Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma

Andrés-Guerrero, Vanessa; Perucho-González, Lucía; García-Feijoo, Julián; Morales-Fernandez, Laura; Sáenz-Francés, Federico; Herrero-Vanrell, Rocío; Júlvez, Luis Pablo; Llorens, Vicente Polo; Martínez-de-la-Casa, José María; Konstas, Anastasios-Georgios P.

doi:10.1007/s12325-016-0461-z

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Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma

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Author(s): Vanessa Andrés-Guerrero ¹ ^, ² ^, ⁶ , Lucía Perucho-González ¹ ^, ² ^, ⁶ , Julián García-Feijoo ¹ ^, ² ^, ⁶ , Laura Morales-Fernández ¹ ^, ² ^, ⁶ , Federico Saenz-Francés ¹ ^, ² ^, ⁶ , Rocío Herrero-Vanrell ¹ ^, ³ ^, ⁶ , Luis Pablo Júlvez ¹ ^, ⁴ ^, ⁷ , Vicente Polo Llorens ¹ ^, ⁴ ^, ⁷ , José María Martínez-de-la-Casa ¹ ^, ² ^, ⁶ , Anastasios-Georgios P. Konstas ⁵ ^,

Publication date (Electronic): 20 December 2016

Journal: Advances in Therapy

Publisher: Springer Healthcare

Keywords: Angiogenesis, Aflibercept, Bevacizumab, Glaucoma filtration surgery, Neovascular glaucoma, Ranibizumab, VEGF, Wound modulation

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Abstract

The approval of one of the first anti-vascular endothelial growth factor (VEGF) agents for the treatment of neovascular age-related macular degeneration one decade ago marked the beginning of a new era in the management of several sight-threatening retinal diseases. Since then, emerging evidence has demonstrated the utility of these therapies for the treatment of other ocular conditions characterized by elevated VEGF levels. In this article we review current perspectives on the use of anti-VEGF drugs as adjuvant therapy in the management of neovascular glaucoma (NVG). The use of anti-VEGFs for modifying wound healing in glaucoma filtration surgery (GFS) is also reviewed. Selected studies investigating the use of anti-VEGF agents or antimetabolites in GFS or the management of NVG have demonstrated that these agents can improve surgical outcomes. However, anti-VEGF agents have yet to demonstrate specific advantages over the more established agents commonly used today. Further studies are needed to evaluate the duration of action, dosing intervals, and toxicity profile of these treatments.

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Most cited references 82

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Vascular endothelial growth factor is a secreted angiogenic mitogen.

David V. Goeddel, D Leung, N Ferrara … (1989)

Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.

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The role of vascular endothelial growth factor in wound healing.

Philip Bao, Arber Kodra, Marjana Tomic-Canic … (2009)

A chronic wound is tissue with an impaired ability to heal. This is often a consequence of one of the following etiologies: diabetes, venous reflux, arterial insufficiency sickle cell disease, steroids, and/or pressure. Healing requires granulation tissue depending on epithelialization and angiogenesis. Currently no growth factor is available to treat patients with impaired healing that stimulates both epithelialization and angiogenesis. The objective is to review is the multiple mechanisms of vascular endothelial growth factor (VEGF) in wound healing. The authors reviewed the literature on the structure and function of VEGF, including its use for therapeutic angiogenesis. Particular attention is given to the specific role of VEGF in the angiogenesis cascade, its relationship to other growth factors and cells in a healing wound. VEGF is released by a variety of cells and stimulates multiple components of the angiogenic cascade. It is up-regulated during the early days of healing, when capillary growth is maximal. Studies have shown the efficacy of VEGF in peripheral and cardiac ischemic vascular disease with minimal adverse effects. Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound. VEGF stimulates wound healing through angiogenesis, but likely promotes collagen deposition and epithelialization as well. Further study of the molecule by utilizing the protein itself, or novel forms of delivery such as gene therapy, will increase its therapeutic possibilities to accelerate closure of a chronic wound.

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Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

L G Presta, H. Chen, S J O'Connor … (1997)

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis associated with tumors and other pathological conditions, including proliferative diabetic retinopathy and age-related macular degeneration. The murine anti-human VEGF monoclonal antibody (muMAb VEGF) A.4.6.1 has been shown to potently suppress angiogenesis and growth in a variety of human tumor cells lines transplanted in nude mice and also to inhibit neovascularization in a primate model of ischemic retinal disease. In this report, we describe the humanization of muMAb VEGF A.4.6.1. by site-directed mutagenesis of a human framework. Not only the residues involved in the six complementarity-determining regions but also several framework residues were changed from human to murine. Humanized anti-VEGF F(ab) and IgG1 variants bind VEGF with affinity very similar to that of the original murine antibody. Furthermore, recombinant humanized MAb VEGF inhibits VEGF-induced proliferation of endothelial cells in vitro and tumor growth in vivo with potency and efficacy very similar to those of muMAb VEGF A.4.6.1. Therefore, recombinant humanized MAb VEGF is suitable to test the hypothesis that inhibition of VEGF-induced angiogenesis is a valid strategy for the treatment of solid tumors and other disorders in humans.

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Author and article information

Contributors

Anastasios-Georgios P. Konstas: konstas@med.auth.gr

Journal

Journal ID (nlm-ta): Adv Ther

Journal ID (iso-abbrev): Adv Ther

Title: Advances in Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 0741-238X

ISSN (Electronic): 1865-8652

Publication date (Electronic): 20 December 2016

Publication date PMC-release: 20 December 2016

Publication date (Print): 2017

Volume: 34

Issue: 2

Pages: 378-395

Affiliations

[1 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, , Ocular Pathology National Net OFTARED of the Institute of Health Carlos III, ; Madrid, Spain

[2 ]ISNI 0000 0001 2157 7667, GRID grid.4795.f, Department of Ophthalmology, Hospital Clínico San Carlos, , Complutense University of Madrid, ; Madrid, Spain

[3 ]ISNI 0000 0001 2157 7667, GRID grid.4795.f, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, , Complutense University of Madrid, ; Madrid, Spain

[4 ]ISNI 0000 0000 9854 2756, GRID grid.411106.3, Department of Ophthalmology, , Hospital Universitario Miguel Servet, ; Saragossa, Spain

[5 ]ISNI 0000000109457005, GRID grid.4793.9, 1st and 3rd University Departments of Ophthalmology, AHEPA Hospital, , Aristotle University of Thessaloniki, ; 1 Kyriakidi Street, 546 36 Thessaloniki, Greece

[6 ]Sanitary Research Institute of the San Carlos Clinical Hospital, Madrid, Spain

[7 ]ISNI 0000 0004 1795 1427, GRID grid.419040.8, , Aragon Health Sciences Institute, ; Saragossa, Spain

Article

Publisher ID: 461

DOI: 10.1007/s12325-016-0461-z

PMC ID: 5331081

PubMed ID: 28000166

SO-VID: 5f12c91b-1fc5-42e8-9e2e-fc1ce9c8781d

History

Date received : 17 October 2016

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Keywords: angiogenesis,aflibercept,bevacizumab,glaucoma filtration surgery,neovascular glaucoma,ranibizumab,vegf,wound modulation

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Keywords: angiogenesis, aflibercept, bevacizumab, glaucoma filtration surgery, neovascular glaucoma, ranibizumab, vegf, wound modulation

Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma

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Most cited references 82

Vascular endothelial growth factor is a secreted angiogenic mitogen.

The role of vascular endothelial growth factor in wound healing.

Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

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