Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model

Gore, Ariel; Horwitz, Vered; Cohen, Maayan; Gutman, Hila; Cohen, Liron; Gez, Rellie; Kadar, Tamar; Dachir, Shlomit

doi:10.1016/j.exer.2018.03.010

Cited by 17 publications

(18 citation statements)

References 67 publications

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“…In previous studies of mustard‐induced ocular complications, increased VEGF‐A signaling is strongly associated with the development of corneal neovascularization 40–42 . Furthermore, treatment with anti‐VEGF therapy for mustard‐induced corneal injury significantly reduced corneal neovascularization 43,44 . Hence, VEGF‐A signaling can promote abnormal vascular remodeling in corneas exposed to mustard vapor.…”

Section: Discussionmentioning

confidence: 91%

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Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure

McGraw

Kim

White

et al. 2020

Annals of the New York Academy of Sciences

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Nitrogen mustard (NM) is a highly toxic alkylating agent. Inhalation exposure can cause acute and chronic lung injury. This study's aims were to develop an in vitro coculture model of mustard-induced airway injury and to identify growth factors contributing to airway pathology. Primary human bronchial epithelial cells cultured with pulmonary endothelial cells were exposed to NM (25, 50, 100, 250, or 500 µM) or PBS (control) for 1 hour. Lactate dehydrogenase (LDH) and transepithelial electrical resistance (TEER) were measured before and 24 h after NM exposure. Fixed cultures were stained for hematoxylin and eosin or live/dead staining. Culture media were analyzed for 11 growth factors. A 1-h vapor exposure to greater than or equal to 50 µM NM increased supernatant LDH, decreased TEER, and caused airway epithelial cell detachment. Endothelial cell death occurred at 500 µM NM. Vascular endothelial growth factor A (VEGF-A) and placental growth factor (PlGF) expression increased in 500 µM NM−exposed cultures compared with PBS-exposed control cultures. NM vapor exposure causes differential cytotoxicity to airway epithelial and endothelial injury in culture. Increased VEGF-A and PlGF expression occurred acutely in airway cocultures. Future studies are required to validate the role of VEGF signaling in mustardinduced airway pathology.

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Section: Discussionmentioning

confidence: 91%

“…[40][41][42] Furthermore, treatment with anti-VEGF therapy for mustard-induced corneal injury significantly reduced corneal neovascularization. 43,44 Hence, VEGF-A signaling can promote abnormal vascular remodeling in corneas exposed to mustard vapor.…”

Section: Discussionmentioning

confidence: 99%

Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure

McGraw

Kim

White

et al. 2020

Annals of the New York Academy of Sciences

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“…Previously, we showed that multiple bevacizumab treatments reduced existing corneal NV, although this effect was partial and temporary [17] , [23] . The reduced effect of antiangiogenic treatments, such as bevacizumab, pegaptanib or ranibizumab, can be explained by their VEGF-A specificity [38] , [8] .…”

Section: Introductionmentioning

confidence: 94%

“…Initially, exposure to SM causes severe ocular inflammation, erosions, endothelial cell density reduction, degeneration of corneal innervation and loss of conjunctival goblet cells. This can resolve and is followed by a delayed or long-term phase in parts of the eye, leading to chronic inflammation, opacity, corneal neovascularization (NV) and epithelial defects [17] , [18] , [20] , [26] . This severe insult may eventually lead to irreversible corneal impairment [27] , [9] .…”

Section: Introductionmentioning

confidence: 99%

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model

et al. 2023

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“…Anterior segment toxicities and efficacies of ziv-aflibercept and bevacizumab were assessed in a New Zealand White rabbit model of ocular chemical insult (exposure to sulphur mustard) (Gore et al 2018). Treatment groups received single subconjunctival injections of ziv-aflibercept (2 mg) or twice weekly subconjunctival bevacizumab (5 mg) for 3 weeks, with nontreated exposed eyes serving as controls.…”

Section: Animal and Preclinical Studiesmentioning

confidence: 99%

Ziv‐aflibercept: A cost‐effective, off‐label, highly potent antagonist of vascular endothelial growth factor

Mansour

Stewart

Farah

et al. 2019

Acta Ophthalmologica

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Ziv-aflibercept (Zaltrap â ), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea â ), thus making it an attractive option for the off-label treatment of chorioretinal vascular conditions. Ziv-aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv-aflibercept an attractive anti-VEGF treatment option, especially in low-and middle-income countries where its popularity is increasing.

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Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model

Cited by 17 publications

References 67 publications

Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure

Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model

Ziv‐aflibercept: A cost‐effective, off‐label, highly potent antagonist of vascular endothelial growth factor

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