Anti-VEGF therapy: comparison of current and future agents

Pieramici, Dante J.; Rabena, Melvin D.

doi:10.1038/eye.2008.88

Cited by 92 publications

(72 citation statements)

References 22 publications

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“…1 Examples of these drugs include Avastin (Roche Ltd., Basel, Switzerland), Lucentis (Roche Ltd., Basel, Switzerland), and Eylea (Regeneron Pharmaceuticals, Inc., New York, NY). However, because of the high clearance rate of drugs in the vitreous and the chronic nature of these diseases, monthly intravitreal injection is required for a satisfactory treatment, 2,3 which significantly increases the risk of complications.…”

Section: Introductionmentioning

confidence: 99%

Injectable Chemically Crosslinked Hydrogel for the Controlled Release of Bevacizumab in Vitreous: A 6-Month In Vivo Study

Lau

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: To evaluate the biocompatibility and 6-month in vivo release of bevacizumab from a hyaluronic acid/dextran-based in situ hydrogel after intravitreal injection in rabbit eye. Methods:The in situ hydrogel was formed by the catalyst-free chemical crosslinking between vinylsulfone functionalized hyaluronic acid (HA-VS) and thiolated dextran (Dex-SH) at physiological condition. The pH 7.4 buffered mixture containing HA-VS, Dex-SH, and bevacizumab were injected into the vitreous of rabbit eyes by a 30-G needle. The biocompatibility was evaluated by intraocular pressure measurement, binocular indirect ophthalmoscope (BIO), full-field electroretinogram (ERG), and histology. The concentrations of both total and active bevacizumab in rabbit vitreous were determined by enzyme-linked immunosorbent assay. The concentration of bevacizumab in rabbit vitreous after bolus injection was simulated by onecompartment first order elimination model. Results:A transparent gel was seen in the vitreous after injection. BIO images, ERG, and histology showed that the gel does not induce hemorrhage, retinal detachment, inflammation, or other gross pathological changes in rabbit eyes after injection. While the bolus intravitreal injected bevacizumab follows the first order elimination kinetics in rabbit eye, the in situ gel formation was able to prolong the retention of bevacizumab in rabbit eye at therapeutic relevant concentration for at least 6 months. The concentration of bevacizumab 6 months after injection was about 10 7 times higher than bolus injection. Conclusions:The new in situ hydrogel formulation of bevacizumab was biocompatible and able to prolong the retention of drug in rabbit eyes in vivo at therapeutic relevant concentration for at least 6 months.Translational Relevance: Although proven to be effective, monthly intravitreal injection of bevacizumab or other protein drugs may cause various complications. Extending the residence time of protein therapeutics in the eye can reduce the injection frequency, its associated complications, and treatment cost, which will be beneficial to both the patients and doctors. In this study, we showed that the in situ hydrogel-based controlled release system is a feasible option to tackle this problem.

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Section: Introductionmentioning

confidence: 99%

Injectable Chemically Crosslinked Hydrogel for the Controlled Release of Bevacizumab in Vitreous: A 6-Month In Vivo Study

Lau

et al. 2015

Trans. Vis. Sci. Tech.

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“…The most established approach for limiting path ological angiogenesis involves blockade of the vascular endothelial growth factor (VEGF) pathway (3)(4)(5); however, several studies have shown that VEGF blockade damages healthy vessels and results in toxic side effects (6,7) and that interrupting the VEGF blockade induces rapid vascular regrowth in tumors (8). Clinical trials involving patients with neovascular age related macular degeneration have shown that VEGF blockade has limited effectiveness in some patients (5). Therefore, several groups have ex plored other targets that could potentially be combined with VEGF blockade (9)(10)(11).…”

mentioning

confidence: 99%

M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis

Kubota¹,

Takubo²,

Shimizu³

et al. 2009

J Cell Biol

130

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“…This result may be attributable to the findings that both full-length antibody (bevacizumab) and Fab fragment (ranibizumab) drugs are able to penetrate into all retinal layers, reach the choroid, and accumulate in the wall of the choroidal vessel (26)(27)(28) . As VEGF functions by inducing vessel dilation and increasing ocular blood flow, which is mediated by increased nitric oxide production (29) , VEGF inhibition by these drugs may cause constriction of the choroidal vessels.…”

Section: Discussionmentioning

confidence: 97%

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

Kniggendorf¹,

Novais²,

Kniggendorf³

et al. 2016

Arquivos Brasileiros De Oftalmologia

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Approved by the following research ethics committee: UNIFESP (#1.093.853). ABSTRACTPurpose: To evaluate choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT) imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). Methods: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab) in a pro re nata (PRN) regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. Results: Thirty-nine eyes (15 females, 24 males) from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years). Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5). Mean nasal, subfoveal, and temporal choroidal thickness (CT) measurements at baseline were 234.10 ± 8.63 μm, 246.89 ± 8.94 μm, and 238.12 ± 8.20 μm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 μm, 215.66 ± 8.29 μm, and 212.43 ± 8.14 μm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327). Conclusions: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation.

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Anti-VEGF therapy: comparison of current and future agents

Cited by 92 publications

References 22 publications

Injectable Chemically Crosslinked Hydrogel for the Controlled Release of Bevacizumab in Vitreous: A 6-Month In Vivo Study

Injectable Chemically Crosslinked Hydrogel for the Controlled Release of Bevacizumab in Vitreous: A 6-Month In Vivo Study

M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

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