{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:49:15Z","timestamp":1781225355024,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an \u2018optimal treatment\u2019 control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.<\/jats:p>","DOI":"10.1038\/s41598-022-06362-w","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T11:24:46Z","timestamp":1645183486000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A model to quantify the influence of treatment patterns and optimize outcomes in nAMD"],"prefix":"10.1038","volume":"12","author":[{"given":"Focke","family":"Ziemssen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansj\u00fcrgen","family":"Agostini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Feltgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Finger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Haritoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hoerauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Iwersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Porstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Gmeiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"6362_CR1","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/NEJMoa054481","volume":"355","author":"PJ Rosenfeld","year":"2006","unstructured":"Rosenfeld, P. J. et al. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1419\u20131431 (2006).","journal-title":"N. Engl. J. Med."},{"key":"6362_CR2","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1056\/NEJMoa062655","volume":"355","author":"DM Brown","year":"2006","unstructured":"Brown, D. M. et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1432\u20131444 (2006).","journal-title":"N. Engl. J. Med."},{"key":"6362_CR3","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","volume":"119","author":"JS Heier","year":"2012","unstructured":"Heier, J. S. et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology 119, 2537\u20132548 (2012).","journal-title":"Ophthalmology"},{"key":"6362_CR4","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.ophtha.2019.04.017","volume":"127","author":"PU Dugel","year":"2020","unstructured":"Dugel, P. U. et al. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 127, 72\u201384 (2020).","journal-title":"Ophthalmology"},{"key":"6362_CR5","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1136\/bjophthalmol-2014-305702","volume":"98","author":"U Schmidt-Erfurth","year":"2014","unstructured":"Schmidt-Erfurth, U. et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br. J. Ophthalmol. 98, 1144\u20131167 (2014).","journal-title":"Br. J. Ophthalmol."},{"key":"6362_CR6","doi-asserted-by":"crossref","unstructured":"Khanna, S. et al. Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review. BMJ Open Ophthalmol. 4, e000398 (2019).","DOI":"10.1136\/bmjophth-2019-000398"},{"key":"6362_CR7","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/eye.2014.258","volume":"29","author":"C Gianniou","year":"2015","unstructured":"Gianniou, C. et al. Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results. Eye 29, 342\u2013349 (2015).","journal-title":"Eye"},{"key":"6362_CR8","doi-asserted-by":"crossref","unstructured":"The CATT Research Group et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 364, 1897\u20131908 (2011).","DOI":"10.1056\/NEJMoa1102673"},{"key":"6362_CR9","doi-asserted-by":"crossref","unstructured":"Ho, A. C. et al. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 121, 2181\u20132192 (2014).","DOI":"10.1016\/j.ophtha.2014.05.009"},{"key":"6362_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ophtha.2017.07.014","volume":"125","author":"R Silva","year":"2018","unstructured":"Silva, R. et al. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: Results with ranibizumab from the TREND study. Ophthalmology 125, 57\u201365 (2018).","journal-title":"Ophthalmology"},{"key":"6362_CR11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.preteyeres.2017.12.002","volume":"65","author":"H Mehta","year":"2018","unstructured":"Mehta, H. et al. Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors. Prog. Retin. Eye Res. 65, 127\u2013146 (2018).","journal-title":"Prog. Retin. Eye Res."},{"key":"6362_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.oret.2019.05.017","volume":"4","author":"TA Ciulla","year":"2020","unstructured":"Ciulla, T. A., Hussain, R. M., Pollack, J. S. & Williams, D. F. Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: A real-world analysis of 49 485 eyes. Ophthalmol. Retina 4, 19\u201330 (2020).","journal-title":"Ophthalmol. Retina"},{"key":"6362_CR13","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1097\/IAE.0000000000002670","volume":"40","author":"FG Holz","year":"2020","unstructured":"Holz, F. G. et al. Ranibizumab treatment in treatment-naive neovascular age-related macular degeneration. Retina Phila. Pa 40, 1673\u20131685 (2020).","journal-title":"Retina Phila. Pa"},{"key":"6362_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000502747","volume":"243","author":"J Mon\u00e9s","year":"2020","unstructured":"Mon\u00e9s, J. et al. Undertreatment of neovascular age-related macular degeneration after 10 years of anti-vascular endothelial growth factor therapy in the real world: The need for a change of mindset. Ophthalmologica 243, 1\u20138 (2020).","journal-title":"Ophthalmologica"},{"key":"6362_CR15","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1001\/jamaophthalmol.2021.1660","volume":"139","author":"M Okada","year":"2021","unstructured":"Okada, M. et al. Defining nonadherence and nonpersistence to anti-vascular endothelial growth factor therapies in neovascular age-related macular degeneration. JAMA Ophthalmol. 139, 769\u2013776 (2021).","journal-title":"JAMA Ophthalmol."},{"key":"6362_CR16","doi-asserted-by":"crossref","unstructured":"Sim, P. Y., Gajree, S., Dhillon, B. & Borooah, S. Investigation of time to first presentation and extrahospital factors in the treatment of neovascular age-related macular degeneration: A retrospective cross-sectional study. BMJ Open 7, e017771 (2017).","DOI":"10.1136\/bmjopen-2017-017771"},{"key":"6362_CR17","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.ajo.2011.09.013","volume":"153","author":"JH Lim","year":"2012","unstructured":"Lim, J. H. et al. Delay to treatment and visual outcomes in patients treated with anti-vascular endothelial growth factor for age-related macular degeneration. Am. J. Ophthalmol. 153, 678-686.e2 (2012).","journal-title":"Am. J. Ophthalmol."},{"key":"6362_CR18","doi-asserted-by":"crossref","unstructured":"Naravane, A. V. et al. Short term visual and structural outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment delay during the first COVID-19 wave: A pilot study. PLOS ONE 16, e0247161 (2021).","DOI":"10.1371\/journal.pone.0247161"},{"key":"6362_CR19","doi-asserted-by":"publisher","first-page":"730","DOI":"10.4103\/ijo.IJO_2807_20","volume":"69","author":"MD Sindal","year":"2021","unstructured":"Sindal, M. D., Chhabra, K. & Khanna, V. Profile of patients receiving intravitreal anti-vascular endothelial growth factor injections during COVID-19-related lockdown. Indian J. Ophthalmol. 69, 730\u2013733 (2021).","journal-title":"Indian J. Ophthalmol."},{"key":"6362_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2020.12.020","author":"W Song","year":"2021","unstructured":"Song, W., Singh, R. P. & Rachitskaya, A. V. The effect of delay in care among patients requiring intravitreal injections. Ophthalmol. Retina https:\/\/doi.org\/10.1016\/j.oret.2020.12.020 (2021).","journal-title":"Ophthalmol. Retina"},{"key":"6362_CR21","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1167\/iovs.09-3813","volume":"51","author":"FG Holz","year":"2010","unstructured":"Holz, F. G. et al. The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: Outcomes of a drug and disease model. Invest. Ophthalmol. Vis. Sci. 51, 405\u2013412 (2010).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"6362_CR22","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1002\/psp4.12322","volume":"7","author":"Z Mulyukov","year":"2018","unstructured":"Mulyukov, Z. et al. Neovascular age-related macular degeneration: A visual acuity model of natural disease progression and ranibizumab treatment effect. CPT Pharmacomet. Syst. Pharmacol. 7, 660\u2013669 (2018).","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"6362_CR23","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1080\/02713683.2020.1731832","volume":"45","author":"H Agostini","year":"2020","unstructured":"Agostini, H. et al. Comparison of the efficacy of brolucizumab with natural disease progression in wet AMD using clinical data from the phase III HAWK and HARRIER trials and modelled placebo data. Curr. Eye Res. 45, 1298\u20131301 (2020).","journal-title":"Curr. Eye Res."},{"key":"6362_CR24","doi-asserted-by":"crossref","unstructured":"Wachtlin, J. et al. Use of imaging modalities in real life: impact on visual acuity outcomes of ranibizumab treatment for neovascular age-related macular degeneration in Germany. J. Ophthalmol. 2020, e8024258 (2020).","DOI":"10.1155\/2020\/8024258"},{"key":"6362_CR25","doi-asserted-by":"crossref","unstructured":"Busbee, B. G. et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 120, 1046\u20131056 (2013).","DOI":"10.1016\/j.ophtha.2012.10.014"},{"key":"6362_CR26","doi-asserted-by":"publisher","unstructured":"Prevalence of age-related macular degeneration in a large European cohort: Results from the population-based Gutenberg Health Study. https:\/\/doi.org\/10.1007\/s00417-014-2591-9.","DOI":"10.1007\/s00417-014-2591-9"},{"key":"6362_CR27","first-page":"6383","volume":"25","author":"L L\u00fcdtke","year":"2019","unstructured":"L\u00fcdtke, L., J\u00fcrgens, C., Ittermann, T., V\u00f6lzke, H. & Tost, F. Age-related macular degeneration and associated risk factors in the population-based study of health in pomerania (SHIP-Trend). Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 25, 6383\u20136390 (2019).","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"6362_CR28","doi-asserted-by":"crossref","unstructured":"Sagkriotis, A. et al. Application of machine learning methods to bridge the gap between non-interventional studies and randomized controlled trials in ophthalmic patients with neovascular age-related macular degeneration. Contemp. Clin. Trials 104, 106364 (2021).","DOI":"10.1016\/j.cct.2021.106364"},{"key":"6362_CR29","first-page":"287","volume":"62","author":"R Khoramnia","year":"2021","unstructured":"Khoramnia, R. et al. Comparison of real-life treatment of na\u00efve patients with ranibizumab over 24 months for neovascular AMD, diabetic macular edema, retinal vein occlusion and myopic CNV\u2014results of the current interim analysis of the PACIFIC study. Invest. Ophthalmol. Vis. Sci. 62, 287\u2013287 (2021).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"6362_CR30","doi-asserted-by":"crossref","unstructured":"GERMAN SOCIETY OF OPHTHALMOLOGY. Stellungnahme der DOG, der RG und des BVA zur Therapie des diabetischen Makula\u00f6dems. Ophthalmologe 117, 218\u2013247 (2020).","DOI":"10.1007\/s00347-019-01015-2"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-06362-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-06362-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-06362-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T23:08:17Z","timestamp":1669331297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-06362-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["6362"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-06362-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"assertion":[{"value":"9 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"F. Z.: Consultant: Alimera Sciences, Allergan\/Abbvie, Bayer, Boehringer-Ingelheim, Novartis, NovoNordisk, MSD, Oxurion, Roche\/Genentech; Speaker: Alimera, Allergan\/Abbvie, Bayer, BDI, CME Health, Novartis, ODOS, Roche, Research: Bayer, BMBF, Clearside, DFG, Kodiak, Iveric, Ophtea, Novartis, Regeneron, R. H. A.: No competing interests. N. F.: Consultant: Alimera Sciences, Novartis, and Roche; Speaker: Allergan, Alimera, Bayer, Heidelberg Engineering, Novartis, and Roche. R. P. F.: Personal Fees: Novartis, Bayer, Roche\/Genentech, B\u00f6hringer-Ingelheim, Allergan, Alimera, Chiesi, ProQR, Ellex, Santhera, Opthea. Research Support: Novartis, Heidelberg Engineering, Zeiss Meditec, CentreVue, Biogen. C. H.: Consultant: Allergan; Speaker: Bayer, Novartis. H. H.: Consultant: Allergan, Bayer, Novartis; Speaker: Allergan, Bayer, Novartis; Shareholder: Bayer, Novartis. M. I. reports full time employment at Novartis Pharma GmbH. M. P. reports full time employment at Novartis Pharma GmbH. A. C. reports full time employment and shareholder of Novartis Pharma AG. B. G. reports full time employment at Novartis Pharma GmbH and shareholder of Novartis Pharma AG.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2789"}}