{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:14:54Z","timestamp":1792671294300,"version":"4.5.0"},"reference-count":45,"publisher":"BMJ","issue":"9","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Br J Ophthalmol"],"accepted":{"date-parts":[[2023,12,31]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (\u221213.0 ETDRS letters; 95% CL \u201322.1 to \u20133.9; p=0.006).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bjo-2023-324713","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T18:20:51Z","timestamp":1706638851000},"page":"1240-1248","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation"],"prefix":"10.1136","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-3506","authenticated-orcid":false,"given":"Paolo","family":"Forte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Muzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Di Cello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-7362","authenticated-orcid":false,"given":"Paolo","family":"Corazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Musetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-9267","authenticated-orcid":false,"given":"Aldo","family":"Vagge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Enrico","family":"Traverso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-3091","authenticated-orcid":false,"given":"Massimo","family":"Nicol\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"2024082203451040000_108.9.1240.1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e3181669504"},{"key":"2024082203451040000_108.9.1240.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2014.07.006"},{"key":"2024082203451040000_108.9.1240.3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00166756"},{"key":"2024082203451040000_108.9.1240.4","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e3181619c55"},{"key":"2024082203451040000_108.9.1240.5","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1097\/IAE.0000000000003598","article-title":"Optical coherence tomography angiography characterization of evolving lesions in fellow eyes of exudative type 3 macular neovascularization patients","volume":"42","author":"Sacconi","year":"2022","journal-title":"Retina (Philadelphia, Pa)"},{"key":"2024082203451040000_108.9.1240.6","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.oret.2022.02.010","article-title":"OCT predictors of 3-year visual outcome for type 3 macular neovascularization","volume":"6","author":"Sacconi","year":"2022","journal-title":"Ophthalmol Retina"},{"key":"2024082203451040000_108.9.1240.7","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e3181fe54c7"},{"key":"2024082203451040000_108.9.1240.8","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.ophtha.2015.10.034","article-title":"Outcomes in eyes with retinal angiomatous proliferation in the comparison of age-related macular degeneration treatments trials (CATT)","volume":"123","author":"Daniel","year":"2016","journal-title":"Ophthalmology"},{"key":"2024082203451040000_108.9.1240.9","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/IAE.0000000000003330","article-title":"The rap study, report 5: rediscovering macular neovascularization type 3","volume":"42","author":"Haj Najeeb","year":"2022","journal-title":"Retina"},{"key":"2024082203451040000_108.9.1240.10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ajo.2022.09.008","article-title":"Review of fibrosis in neovascular age-related macular degeneration","volume":"246","author":"Cheong","year":"2023","journal-title":"Am J Ophthalmol"},{"key":"2024082203451040000_108.9.1240.11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ajo.2020.02.016","article-title":"Spectral-domain optical coherence tomography analysis of Fibrotic lesions in neovascular age-related macular degeneration","volume":"214","author":"Souied","year":"2020","journal-title":"Am J Ophthalmol"},{"key":"2024082203451040000_108.9.1240.12","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.ophtha.2018.01.004","article-title":"Development and course of scars in the comparison of age-related macular degeneration treatments trials","volume":"125","author":"Daniel","year":"2018","journal-title":"Ophthalmology"},{"key":"2024082203451040000_108.9.1240.13","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1001\/jamaophthalmol.2020.3001","article-title":"Associations of variation in retinal thickness with visual acuity and anatomic outcomes in eyes with neovascular age-related macular degeneration lesions treated with anti-vascular endothelial growth factor agents","volume":"138","author":"Evans","year":"2020","journal-title":"JAMA Ophthalmol"},{"key":"2024082203451040000_108.9.1240.14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ajo.2021.09.033","article-title":"Associations and outcomes of patients with Submacular hemorrhage secondary to age-related macular degeneration in the IVAN trial","volume":"236","author":"Mehta","year":"2022","journal-title":"Am J Ophthalmol"},{"key":"2024082203451040000_108.9.1240.15","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.oret.2020.02.012","article-title":"Subretinal fibrosis in HARBOR varies by choroidal neovascularization subtype","volume":"4","author":"Adrean","year":"2020","journal-title":"Ophthalmol Retina"},{"key":"2024082203451040000_108.9.1240.16","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1097\/IAE.0000000000002779","article-title":"Prevalence and risk factors for the development of physician-graded subretinal fibrosis in eyes treated for neovascular age-related macular degeneration","volume":"40","author":"Teo","year":"2020","journal-title":"Retina (Philadelphia, Pa)"},{"key":"2024082203451040000_108.9.1240.17","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2018-311850"},{"key":"2024082203451040000_108.9.1240.18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/IAE.0000000000003261","article-title":"Fluid-based visual prognostication in type 3 macular neovascularization-flip-3 study","volume":"42","author":"Sharma","year":"2022","journal-title":"Retina (Philadelphia, Pa)"},{"key":"2024082203451040000_108.9.1240.19","unstructured":"I-Maculaweb: A Tool to Support Data Reuse in Ophthalmology - PubMed, . 2023 Available: https:\/\/pubmed.ncbi.nlm.nih.gov\/27170913\/"},{"key":"2024082203451040000_108.9.1240.20","doi-asserted-by":"crossref","unstructured":"Su D , Lin S , Phasukkijwatana N , et al . An updated staging system of type 3 neovascularization using spectral domain optical coherence tomography. Retina 2016:S40\u20139. doi:10.1097\/IAE.0000000000001268","DOI":"10.1097\/IAE.0000000000001268"},{"key":"2024082203451040000_108.9.1240.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.11.004"},{"key":"2024082203451040000_108.9.1240.22","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1001\/archophthalmol.2012.2491","article-title":"Optical coherence Tomographic imaging of sub-retinal pigment epithelium lipid","volume":"130","author":"Mukkamala","year":"2012","journal-title":"Arch Ophthalmol"},{"key":"2024082203451040000_108.9.1240.23","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2415-14-159","article-title":"A hyporeflective space between hyperreflective materials in pigment epithelial detachment and Bruch\u2019s membrane in neovascular age-related macular degeneration","volume":"14","author":"Mukai","year":"2014","journal-title":"BMC Ophthalmol"},{"key":"2024082203451040000_108.9.1240.24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/11206721231185903","article-title":"Prechoroidal cleft regression after switch to intravitreal brolucizumab","volume":"34","author":"Forte","year":"2024","journal-title":"Eur J Ophthalmol"},{"key":"2024082203451040000_108.9.1240.25","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.oret.2017.08.019","article-title":"Tomographic biomarkers predicting progression to fibrosis in treated neovascular age-related macular degeneration: a multimodal imaging study","volume":"2","author":"Casalino","year":"2018","journal-title":"Ophthalmol Retina"},{"key":"2024082203451040000_108.9.1240.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.10.019"},{"key":"2024082203451040000_108.9.1240.27","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3994"},{"key":"2024082203451040000_108.9.1240.28","doi-asserted-by":"publisher","DOI":"10.1080\/09286586.2020.1786590"},{"key":"2024082203451040000_108.9.1240.29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/1536867X0900900102","article-title":"Accommodating covariates in ROC analysis","volume":"9","author":"Janes","year":"2009","journal-title":"Stata J"},{"key":"2024082203451040000_108.9.1240.30","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c30fb2"},{"key":"2024082203451040000_108.9.1240.31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ophtha.2013.06.024","article-title":"Appearance of regressing drusen on optical coherence tomography in age-related macular degeneration","volume":"121","author":"Querques","year":"2014","journal-title":"Ophthalmology"},{"key":"2024082203451040000_108.9.1240.32","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1097\/IAE.0000000000000761","article-title":"Vascularized drusen: slowly progressive type 1 neovascularization mimicking Drusenoid retinal pigment epithelium elevation","volume":"35","author":"Querques","year":"2015","journal-title":"Retina"},{"key":"2024082203451040000_108.9.1240.33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/IAE.0000000000002815","article-title":"Sub-retinal pigment epithelium Multilaminar Hyperreflectivity at the onset of type 3 macular neovascularization","volume":"41","author":"Miere","year":"2021","journal-title":"Retina"},{"key":"2024082203451040000_108.9.1240.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.07.008"},{"key":"2024082203451040000_108.9.1240.35","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.oret.2019.06.002","article-title":"The evolution of fibrosis and atrophy and their relationship with visual outcomes in Asian persons with neovascular age-related macular degeneration","volume":"3","author":"Cheung","year":"2019","journal-title":"Ophthalmol Retina"},{"key":"2024082203451040000_108.9.1240.36","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1167\/iovs.15-18694","article-title":"Automated identification and quantification of subretinal fibrosis in neovascular age-related macular degeneration using polarization-sensitive OCT","volume":"57","author":"Roberts","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024082203451040000_108.9.1240.37","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1097\/IAE.0000000000002198","article-title":"Reduced choriocapillaris flow in eyes with type 3 neovascularization and age-related macular degeneration","volume":"38","author":"Borrelli","year":"2018","journal-title":"Retina (Philadelphia, Pa)"},{"key":"2024082203451040000_108.9.1240.38","doi-asserted-by":"crossref","first-page":"e521","DOI":"10.1111\/aos.14905","article-title":"The role of retinal fluid location in atrophy and fibrosis evolution of patients with Neovascular age-related macular degeneration long-term treated in real world","volume":"100","author":"Llorente-Gonz\u00e1lez","year":"2022","journal-title":"Acta Ophthalmol"},{"key":"2024082203451040000_108.9.1240.39","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ophtha.2018.11.025","article-title":"Tolerating Subretinal fluid in Neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results","volume":"126","author":"Guymer","year":"2019","journal-title":"Ophthalmology"},{"key":"2024082203451040000_108.9.1240.40","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/j.optom.2022.08.001","article-title":"The upcoming role of artificial intelligence (AI) for retinal and glaucomatous diseases","volume":"15","author":"Ferro Desideri","year":"2022","journal-title":"J Optom"},{"key":"2024082203451040000_108.9.1240.41","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1097\/IAE.0000000000000627","article-title":"Treat-and-extend regimens with anti-VEGF agents in retinal diseases: A literature review and consensus recommendations","volume":"35","author":"Freund","year":"2015","journal-title":"Retina"},{"key":"2024082203451040000_108.9.1240.42","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.survophthal.2023.03.004","article-title":"Fibrosis in neovascular age-related macular degeneration: a review of definitions based on clinical imaging","volume":"68","author":"Bachmeier","year":"2023","journal-title":"Surv Ophthalmol"},{"key":"2024082203451040000_108.9.1240.43","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1097\/IAE.0000000000000877","article-title":"Correlation of visual acuity with fibrotic scar location in treated Neovascular age-related macular degeneration eyes","volume":"36","author":"Ryu","year":"2016","journal-title":"Retina"},{"key":"2024082203451040000_108.9.1240.44","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.oret.2018.04.016","article-title":"Nascent type 3 neovascularization in age-related macular degeneration","volume":"2","author":"Sacconi","year":"2018","journal-title":"Ophthalmol Retina"},{"key":"2024082203451040000_108.9.1240.45","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh101"}],"container-title":["British Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bjo-2023-324713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T10:56:39Z","timestamp":1724324199000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjo.bmj.com\/lookup\/doi\/10.1136\/bjo-2023-324713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,8,22]]},"published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1136\/bjo-2023-324713"],"URL":"https:\/\/doi.org\/10.1136\/bjo-2023-324713","relation":{},"ISSN":["0007-1161","1468-2079"],"issn-type":[{"value":"0007-1161","type":"print"},{"value":"1468-2079","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]}}}