血管空鞘在抗 VEGF 治疗后仍存在于脉络膜新生血管中，这在动物模型和人类中均有体现。
Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.
机构信息
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Doheny Eye Institute, Pasadena, CA, USA.
出版信息
Graefes Arch Clin Exp Ophthalmol. 2023 Aug;261(8):2189-2197. doi: 10.1007/s00417-023-06018-z. Epub 2023 Mar 4.
PURPOSE
Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy.
METHODS
We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA).
RESULTS
In the CNV mouse model, the CD31 vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7 ± 10864.7 vs. 10745.9 ± 5755.9 μm, P < 0.05), whereas a significant difference was not observed in the area of type IV collagen vascular empty sleeve after the treatment compared with the control (29135.0 ± 7432.9 vs. 24592.0 ± 5935.3 μm, P = 0.7). The proportions of CD31 to type IV collagen areas were significantly decreased after the treatment (38.7 ± 7.4% vs. 17.1 ± 5.4%, P < 0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2 ± 23.4 months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%).
CONCLUSIONS
Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.
目的
血管内皮生长因子（VEGF）治疗时常出现脉络膜新生血管（CNV）复发，但血管再生长的机制知之甚少。有人提出，血管再生长沿着基膜的空套管，是肿瘤中 VEGF 抑制逆转后复发的机制。本研究旨在探讨该机制是否参与 VEGF 治疗中的 CNV。
方法
我们利用小鼠模型和 CNV 患者进行了两项观察。利用激光诱导的 CNV 小鼠，分别用 IV 型胶原和 CD31 的免疫组织化学方法检测基膜的血管空套管和 CNV。一项回顾性队列研究纳入了 17 例接受抗 VEGF 治疗的 CNV 患者的 17 只眼。采用光学相干断层扫描血管造影（OCTA）评估抗 VEGF 治疗期间的血管再生长。
结果
在 CNV 小鼠模型中，与 IgG 对照组相比，抗 VEGF 治疗期间 CD31 血管内皮面积减少（33516.7±10864.7 比 10745.9±5755.9μm，P<0.05），而治疗后血管空套管的 IV 型胶原面积与对照组相比无显著差异（29135.0±7432.9 比 24592.0±5935.3μm，P=0.7）。治疗后 CD31 与 IV 型胶原面积的比例明显下降（38.7±7.4%比 17.1±5.4%，P<0.05）。在 OCTA 观察中，回顾性队列研究的随访时间为 58.2±23.4 个月。在 17 只眼中观察到 682 条新生血管的 CNV 再生长。在第 1 组中，CNV 消退和再生长为同一形式（129 条新生血管，18.9%）。在第 2 组中，CNV 消退和再生长为不同形式（170 条新生血管，24.9%）。在第 3 组中，CNV 再生长为不同形式，无消退（383 条新生血管，56.2%）。
结论
部分 CNV 再生长可能发生在抗 VEGF 治疗后残留的血管空套管中。
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