Quantitative response of macular neovascularisation to loading phase of aflibercept in neovascular age-related macular degeneration.
Humans
Follow-Up Studies
Receptors, Vascular Endothelial Growth Factor
/ therapeutic use
Recombinant Fusion Proteins
/ therapeutic use
Neovascularization, Pathologic
/ drug therapy
Tomography, Optical Coherence
/ methods
Macular Degeneration
/ drug therapy
Intravitreal Injections
Angiogenesis Inhibitors
/ therapeutic use
Wet Macular Degeneration
/ drug therapy
Journal
Eye (London, England)
ISSN: 1476-5454
Titre abrégé: Eye (Lond)
Pays: England
ID NLM: 8703986
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
03
10
2022
accepted:
03
05
2023
revised:
02
05
2023
pmc-release:
01
12
2024
medline:
24
11
2023
pubmed:
1
6
2023
entrez:
31
5
2023
Statut:
ppublish
Résumé
To evaluate quantitative morphological changes in macular neovascularisation (MNV) network after aflibercept therapy in neovascular age-related macular degeneration (nAMD) patients. Consecutive treatment-naïve patients with optical coherence tomography (OCT) angiography confirmed MNV due to nAMD who completed a loading phase of intravitreal aflibercept injections. A quantitative analysis of the vascular network remodelling was performed using a computational software (Angiotool). A total of 53 eyes of 52 patients were included in the analysis. The total MNV area decreased significantly after three aflibercept injections (p = 0.003). Total vessel area and vessel density decreased respectively of 20% and 12% at V3 (p < 0.001 in both cases). Other parameters that reduced significantly were total vessel length, average vessel length and density of vascular junctions (p = 0.018, p = 0.002, and p = 0.044, respectively). The number of vascular endpoints (p = 0.001) and lacunarity (p = 0.011) increased significantly, whilst the number of vascular junctions did not vary significantly (p = 0.068). Changes in vascular metrics were predominantly driven by MNV type 1 and 2. No clear relationship was observed between any of the vascular metrics and the macular fluid status. Although objective quantification of vascular parameters showed a significant remodelling of the MNV post-loading phase of aflibercept in type 1 and 2 MNV subtypes, none of the quantified vascular metrics correlated to the macular fluid response. These findings highlight a dissociation of anti-angiogenic and anti-permeability properties of aflibercept therapy during the loading phase.
Identifiants
pubmed: 37258659
doi: 10.1038/s41433-023-02574-0
pii: 10.1038/s41433-023-02574-0
pmc: PMC10686403
doi:
Substances chimiques
aflibercept
15C2VL427D
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Recombinant Fusion Proteins
0
Angiogenesis Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3648-3655Informations de copyright
© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.
Références
Sarwar S, Clearfield E, Soliman MK, Sadiq MA, Baldwin AJ, Hanout M, et al. Aflibercept for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2016;2:CD011346.
pubmed: 26857947
Spaide RF, Jaffe GJ, Sarraf D, Freund KB, Sadda SR, Staurenghi G, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group. Ophthalmology. 2020;127:616–36. https://doi.org/10.1016/j.ophtha.2019.11.004 .
doi: 10.1016/j.ophtha.2019.11.004
pubmed: 31864668
Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, Souied E, Schlingemann R, et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol. 2014;98:1144–67. https://pubmed.ncbi.nlm.nih.gov/25136079 .
doi: 10.1136/bjophthalmol-2014-305702
pubmed: 25136079
Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Prog Retin Eye Res. 2018;64:1–55.
doi: 10.1016/j.preteyeres.2017.11.003
pubmed: 29229445
Lupidi M, Cerquaglia A, Chhablani J, Fiore T, Singh SR, Cardillo Piccolino F, et al. Optical coherence tomography angiography in age-related macular degeneration: the game changer. Eur J Ophthalmol. 2018;28:349–57.
doi: 10.1177/1120672118766807
pubmed: 29623720
Told R, Reiter GS, Schranz M, Reumueller A, Hacker V, Mittermueller TJ, et al. Correlation of retinal thickness and swept-source optical coherence tomography angiography derived vascular changes in patients with neovascular age-related macular degeneration. Curr Eye Res. 2021;46:1002–9.
doi: 10.1080/02713683.2020.1849734
pubmed: 33211556
Told R, Reiter GS, Mittermüller TJ, Schranz M, Reumueller A, Schlanitz FG, et al. Profiling neovascular age-related macular degeneration choroidal neovascularization lesion response to anti-vascular endothelial growth factor therapy using SSOCTA. Acta Ophthalmol. 2021;99:e240–e246.
doi: 10.1111/aos.14554
pubmed: 32706171
Choi M, Kim S-W, Yun C, Oh J-H, Oh J. Predictive role of optical coherence tomography angiography for exudation recurrence in patients with type 1 neovascular age-related macular degeneration treated with pro-re-nata protocol. Eye (Lond). 2023;37:34–41. https://doi.org/10.1038/s41433-021-01879-2 .
doi: 10.1038/s41433-021-01879-2
pubmed: 34992249
Takeuchi J, Kataoka K, Ito Y, Takayama K, Yasuma T, Kaneko H, et al. Optical coherence tomography angiography to quantify choroidal neovascularization in response to aflibercept. Ophthalmologica. 2018;240:90–98.
doi: 10.1159/000487611
pubmed: 29739007
von der Emde L, Thiele S, Pfau M, Nadal J, Meyer J, Möller PT, et al. Assessment of exudative activity of choroidal neovascularization in age-related macular degeneration by OCT angiography. Ophthalmologica. 2020;243:120–8. https://www.karger.com/DOI/10.1159/000503609 .
doi: 10.1159/000503609
pubmed: 31665719
Cabral D, Coscas F, Pereira T, Français C, Geraldes C, Laiginhas R, et al. Quantitative optical coherence tomography angiography biomarkers in a treat-and-extend dosing regimen in neovascular age-related macular degeneration. Transl Vis Sci Technol. 2020;9:18 https://pubmed.ncbi.nlm.nih.gov/32714644 .
doi: 10.1167/tvst.9.3.18
pubmed: 32714644
pmcid: 7351878
Scharf J, Corradetti G, Corvi F, Sadda S, Sarraf D. Optical coherence tomography angiography of the choriocapillaris in age-related macular degeneration. J Clin Med. 2021;10:751.
doi: 10.3390/jcm10040751
pubmed: 33668537
pmcid: 7918036
Al-Sheikh M, Iafe NA, Phasukkijwatana N, Sadda SR, Sarraf D. Biomarkers of neovascular activity in age-related macular degeneration using optical coherence tomography angiography. Retina. 2018;38. https://journals.lww.com/retinajournal/Fulltext/2018/02000/BIOMARKERS_OF_NEOVASCULAR_ACTIVITY_IN_AGE_RELATED.2.aspx .
Coscas GJ, Lupidi M, Coscas F, Cagini C, Souied EH. Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration: a new diagnostic challenge. Retina. 2015;35:2219–28.
doi: 10.1097/IAE.0000000000000766
pubmed: 26398697
Rocholz R, Teussink MM, Dolz-Marco R, Holzhey C, Dechent JF, Tafreshi, et al. SPECTRALIS optical coherence tomography angiography (OCTA): principles and clinical applications. https://www.heidelbergengineering.com/media/e-learning/Totara/Dateien/pdf-tutorials/210111-001_SPECTRALIS%20OCTA%20-%20Principles%20and%20Clinical%20Applications_EN.pdf .
Zudaire E, Gambardella L, Kurcz C, Vermeren S. A computational tool for quantitative analysis of vascular networks. PLoS One. 2011;6:e27385.
doi: 10.1371/journal.pone.0027385
pubmed: 22110636
pmcid: 3217985
Liu J, Song S, Yu X. Predicting lesion shrinkage in eyes with myopic choroidal neovascularization from features on optical coherence tomography angiography. Retina. 2022;42:1665–1672. https://doi.org/10.1097/IAE.0000000000003526 .
doi: 10.1097/IAE.0000000000003526
pubmed: 35594547
Roberts PK, Nesper PL, Gill MK, Fawzi AA. Semiautomated quantitative approach to characterize treatment response in neovascular age-related macular degeneration: a real-world study. Retina. 2017;37. https://journals.lww.com/retinajournal/Fulltext/2017/08000/SEMIAUTOMATED_QUANTITATIVE_APPROACH_TO.8.aspx .
Popovic N, Radunovic M, Badnjar J, Popovic T. Fractal dimension and lacunarity analysis of retinal microvascular morphology in hypertension and diabetes. Microvasc Res. 2018;118:36–43. https://www.sciencedirect.com/science/article/pii/S0026286218300104 .
doi: 10.1016/j.mvr.2018.02.006
pubmed: 29476757
Lumbroso B, Rispoli M, Savastano MC, Jia Y, Tan O, Huang D. Optical coherence tomography angiography study of choroidal neovascularization early response after treatment. Dev Ophthalmol. 2016;56:77–85.
doi: 10.1159/000442782
pubmed: 27022967
Lumbroso B, Rispoli M, Savastano MC. Longitudinal optical coherence tomography-angiography study of type 2 naive choroidal neovascularization early response after treatment. Retina. 2015;35:2242–51.
doi: 10.1097/IAE.0000000000000879
pubmed: 26457401
Miere A, Butori P, Cohen SY, Semoun O, Capuano V, Jung C, et al. Vascular remodeling of choroidal neovascularization after anti-vascular endothelial growth factor therapy visualized on optical coherence tomography angiography. Retina. 2019;39:548–57.
doi: 10.1097/IAE.0000000000001964
pubmed: 29210939
Papadopoulou DN, Mendrinos E, Mangioris G, Donati G, Pournaras CJ. Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration. Ophthalmology. 2009;116:1755–61. https://www.sciencedirect.com/science/article/pii/S0161642009002814 .
doi: 10.1016/j.ophtha.2009.03.017
pubmed: 19560206
Siemerink MJ, Klaassen I, van Noorden CJF, Schlingemann RO. Endothelial tip cells in ocular angiogenesis: potential target for anti-angiogenesis therapy. J Histochem Cytochem. 2013;61:101–15.
doi: 10.1369/0022155412467635
pubmed: 23092791
pmcid: 3636692
Norton K-A, Popel AS. Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis. Sci Rep. 2016;6:36992 https://doi.org/10.1038/srep36992 .
doi: 10.1038/srep36992
pubmed: 27841344
pmcid: 5107954
Ishibashi T, Miller H, Orr G, Sorgente N, Ryan SJ. Morphologic observations on experimental subretinal neovascularization in the monkey. Invest Ophthalmol Vis Sci. 1987;28:1116–30.
pubmed: 2439474
Spaide RF. Optical coherence tomography angiography signs of vascular abnormalization with antiangiogenic therapy for choroidal neovascularization. Am J Ophthalmol. 2015;160:6–16.
doi: 10.1016/j.ajo.2015.04.012
pubmed: 25887628
Faatz H, Rothaus K, Ziegler M, Book M, Heimes-Bussmann B, Pauleikhoff D, et al. Vascular analysis of type 1, 2, and 3 macular neovascularization in age-related macular degeneration using swept-source optical coherence tomography angiography shows new insights into differences of pathologic vasculature and may lead to a more personal understanding. Biomedicines. 2022;10:694.
doi: 10.3390/biomedicines10030694
pubmed: 35327496
pmcid: 8945474
Phasukkijwatana N, Tan ACS, Chen X, Freund KB, Sarraf D. Optical coherence tomography angiography of type 3 neovascularisation in age-related macular degeneration after antiangiogenic therapy. Br J Ophthalmol. 2017;101:597–602.
doi: 10.1136/bjophthalmol-2016-308815
pubmed: 27503396
Ahmed M, Syrine BM, Nadia BA, Anis M, Karim Z, Mohamed G, et al. Optical coherence tomography angiography features of macular neovascularization in wet age-related macular degeneration: a cross-sectional study. Ann Med Surg. 2021;70:102826 https://www.sciencedirect.com/science/article/pii/S2049080121007767 .
doi: 10.1016/j.amsu.2021.102826
Querques G, Miere A, Souied EH. Optical coherence tomography angiography features of type 3 neovascularization in age-related macular degeneration. Dev Ophthalmol. 2016;56:57–61.
doi: 10.1159/000442779
pubmed: 27023917
Coscas F, Cabral D, Pereira T, Geraldes C, Narotamo H, Miere A, et al. Quantitative optical coherence tomography angiography biomarkers for neovascular age-related macular degeneration in remission. PLoS One. 2018;13:e0205513.
doi: 10.1371/journal.pone.0205513
pubmed: 30300393
pmcid: 6177171
Sacconi R, Fragiotta S, Sarraf D, Sadda SR, Freund KB, Parravano M, et al. Towards a better understanding of non-exudative choroidal and macular neovascularization. Prog Retin Eye Res. 2022;92:101113.
doi: 10.1016/j.preteyeres.2022.101113
pubmed: 35970724
Arrigo A, Aragona E, Bandello F. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy. Ann Med. 2022;54:1089–111. https://doi.org/10.1080/07853890.2022.2064541 .
doi: 10.1080/07853890.2022.2064541
pubmed: 35451900
pmcid: 9891228
Li Y, Baccouche B, Olayinka O, Serikbaeva A, Kazlauskas A. The role of the Wnt pathway in VEGF/Anti-VEGF-dependent control of the endothelial cell barrier. Invest Ophthalmol Vis Sci. 2021;62:17 https://doi.org/10.1167/iovs.62.12.17 .
doi: 10.1167/iovs.62.12.17
pubmed: 34787640
pmcid: 8606873
Schranz M, Told R, Hacker V, Reiter GS, Reumueller A, Vogl W-D, et al. Correlation of vascular and fluid-related parameters in neovascular age-related macular degeneration using deep learning. Acta Ophthalmol. 2022. https://doi.org/10.1111/aos.15219 .
Ablonczy Z, Dahrouj M, Marneros AG. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels. FASEB J. 2014;28:2369–79. https://doi.org/10.1096/fj.13-248021 .
doi: 10.1096/fj.13-248021
pubmed: 24558195
pmcid: 3986839
Sarkar A, Jayesh Sodha S, Junnuthula V, Kolimi P, Dyawanapelly S. Novel and investigational therapies for wet and dry age-related macular degeneration. Drug Discov Today. 2022. https://www.sciencedirect.com/science/article/pii/S135964462200160X .