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      Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti–vascular endothelial growth factor therapy of macular diseases

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          Abstract

          Background

          Intravitreal anti–vascular endothelial growth factor (VEGF) therapy is now considered the gold standard for the treatment of various retinal disorders. As therapy has evolved, so too have the treatment regimens employed by physicians in clinical practice; however, visual outcomes observed in the real world have typically not reflected those reported in clinical trials. Possible reasons for this include a lack of consensus on treatment regimens and a lack of clarity about what the aims of treatment should be.

          Methods

          The Vision Academy Steering Committee met to discuss the principles of an ideal treatment regimen, using evidence from the literature to substantiate each point. Literature searches were performed using the MEDLINE/PubMed database (cut-off date: March 2016) and restricted to English-language publications. Studies with fewer than ten patients were excluded from this review.

          Results

          The Steering Committee identified the following four key principles for the ideal treatment regimen for anti-VEGF management of retinal diseases:

          1. Maximize and maintain visual acuity (VA) benefits for all patients

          2. Decide when to treat next, rather than whether to treat now

          3. Titrate the treatment intervals to match patients’ needs

          4. Treat at each monitoring visit.

          Conclusions

          It is proposed that the adoption of a proactive and more personalized approach in the clinic such as a treat-and-extend regimen will lead to benefits for both the patient and the physician, through a reduction in the associated treatment burden and better utilization of clinic resources. Implementation of the four principles should also lead to better VA outcomes for each patient, with a minimized risk of vision loss.

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          Most cited references57

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          Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.

          Effective ways to prevent arthropathy in severe hemophilia are unknown. We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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            Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies.

            To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period. Two randomized, double-masked, active-controlled, phase 3 trials. Two thousand four hundred fifty-seven patients with neovascular AMD. From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks. Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA. Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9-15.9] and 9.0% [95% CI, 3.0-15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of -0.64 [95% CI, -0.89 to -0.40] and -0.55 [95% CI, -0.79 to -0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96. All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials.

              To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).
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                Author and article information

                Contributors
                +39 0432 559905 , paolo.lanzetta@uniud.it
                Journal
                Graefes Arch Clin Exp Ophthalmol
                Graefes Arch. Clin. Exp. Ophthalmol
                Graefe's Archive for Clinical and Experimental Ophthalmology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0721-832X
                1435-702X
                19 May 2017
                19 May 2017
                2017
                : 255
                : 7
                : 1259-1273
                Affiliations
                [1 ]ISNI 0000 0001 2113 062X, GRID grid.5390.f, Department of Medicine – Ophthalmology, , University of Udine, ; Piazzale S. Maria della Misericordia, 33100 Udine, Italy
                [2 ]ISNI 0000 0001 0518 6922, GRID grid.413449.f, , Tel Aviv Sourasky Medical Center, ; Tel Aviv, Israel
                Article
                3647
                10.1007/s00417-017-3647-4
                5486551
                28527040
                937e7f42-01b2-455e-81a6-119b14406783
                © The Author(s) 2017

                Open Access This 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.

                History
                : 5 October 2016
                : 22 January 2017
                : 20 March 2017
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag GmbH Germany 2017

                Ophthalmology & Optometry
                anti–vascular endothelial growth factor,retinal disease,treatment regimens,visual acuity,aflibercept,treat-and-extend

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