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      One-Year Outcome of Aflibercept and Photodynamic Therapy in a Caucasian Patient with Polypoidal Choroidal Vasculopathy Refractory to Ranibizumab and Photodynamic Therapy

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          Abstract

          Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration characterised by an abnormal branching vascular network with aneurysmal polypoidal choroidal vascular lesions. PCV is more prevalent in Asian populations than in Caucasians, which may explain its underdiagnosis in Western countries. Evidence regarding the efficacy of different anti-vascular endothelial growth factor (anti-VEGF) agents on PCV is scarce, with most of these studies being conducted in Asian treatment-naïve patients. Ranibizumab was the first anti-VEGF agent to demonstrate the superiority of a combination of photodynamic therapy (PDT) and anti-VEGF over PDT or anti-VEGF monotherapy for inducing polyp regression in Asian patients with PCV. The efficacy of other anti-VEGF agents has been less studied. Resistance to ranibizumab has been described. Aflibercept offers another mechanism of targeting choroidal neovascular lesions. A 75-year-old Caucasian woman presenting to our office was diagnosed with PCV using indocyanine green angiography. Combination therapy with a loading dose of 0.5 mg intravitreal ranibizumab followed by PDT at standard fluence at month 4 and a fourth dose of ranibizumab at month 5 yielded no visual or anatomic outcomes. Treatment was switched to intravitreal aflibercept at month 6 (3 monthly loading doses of 2.0 mg) followed by half-fluence PDT (month 9). Optical coherence tomography revealed remission of the anatomic lesions. Right-eye visual acuity increased to 0.6. Aflibercept injections were administered bimonthly afterwards. Follow-up during 1 year has shown functional and anatomic stability.

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          Most cited references11

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          Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians.

          Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people globally. It is estimated that there will be more Asians with AMD than the rest of the world combined by 2050. In Asian populations, polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative AMD, while choroidal neovascularization secondary to AMD (CNV-AMD) is the typical subtype in Western populations. The two subtypes share many common clinical features and risk factors, but also have different epidemiological and clinical characteristics, natural history and treatment outcomes that point to distinct pathophysiological processes. Recent research in the fields of genetics, proteomics and imaging has provided further clarification of differences between PCV and CNV-AMD. Importantly, these differences have manifested as disparity in response to intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) treatment between PCV and CNV-AMD, emphasizing the need for accurate diagnosis of PCV and in distinguishing PCV from CNV-AMD, particularly in Asian patients. Current clinical trials of intravitreal anti-VEGF therapy and photodynamic therapy will provide clearer perspectives of evidence-based management of PCV and may lead to paradigm shifts in therapeutic strategies away from those currently employed in the treatment of CNV-AMD. Further research is needed to clarify the relative contribution of specific pathways in inflammation, complement activation, extracellular matrix dysregulation, lipid metabolism and angiogenesis to the pathogenesis of PCV. Findings from this research, together with improved diagnostic technology and new therapeutics, will facilitate more optimal management of Asian AMD.
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            Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment.

            Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy affecting vision, with clinical features distinct from neovascular age-related macular degeneration. Currently, no evidence-based guidelines exist for its diagnosis and treatment. A panel of experts analyzed a systematic literature search on PCV together with results of the EVEREST trial, the only published randomized controlled clinical trial in PCV. At a subsequent Roundtable meeting, recommendations for the management of PCV were agreed based on this analysis and their own expert opinion. Diagnosis of PCV should be based on early-phase nodular hyperfluorescence from choroidal vasculature visualized using indocyanine green angiography. Recommended initial treatment of juxtafoveal and subfoveal PCV is either indocyanine green angiography-guided verteporfin photodynamic therapy or verteporfin photodynamic therapy plus 3 × 0.5 mg ranibizumab intravitreal injections 1 month apart. If there is incomplete regression of polyps by indocyanine green angiography, eyes should be retreated with verteporfin photodynamic therapy monotherapy or verteporfin photodynamic therapy plus ranibizumab. If there is complete regression of polyps by indocyanine green angiography, but there is leakage on fluorescein angiography and other clinical or anatomical signs of disease activity, eyes should be retreated with ranibizumab. Practical guidance on the clinical management of PCV is proposed based on expert evaluation of current evidence.
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              Refractory neovascular age-related macular degeneration secondary to polypoidal choroidal vasculopathy.

              To describe a neovascular pattern associated with treatment-refractory neovascular age-related macular degeneration (AMD). A retrospective observational case series. Clinical practice. Twelve eyes of 12 patients with neovascular AMD in which a poor anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was related to polypoidal choroidal vasculopathy (PCV). Slit-lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine green angiography. Snellen visual acuity (VA), anatomic response to therapy including presence or absence of retinal edema, hemorrhage, and lipid exudates. New or persistent PCV was identified in a cohort of patients demonstrating increasing macular exudation despite regular intravitreal ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months. Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination therapy, or continued anti-VEGF monotherapy resulted in complete resolution of exudation in 9 of 12 patients and partial resolution of exudation in the remaining 3 patients. Treatment-refractory neovascular AMD may harbor vascular abnormalities such as PCV. Modifications in therapeutic protocols may be indicated in order to improve visual and anatomic outcomes in this population.
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                Author and article information

                Journal
                COP
                COP
                10.1159/issn.1663-2699
                Case Reports in Ophthalmology
                S. Karger AG
                1663-2699
                2018
                January – April 2018
                02 March 2018
                : 9
                : 1
                : 172-178
                Affiliations
                [_a] aUnidad de Retina y Vítreo, Hospital Universitario Puerto Real, Cádiz, Spain
                [_b] bUnidad de Retina y Vítreo, Hospital Universitario Puerta del Mar, Cádiz, Spain
                Author notes
                *Marta Medina-Baena, MD, Avda. José León de Carranza, nº 4 triplicado, 12ºA, ES–11011 Cádiz (Spain), E-Mail martaojos@hotmail.com
                Article
                487227 PMC5903101 Case Rep Ophthalmol 2018;9:172–178
                10.1159/000487227
                PMC5903101
                29681832
                987a096f-d43b-4f51-a8d1-0ba4c112bd00
                © 2018 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. 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
                : 21 November 2017
                : 25 January 2018
                Page count
                Figures: 3, Pages: 7
                Categories
                Case Report

                Vision sciences,Ophthalmology & Optometry,Pathology
                Combination therapy,Polypoidal choroidal vasculopathy,Aflibercept,Polypoidal lesion,Photodynamic therapy

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