Clinical Outcomes and Changes in Aqueous Vascular Endothelial Growth Factor Levels After Intravitreal Bevacizumab for Iris Neovascularization and Neovascular Glaucoma: A Retrospective Two-Dose Comparative Study

Sasamoto, Yuzuru; Oshima, Yusuke; Miki, Atsuya; Wakabayashi, Taku; Song, Dan; Matsushita, Kazunobu; Hamasaki, Toshimitsu; Nishida, Kohji

doi:10.1089/jop.2011.0059

Cited by 20 publications

(18 citation statements)

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“…[25][26][27] We found that offlabel intracameral administration of bevacizumab (anti-VEGF monoclonal antibody) was effective in controlling iris neovascularization in patients with neovascular glaucoma. 28 Sasamoto et al 29 found reduction in VEGF levels in the aqueous humor after intravitreal injection of bevacizumab. In our series of patients with neovascular glaucoma, PRP failed to control the neovascularization of iris and anterior chamber angle, and intraocular hypertension could not be controlled.…”

Section: Discussionmentioning

confidence: 99%

Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular Glaucoma

2014

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ascular endothelial growth factor (VEGF), a secreted 46-kDa glycoprotein, is an endothelial cell-specific angiogenic and vasopermeable factor. [1][2][3][4][5][6] Vascular endothelial growth factor mediates its effects through highaffinity, cell-surface transmembrane receptors, including tyrosine kinase and fetal liver kinase 1. 6 Hypoxia regulates its gene expression in vitro and in vivo. 7,8 Expression of VEGF messenger RNA (mRNA) is induced rapidly in a variety of cultured cells, including retinal pigmented epithelium cells, by exposure to low levels of oxygen. [8][9][10] Neovascular glaucoma is a serious complication of a number of vascular disease processes that affect the eye. Diabetic retinopathy, retinal venous obstruction, and sickle cell disease are the leading etiologic factors for the development of neovascular glaucoma. 11,12 The common features in these diseases are retinal ischemia and hypoxia, which stimulate the synthesis and secretion of VEGF in the retina [13][14][15] ; subsequent diffusion of VEGF into the vitreous and aqueous humor causes intraocular neovascularization. 16 Application of panretinal photocoagulation (PRP) to an ischemic retina may induce regression of iris neovascularization in most patients. 17 In several refractory cases, contact Nd:YAG laser cyclophotocoagulation resulted in complete regression of iris neovascularization. 18 These observations prompted us to consider the involvement of nonretinal tissue in the synthesis and secretion of VEGF. Vascular endothelial growth factor was noted in the iris and ciliary body in primary uveal melanoma. 19 To search for other sites of VEGF production, we investigated the ciliary epithelium as a possible source of this growth factor with immunohistochemical analysis and in situ hybridization. Methods Tissue PreparationSixteen human enucleated eyes were investigated for the presence of VEGF with immunohistochemical analysis (VEGF protein) and in situ hybridization (VEGF mRNA). Eight human IMPORTANCE Retinal ischemia-induced upregulation of vascular endothelial growth factor (VEGF) leads to endothelial proliferation of the anterior segment, resulting in neovascular glaucoma.OBJECTIVE To investigate the ciliary epithelium as a possible source of VEGF in human eyes enucleated for intractable neovascular glaucoma. DESIGN, SETTING, AND PARTICIPANTSIn this proof-of-concept, laboratory-based study, 16 human enucleated eyes (8 with neovascular glaucoma and 8 as controls) were investigated. MAIN OUTCOMES AND MEASURESPresence of VEGF by immunohistochemical analysis (VEGF protein) and in situ hybridization (VEGF messenger RNA). RESULTSIn eyes with neovascular glaucoma, strong VEGF immunoreaction in the nonpigmented epithelial cells of the ciliary processes and in the retina was noted. In situ hybridization for VEGF messenger RNA revealed a similar pattern, with positive stain results only in eyes with neovascular glaucoma. A minimal amount of VEGF immunostaining was seen in control eyes. CONCLUSIONS AND RELEVANCEThe nonpigmented ciliary epithelium i...

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Section: Discussionmentioning

confidence: 99%

Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular Glaucoma

2014

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“…Angiogenesis was thought to be a result of over expression of pro-angiogenic factors, including VEGF, bFGF, PIGF (Sasamoto et al 2012;Zhou et al 2013). High levels of VEGF have been found in the aqueous and vitreous from subjects with DR (Endo et al 2000), neovascular age-related macular degeneration (AMD) (Jonas et al 2012;Miao et al 2012;Muether et al 2013), retinal vein occlusion (RVO) (Feng et al 2013) and retinopathy of prematurity (ROP) (Velez-Montoya et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Growth factors (de Oliveira Dias et al 2011;Sasamoto et al 2012;Zhou et al 2013), inflammatory cytokines (Amadi-Obi et al 2012;Hoh Kam et al 2013;Whitcup et al 2013) and adhesion molecules (Grunin et al 2012;Juel et al 2012;Muether et al 2013) are important in angiogenesis and fibrosis formation. Their roles in inducing neovascular growth have been proved.…”

Section: Introductionmentioning

confidence: 99%

“…Their roles in inducing neovascular growth have been proved. At the same time, antagonizing growth factors (for instance, intravitreal injection of antivascular endothelial growth factors) (Altintas et al 2012;Bikbov et al 2012;Sasamoto et al 2012;Tozer et al 2013) or suppressing inflammation (for example, intravitreal injection of triamcinolone) (Penfold et al 2000;Katome et al 2009;Becerra et al 2011) have been proved to be effective treatment modalities for NVG. These cytokines have also found to be involved in tissue fibrosis (Ceelen et al 2013;Greaves et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Expression of cytokines on the iris of patients with neovascular glaucoma

Hou

Miao

Tao

et al. 2014

Acta Ophthalmologica

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ABSTRACT.Purpose: To determine the expression levels of cytokines, including growth factors, inflammatory cytokines, and cell migration associated factors on the iris from subjects with neovascular glaucoma (NVG). Methods: After receiving formal consent from 12 subjects with NVG secondary to proliferative diabetic retinopathy and 12 subjects with primary open angle glaucoma (POAG), trabeculectomy was performed and iris specimens were collected during the surgery. Each subject with NVG received intravitreal injection of bevacizumab 1 week prior to the surgery. The mRNA level of vascular endothelial growth factor, basic fibroblastic growth factor, placentalinduced growth factor, interleukin-2, interleukin 6, tumour necrosis factor a, intercellular adhesion molecule 1 (ICAM-1) and integrin subunit a V were determined by real-time polymerase chain reaction. The mRNA levels were compared between the two groups. Results: The mRNA levels of all inflammatory cytokines and integrin subunit a V were significantly increased in the NVG group compared with POAG controls. However, the mRNA level of growth factors and ICAM-1 did not show any difference between the two groups. Conclusions: Inflammatory process maybe an important cause of iris neovascularization in subjects with NVG in addition to growth factors alone. Further studies should focus on the effect of growth factors in different phases in the pathogenesis of NVG.

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“…Норма-лизация ВГД наблюдалась в 55 % случаев в пер-вой группе и в 47 % -во второй. В целом не было замечено существенных различий в эффек-тивности различных доз лекарства [65].…”

Section: применение ингибиторов Vegf при неоваскулярной глаукомеunclassified

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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Clinical Outcomes and Changes in Aqueous Vascular Endothelial Growth Factor Levels After Intravitreal Bevacizumab for Iris Neovascularization and Neovascular Glaucoma: A Retrospective Two-Dose Comparative Study

Abstract: Aqueous humor levels of VEGF were significantly correlated with the IOP. Low-dose (0.1 mg) IVB was as effective as the currently used higher dose (1.0 mg) for treating NVG within at least 6 months after the initial injection.

Cited by 20 publications

References 39 publications

Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular Glaucoma

Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular Glaucoma

Expression of cytokines on the iris of patients with neovascular glaucoma

VEGF inhibitors in glaucoma surgery

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