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      Microvascular abnormalities and long-term efficacy after stereotactic radiotherapy under continued intravitreal anti-VEGF treatment for neovascular AMD

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          Abstract

          Background

          For treatment of neovascular age-related macular degeneration (nAMD), multiple intravitreal injections of drugs targeting vascular endothelial growth factors (VEGF) result in a high burden for patients and healthcare systems. Low-energy stereotactic radiotherapy (SRT) might reduce the anti-VEGF need. This study evaluated the long-term efficacy and safety of adjunct SRT to anti-VEGF injections in a treat-and-extend regimen in nAMD.

          Methods

          50 consecutive patients were followed 3 years after single-session SRT, a safety analysis including standardised study imaging, and a reading centre based image analysis was performed after 2 years.

          Results

          After increase from baseline (4.24±0.66 weeks) to 12 months (7.52±3.05 weeks, p<0.001), mean recurrence-free anti-VEGF treatment interval remained stable at 24 (7.40±3.17, p=0.746) and 36 months (6.89±3.00, p=0.175). Mean visual acuity change was −5.8±15.9 and −11.0±20.1 letters at 24 and 36 months, respectively. 36% of eyes showed microvascular abnormalities (MVAs) on colour fundus photography and/or fluoresceine angiography most frequently located in parafoveal inferior and nasal regions.

          Conclusion

          In real life, low-energy SRT was associated with a reduced anti-VEGF injection frequency through year 3. However, due to an observed visual acuity reduction and remarkable number of MVAs, a close follow-up of these patients is recommended. The real-life use, optimal treatment schedule and dose should be rediscussed critically.

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          Most cited references42

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          Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.

          To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. Multicenter, randomized clinical trial. Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Mean change in visual acuity. Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration

            Background/aims Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. Methods Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. Results 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. Conclusions In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. Trial registration number NCT01447043.
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              2002 global update of available data on visual impairment: a compilation of population-based prevalence studies.

              For the past 25 years, the WHO Programme for the Prevention of Blindness and Deafness has maintained a Global Data Bank on visual impairment with the purpose of storing the available epidemiological data on blindness and low vision. The Data Bank has now been updated to include studies conducted since the last update in 1994. An extensive literature search was conducted in international and national scientific and medical journals to identify epidemiological studies that fulfilled basic criteria for inclusion in the Data Bank, namely a clearly stated definition of blindness and low vision, and prevalence rates derived from population-based surveys. Sources such as National Prevention of Blindness Programmes, academic institutions or WHO country or regional reports were also investigated. Two-hundred-and-eight population-based studies on visual impairment for 68 countries are reported in detail, providing an up-to-date, comprehensive compilation of the available information on visual impairment and its causes globally.
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                Author and article information

                Journal
                Br J Ophthalmol
                Br J Ophthalmol
                bjophthalmol
                bjo
                The British Journal of Ophthalmology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0007-1161
                1468-2079
                March 2022
                21 December 2020
                : 106
                : 3
                : 415-421
                Affiliations
                [1 ] Vista Klinik , Binningen, Switzerland
                [2 ] University of Basel Faculty of Medicine , Basel, BS, Switzerland
                [3 ] departmentDepartment of Radiation Oncology , University Hospital Basel , Basel, BS, Switzerland
                [4 ] EyeRAD Swiss Medical Center , Binningen, Switzerland
                [5 ] departmentDepartment of Radiation Oncology , University of Patras Department of Medicine , Patras, Achaea, Greece
                [6 ] departmentDepartment of Ophthalmology , University of Basel , Basel, BS, Switzerland
                [7 ] Institute of Molecular and Clinical Ophthalmology , Basel, Switzerland
                [8 ] departmentDepartment of Ophthalmology and Optometry , Medical University of Vienna , Wien, Austria
                Author notes
                [Correspondence to ] Dr Katja Hatz, Vista Klinik, Binningen, Binningen, Switzerland; katja.hatz@ 123456unibas.ch
                Author information
                http://orcid.org/0000-0003-2807-0310
                http://orcid.org/0000-0002-7788-7311
                http://orcid.org/0000-0001-8940-8130
                Article
                bjophthalmol-2020-317563
                10.1136/bjophthalmol-2020-317563
                8867264
                33355151
                0a4dba37-93dd-40cb-ad89-71f8408b37fc
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 28 July 2020
                : 23 October 2020
                : 30 October 2020
                Funding
                Funded by: Carl-Zeiss Meditec AG, Germany;
                Award ID: Grant ID: MCS-BS IRAY Therapy
                Categories
                Clinical Science
                1506
                Custom metadata
                unlocked

                Ophthalmology & Optometry
                retina,treatment other,macula
                Ophthalmology & Optometry
                retina, treatment other, macula

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