Purpose: To determine intraocular pharmacokinetics of aflibercept and VEGF-A in patients with neovascular age-related macular degeneration (nAMD) during a treatment period of 6 months.
Methods: Seven nonvitrectomized patients diagnosed with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of aflibercept. Patients were treatment naïve at least for the last 2 months and received intravitreal injection of 2 mg aflibercept for the first time. Aqueous humor samples were obtained prior to each injection procedure during a 6-month period: three times monthly, then bimonthly. Over all 35 samples were analyzed with ELISA for unbound VEGF-A and a self-developed assay for unbound aflibercept.
Results: In all cases, wet AMD was inactive after IVI. Unbound aflibercept could be detected in all samples. Initial mean concentration of aflibercept was 305.4 ± 43.8 μg/mL and remained stable after the first injection with 0.8 ± 0.5 μg/mL. Initial mean level of unbound VEGF-A was 190.7 ± 26.9 pg/mL. A significant decrease of the concentration to 92.6 ± 10.2 pg/mL (P < 0.05, Wilcoxon rank sum test) after the first injection was observed. This level remained stable during further treatment.
Conclusions: Levels of unbound aflibercept and unbound VEGF-A remained stable after every month and every second month of IVI. The findings of these small case series support suggestions that treatment intervals with bimonthly IVI of aflibercept are sufficient due to a detectable remaining biologic active concentration of aflibercept.
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http://dx.doi.org/10.1167/iovs.15-16418 | DOI Listing |
Biomolecules
January 2025
Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
We developed ligandomics for the in vivo profiling of vascular ligands in mice, discovering secretogranin III (Scg3) as a novel angiogenic factor that selectively binds to retinal vessels of diabetic but not healthy mice. This discovery led to the development of anti-Scg3 therapy for ocular vasculopathies. However, in vivo ligandomics requires intracardial perfusion to remove unbound phage clones, limiting its use to vascular endothelial cells (ECs).
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
January 2025
School of Materials Science and Engineering, Henan Engineering Research Center of Design and Recycle for Advanced Electrochemical Energy Storage Materials, Henan Normal University, Xinxiang, Henan 453007, P. R.China; School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Henan Normal University, Xinxiang, Henan 453007, P. R. China. Electronic address:
The overexpression of vascular endothelial growth factor 165 (VEGF) in cancer cells plays a pivotal role in promoting tumor metastasis by facilitating their excessively rapid proliferation and division. Hence, the development of analytical methods possessing high sensitivity and resistance to interference is imperative for the detection of VEGF. Various types of aptasensors have been devised for VEGF detection; however, the performance of these biosensors can be influenced by non-target signals caused by conformational changes in unbound aptamers.
View Article and Find Full Text PDFBr J Clin Pharmacol
April 2024
EA4245 Transplantation, Immunologie, Inflammation, Tours University, Tours, France.
Aims: The exposure-response relationship of bevacizumab may be confounded by various factors, including baseline characteristics, time-dependent target engagement and recursive relationships between exposure and response, requiring effective mitigation. This study aimed to investigate the exposure-response relationships of bevacizumab in metastatic colorectal cancer (mCRC) patients while mitigating potential biases.
Methods: Bevacizumab pharmacokinetics was described using target-mediated drug disposition modelling.
Biomater Sci
December 2023
Department of Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago Christchurch, New Zealand.
Synthetic polymers, such as poly(vinyl alcohol) (PVA), are popular biomaterials for the fabrication of hydrogels for tissue engineering and regenerative medicine (TERM) applications, as they provide excellent control over the physico-chemical properties of the hydrogel. However, their bioinert nature is known to limit cell-biomaterial interactions by hindering cell infiltration, blood vessel recruitment and potentially limiting their integration with the host tissue. Efforts in the field have therefore focused on increasing the biofunctionality of synthetic hydrogels, without limiting the advantages associated with their tailorability and controlled release capacity.
View Article and Find Full Text PDFJ Biomater Appl
September 2023
Department of Orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
A major obstacle to bone tissue repair is the difficulty in establishing a rapid blood supply areas of bone defects. Vascular endothelial growth factor (VEGF)-infused tissue-engineered scaffolds offer a possible therapeutic option for these types of injuries. Their role is to accelerate angiogenesis and improve bone healing.
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