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      Retinal vasoproliferative tumor regression after intravitreal aflibercept

      case-report

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          Abstract

          Retinal vasoproliferative tumors (RVPTs) are rare benign retinal lesions typically located in the inferotemporal peripheral retina. Several treatment options exist for the management of RVPTs, but no consensus has been proposed. There are only a few reports on the use of anti-vascular endothelial growth factor with bevacizumab to treat exudative or neovascular retinal changes secondary to RVPTs. This report describes a 68-year-old female with a history of systemic hypertension that presented with a 2-week history of gradual loss of visual acuity in the right eye. Fundoscopic examination showed a RVPTs with atypical location that had a favorable response to two-intravitreal aflibercept injections 1 month apart, with resulting subretinal fluid absorption and tumor regression.

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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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            VEGF-Trap: a VEGF blocker with potent antitumor effects.

            Jocelyn Holash, Sam Davis, Nick Papadopoulos … (2002)
            Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. Initial attempts to block VEGF by using a humanized monoclonal antibody are beginning to show promise in human cancer patients, underscoring the importance of optimizing VEGF blockade. Previous studies have found that one of the most effective ways to block the VEGF-signaling pathway is to prevent VEGF from binding to its normal receptors by administering decoy-soluble receptors. The highest-affinity VEGF blocker described to date is a soluble decoy receptor created by fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region; however, this fusion protein has very poor in vivo pharmacokinetic properties. By determining the requirements to maintain high affinity while extending in vivo half life, we were able to engineer a very potent high-affinity VEGF blocker that has markedly enhanced pharmacokinetic properties. This VEGF-Trap effectively suppresses tumor growth and vascularization in vivo, resulting in stunted and almost completely avascular tumors. VEGF-Trap-mediated blockade may be superior to that achieved by other agents, such as monoclonal antibodies targeted against the VEGF receptor.
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              Clinical pharmacology of intravitreal anti-VEGF drugs

              Eleonora Rofi, Romano Danesi, Stefano Fogli … (2018)
              Clinical efficacy of intravitreal anti-VEGF drugs has been widely demonstrated in several angiogenesis-driven eye diseases including diabetic macular edema and the neovascular form of age-related macular degeneration. Pegaptanib, ranibizumab, and aflibercept have been approved for use in the eye, whereas bevacizumab is widely used by ophthalmologists to treat patients “off-label”. These drugs are active in the nanomolar to picomolar range; however, caution is required when establishing the rank order of affinity and potency due to in vitro inter-experimental variation. Despite the small doses used for eye diseases and the intravitreal route of administration may limit systemic side effects, these drugs can penetrate into blood circulation and alter systemic VEGF with unknown clinical consequences, particularly in vulnerable groups of patients. Clinical pharmacokinetics of ocular anti-VEGF agents should therefore be taken into account when choosing the right drug for the individual patient. The gaps in current understanding that leave open important questions are as follows: (i) uncertainty about which drug should be given first, (ii) how long these drugs can be used safely, and (iii) the choice of the best pharmacological strategy after first-line treatment failure. The current review article, based on the information published in peer-reviewed published papers relevant to anti-VEGF treatments and available on the PubMed database, describes in detail the clinical pharmacology of this class of drugs to provide a sound pharmacological basis for their proper use in ophthalmology clinical practice.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Taiwan J Ophthalmol
                Journal ID (iso-abbrev): Taiwan J Ophthalmol
                Journal ID (publisher-id): TJO
                Journal ID (publisher-id): Taiwan J Ophthalmol
                Title: Taiwan Journal of Ophthalmology
                Publisher: Wolters Kluwer - Medknow (India )
                ISSN (Print): 2211-5056
                ISSN (Electronic): 2211-5072
                Publication date Collection: Apr-Jun 2023
                Publication date (Electronic): 30 May 2022
                Volume: 13
                Issue: 2
                Pages: 249-252
                Affiliations
                [1 ] Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan
                [2 ] Department of Optometry, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
                [3 ] Department of Medicine, Mackay Medical College, Taipei, Taiwan
                Author notes
                [* ] Address for correspondence: Dr. Shawn H. Tsai, Department of Ophthalmology, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan N. Road, Taipei 10449, Taiwan. E-mail: shawntsa ishawntsai@ 123456gmail.com
                Article
                Publisher ID: TJO-13-249
                DOI: 10.4103/tjo.tjo_21_22
                PMC ID: 10361429
                SO-VID: 6d19258d-18b8-4123-a8ce-fa7de2eb496f
                Copyright © Copyright: © 2022 Taiwan J Ophthalmol
                License:

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                Date received : 21 February 2022
                Date accepted : 17 March 2022
                Categories
                Subject: Case Report

                Keywords: aflibercept,angiogenesis inhibitors,retinal neoplasms
                Data availability:
                Keywords: aflibercept, angiogenesis inhibitors, retinal neoplasms

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