Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema.
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ABSTRACT:
SUBMITTER: Moradi A
PROVIDER: S-EPMC3874490 | biostudies-other | 2013 Dec
REPOSITORIES: biostudies-other
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Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema.
Moradi Ahmadreza A Sepah Yasir Jamal YJ Sadiq Mohammad Ali MA Nasir Humzah H Kherani Salima S Sophie Raafay R Do Diana V DV Nguyen Quan Dong QD
World journal of diabetes 20131201 6
Diabetic retinopathy (DR) is the most common cause of visual loss among working age individuals. Diabetic macular edema (DME) is an important complication of DR that affects around one third of the patients with DR. Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor (VEGF) antagonists. The index review discusses aflibercept (EYLEA(®)-Regeneron Pharmaceuticals, Inc., Tar ...[more]
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Project description:Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients.
| S-EPMC3855829 | biostudies-literature
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.
| S-EPMC6568257 | biostudies-literature
Project description:BackgroundThe relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.MethodsAt 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year.ResultsFrom baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56).ConclusionsIntravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).
| S-EPMC4422053 | biostudies-literature
Project description:PurposeTo determine the effect of anti-vascular endothelial growth factor (VEGF) therapy on choroidal thickness in eyes with diabetic macular edema (DME).DesignA retrospective, cohort analysis of 59 eyes from 59 patients with DME without prior anti-VEGF therapy.MethodsChoroidal thickness was measured using semiautomated segmentation of enhanced depth imaging optical coherence tomography images at 0.5-mm intervals from 2.5 mm nasal to 2.5 mm temporal to the fovea. Changes in choroidal thickness with and without anti-VEGF treatment over 6 months were compared. Best-corrected visual acuity and central foveal thickness were analyzed to evaluate the association of choroidal thickness with functional and anatomic outcomes.ResultsOf the 59 eyes with DME, 26 eyes were observed without treatment, whereas 33 underwent intravitreal anti-VEGF therapy (mean number of injections, 2.73) over 6 months. In untreated eyes, there was no significant change in best-corrected visual acuity (P = .098), central foveal thickness (P = .472), or choroidal thickness at all measurements along the macula (P = .057 at the fovea). In eyes treated with anti-VEGF injections, choroidal thickness decreased significantly at the fovea (246.6 to 224.8 μm; P < .001) and at 0.5 mm nasal (240.9 to 221.9 μm; P = .002) and 0.5 mm temporal (249.3 to 224.8 μm; P = .011) to the fovea. The decrease in subfoveal choroidal thickness after anti-VEGF treatment was not associated with the cumulative number of anti-VEGF injections (R(2) = 0.031; P = .327) or to changes in best-corrected visual acuity (R(2) = 0.017; P = .470) or central foveal thickness (R(2) = 0.040; P = .263).ConclusionsCentral choroidal thickness decreases after anti-VEGF therapy for DME after 6 months, but may not be associated with functional or anatomic outcomes in eyes with DME.
| S-EPMC4443902 | biostudies-literature
Project description:Background: Antiangiogenic therapy with anti-vascular endothelial growth factor (VEGF) is commonly used to treat diabetic macular edema (DME), which can reduce edema, improve vision, and prevent further visual loss. There is little head-to-head trial data to guide the selection of an individual VEGF inhibitor. Therefore, we aimed to investigate the efficacy and safety of anti-VEGF for patients with DME and to assess the differences between clinically relevant options by using network meta-analysis (NMA). Methods: MEDLINE, Embase, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Wanfang, China National Knowledge Infrastructure, and VIP databases were searched for published randomized controlled trials (RCTs) from their inception to November 2020. We included RCTs of anti-VEGF drugs (intravitreal aflibercept (IVT-AFL), intravitreal ranibizumab (IVR), and intravitreal conbercept (IVC)) treating adult patients who were diagnosed with DME, regardless of stage or duration of the disease. We estimated summary odds ratios (ORs) and mean differences (MDs) with 95% credible intervals (CrIs) using a Bayesian NMA. This study's registration number is CRD42021259335. Results: We identified 43 RCTs comprising 8,234 patients. Beneficial effects were observed in patients who used IVT-AFL compared with those who used other anti-VEGF therapies at 1-year follow-up on corrected visual acuity (BCVA) improvements (all patients: versus IVR: MD 2.83, 95% CrIs 1.64, 4.01, versus IVC: MD 2.41, 95% CrIs -0.52, 5.32; patients with worse baseline visual acuity (VA): versus IVR: MD 3.39, 95% CrIs 1.89, 4.9, versus IVC: MD 3.49, 95% CrIs 0.49, 6.44) and the proportion of patients with a gain of at least 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (all patients: versus IVR: OR 1.55, 95% CrIs 1.11, 2.17, versus IVC: OR 2.78, 95% CrIs 1.23, 6.04; patients with worse baseline VA: versus IVR: OR 2.05, 95% CrIs 1.18, 3.58, versus IVC: OR 2.85, 95% CrIs 1.24, 6.41). The effect of improvement in BCVA was identified for IVT-AFL compared to intravitreal bevacizumab. Based on the surface under the cumulative ranking curve (SUCRA), IVT-AFL had the highest probability of being the most effective option (99.9% and 99.5% in terms of the two primary outcomes, respectively). At the 2-year follow-up, numerical differences were identified favoring IVT-AFL; however, they did not reach statistical significance when comparing IVT-AFL to IVR. In the analysis of adverse events, IVT-AFL showed a lower risk of incidence of ocular adverse events compared to other anti-VEGF therapies at 1-year follow-up (versus IVR: OR 0.45, 95% CrIs 0.28, 0.7; versus IVC: OR 0.36, 95% CrIs 0.21, 0.63). Conclusion: IVT-AFL resulted in greater beneficial effects on BCVA and a higher proportion of patients with a gain of at least 15 ETDRS letters compared to IVR or IVC one year after treatment (especially in DME patients with worse baseline VA). In addition, fewer ocular adverse events occurred in the IVT-AFL group compared to the IVR or IVC groups. After two years, there was insufficient evidence to identify which anti-VEGF has superior efficacy or safety. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021259335, CRD42021259335.
| S-EPMC9260109 | biostudies-literature
Project description:Is to show the 3-month efficacy and safety of treatment diabetic macular edema treated with intravitreal ziv-aflibercept as studies have shown that Ziv-aflibercept does not cause retinal pigment epithelial toxicity and to study it cost effectiveness.Ten eyes in eight patients diagnosed with central diabetic macular edema were enrolled for three consecutive intravitreal injection of ziv-aflibercept 1.25 mg every 4 weeks, a complete exam including BCVA and CRT at baseline and 12 weeks with evaluation of ocular and systemic complications.Improvement of best corrected visual acuity was clinically significant from baseline LogMAR 0.77 and 0.35 at 12 weeks and statistically significant (P<0.05) along with reduction of central retinal thickness from 562,4 μm and 317.7 μm at 12 weeks follow up (P<0.05) with no signs of ocular nor systemic complications.Ziv aflibercept is a safe and effective in diabetic macular edema treatment for 12 weeks follow up with cost effectiveness especially in countries where aflibercept is not available.
| S-EPMC4917211 | biostudies-other
Project description:PurposeTo investigate the safety and efficacy of micropulse (MP) macular laser in combination with intravitreal aflibercept for the treatment of center-involved diabetic macular edema (CI-DME).MethodsA single-blind prospective randomized controlled pilot trial was performed. In total, 30 eyes of 30 patients with CI-DME and best corrected visual acuity (BCVA) between, and including, 20/30 and 20/400 were enrolled. Enrolled eyes were randomized to 2 groups. Group 1 received intravitreal aflibercept injections (IVT-AFL) with sham laser. Group 2 received IVT-AFL with MP laser. Both groups were followed every 4 weeks for 48 weeks and retreatment was performed on pro re nata basis according to preset criteria. The main outcome measure was the average number of intravitreal injections for each group at 48 weeks. Secondary outcome measures included changes in BCVA and central macular thickness (CMT) at 24 and 48 weeks.ResultsThe average number of intravitreal injections at 48 weeks was similar between the groups (8.5±3.3 in Group 1 vs 7.9±3.6 in Group 2, p=0.61). After 48 weeks, both groups demonstrated an improvement in BCVA and CMT. However, the difference in improvement between the groups was not statistically significant (p=0.18 for BCVA and p=0.57 for CMT).ConclusionIntravitreal injections of aflibercept led to improvements in BCVA and CMT at 24 and 48 weeks. Addition of MP laser to eyes in group 2 did not offer additional benefit in reducing treatment burden or improving CMT. Eyes that received MP laser showed a numerically greater improvement in BCVA, although this was not statistically significant.Clinicaltrialsgov identifierNCT03143192 March 8, 2017.
| S-EPMC9005121 | biostudies-literature
Project description:PurposeTo evaluate retinal hemodynamic responses to anti-vascular endothelial growth factor (VEGF) injection in eyes with diabetic macular edema using optical coherence tomography angiography (OCTA). We performed a comparison of two different thresholding methods to identify the most accurate for studying the vessel density (VD) in diabetic macular edema eyes.MethodsThe study prospectively included 26 eyes of 22 subjects (aged 60.2 ± 13.7 years) who underwent OCTA scan before and after anti-VEGF injection (mean interval between OCTA = 31.1 ± 17.3 days). We analyzed adjusted flow index, VD, and Skeletonized vessel length density in the parafoveal area (3-mm annulus with a 1-mm inner circle), along with full-thickness fovea avascular zone area and central foveal thickness (CFT). Using averaged scans VD as the ground truth, we compared two different algorithms for VD at the different plexuses. Longitudinal changes were assessed using a generalized linear model correcting for central foveal thickness and Q-score.ResultsWe found significantly decreased adjusted flow index in the DCP layer (P = 0.010) at the follow-up. Furthermore, foveal avascular zone (P < 0.001) and central foveal thickness (P = 0.003) showed significant decrease on follow-up compared with baseline. Comparing the thresholding algorithms showed that vessel length density-based thresholding was more accurate for quantifying the DCP VD.ConclusionsThe adjusted flow index decreased significantly in the DCP layer on follow-up OCTA scan, suggesting vascular flow disruption and decreased deep retinal perfusion after anti-VEGF injection. Our results also highlight the fact that the choice of thresholding method is particularly critical for DCP quantification in eyes with diabetic macular edema.Translational relevanceFindings confirmed impaired deep retinal capillary flow after anti-VEGF injection.
| S-EPMC9547366 | biostudies-literature
Project description:ImportanceThe DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important.ObjectiveTo evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment.Design, setting, and participantsThis economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019.InterventionsAflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response.Main outcomes and measuresBetween February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs.ResultsThis study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, -0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more.Conclusions and relevanceVariability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.
| S-EPMC9896372 | biostudies-literature
Project description:AimTo evaluate the ef?cacy of switching from bevacizumab to ranibizumab or aflibercept in eyes with diabetic macular edema (DME) unresponsive to bevacizumab.MethodsSingle-center retrospective comparative study of patients with DME unresponsive to intravitreal bevacizumab that was switched to ranibizumab or aflibercept. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were analysed prior to and 4 months after the switch. Ocular coherence tomography (OCT) biomarkers were also analysed.ResultsFifty-six eyes from 40 patients were included in the study, 33 eyes switched to ranibizumab and 23 to aflibercept. A significant median CFT decrease was observed in both groups (p<0.001), with no between-group differences. BCVA gain was only significant in the ranibizumab group (p<0.001). None of the pre-baseline or baseline parameters were associated with the response to ranibizumab or aflibercept.ConclusionIn persistent DME unresponsive to bevacizumab, both anatomical and functional improvements were observed with ranibizumab whereas aflibercept only showed an anatomical improvement. Clinicaltrials.gov NCT04018833.
| S-EPMC7837538 | biostudies-literature