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      Protective Effect of Intravitreal Bevacizumab and Sub-Tenon Triamcinolone Acetonide against Occlusion of Choriocapillaris Induced by Photodynamic Therapy

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          Abstract

          Purpose: To evaluate the protective effect of intravitreal bevacizumab (IVB) and sub-Tenon triamcinolone acetonide (TA) against choriocapillaris occlusion induced by photodynamic therapy (PDT). Methods: This prospective, nonrandomized, consecutive study included 80 eyes of 80 patients with polypoidal choroidal vasculopathy who underwent an initial PDT. The posttherapeutic follow-up periods were more than 3 months (mean, 9.3 months). Patients were divided into three groups consecutively: the PDT group included 21 eyes of 21 patients treated with only PDT, the TA group included 32 eyes of 32 patients treated with PDT and a sub-Tenon injection of 20 mg TA, and the IVB group included 27 eyes of 27 patients treated with PDT and an intravitreal injection of 1.25 mg bevacizumab. Indocyanine green angiography (ICGA) was performed before and 3 months after PDT. The degree of choriocapillaris occlusion was assessed in the marginal zone of the PDT area based on the background hypofluorescence seen on ICGA quantified by densitometry (Imagenet). Results: ICGA at 1 and 5 min showed hypofluorescence in the marginal zone in all eyes 3 months after PDT. The hypofluorescence became indistinguishable from the background fluorescence 15 min after treatment in some eyes; however, the relative hypofluorescence persisted in some cases. The rates of fluorescence intensity in the marginal zone compared to those in the untreated area, i.e. the percentage of baseline fluorescence, were 0.60, 0.65 and 0.73 at 1, 5 and 15 min after dye injection in the PDT group, respectively, 0.64, 0.68 and 0.82 in the TA group, and 0.64, 0.73 and 0.90 in the IVB group. The intensity of the fluorescence was significantly (p < 0.05) higher in the TA group at 15 min and in the IVB group at 1, 5 and 15 min compared with the PDT group. Conclusions: IVB and TA reduced choriocapillaris occlusion after PDT. IVB appeared to have a stronger protective effect than TA in this therapeutic regimen.

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          Most cited references31

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          Clinical characteristics of exudative age-related macular degeneration in Japanese patients.

          To clarify the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients. Retrospective, observational, consecutive case series. Two hundred and eighty-nine patients with neovascular AMD were examined. The authors classified the patients into three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one eye had PCV and the other eye had typical AMD. Most patients with PCV and typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3 years for women) than patients with other subtypes. Serous and hemorrhagic pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22 patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the patients with unilateral disease in each subtype, large drusen in the unaffected eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP. Neovascular AMD in Japanese patients has different demographic features compared with that in White patients. In Japanese patients, there is a preponderance of PCV, male gender, unilaterality, and absence of drusen in the second eye, with the exception of RAP.
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            Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells.

            The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.
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              VEGF164-mediated Inflammation Is Required for Pathological, but Not Physiological, Ischemia-induced Retinal Neovascularization

              Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte–mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2010
                August 2010
                25 February 2010
                : 224
                : 5
                : 267-273
                Affiliations
                Department of Ophthalmology, University of Gunma School of Medicine, Maebashi, Japan
                Article
                287348 Ophthalmologica 2010;224:267–273
                10.1159/000287348
                20185940
                9ceb01f2-e276-4674-ace3-dacf0a76bd6b
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 19 February 2009
                : 17 September 2009
                Page count
                Figures: 3, References: 42, Pages: 7
                Categories
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Hypofluorescence,Intravitreal bevacizumab,Choriocapillaris occlusion,Triamcinolone acetonide,Photodynamic therapy

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