes in patients undergoing vitrectomy for the complications of PDR.MethodsA literature search was conducted using the PubMed, Cochrane, and ClinicalTrials.gov databases to identify all related studies published before 31/10/2020. Prespecified outcome measures were operation time, intraoperative iatrogenic retinal breaks, best-corrected visual acuity in the last follow-up visit, the presence of any postoperative vitreous haemorrhage and the need to re-operate. Evidence synthesis was performed using Fixed or Random Effects models, depending on the heterogeneity of the included studies. Heterogeneity was assessed using Q-statistic and I2. Additional meta-regression models, subgroup analyses and sensitivity analyses were performed as appropriate.ResultsThirteen randomized control trials, with a total of 688 eyes were included in this review. Comparison of the intraoperative data showed that bevacizumab reduced operation time (p < 0.001), minimized iatrogenic retinal breaks (p < 0.001), provided better long-term visual acuity outcomes (p = 0.005), and prevented vitreous haemorrhage (p < 0.001) and the need for reoperation (p = 0.001 < 0.05). Findings were strongly corroborated by additional sensitivity and subgroup analyses.ConclusionPreoperative administration of bevacizumab is effective in reducing intraoperative complications and improving the postoperative prognosis of diabetic vitrectomy.PROSPERO registration number: CRD42021219280.
| S-EPMC8655445 | biostudies-literature
Project description:PurposeTo assess the 5-year visual outcome of intravitreal bevacizumab in inflammatory ocular neovascularization.MethodsRetrospective, multicenter, consecutive case series of eight patients with inflammatory ocular neovascularization refractory to standard therapy who were treated with intravitreal bevacizumab and followed for 5 years after first injection. The outcome measures included improvement of best-corrected visual acuity expressed as logarithm of minimum angle of resolution.ResultsMean best-corrected visual acuity significantly improved from 0.58 at baseline (6/23 or 20/76; standard deviation = 0.32) to 0.20 at final assessment (6/10 or 20/32; standard deviation = 0.25) (n = 8; P = 0.02), a gain of 3.8 lines (median: three injections; eight eyes; eight patients). No ocular or systemic complications from intravitreal bevacizumab were noted.ConclusionAt 5 years, intravitreal bevacizumab sustained significant visual improvement in ocular neovascularization due to a variety of inflammatory ocular diseases without major complications after a median of three injections.
| S-EPMC3422149 | biostudies-literature
Project description:PurposeTo evaluate the outcomes of intravitreal bevacizumab (IVB) use in patients with a vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR).DesignRetrospective, interventional case series.MethodsPatients who presented to Scheie Eye Institute between January 2008 and January 2015 with a new VH secondary to PDR and treated with IVB were included. Exclusion criteria consisted of IVB treatment prior to the study, a history of pars plana vitrectomy (PPV), and less than 1 year of follow-up. Outcomes of interest were additional treatments including PPV, injections, and panretinal photocoagulation (PRP), as well as visual acuity at baseline and at 1 year.ResultsOf the 111 eligible eyes, 55 (49.5%) had PRP, 35 (31.6%) were managed with injections alone, and 21 (18.9%) had PPV after 1 year. The overall average number of injections during this time was 2 (range, 1-9), and 13 (11.7%) eyes were managed with a single injection alone. Of the 69 eyes with 2 years of follow-up, 43 (62.3%) had PRP, 16 (23.2%) were treated with injections alone, and 10 (14.5%) had PPV.ConclusionsThis study underscores the potentially important role that IVB injections have in the management of patients with VH secondary to PDR. The results indicate that a proportion of patients may be treated with a minimal amount of intervention requiring 1 or 2 anti-vascular endothelial growth factor injections only. Also, the rate of PPV at 2 years (27.9%, n = 31) suggests that most patients may be managed nonsurgically.
| S-EPMC5376507 | biostudies-literature
Project description:Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs.
| S-EPMC4974503 | biostudies-literature
Project description:Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.
| S-EPMC10157735 | biostudies-literature
Project description:The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.
| S-EPMC9637204 | biostudies-literature