Subconjunctival Bevacizumab Versus Mitomycin C Adjunctive to Trabeculectomy

Nilforushan, Naveed; Yadgari, Maryam; Kish, Shahin Khosh; Nassiri, Nariman

doi:10.1016/j.ajo.2011.08.005

Cited by 111 publications

(100 citation statements)

References 23 publications

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“…[42][43][44] Furthermore, our tube formation assay demonstrated that the supernatant of HConFs treated by SAHA inhibited angiogenic activity of those treated with TGFb2. As anti-VEGF treatments were shown to improve the surgical success rate of GFS in animal experiments and clinical studies by reducing bleb vascularity, 45,46 our findings suggest that SAHA may support the maintenance of filtration blebs by its antiangiogenic effects in addition to its antifibrotic effects.…”

Section: Discussionmentioning

confidence: 89%

Molecular Mechanisms Underlying the Filtration Bleb-Maintaining Effects of Suberoylanilide Hydroxamic Acid (SAHA)

Futakuchi

Inoue

Fujimoto

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Suberoylanilide hydroxamic acid (SAHA) has been shown to support the maintenance of experimental filtration blebs in animal models. This study was performed to investigate the molecular mechanisms underlying the bleb-maintaining effects of SAHA in modulating wound healing activities of conjunctival fibroblasts.METHODS. Human conjunctival fibroblasts (HConFs) were pretreated with SAHA before treatment with TGF-b2. Microarray-based screening was used to investigate the gene expression profiles. Gene ontology (GO) analysis was conducted to categorize the gene functions. The expression of TGF-b-induced signaling molecules, a-smooth muscle actin, and extracellular matrix (ECM) proteins were evaluated by Western blot analyses. Multiplex immunoassay was performed to evaluate supernatant cytokine concentrations. Tube formation assay was used to evaluate angiogenesis using human umbilical vein endothelial cells.RESULTS. GO analysis showed that SAHA, in the presence of TGF-b2, induced changes in expression of genes involved in the TGF-b receptor signaling pathway, cell proliferation, extracellular matrix organization, inflammatory responses, and angiogenesis. Subsequent in vitro experiments showed that SAHA partly inhibited the phosphorylation of Smad2, Smad3, and Akt. SAHA pretreatment potently suppressed TGF-b2-driven cell proliferation, myofibroblast differentiation, contraction, ECM production, and angiogenic cytokine expression. The supernatant of HConFs treated with SAHA inhibited tube formation.CONCLUSIONS. SAHA has been shown to suppress angiogenesis and activation of conjunctival fibroblasts partly via inhibition of Smad and non-Smad TGF-b signaling. This in vitro study provides new evidence for the molecular basis of the potential bleb-maintaining effects of SAHA, a novel candidate drug in modulating scar formation after glaucoma filtration surgery.

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Section: Discussionmentioning

confidence: 89%

Molecular Mechanisms Underlying the Filtration Bleb-Maintaining Effects of Suberoylanilide Hydroxamic Acid (SAHA)

Futakuchi

Inoue

Fujimoto

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…A previous meta-analysis [11], which included trials by Akkan and Cilsim [22] and Pro et al [23], showed that MMC usage resulted in significantly better control of IOP than anti-VEGF antibodies at the 12-month follow-up [11,22,23]. Of note, Nilforushan et al [24] reported that MMC offered better control of IOP than bevacizumab alone at the 1-month (p < 0.001) and 6-month (p = 0.003) follow-ups. According to our pooled results, adding MMC to bevacizumab may overcome the limitations of bevacizumab alone in IOP control.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Bevacizumab Combined with Mitomycin C or 5-Fluorouracil in Primary Trabeculectomy: A Meta-Analysis of Randomized Clinical Trials

et al. 2018

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Aim: The objective of this study was to evaluate the efficacy and safety of bevacizumab combined with antimetabolite as an adjunctive therapy in primary trabeculectomy for glaucoma. Materials and Methods: PubMed, Cochrane Library, and EMBASE were searched for relevant randomized controlled trials. Efficacy was evaluated by the postoperative mean intraocular pressure (IOP), complete success, and qualified success rates. Safety was evaluated by postoperative complications and surgical interventions. Results: A total of 3 randomized controlled trials were included in the meta-analysis. The primary outcome was postoperative mean IOP at the 12-month follow-up. No significant difference in IOP was found between the bevacizumab + antimetabolite (mitomycin c or 5-fluorouracil) group and the antimetabolite alone group (weighted mean difference –0.27; 95% CI –1.38 to 0.83). There were no significant differences in complete success rates, qualified success rates, postoperative complications, and surgical interventions between the experimental treatment group and the conventional treatment group. Conclusions: Results of the meta-analysis demonstrated that the combination of bevacizumab (1.25 mg/mL) with a regular concentration of antimetabolite did not show more benefit or harm compared with using antimetabolite alone. Further randomized controlled trials are needed to evaluate the efficacy and safety of bevacizumab combined with lower concentrations and a shorter application time of antimetabolite.

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“…Результаты в ранние по-слеоперационные сроки были сопоставимы. Од-нако в конце двухлетнего наблюдения отмечалась разница в ВГД, компенсированном без гипотен-зивного режима в большем проценте случаев в группе введения митомицина С [58].…”

Section: применение ингибиторов Vegf после фистулизирующих антиглаукоunclassified

VEGF inhibitors in glaucoma surgery

Mamikonyan¹,

Petrov²,

Сафонова³

2016

Ophthalmology Reports

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Vascular endothelial growth factor (VEGF) is a signaling protein, that controls vasculogenesis, angiogenesis, vascular support and stimulates permeability of small blood vessels. The following isoforms are presently known: VEGF-A, VEGF-B, VEGF-C, VEGF-В and PGF. VEGF-A, that regulates neoangiogenesis and fibroblast formation, is thought to play the most important role in human organism. Increased expression of VEGF may lead to development and aggravation of pathological conditions including oncology. The article presents a review of preclinical and clinical studies of the main VEGF-inhibitors - bevacizumab and ranibizumab, as well as a brief account on other existing medications of this group. It describes ophthalmological indications for the use of antiangiogenetic agents, as well as the ways of their possible off-label use. The review presents investigations of intravitreal and intracameral injections of VEGF-inhibitors in patients with retinal, chorioidal, iris, and anterior chamber angle neovascularization. It gives examples of successful anti-VEGF use before Ahmed glaucoma valve drainage device implantation and in cases of neovascular glaucoma, induced by radiation therapy for intraocular tumors. Tenon’s capsule’s fibroblasts take part in the process of postoperative wound healing and scarring. According to the latest research, this process could be modulated by angiogenesis inhibitors. This review also recounts the use of anti-angiogenic agents to inhibit postoperative fibroblast proliferation, when used as monotherapy, or as an adjuvant to mitomycin С or 5-fluorouracil. It reviews the research on VEGF-inibitors use in combination with postoperative needling.

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Subconjunctival Bevacizumab Versus Mitomycin C Adjunctive to Trabeculectomy

Cited by 111 publications

References 23 publications

Molecular Mechanisms Underlying the Filtration Bleb-Maintaining Effects of Suberoylanilide Hydroxamic Acid (SAHA)

Molecular Mechanisms Underlying the Filtration Bleb-Maintaining Effects of Suberoylanilide Hydroxamic Acid (SAHA)

Efficacy and Safety of Bevacizumab Combined with Mitomycin C or 5-Fluorouracil in Primary Trabeculectomy: A Meta-Analysis of Randomized Clinical Trials

VEGF inhibitors in glaucoma surgery

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