{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:15:48Z","timestamp":1791814548099,"version":"4.3.4"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BrightFocus Foundation","award":["1R01EY033805"],"award-info":[{"award-number":["1R01EY033805"]}]},{"name":"BrightFocus Foundation","award":["1R01EY034325"],"award-info":[{"award-number":["1R01EY034325"]}]},{"name":"BrightFocus Foundation","award":["1R01EY033000"],"award-info":[{"award-number":["1R01EY033000"]}]},{"name":"BrightFocus Foundation","award":["2P30EY002520"],"award-info":[{"award-number":["2P30EY002520"]}]},{"name":"BrightFocus Foundation","award":["P30 EY007003"],"award-info":[{"award-number":["P30 EY007003"]}]},{"name":"BrightFocus Foundation","award":["CDMRP HT9425-23-10179"],"award-info":[{"award-number":["CDMRP HT9425-23-10179"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.<\/jats:p>","DOI":"10.3390\/biom14030252","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T04:23:10Z","timestamp":1708489390000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization"],"prefix":"10.3390","volume":"14","author":[{"given":"Yingbin","family":"Fu","sequence":"first","affiliation":[{"name":"Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Webster","sequence":"additional","affiliation":[{"name":"Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis M.","family":"Paulus","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA"},{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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