{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:09:10Z","timestamp":1790996950324,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Anti-vascular endothelial growth factor medications are a cornerstone in the treatment of many macular diseases in modern ophthalmology. These medications accrue significant economic burdens to individuals and health systems, and recent data on health-system level practice patterns involving agent selection is lacking. We sought to examine utilization of intravitreal anti\u2013VEGF agents from 2017 to 2023 across various payors and diagnoses in the United States in order to analyze trends in usage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective cross-sectional study was performed\n                      <jats:italic>.<\/jats:italic>\n                      Data were obtained from the Epic Cosmos database, comprised of de-identified data from the electronic health record, Epic, of 238 million patients from all 50 states from January 1, 2017 to December 31, 2023. Encounters where a patient received an intravitreal injection in an ophthalmology clinic were categorized by intravitreal medication ordered, visit diagnosis, and primary insurance payor. The overall usage rates of each medication across different diagnoses and primary payor were compared. Total number of injections per year of anti-VEGF medication, the rate per 100000 ophthalmology encounters (OE), and the rate in different retinal conditions and with various insurance providers were the main outcome measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 2017\u20132023, there were 571,545 anti-VEGF injections administered, with 53.6% aflibercept 2 mg (306,247\/571,545; 625.8\/000 OE), 34.8% bevacizumab 1.25 mg (198,696\/571,545; 414.7\/100000 OE), 7.83% ranibizumab 0.3 mg and 0.5 mg (44,803\/571,545; 99.2\/100000 OE), and 3.43% faricimab 6 mg (19,624\/571,545; 32.8\/100000 OE). Brolucizumab 6 mg, ranibizumab-eqrn 0.5 mg, ranibizumab-nuna 0.5 mg, and aflibercept 8 mg accounted for &lt;1% of all injections. From 2017\u20132023, the rate of aflibercept 2 mg increased from 361.3 injections\/100000 OE to 913.1, bevacizumab increased from 274.1 to 538.1, and ranibizumab decreased from 92.4 to 64.0. The rate of faricimab increased from 37.9\/100000 OE to 189.9 from 2022\u20132023. Patients with Medicare received aflibercept 2 mg at higher rates than bevacizumab (364.3\/100000 OE vs 187.1, respectively) [t(6) = 5.67, p\u2009=\u20090.001] and faricimab (19.4\/100000 OE), a pattern not seen in commercially insured [t(6)=2.07, p\u2009&gt;\u20090.05] patients. Medicaid patients had a marginally significant difference in use of bevacizumab (M\u2009=\u200919.9\/100000 OE, SD\u2009=\u20097.32) and aflibercept 2 mg (16.1\/100000 OE, SD\u2009=\u20097.22) [t(6)]=2.95, p\u2009=\u20090.026].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Aflibercept 2 mg was the most common drug used overall from 2017\u20132023. Faricimab had the highest absolute and relative increase in utilization from 2022\u20132023. Patients with Medicare B or C were significantly more likely to receive aflibercept over bevacizumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335390","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:39:36Z","timestamp":1768329576000},"page":"e0335390","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["U.S. trends of anti-vascular endothelial growth factor use from 2017\u20132023: An analysis of medicare, medicaid, and commercial insurance"],"prefix":"10.1371","volume":"21","author":[{"given":"Kiran","family":"Malhotra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8123-3448","authenticated-orcid":true,"given":"Joseph","family":"Colcombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachi","family":"Patil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3369-4224","authenticated-orcid":true,"given":"Ravi","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"issue":"1","key":"pone.0335390.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.oret.2018.08.002","article-title":"A multinational comparison of anti-vascular endothelial growth factor use: the United States, the United Kingdom, and Asia-Pacific","volume":"3","author":"R Parikh","year":"2019","journal-title":"Ophthalmol Retina"},{"key":"pone.0335390.ref002","article-title":"Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study","author":"A Bilgic","year":"2023","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"pone.0335390.ref003","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.2147\/DDDT.S427416","article-title":"Faricimab: transforming the future of macular diseases treatment - a comprehensive review of clinical studies","volume":"17","author":"GD Panos","year":"2023","journal-title":"Drug Des Devel Ther"},{"issue":"7","key":"pone.0335390.ref004","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1097\/IAE.0000000000003769","article-title":"Retinal vasculitis or vascular occlusion after brolucizumab for neovascular age-related macular degeneration: a systematic review of real-world evidence","volume":"43","author":"CC Wykoff","year":"2023","journal-title":"Retina"},{"issue":"3","key":"pone.0335390.ref005","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ophtha.2016.10.036","article-title":"Trends of anti-vascular endothelial growth factor use in ophthalmology among privately insured and medicare advantage patients","volume":"124","author":"R Parikh","year":"2017","journal-title":"Ophthalmology"},{"issue":"20","key":"pone.0335390.ref006","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1001\/jama.2015.15217","article-title":"Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial","volume":"314","author":"Writing Committee for the Diabetic Retinopathy Clinical Research Network","year":"2015","journal-title":"JAMA"},{"issue":"13","key":"pone.0335390.ref007","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1056\/NEJMoa1414264","article-title":"Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema","volume":"372","author":"Diabetic Retinopathy Clinical Research Network","year":"2015","journal-title":"N Engl J Med"},{"issue":"10085","key":"pone.0335390.ref008","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/S0140-6736(17)31193-5","article-title":"Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial","volume":"389","author":"S Sivaprasad","year":"2017","journal-title":"Lancet"},{"issue":"2","key":"pone.0335390.ref009","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.oret.2020.07.018","article-title":"Anti-vascular endothelial growth factor and panretinal photocoagulation use after protocol S for proliferative diabetic retinopathy","volume":"5","author":"AD Azad","year":"2021","journal-title":"Ophthalmol Retina"},{"issue":"12","key":"pone.0335390.ref010","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.ophtha.2020.06.012","article-title":"Intravitreal anti-vascular endothelial growth factor cost savings achievable with increased bevacizumab reimbursement and use","volume":"127","author":"DB Glasser","year":"2020","journal-title":"Ophthalmology"},{"issue":"10","key":"pone.0335390.ref011","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1001\/jama.2018.1150","article-title":"Health care spending in the united states and other high-income countries","volume":"319","author":"I Papanicolas","year":"2018","journal-title":"JAMA"},{"issue":"4","key":"pone.0335390.ref012","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1001\/jamaophthalmol.2018.6395","article-title":"Comparison of ophthalmic medication prices between the United States and Australia","volume":"137","author":"R Parikh","year":"2019","journal-title":"JAMA Ophthalmol"},{"key":"pone.0335390.ref013","unstructured":"Information for EYLEA HD (aflibercept) Injection 8mg U.S. List Price. REGENERON; 2023. Available from: https:\/\/investor.regeneron.com\/static-files\/146d7101-2db1-4d35-b6d0-b9b94b11c6fb"},{"key":"pone.0335390.ref014","unstructured":"VABYSMO injection ordering guide; 2022. Available from: https:\/\/www.vabysmo-hcp.com\/content\/dam\/gene\/vabysmo-hcp\/pdfs\/injection-ordering-guide.pdf"},{"key":"pone.0335390.ref015","article-title":"Study finds beovu and eylea achieve similar visual improvements in macular edema","author":"D Myshko"},{"issue":"2","key":"pone.0335390.ref016","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":"WL Wong","year":"2014","journal-title":"Lancet Glob Health"},{"issue":"10397","key":"pone.0335390.ref017","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"KL Ong","year":"2023","journal-title":"Lancet"},{"issue":"1","key":"pone.0335390.ref018","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40942-021-00343-3","article-title":"Future of anti-VEGF: biosimilars and biobetters","volume":"8","author":"M Kapur","year":"2022","journal-title":"Int J Retina Vitreous"},{"issue":"9","key":"pone.0335390.ref019","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.ophtha.2023.04.019","article-title":"The biosimilar paradox: how anti-vascular endothelial growth factor biosimilars could increase patient and overall health care costs","volume":"130","author":"C Zhang","year":"2023","journal-title":"Ophthalmology"},{"issue":"12","key":"pone.0335390.ref020","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1097\/IAE.0000000000003626","article-title":"Anti-vascular endothelial growth factor biosimilars in ophthalmology","volume":"42","author":"PK Kaiser","year":"2022","journal-title":"Retina"},{"issue":"3","key":"pone.0335390.ref021","doi-asserted-by":"crossref","DOI":"10.1111\/aos.15756","article-title":"Treatment patterns and visual acuity change of AMD patients, before, during and after the COVID\u201019 pandemic lockdowns: a large cohort","volume":"102","author":"D Barequet","year":"2023","journal-title":"Acta Ophthalmol"},{"issue":"3","key":"pone.0335390.ref022","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/IAE.0000000000003679","article-title":"Intravitreal anti-vascular endothelial growth factor pharmaceutical utilization and financial impact in a value-based care program","volume":"43","author":"C Daruwalla","year":"2023","journal-title":"Retina"},{"issue":"6","key":"pone.0335390.ref023","first-page":"596","article-title":"Impact of the French 2020 COVID-19 lockdown on the treatment and follow-up of patients with exudative age-related macular degeneration","volume":"46","author":"A Auger","year":"2023","journal-title":"J Fr Ophtalmol"},{"issue":"6","key":"pone.0335390.ref024","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1080\/09286586.2021.2015394","article-title":"Impact of early COVID-19 pandemic on common ophthalmic procedures volumes: a US claims-based analysis","volume":"29","author":"AD Azad","year":"2022","journal-title":"Ophthalmic Epidemiol"},{"issue":"1","key":"pone.0335390.ref025","article-title":"The Cosmos Collaborative: a vendor-facilitated electronic health record data aggregation platform","volume":"5","author":"Y Tarabichi","year":"2021","journal-title":"ACI Open"},{"issue":"23","key":"pone.0335390.ref026","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1001\/jama.2020.23027","article-title":"Effect of intravitreous aflibercept vs vitrectomy with panretinal photocoagulation on visual acuity in patients with vitreous hemorrhage from proliferative diabetic retinopathy: a randomized clinical trial","volume":"324","author":"AN Antoszyk","year":"2020","journal-title":"JAMA"},{"issue":"7","key":"pone.0335390.ref027","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1001\/jamaophthalmol.2021.0606","article-title":"Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol W randomized clinical trial","volume":"139","author":"RK Maturi","year":"2021","journal-title":"JAMA Ophthalmol"},{"issue":"9","key":"pone.0335390.ref028","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1097\/IAE.0000000000001782","article-title":"Efficacy and frequency of intravitreal aflibercept versus bevacizumab for macular edema secondary to central retinal vein occlusion","volume":"38","author":"A Lotfy","year":"2018","journal-title":"Retina"},{"issue":"8","key":"pone.0335390.ref029","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1056\/NEJMoa2204225","article-title":"Aflibercept monotherapy or bevacizumab first for diabetic macular edema","volume":"387","author":"CD Jhaveri","year":"2022","journal-title":"N Engl J Med"},{"issue":"20","key":"pone.0335390.ref030","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1001\/jama.2017.4568","article-title":"Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial","volume":"317","author":"IU Scott","year":"2017","journal-title":"JAMA"},{"issue":"10326","key":"pone.0335390.ref031","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials","volume":"399","author":"JS Heier","year":"2022","journal-title":"Lancet"},{"issue":"10326","key":"pone.0335390.ref032","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(22)00018-6","article-title":"Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials","volume":"399","author":"CC Wykoff","year":"2022","journal-title":"Lancet"},{"issue":"9","key":"pone.0335390.ref033","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.ophtha.2023.04.019","article-title":"The biosimilar paradox: how anti-vascular endothelial growth factor biosimilars could increase patient and overall health care costs","volume":"130","author":"C Zhang","year":"2023","journal-title":"Ophthalmology"},{"issue":"20","key":"pone.0335390.ref034","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1056\/NEJMoa1102673","article-title":"Ranibizumab and bevacizumab for neovascular age-related macular degeneration","volume":"364","author":"CATT Research Group","year":"2011","journal-title":"N Engl J Med"},{"issue":"13","key":"pone.0335390.ref035","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1056\/NEJMoa1414264","article-title":"Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema","volume":"372","author":"Diabetic Retinopathy Clinical Research Network","year":"2015","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0335390.ref036","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/s41433-020-1111-x","article-title":"Brolucizumab-early real-world experience: BREW study","volume":"35","author":"A Sharma","year":"2021","journal-title":"Eye (Lond)"},{"issue":"1","key":"pone.0335390.ref037","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ophtha.2019.04.017","article-title":"HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration","volume":"127","author":"PU Dugel","year":"2020","journal-title":"Ophthalmology"},{"issue":"9","key":"pone.0335390.ref038","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.ophtha.2022.04.028","article-title":"MERLIN: phase 3a, multicenter, randomized, double-masked trial of brolucizumab in participants with neovascular age-related macular degeneration and persistent retinal fluid","volume":"129","author":"AM Khanani","year":"2022","journal-title":"Ophthalmology"},{"key":"pone.0335390.ref039","article-title":"Medicare payments for drugs used to treat wet age related macular degeneration","author":"DR Levinson","year":"2012"},{"issue":"5","key":"pone.0335390.ref040","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajo.2010.11.017","article-title":"Pharmacotherapy for neovascular age-related macular degeneration: an analysis of the 100% 2008 medicare fee-for-service part B claims file","volume":"151","author":"RJ Brechner","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"pone.0335390.ref041","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ajo.2019.05.011","article-title":"Use of bevacizumab and ranibizumab for wet age-related macular degeneration: influence of CATT results and introduction of aflibercept","volume":"207","author":"S Pershing","year":"2019","journal-title":"Am J Ophthalmol"},{"key":"pone.0335390.ref042","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ajo.2018.04.008","article-title":"Estimating medicare and patient savings from the use of bevacizumab for the treatment of exudative age-related macular degeneration","volume":"191","author":"PJ Rosenfeld","year":"2018","journal-title":"Am J Ophthalmol"},{"key":"pone.0335390.ref043","article-title":"Maximizing the benefits of anti-VEGF","author":"C Kent","year":"2014","journal-title":"Review of Ophthalmology"},{"issue":"9","key":"pone.0335390.ref044","doi-asserted-by":"crossref","DOI":"10.1001\/jamahealthforum.2023.2951","article-title":"Medicare part B spending on macular degeneration treatments associated with manufacturer payments to ophthalmologists","volume":"4","author":"SR Dickson","year":"2023","journal-title":"JAMA Health Forum"},{"key":"pone.0335390.ref045","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ajo.2016.09.026","article-title":"Open payments database: anti-vascular endothelial growth factor agent payments to ophthalmologists","volume":"173","author":"N Singh","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"pone.0335390.ref046","article-title":"Tracking anti-VEGF use among Medicare part B beneficiaries","author":"M Dalton","year":"2020","journal-title":"Modern Retina"},{"issue":"8","key":"pone.0335390.ref047","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1001\/jamaophthalmol.2019.1971","article-title":"Analysis of anti-vascular endothelial growth factor injection claims data in US Medicare part B beneficiaries From 2012 to 2015","volume":"137","author":"ST Berkowitz","year":"2019","journal-title":"JAMA Ophthalmol"},{"issue":"8","key":"pone.0335390.ref048","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1001\/jamaophthalmol.2016.1669","article-title":"Cost-effectiveness of aflibercept, bevacizumab, and ranibizumab for diabetic macular edema treatment: analysis from the diabetic retinopathy clinical research network comparative effectiveness Trial","volume":"134","author":"EL Ross","year":"2016","journal-title":"JAMA Ophthalmol"},{"issue":"5","key":"pone.0335390.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0197670","article-title":"The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration-A cost-effectiveness analysis from a societal perspective","volume":"13","author":"F van Asten","year":"2018","journal-title":"PLoS One"},{"key":"pone.0335390.ref050","unstructured":"U.S. Department of Health & Human Services Centers for Medicare & Medicaid Services. Understanding medicare advantage plans; 2023. Available from: https:\/\/www.medicare.gov\/Pubs\/pdf\/12026-Understanding-Medicare-Advantage-Plans.pdf"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:39:43Z","timestamp":1768329583000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335390"}},"subtitle":[],"editor":[{"given":"Daisuke","family":"Nagasato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335390","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}