Aflibercept for neovascular age-related macular degeneration.
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ABSTRACT:
SUBMITTER: Sarwar S
PROVIDER: S-EPMC5030844 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Aflibercept for neovascular age-related macular degeneration.
Sarwar Salman S Clearfield Elizabeth E Soliman Mohamed Kamel MK Sadiq Mohammad Ali MA Baldwin Andrew J AJ Hanout Mostafa M Agarwal Aniruddha A Sepah Yasir J YJ Do Diana V DV Nguyen Quan Dong QD
The Cochrane database of systematic reviews 20160208
<h4>Background</h4>Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and afliberce ...[more]
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Project description:PurposeTo evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).Study designRetrospective, interventional case series.MethodsWe retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined.ResultsBCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss.ConclusionsIntravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.
| S-EPMC11420316 | biostudies-literature
Project description:BackgroundNeovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Low-grade inflammation is well-known as one of the pathogenic mechanisms in nAMD. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, although macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. Here, we show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment.MethodsTwenty-eight nAMD patients received three consecutive monthly IVA, followed by a pro re nata regimen for 2 years. AH specimens were collected before first IVA (pre-IVA) and before third IVA (post-IVA). AH cytokine levels, visual acuity (VA), and central retinal thickness (CRT) were measured.ResultsTwo-year incidence of MA was 21.4%. In nAMD eyes developing MA [MA (+) group], pre-IVA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1β, VEGF and post-IVA level of MCP-1 were higher than those in nAMD eyes without MA [MA (-) group]. In hierarchical cluster analysis, pre-IVA MCP-1 and VEGF were grouped into the same subcluster, as were post-IVA MCP-1 and CRT. In principal component analysis, principal component loading (PCL) of pre-IVA interferon-γ-inducible protein 10 (IP-10) was 0.61, but PCL of post-IVA IP-10 decreased to -0.09. In receiver operating characteristic analysis and Kaplan-Meier curves, pre-IVA MCP-1, MIP-1β, and VEGF and post-IVA interleukin-6, MCP-1, and MIP-1β were detected as predictive factors for MA incidence. In 2-year clinical course, changes of VA in groups with high levels of pre-IVA MIP-1β (over 39.9 pg/ml) and VEGF (over 150.4 pg/ml) were comparable to those in MA (+) group.ConclusionSubstantial loss of IP-10 effects and persistent inflammation contribute to incidence of MA, and screening of AH cytokine levels could be a useful method to predict MA incidence in nAMD eyes under anti-VEGF therapy.
| S-EPMC8548619 | biostudies-literature
Project description:PurposeTo evaluate quantitative morphological changes in macular neovascularisation (MNV) network after aflibercept therapy in neovascular age-related macular degeneration (nAMD) patients.MethodsConsecutive treatment-naïve patients with optical coherence tomography (OCT) angiography confirmed MNV due to nAMD who completed a loading phase of intravitreal aflibercept injections. A quantitative analysis of the vascular network remodelling was performed using a computational software (Angiotool).ResultsA total of 53 eyes of 52 patients were included in the analysis. The total MNV area decreased significantly after three aflibercept injections (p = 0.003). Total vessel area and vessel density decreased respectively of 20% and 12% at V3 (p < 0.001 in both cases). Other parameters that reduced significantly were total vessel length, average vessel length and density of vascular junctions (p = 0.018, p = 0.002, and p = 0.044, respectively). The number of vascular endpoints (p = 0.001) and lacunarity (p = 0.011) increased significantly, whilst the number of vascular junctions did not vary significantly (p = 0.068). Changes in vascular metrics were predominantly driven by MNV type 1 and 2. No clear relationship was observed between any of the vascular metrics and the macular fluid status.ConclusionAlthough objective quantification of vascular parameters showed a significant remodelling of the MNV post-loading phase of aflibercept in type 1 and 2 MNV subtypes, none of the quantified vascular metrics correlated to the macular fluid response. These findings highlight a dissociation of anti-angiogenic and anti-permeability properties of aflibercept therapy during the loading phase.
| S-EPMC10686403 | biostudies-literature
Project description:Age-related macular degeneration (AMD) is a progressive, chronic disease of the central area of the retina, which, if untreated, leads to blindness. This study aimed to compare the effectiveness of therapy using anti-VEGF drugs, namely brolucizumab and aflibercept, in patients with neovascular AMD (nAMD) during a monitoring period lasting around 20 weeks. The analysis consisted of 40 patients diagnosed with neovascular age-related macular degeneration, with 20 patients receiving aflibercept (Eylea, Bayer) at a dose of 2 mg/50 µL into the vitreous chamber at the following intervals-3 doses, 4 weeks apart, followed by a fourth dose after 8 weeks. The remaining 20 patients received brolucizumab (Beovu, Novartis) at a dose of 6 mg/50 µL, administered in the following schedule-3 initial doses, 4 weeks apart, with the administration of a fourth dose decided for each patient individually by the doctor, depending on disease activity, assessed through imaging tests. To evaluate treatment effectiveness, the following measurements were used: 'read distance and near visual acuity' for each eye separately using the Snellen chart; and non-invasive retinal imaging techniques-optical coherence tomography (OCT) and OCT angiography (OCTA). In patients treated using brolucizumab, during the observation period, statistically significant differences were found in the following parameters: flow area (p = 0.0277); select area (p = 0.0277); FOVEA (p = 0.0073); visus (p = 0.0064). In brolucizumab-treated patients, changes in OCT and OCTA, indicating an improvement, were already visible after the first injection of the drug, whereas in the aflibercept-treated group, changes were only visible after the fourth injection. We found a higher effectiveness of brolucizumab therapy compared to aflibercept in patients with nAMD during an observations period lasting 20 weeks. Our observations are significant, although they require further research.
| S-EPMC8872595 | biostudies-literature
Project description:Intravitreal injections of anti-vascular endothelial growth factor agents such as ranibizumab and aflibercept are the first-line treatment for neovascular age-related macular degeneration (AMD). However, data about long-term outcome in real-world clinical practice is scarce. We recruited 98 AMD patients and investigated four-year visual outcome. During the four years, 25 patients dropped out. The survivors received 7.0 ± 0.1 injections during the first year and 8.0 ± 7.4 injections in the following three years. The logarithm of minimum angle of resolution (logMAR) at baseline, year one, and year four was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes (typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation; P = 0.513) Among the investigated factors, the presence of external limiting membrane (ELM), the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year four (coefficient beta = -0.388, 0.201, and -0.001; P = 7.34 × 10-6; 0.01, and 0.028, respectively). In the present study, vision was retained at baseline level after the four-year treatment with aflibercept. The status of ELM, vitreoretinal adhesion, and choroidal thickness were predictive factors for final vision.
| S-EPMC6403223 | biostudies-literature
Project description:Wet age-related macular degeneration (AMD) is the most common reason for vision loss in the United States. Many treatments, such as laser therapy and photodynamic therapies, have been used but their efficacy is limited. Emerging anti-vascular endothelial growth factor (VEGF) therapies are now considered the standard of care. Anti-VEGF agents inhibit angiogenesis in the eye by suppressing abnormal blood vessel growth, leading to vision improvement. Ranibizumab and bevacizumab are two examples of anti-VEGF drugs that have been approved; both showed promise based on the visual acuity scale. Aflibercept, another new therapy known to trap VEGF and inhibit multiple growth factors, is promising not only because it can be taken bimonthly based on year 1 of the VIEW trials, but it can also be extended, as demonstrated in year 2 of the VIEW trials. Based on a cost-effect analysis, aflibercept is comparable to other leading therapies. This is a review of relevant clinical trials that have proven the non-inferiority and safety of aflibercept compared to the standard of care and its unique role in the current management of wet AMD.
| S-EPMC3595183 | biostudies-other
Project description:BACKGROUNDStudies assessing the efficacy of therapies for neovascular age-related macular degeneration (nvAMD) have demonstrated that aflibercept may have a longer treatment interval than its less-expensive alternative, bevacizumab. However, whether this benefit justifies the additional cost of aflibercept remains under debate. We have recently reported that a treat-and-extend-pause/monitor approach can be used to successfully wean 31% of patients with nvAMD off anti-VEGF therapy. Here, we examined whether the choice of therapy influences the outcomes of this approach.METHODSIn this retrospective analysis, 122 eyes of 106 patients with nvAMD underwent 3 consecutive monthly injections with either aflibercept (n = 70) or bevacizumab (n = 52), followed by a treat-and-extend protocol, in which the decision to extend the interval between treatments was based on visual acuity, clinical exam, and the presence or absence of fluid on optical coherence tomography. Eyes that remained stable 12 weeks from their prior treatment were given a 6-week trial of holding further treatment, followed by quarterly monitoring. Treatment was resumed for worsening vision, clinical exam, or optical coherence tomography findings.RESULTSAt the end of 1 year, eyes receiving bevacizumab had similar vision but required more injections (8.7 ± 0.3 treatments vs. 7.2 ± 0.3 treatments) compared with eyes receiving aflibercept. However, eyes treated with aflibercept were almost 3 times more likely to be weaned off treatment (43% vs. 15%) compared with eyes treated with bevacizumab at the end of 1 year.CONCLUSIONThese observations expose an advantage of aflibercept over bevacizumab and have important clinical implications for the selection of therapy for patients with nvAMD.FUNDINGThis work was supported by the National Eye Institute, NIH grants R01EY029750 and R01EY025705, Research to Prevent Blindness, the Alcon Young Investigator Award from the Alcon Research Institute, and the Branna and Irving Sisenwein Professorship in Ophthalmology.
| S-EPMC9843049 | biostudies-literature
Project description:The advent of biomacromolecules antagonizing vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). However, frequent intravitreal injections of these biomacromolecules impose an enormous burden on patients and create a massive workload for healthcare providers. This causes patients to abandon therapy, ultimately leading to progressive and irreversible vision loss. In order to address this unmet clinical need, a noninvasive treatment for nAMD is developed. An optimized cell-penetrating peptide derivative, bxyPenetratin (bxyWP), is used to non-covalently complex with the anti-VEGF protein aflibercept (AFL) via reversible hydrophobic interaction. The interaction is crucial for AFL delivery, neither impairing the affinity of AFL to pathological VEGF, nor being interfered by endogenous proteins in tear fluids. AFL/bxyWP eye drops exhibit prolonged retention on the eye and excellent absorption into the posterior ocular segment following topical administration, with significant drug distribution to the retina and choroid. In a laser-induced choroidal neovascularization model on cynomolgus monkeys, AFL/bxyWP eye drops efficiently reduce lesion size and leakage comparable to conventional intravitreal injection of AFL. These results suggest that AFL/bxyWP eye drops are feasible self-administered treatment for neovascular retinal diseases and potentially become a substitute for intravitreal injections.
| S-EPMC11923875 | biostudies-literature
Project description:BackgroundAnti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12 months of ranibizumab treatment in routine clinical practice in France.MethodsTITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12 months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ≥1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12 months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.ResultsWe analysed safety data (N = 217) and clinical outcomes from patients in the per-protocol population (n = 125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was + 1.5 letters (P = 0.105) and the mean CRT change was - 45.0 μm (P < 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P = 0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).ConclusionsSwitching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.Trial registrationClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.
| S-EPMC7890834 | biostudies-literature
Project description:PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.
| S-EPMC5518842 | biostudies-literature