Inhibition of Vascular Endothelial Growth Factor Reduces Scar Formation after Glaucoma Filtration Surgery

Li, Zhongqiu; Bergen, Tine Van; Veire, Sara Van de; Vel, Isabelle Van de; Moreau, H; Dewerchin, Mieke; Maudgal, P C; Zeyen, Thierry; Spileers, Werner; Moons, Lieve; Stalmans, Ingeborg

doi:10.1167/iovs.08-2662

Cited by 207 publications

(225 citation statements)

References 46 publications

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“…19 A growing number of studies have been published that focus on angiogenesis as a potential target for increasing the surgical success associated with routine trabeculectomies; these studies mainly focus on the effects of bevacizumab and ranibizumab. [9][10][11]20 The dose, route of administration, and new drug release mechanisms should be studied to improve the effectiveness of a bevacizumab-augmented trabeculectomy to reduce fibrosis. Several issues need to be addressed regarding the offlabel use of bevacizumab, such as the duration of action of the drug and its toxicity profile in ocular tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, these cells also express these cognate VEGF receptors. 11,25 Other systems that permit the sustained release of bevacizumab have been described by Abrishami et al 26 and Andrew et al, 27 but these systems utilized a liposomal delivery system (nanoliposomes) and an inorganic polymer (mesoporous silicon oxide), respectively. They were developed to treat diseases of the posterior segment of the FIG.…”

Section: Paula Et Almentioning

confidence: 99%

“…5 Bevacizumab, which is an anti-VEGF monoclonal antibody that contains human interaction regions, has been successfully used to aid in the wound-healing process that is associated with glaucoma surgery. [9][10][11] There remains uncertainty regarding how to optimally deliver bevacizumab. One possibility is subconjunctival delivery, but it is expected to have a short duration of action and would therefore require repetitive injections.…”

Section: Introductionmentioning

confidence: 99%

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Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Paula

Ribeiro

Chahud

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Vascular endothelial growth factor (VEGF) may contribute to the scarring process resulting from glaucoma filtration surgery, since this cytokine may stimulate fibroblast proliferation. The aim of this study was to describe a new bevacizumab-loaded polyurethane implant (BPUI) and to evaluate its effectiveness as a new drug delivery system of anti-VEGF antibody in a rabbit model of glaucoma filtration surgery. Methods: An aqueous dispersion of polyurethane was obtained via the conventional process. Bevacizumab (1.5 mg) was then incorporated into the dispersion and was subsequently dried to form the polymeric films. Films with dimensions of 3 · 3 · 1 mm that either did (group BPUI, n = 10) or did not contain bevacizumab (group PUI, n = 10) were implanted in the subconjunctival space, at the surgical site in 1 eye of each rabbit. The in vitro bevacizumab release was evaluated using size-exclusion high-performance liquid chromatography (HPLC), and the in vivo effects of the drug were investigated in a rabbit experimental trabeculectomy model by examining the bleb characteristics and collagen accumulation, and by performing immunohistological analyses of VEGF expression. Results: HPLC showed that only 10% of the bevacizumab in the implants had been released by postoperative day 5. In vivo studies demonstrated that the drug had no adverse effects; however, no significant differences in either the bleb area score or the collagen deposit intensity between the group PUI and the group that BPUI were observed. Moreover, the group BPUI presented a significantly lower proportion of VEGF-expressing fibroblasts than group PUI (0.17 -0.03 vs. 0.35 -0.05 cells/field, P = 0.005). Conclusions: This study demonstrated that bevacizumab release from the BPUIs only occurred for a short time probably from the surface of the films. Nevertheless, they were well tolerated in rabbit eyes and reduced the number of VEGF-expressing fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Section: Paula Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Paula

Ribeiro

Chahud

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

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“…O grau de inflamação foi avaliado visto que existem estudos que, apesar da droga não apresentar efeitos anti-inflamatórios diretos, mostram evidencias de um efeito em fibroblastos (21)(22) . A ação na inflamação aguda ainda não havia sido estudada mais profundamente, sendo sugerido uma diminuição na invasão de neutrófilos na ferida (23) .…”

Section: Discussionunclassified

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

Mello¹,

Lupion²,

Oliveira³

et al. 2011

Arq. Bras. Oftalmol.

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Nota Editorial: Depois de concluída a análise do artigo sob sigilo editorial e com a anuência do Dr. Vinícius Coral Ghanem e Procópio Miguel dos Santos sobre a divulgação de seu nome como revisor, agradecemos sua participação neste processo.Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química ABSTRACT Purposes:To evaluate the effect of subconjunctival bevacizumab in an experimental model of neovascularization in rabbit cornea. Determine its effect on vessels extension, inflammation, epithelialization of the cornea and whether the evaluation method used is appropriate to compare neovascular models. Methods: Experimental, prospective, randomized, blinded study in twenty rabbits subjected to chemical trauma with sodium hydroxide at 1N divided into two groups. The study group received subconjunctival injection of 0.15 ml (3.75 mg) of bevacizumab and was compared with the control group that received subconjunctival injection of 0.15 ml saline solution. After 25 days, digital photographic analysis was performed to assess the vessel's extension and inflammation/diameter according to pre-established criteria. Histopathology of the cornea, which evaluated the state of the epithelium and the number of polymorphonuclear cells was also studied. Results:The length of the neovessels was greater in the control group compared to the study group (P=<0.001). There was no difference in inflammation/vessel diameter between groups. Histopathology analysis showed that there was no difference between groups for the variables state of the epithelium and number of polymorphonuclear cells. The concordance analysis for the variable extension of the vessels and the variable inflammation/vessel diameter was estimated with Kappa coefficients of 0.705 and 0.500 respectively, indicating a good level of agreement in different evaluations and validating the method. Conclusions:The experimental model is adequate and can be reproduced to evaluate other drugs in the cornea. Bevacizumab inhibit the neovessels' growth but was not effective in preventing the inflammatory response. The drug did not delay the reepithelialization of the cornea.

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“…In fact, with the existance of a filtering pathway, the drug might flow to the subconjunctival space, and subconjunctival bevacizumab has been suggested to reduce scar formation of the bleb. 11,12 In conclusion, we suggest immediate combined surgery for NVG, which includes trabeculectomy with mitomycin C, PPV with endolaser PRP, IVB and ICB. This strategy has shown to be successful in controlling IOP and preserving useful vision.…”

Section: -5mentioning

confidence: 93%

Combined Trabeculectomy with Mitomycinc, Pars Plana Vitrectomy with Panretinal Photocoagulation, and Intravitreal and Intracameral Bevacizumab for Neovascular Glaucoma

Lin¹,

Lee²

2016

Ophthalmol Open J

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CitationLin H-Z, Lee Y-C. Combined trabeculectomy with mitomycinC, pars plana vitrectomy with panretinal photocoagulation, and intravitreal and intracameral bevacizumab for neovascular glaucoma. Otolaryngol Open J. The intraocular pressure returned to normal range soon after operation. The neovascularization of iris regressed in a few days. Mild hyphema developed in three patients. All six patients had improved or stable visual acuity, and achieved normal intraocular pressure without antiglaucoma medications three months after operation. Conclusions: This combined surgery may break the vicious cycle of neovascularglaucoma and preserve useful vision in these patients.

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Inhibition of Vascular Endothelial Growth Factor Reduces Scar Formation after Glaucoma Filtration Surgery

Cited by 207 publications

References 46 publications

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

Combined Trabeculectomy with Mitomycinc, Pars Plana Vitrectomy with Panretinal Photocoagulation, and Intravitreal and Intracameral Bevacizumab for Neovascular Glaucoma

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