{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:28:10Z","timestamp":1785439690656,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A1025511"],"award-info":[{"award-number":["2018R1A5A1025511"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>We investigated the efficacy of monthly alternating injections of aflibercept and bevacizumab (MAAB) for maintenance treatment in patients with neovascular age-related macular degeneration (AMD) who showed improvement with the initial monthly injections but presented with rapid worsening after conversion to bimonthly injections. We included 72 patients with neovascular AMD who showed improvement with loading injections of aflibercept. For maintenance treatment, bevacizumab was administered every alternate month between the bimonthly aflibercept injections in 24 (33.3%) eyes showing worsening (MAAB group). The other eyes were treated with aflibercept (BiA group) bimonthly. Baseline low retinal thickness, thick choroid, and presence of intraretinal fluid were associated with worsening after extending the injection intervals. Visual improvement was lower in the MAAB group than in the BiA group, but the final visual outcomes were comparable. Additional bevacizumab stabilized the early fluctuation of retinal thickness, thus maintaining long-term visual stability without increasing the risk of geographic atrophy or disciform scar until the second year. Previously treated eyes or those with polypoidal choroidal vasculopathy responded less to the initial loading doses and showed worsening under the bimonthly regimen. MAAB was effective in preventing anatomical and functional deterioration when bimonthly aflibercept proved insufficient for the maintenance treatment of neovascular AMD.<\/jats:p>","DOI":"10.3390\/jcm11061543","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T12:58:36Z","timestamp":1647003516000},"page":"1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-8033","authenticated-orcid":false,"given":"Junyeop","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Na","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June-Gone","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1056\/NEJMra0801537","article-title":"Age-related macular degeneration","volume":"358","author":"Jager","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11393","DOI":"10.1073\/pnas.172398299","article-title":"VEGF-Trap: A VEGF blocker with potent antitumor effects","volume":"99","author":"Holash","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","article-title":"Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration","volume":"119","author":"Heier","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ophtha.2013.08.011","article-title":"Intravitreal aflibercept injection for neovascular age-related macular degeneration: Ninety-six-week results of the VIEW studies","volume":"121","author":"Kaiser","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e510","DOI":"10.1111\/aos.12681","article-title":"Initial improvements when converting eyes with treatment-resistant exudative AMD to aflibercept are substantially diminished after increasing treatment intervals from 4 to 8 weeks","volume":"93","author":"Jorstad","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ophtha.2013.08.035","article-title":"Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration","volume":"121","author":"Chang","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.2147\/OPTH.S88624","article-title":"Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration","volume":"9","author":"Khanani","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00417-018-04232-8","article-title":"Durability of every-8-week aflibercept maintenance therapy in treatment-experienced neovascular age-related macular degeneration","volume":"257","author":"Dans","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/IAE.0000000000001496","article-title":"Two Year Outcomes of \u201cTreat and Extend\u201d Intravitreal Therapy Using Aflibercept Preferentially for Neovascular Age-Related Macular Degeneration","volume":"38","author":"Barthelmes","year":"2018","journal-title":"Retina"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10456-011-9249-6","article-title":"Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab","volume":"15","author":"Papadopoulos","year":"2012","journal-title":"Angiogenesis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1021\/mp500160v","article-title":"Comparison of binding characteristics and in vitro activities of three inhibitors of vascular endothelial growth factor A","volume":"11","author":"Yang","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fphar.2015.00248","article-title":"Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: A computational approach","volume":"6","author":"Platania","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/eye.2014.329","article-title":"Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model","volume":"29","author":"Park","year":"2015","journal-title":"Eye"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ophtha.2017.10.010","article-title":"Real-World Vision in Age-Related Macular Degeneration Patients Treated with Single Anti-VEGF Drug Type for 1 Year in the IRIS Registry","volume":"125","author":"Rao","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_16","first-page":"6835782","article-title":"Switch to Aflibercept in the Treatment of Neovascular AMD: Long-Term Results","volume":"2017","author":"Pinheiro","year":"2017","journal-title":"J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40942-016-0028-9","article-title":"Conversion back to bevacizumab or ranibizumab for recurrent neovascular activity with aflibercept in age-related macular degeneration: A case series","volume":"2","author":"Slean","year":"2016","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"469","DOI":"10.5301\/ejo.5000781","article-title":"Response to bevacizumab after treatment with aflibercept in eyes with neovascular AMD","volume":"26","author":"Waizel","year":"2016","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s10384-018-0619-0","article-title":"Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing","volume":"62","author":"Mimouni","year":"2018","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3928\/23258160-20160419-09","article-title":"Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration","volume":"47","author":"Cheng","year":"2016","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1097\/IAE.0000000000001451","article-title":"Recurrence of Choroidal Neovascularization Lesion Activity after Aflibercept Treatment for Age-Related Macular Degeneration","volume":"37","author":"Wakazono","year":"2017","journal-title":"Retina"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29619","DOI":"10.1038\/srep29619","article-title":"Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: Implications of serous pigment epithelial detachment","volume":"6","author":"Nagai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ophtha.2015.10.039","article-title":"Subfoveal Choroidal Thickness during Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: Twelve-Month Results","volume":"123","author":"Koizumi","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1007\/s00417-017-3776-9","article-title":"Inner nuclear layer cystoid spaces are a poor prognostic factor in typical age-related macular degeneration and polypoidal choroidal vasculopathy","volume":"255","author":"Kang","year":"2017","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/bjo.2008.150029","article-title":"Continuous anti-VEGF treatment with ranibizumab for polypoidal choroidal vasculopathy: 6-month results","volume":"94","author":"Kokame","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1007\/s10384-010-0813-1","article-title":"Treatment of polypoidal choroidal vasculopathy by intravitreal injection of bevacizumab","volume":"54","author":"Tsujikawa","year":"2010","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00417-016-3489-5","article-title":"Efficacy of fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy: 1-year results of the VAULT study","volume":"255","author":"Lee","year":"2017","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/6\/1543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:50Z","timestamp":1760135690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/6\/1543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,11]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jcm11061543"],"URL":"https:\/\/doi.org\/10.3390\/jcm11061543","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,11]]}}}