Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization

Papathanassiou, Miltiadis; Theodoropoulou, Sofia; Analitis, Antonis; Τζώνου, Αναστασία; Theodossiadis, Panagiotis

doi:10.1097/ico.0b013e3182542613

Cited by 46 publications

(43 citation statements)

References 60 publications

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“…[17][18][19][20] It is hypothesized to enable a more persistent and longer lasting VEGF blockade, and a number of studies have shown that intravitreal aflibercept is more effective than the conventional anti-VEGF agents. [17][18][19][20] If intravitreal aflibercept could penetrate the retinal surface and the entire retinal thickness to induce regression of corneal NV, [16][17][18][19] topical aflibercept administration would probably permeate and penetrate the ocular surface to induce regression of corneal NV and modulate the neovascular process.…”

Section: Discussionmentioning

confidence: 99%

“…1,4,15,16 As VEGF plays a crucial role in the creation of corneal NV, its treatment with anti-VEGF antibodies seems to be the right method, and it has been proven in numerous studies using subconjunctival and topical anti-VEGF, such as bevacizumab and ranibizumab. 11,[18][19][20] A novel anti-VEGF, named aflibercept, has gained popularity since its approval from the Food and Drug Administration in 2011.…”

Section: Discussionmentioning

confidence: 99%

“…Aflibercept, a VEGF antagonist, is a soluble fusion protein combining the truncated form of the fms-like tyrosine kinase (Flt), the kinase insert domain-containing receptor (KDR), and the Fc portion of human immunoglobulin G. 16 Aflibercept is designated to sequester and antagonize the VEGF and to prevent blood vessel formation. Several studies have also reported that aflibercept has antiangiogenic properties.…”

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confidence: 99%

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Inhibitory Effect of Topical Aflibercept on Corneal Neovascularization in Rabbits

Park

Chung

2015

Cornea

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibitory Effect of Topical Aflibercept on Corneal Neovascularization in Rabbits

Park

Chung

2015

Cornea

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“…VEGF-A blockade has recently been validated as an effective strategy for the inhibition of new blood vessel growth in cancer and ocular pathologies. Anti-VEGF therapy was indicated to be effective in the inhibition of corneal NV [4,5,6,7,8]. However, several studies have also shown that anti-VEGF therapy may not be effective in the treatment of established unwanted blood vessels, suggesting that these vessels may become less dependent on VEGF-A for survival.…”

Section: Introductionmentioning

confidence: 99%

KH902, a Recombinant Human VEGF Receptor Fusion Protein, Reduced the Level of Placental Growth Factor in Alkali Burn Induced-Corneal Neovascularization

Zhou¹,

Bai²,

Zhao³

et al. 2013

Ophthalmic Res

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Aims: To investigate the expression of placental growth factor (PIGF) in alkali burn-induced murine corneal neovascularization (NV); to evaluate the effects of KH902, a vascular endothelial growth factor receptor decoy, on prevention and regression of new vessels growths in the cornea; and to determine the influence of KH902 on the levels of vascular endothelial growth factor (VEGF) and PIGF in alkali burn-induced corneal NV. Methods: Mouse corneal NV was induced by alkali burn. The expression of PIGF was detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate the effects of KH902, corneal NV was observed and photographed every 3 days for a total of 28 days after the alkali burn. The percentage of NV area was measured and compared with that of the control group. The VEGF and PIGF levels in the cornea were evaluated by enzyme linked immunosorbent assay (ELISA). Results: PIGF was expressed during the alkali burn-induced corneal neovascularization. On day 3 (D3), day 6 (D6) and day 9 (D9) after chemical cauterization, the length of the longest new vessel and the neovascularization areas in the KH902-treated groups were significantly smaller than those of the PBS-treated group (p < 0.05). The areas of established corneal NV of the KH902-treated groups regressed with time, but the control groups showed no natural regression. The VEGF and PIGF levels of the cornea in the treated groups were significantly decreased compared to those of the control group (p < 0.05). Conclusions: PIGF may be involved in alkali burn-induced corneal NV. KH902 significantly inhibited new vessel growth and promoted the regression of established vessels in a mouse model of corneal NV, and it also reduced the levels of VEGF and PIGF in the cornea.

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“…7 Several clinical investigations have shown the efficacy of ranibizumab in the treatment of corneal neovascularization. [8][9][10] Aflibercept is a newly developed anti-VEGF agent that combines a truncated form of fms-like tyrosine kinase (Flt), kinase insert domaincontaining receptor (KDR), and the Fc portion of human immunoglobulin G. 11 Studies have reported potent antiangiogenic effects of aflibercept after topical or subconjunctival administration. [12][13][14] The objective of this study was to compare the effects of 3 anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept) on corneal epithelial cell viability and wound healing using human corneal epithelial cells (HCECs).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Bevacizumab, Ranibizumab, and Aflibercept on the Viability and Wound Healing of Corneal Epithelial Cells

Kang

Choi

Rho

2016

Journal of Ocular Pharmacology and Therapeutics

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Purpose: This study compared the effects of 3 antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) on corneal epithelial cell viability and wound healing using human corneal epithelial cells (HCECs). Methods: To determine the cytotoxic effects of anti-VEGF agents on HCECs, HCEC viability was determined at various concentrations of these agents. An in vitro migration assay was used to investigate the migration of HCECs treated with 3 anti-VEGF agents. The protein level of extracellular signal-regulated kinase was used to evaluate the effect of anti-VEGF treatment on cell proliferation. The protein levels of p38 mitogen-activated protein kinase (MAPK) were analyzed by Western blotting to investigate cell migration. Results: After 24 or 48 h of exposure, aflibercept treatment showed no apparent effect on cell viability; however, bevacizumab and ranibizumab treatment decreased cell viability at high concentrations (1 and 2 mg/ mL). A migration assay showed that HCEC migration was different among the 3 anti-VEGF treatment groups. Bevacizumab significantly delayed HCEC migration. Western blotting showed that bevacizumab treatment decreased the expression levels of phosphorylated p38 MAPK. Conclusions: Bevacizumab, the most widely used and investigated anti-VEGF agent, decreased epithelial cell migration and viability. Anti-VEGF agents other than bevacizumab might therefore be better for treating corneal neovascularization complicated with epithelial defects.

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Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization

Abstract: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

Cited by 46 publications

References 60 publications

Inhibitory Effect of Topical Aflibercept on Corneal Neovascularization in Rabbits

Inhibitory Effect of Topical Aflibercept on Corneal Neovascularization in Rabbits

KH902, a Recombinant Human VEGF Receptor Fusion Protein, Reduced the Level of Placental Growth Factor in Alkali Burn Induced-Corneal Neovascularization

Differential Effects of Bevacizumab, Ranibizumab, and Aflibercept on the Viability and Wound Healing of Corneal Epithelial Cells

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