Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model

Sella, Ruti; Gal-Or, Orly; Livny, Eitan; Dachbash, Mor; Nisgav, Yael; Weinberger, Dov; Livnat, Tami; Bahar, Irit

doi:10.1016/j.exer.2016.03.021

Cited by 24 publications

(28 citation statements)

References 48 publications

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“…In this study, larger corneal burns (3 mm) were observed compared to those obtained in previous studies using sticks coated with silver and potassium nitrate 8,15 . Thus, we expected the corneal fractions containing vessels to be much larger than those reported in previous studies.…”

Section: ■ Discussionmentioning

confidence: 37%

“…The alkaline cauterization produced in corneas in this study leads to a timely inflammatory response 8,[11][12][13][14][15][16] , where the release of chemokines recruits leukocytes that produce angiogenic factors, such as the vascular endothelial growth factor, the fibroblast growth factor 2 and the tumor necrosis factor, among others. These growth factors attract endothelial cells, smooth muscle cells, fibroblasts, leukocytes, and platelets, triggering the process of neovascularization 26 .…”

Section: ■ Discussionmentioning

confidence: 99%

“…Interestingly, however, they were smaller. Sella et al 15 induced 2-mm burns and observed that the vascularized percentage of the corneal area was 42.6 ± 19.59% on the 7 th day after the procedure. Manzano et al 12 and Hepsen et al 11 induced cauterizations of 1.8 mm and 5 mm, and observed vascularization in 63.5% and 56.9% of the corneal areas, respectively.…”

Section: ■ Discussionmentioning

confidence: 99%

“…In the literature, corneal cauterization times with alkali using a combination of 75% silver and 25% potassium nitrate range from 8 to 60 seconds 8,[11][12][13][14][15][16] . The cauterizing instrument is usually a stick or filter paper, whose diameter ranges from 1.8 mm to 5 mm 8,[11][12][13][14][15][16] .…”

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Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

et al. 2017

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Purpose: To establish and compare protocols of alkaline cauterization for inducing corneal angiogenesis in murine models. Methods: Twenty-four adult Wistar rats were distributed into four groups (G1, G2, G3, and G4). The right eye cornea from each rat was cauterized using filter paper (3 mm), soaked in a solution of silver and potassium nitrates (3:1). Cauterization times were 10 (G1 and G4), or 20 seconds (G2 and G3). Cauterized corneas were washed with Ringer's lactate solution. The filter paper was either removed before washing (G1 and G2), or kept on the corneas (G3 and G4). Corneas were photographed at multiple time points (2, 4, 6, 8, 11, 13, and 15 days after the procedure), and neovascularization parameters were assayed. Results: Neovascularization was observed in 66% of G1 corneas, and 100% of G2, G3, and G4 corneas. On day 15, G1 corneas showed smaller vascularized areas (12.63 ± 12.59%) compared to those in the G3 (41.95 ± 17.32%) and G4 (33 ± 11.74%) (P < 0.05) groups. Conclusions: The silver and potassium nitrate solution effectively induced corneal angiogenesis. The G2, G3, and G4 protocols showed excellent reproducibility, and induced vascularization in 100% of corneas.

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Section: ■ Discussionmentioning

confidence: 37%

Section: ■ Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

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confidence: 99%

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Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

et al. 2017

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“…[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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Initial outcomes of mitomycin intravascular chemoembolization (MICE) for corneal neovascularization

Ouano¹

2022

Int Ophthalmol

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Purpose To report on the preliminary outcomes of mitomycin C (MMC) intravascular chemoembolization (MICE) for corneal neovascularization (NV). Methods This is a retrospective case series of three consecutive eyes that underwent MICE for progressive corneal NV with sight threatening lipid keratopathy . A 1.0 cc syringe was partially filled with MMC (0.4 mg/mL) and attached to a 33-gauge needle used to cannulate the vessels. The MMC (0.01–0.05 ml) was injected with enough retrograde hydrostatic force to fill efferent and afferent vessels. Follow-up ranged from 4 months to 1 year. Results Three eyes of three patients aged 59, 73 and 33 years were included. There were no intraoperative or postoperative complications associated with the MICE procedure. Patient 1 presented with progressive corneal NV and lipid keratopathy secondary to herpes zoster ophthalmicus (HZO) and a best-corrected spectacle visual acuity (BSCVA) of 20/100 Snellen. At one-year post-MICE, there was no recurrence (BSCVA was 20/20 Snellen). Patient 2 presented with idiopathic lipid keratopathy (BSCVA 20/50 Snellen). At four months post-MICE, there were no signs of recurrence (BSCVA 20/20 Snellen). Patient 3 presented with corneal NV and lipid keratopathy secondary to HZO (BSCVA 20/30 Snellen). At four months following two MICE treatments, resolution of the lipid keratopathy was noted (BSCVA 20/20 Snellen). Conclusions Preliminary findings suggest that MICE may be an additional modality for treating progressive corneal NV with lipid keratopathy. Larger comparative studies with longer follow-up are warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s10792-022-02240-6.

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Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model

Cited by 24 publications

References 48 publications

Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

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

Initial outcomes of mitomycin intravascular chemoembolization (MICE) for corneal neovascularization

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