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      Therapeutic approaches for corneal neovascularization

      review-article
      , ,
      Eye and Vision
      BioMed Central
      Corneal neovascularization, Angiogenesis, Angiogenic therapies

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          Abstract

          Angiogenesis refers to new blood vessels that originate from pre-existing vascular structures. Corneal neovascularization which can lead to compromised visual acuity occurs in a wide variety of corneal pathologies. A large subset of measures has been advocated to prevent and/or treat corneal neovascularization with varying degrees of success. These approaches include topical corticosteroid administration, laser treatment, cautery, and fine needle diathermy. Since the imbalance between proangiogenic agents and antiangiogenic agents primarily mediate the process of corneal neovascularization, recent therapies are intended to disrupt the different steps in the synthesis and actions of proangiogenic factors. These approaches, however, are only partially effective and may lead to several side effects. The aim of this article is to review the most relevant treatments for corneal neovascularization available so far.

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          Most cited references110

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          Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies.

          The vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been shown to play major roles not only in physiological but also in most pathological angiogenesis, such as cancer. VEGF belongs to the PDGF supergene family characterized by 8 conserved cysteines and functions as a homodimer structure. VEGF-A regulates angiogenesis and vascular permeability by activating 2 receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk1 in mice). On the other hand, VEGF-C/VEGF-D and their receptor, VEGFR-3 (Flt-4), mainly regulate lymphangiogenesis. The VEGF family includes other interesting variants, one of which is the virally encoded VEGF-E and another is specifically expressed in the venom of the habu snake (Trimeresurus flavoviridis). VEGFRs are distantly related to the PDGFR family; however, they are unique with respect to their structure and signaling system. Unlike members of the PDGFR family that strongly stimulate the PI3K-Akt pathway toward cell proliferation, VEGFR-2, the major signal transducer for angiogenesis, preferentially utilizes the PLCγ-PKC-MAPK pathway for signaling. The VEGF-VEGFR system is an important target for anti-angiogenic therapy in cancer and is also an attractive system for pro-angiogenic therapy in the treatment of neuronal degeneration and ischemic diseases.
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            A review of optical coherence tomography angiography (OCTA)

            Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging technique that generates volumetric angiography images in a matter of seconds. This is a nascent technology with a potential wide applicability for retinal vascular disease. At present, level 1 evidence of the technology’s clinical applications doesn’t exist. In this paper, we introduce the technology, review the available English language publications regarding OCTA, and compare it with the current angiographic gold standards, fluorescein angiography (FA) and indocyanine green angiography (ICGA). Finally we summarize its potential application to retinal vascular diseases. OCTA is quick and non-invasive, and provides volumetric data with the clinical capability of specifically localizing and delineating pathology along with the ability to show both structural and blood flow information in tandem. Its current limitations include a relatively small field of view, inability to show leakage, and proclivity for image artifact due to patient movement/blinking. Published studies hint at OCTA’s potential efficacy in the evaluation of common ophthalmologic diseases such age related macular degeneration (AMD), diabetic retinopathy, artery and vein occlusions, and glaucoma. OCTA can detect changes in choroidal blood vessel flow and can elucidate the presence of choroidal neovascularization (CNV) in a variety of conditions but especially in AMD. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) in diabetic eyes and detection of subtle microvascular abnormalities in diabetic and vascular occlusive eyes. Optic disc perfusion in glaucomatous eyes is notable as well on OCTA. Further studies are needed to more definitively determine OCTA’s utility in the clinical setting and to establish if this technology may offer a non-invasive option of visualizing the retinal vasculature in detail.
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              Corneal neovascularization.

              Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."
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                Author and article information

                Contributors
                +98-21-2258-4733 , +98-21-2259-1616 , sepehrfeizi@yahoo.com
                Journal
                Eye Vis (Lond)
                Eye Vis (Lond)
                Eye and Vision
                BioMed Central (London )
                2326-0254
                10 December 2017
                10 December 2017
                2017
                : 4
                : 28
                Affiliations
                GRID grid.411600.2, Ophthalmic Research Center, Labbafinejad Medical Center, , Shahid Beheshti University of Medical Sciences, ; Tehran, 16666 Iran
                Article
                94
                10.1186/s40662-017-0094-6
                5723406
                29234686
                c4dbaeb9-9292-4ec5-97c7-20227a39e563
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 September 2017
                : 26 November 2017
                Categories
                Review
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                © The Author(s) 2017

                corneal neovascularization,angiogenesis,angiogenic therapies

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