{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:14:52Z","timestamp":1788437692034,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: The timing of exudative recurrence after complete fluid resolution following anti-vascular endothelial growth factor (anti-VEGF) loading in neovascular age-related macular degeneration (nAMD) is unpredictable. We prespecified two questions: whether the speed of fluid resolution during loading, or the baseline pigment epithelial detachment (PED) type, predict recurrence timing. Methods: We retrospectively analyzed 72 treatment-na\u00efve nAMD eyes that achieved complete resolution of subretinal fluid (SRF) and intraretinal fluid (IRF) after three monthly loading injections, then observed them under a pro re nata strategy. Time from the post-loading dry-confirmation visit to first detected recurrence was analyzed with Kaplan\u2013Meier and Cox models; baseline variables with univariable p &lt; 0.10 were entered into a multivariable model. Results: Recurrence was detected in 58 eyes (80.6%); median recurrence-free survival was 139 days (95% CI, 118\u2013158). Resolution of SRF or IRF by one month was not significantly associated with recurrence timing (p = 0.586 and 0.054). Fibrovascular PED was associated with earlier detected recurrence compared with non-fibrovascular PED (adjusted hazard ratio 2.40, 95% CI, 1.17\u20134.92; p = 0.017; median 130 vs. 602 days). Eyes with fibrovascular PED were monitored more frequently, but the association persisted in an interval-censored sensitivity analysis (adjusted HR 2.71, 95% CI, 1.32\u20135.60). Conclusions: The speed of fluid resolution was not significantly associated with recurrence timing, whereas fibrovascular PED was associated with earlier detected recurrence and may represent a candidate prognostic marker requiring prospective validation.<\/jats:p>","DOI":"10.3390\/jcm15176835","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:53Z","timestamp":1788433733000},"page":"6835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time to Exudative Recurrence After Complete Fluid Resolution Following Anti-VEGF Loading in Neovascular Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7821-0614","authenticated-orcid":false,"given":"Kyungyun","family":"Kook","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Dohee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"GeonIl","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8480-8952","authenticated-orcid":false,"given":"Yong-Sok","family":"Ji","sequence":"additional","affiliation":[{"name":"Parangsae Eye Clinic, MSC Research Institute, Gwangju 61486, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"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. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1056\/NEJMoa062655","article-title":"Ranibizumab versus verteporfin for neovascular age-related macular degeneration","volume":"355","author":"Brown","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.ajo.2007.01.028","article-title":"An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration","volume":"143","author":"Fung","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.ophtha.2010.12.019","article-title":"Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: The SUSTAIN study","volume":"118","author":"Holz","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_6","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":"Martin","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group (2012). Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: Two-year results. Ophthalmology, 119, 1388\u20131398.","DOI":"10.1016\/j.ophtha.2012.03.053"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.ophtha.2013.03.046","article-title":"Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON (SEVEN-UP study)","volume":"120","author":"Rofagha","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.ophtha.2016.03.045","article-title":"Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: The Comparison of AMD Treatments Trials","volume":"123","author":"Maguire","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ophtha.2013.08.015","article-title":"Risk of geographic atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials","volume":"121","author":"Grunwald","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15662","DOI":"10.1038\/s41598-022-19400-4","article-title":"Neovascular age-related macular degeneration without exudative recurrence over 24 months after initial remission","volume":"12","author":"Cho","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41433-021-01562-6","article-title":"Continued anti-VEGF treatment does not prevent recurrences in eyes with stable neovascular age-related macular degeneration using a treat-and-extend regimen: A retrospective case series","volume":"36","author":"Garweg","year":"2022","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/IAE.0000000000001923","article-title":"Exit strategy in a treat-and-extend regimen for exudative age-related macular degeneration","volume":"39","author":"Arendt","year":"2019","journal-title":"Retina"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ophtha.2019.11.004","article-title":"Consensus nomenclature for reporting neovascular age-related macular degeneration data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group","volume":"127","author":"Spaide","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1089\/jop.2021.0051","article-title":"Five-year reactivation after ranibizumab or aflibercept treatment for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy","volume":"37","author":"Kim","year":"2021","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1038\/s41598-024-56309-6","article-title":"Prediction of neovascular age-related macular degeneration recurrence using optical coherence tomography images with a deep neural network","volume":"14","author":"Jung","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bogunovi\u0107, H., Mares, V., Reiter, G.S., and Schmidt-Erfurth, U. (2022). Predicting treat-and-extend outcomes and treatment intervals in neovascular age-related macular degeneration from retinal optical coherence tomography using artificial intelligence. Front. Med., 9.","DOI":"10.3389\/fmed.2022.958469"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ajo.2021.07.026","article-title":"Development of intraretinal fluid in neovascular age-related macular degeneration during anti-vascular endothelial growth factor treatment","volume":"234","author":"Cho","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ajo.2016.03.039","article-title":"Response of pigment epithelial detachment to anti-vascular endothelial growth factor treatment in age-related macular degeneration","volume":"166","author":"Cho","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.ophtha.2016.03.037","article-title":"Morphology and visual acuity in aflibercept and ranibizumab therapy for neovascular age-related macular degeneration in the VIEW trials","volume":"123","author":"Waldstein","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.ophtha.2013.01.073","article-title":"Macular morphology and visual acuity in the Comparison of Age-related Macular Degeneration Treatments Trials","volume":"120","author":"Jaffe","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.ophtha.2015.12.002","article-title":"Macular morphology and visual acuity in the second year of the Comparison of Age-related Macular Degeneration Treatments Trials","volume":"123","author":"Sharma","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14943","DOI":"10.1038\/s41598-020-72030-6","article-title":"Fibrovascular pigment epithelial detachment in eyes with subretinal hemorrhage secondary to neovascular AMD or polypoidal choroidal vasculopathy: A morphologic predictor associated with poor treatment outcomes","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1016\/j.ophtha.2015.06.053","article-title":"Factors associated with recurrence of age-related macular degeneration after anti-vascular endothelial growth factor treatment","volume":"122","author":"Kuroda","year":"2015","journal-title":"Ophthalmology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:27:10Z","timestamp":1788434830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":24,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176835"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176835","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}