Analysis of the Vascular Morphology of the Fibrotic Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography AngiographyArticle in several languages: English | deutsch
Purpose Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA).
Methods In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruchʼs membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images.
Results Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006).
Conclusion In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.
Received: 09 April 2020
Accepted: 08 June 2020
31 August 2020 (online)
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- 1 Wong WL, Su X, Li X. et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014; 2: e106-e116 doi:10.1016/S2214-109X(13)70145-1
- 2 Park YG, Rhu HW, Kang S. et al. New approach of anti-VEGF agents for age-related macular degeneration. J Ophthalmol 2012; 2012: 637316 doi:10.1155/2012/637316
- 3 Bressler NM. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. Arch Ophthalmol 2001; 119: 198-207 doi:10.1001/pubs.Ophthalmol.-ISSN-0003-9950-119-2-ecs00156
- 4 Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration?. Retina 2010; 30: 1333-1349 doi:10.1097/IAE.0b013e3181e7976b
- 5 Spaide RF, Fujimoto JG, Waheed NK. et al. Optical coherence tomography angiography. Prog Retin Eye Res 2018; 64: 1-55 doi:10.1016/j.preteyeres.2017.11.003
- 6 Dansingani KK, Tan ACS, Gilani F. et al. Subretinal hyperreflective material imaged with optical coherence tomography angiography. Am J Ophthalmol 2016; 169: 235-248 doi:10.1016/j.ajo.2016.06.031
- 7 Schmidt-Erfurth U, Chong V, Loewenstein A. 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: 1144-1167 doi:10.1136/bjophthalmol-2014-305702
- 8 Faatz H, Farecki M-L, Rothaus K. et al. Optical coherence tomography angiography of types 1 and 2 choroidal neovascularization in age-related macular degeneration during anti-VEGF therapy: evaluation of a new quantitative method. Eye (Lond) 2019; 33: 1466-1471 doi:10.1038/s41433-019-0429-8
- 9 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
- 10 Curcio CA, Balaratnasingam C, Messinger JD. et al. Correlation of type 1 neovascularization associated with acquired vitelliform lesion in the setting of age-related macular degeneration. Am J Ophthalmol 2015; 160: 1024-1033.e3 doi:10.1016/j.ajo.2015.08.001
- 11 Pauleikhoff D, Gunnemann F, Book M. et al. Progression of vascular changes in macular telangiectasia type 2: comparison between SD-OCT and OCT angiography. Graefes Arch Clin Exp Ophthalmol 2019; 257: 1381-1392 doi:10.1007/s00417-019-04323-0
- 12 Farecki M-L, Gutfleisch M, Faatz H. et al. Characteristics of type 1 and 2 CNV in exudative AMD in OCT-angiography. Graefes Arch Clin Exp Ophthalmol 2017; 255: 913-921 doi:10.1007/s00417-017-3588-y
- 13 Faatz H, Farecki M-L, Rothaus K. et al. Changes in the OCT angiographic appearance of type 1 and type 2 CNV in exudative AMD during anti-VEGF treatment. BMJ Open Ophthalmol 2019; 4: e000369 doi:10.1136/bmjophth-2019-000369
- 14 Little K, Ma JH, Yang N. et al. Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration – the potential sources and molecular cues for their recruitment and activation. EBioMedicine 2018; 38: 283-291 doi:10.1016/j.ebiom.2018.11.029
- 15 Willoughby AS, Ying G-S, Toth CA. et al. Subretinal hyperreflective material in the comparison of age-related macular degeneration treatments trials. Ophthalmology 2015; 122: 1846-1853.e5 doi:10.1016/j.ophtha.2015.05.042
- 16 Miere A, Semoun O, Cohen SY. et al. Optical coherence tomography angiography features of subretinal fibrosis in age-related macular degeneration. Retina 2015; 35: 2275-2284 doi:10.1097/IAE.0000000000000819
- 17 Miere A, Butori P, Cohen SY. et al. Vascular remodelling of choroidal neovascularization after anti-vascular endothelial growth factor therapy visualized on optical coherence tomography. Retina 2019; 39: 548-557 doi:10.1097/IAE.0000000000001964
- 18 Lira RP, Oliveira CL, Marques MV. et al. Adverse reactions of fluorescein angiography: a prospective study. Arq Bras Oftalmol 2007; 70: 615-618 doi:10.1590/S0004-27492007000400011
- 19 Sulzbacher F, Pollreisz A, Kaider A. et al. Identification and clinical role of choroidal neovascularization characteristics based on optical coherence tomography angiography. Acta Ophthalmol 2017; 95: 414-420 doi:10.1111/aos.13364
- 20 Babiuch AS, Uchida A, Figueiredo N. et al. Impact of optical coherence tomography angiography review strategy on detection of choroidal neovascularization. Retina 2020; 40: 672-678 doi:10.1097/IAE.0000000000002443
- 21 Schneider EW, Fowler SC. Optical coherence tomography angiography in the management of age-related macular degeneration. Curr Opin Ophthalmol 2018; 29: 217-225 doi:10.1097/ICU.0000000000000469
- 22 Uchida A, Hu M, Babiuch A. et al. Optical coherence tomography angiography characteristics of choroidal neovascularization requiring varied dosing frequencies in treat-and-extend management: an analysis of the AVATAR study. PLoS One 2019; 14: e0218889 doi:10.1371/journal.pone.0218889
- 23 Xu D, Dávila JP, Rahimi M. et al. Long-term progression of type 1 neovascularization in age-related macular degeneration using optical coherence tomography angiography. Am J Ophthalmol 2018; 187: 10-20 doi:10.1016/j.ajo.2017.12.005