Pfister Marcel, Rothweiler Florian, Michaelis Martin, Cinatl Jindrich, Schubert Ralf, Koch Frank H, Koss Michael J
Department of Ophthalmology, Goethe University, Frankfurt, Germany ; Doheny Eye Institute, University of Southern California, Los Angeles, CA, USA.
Clin Ophthalmol. 2013;7:1061-7. doi: 10.2147/OPTH.S42786. Epub 2013 Jun 4.
To assess the levels of inflammatory and angiogenic cytokines in undiluted vitreous from treatment-naïve patients with macular edema secondary to nonischemic branch retinal vein occlusion (BRVO), with flow cytometric bead array (CBA) and to correlate the results with subjective and multiple spectral-domain optical coherence tomography (SD-OCT) parameters.
A total of 43 eyes from 43 patients (mean age 69.7 years, 23 male) were divided into groups of new, "fresh" (n = 28; mean duration after onset 4.1 months) and older BRVO (n = 15; 11.6 months). Because of macular edema, these patients underwent an intravitreal therapy combining a single-site 23 g core vitrectomy with bevacizumab and dexamethasone. Undiluted vitreous was then analyzed for interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor isoform A (VEGF-A) levels with CBA and correlated with visual acuity (VA), clinical parameters of BRVO (type and perfusion status), and morphologic parameters, such as central macular thickness, central retinal thickness, thickness of the neurosensory retina, thickness of the serous retinal detachment, and the disruption of the ellipsoid line (photoreceptor inner and outer segments) and the external limiting membrane, as measured with SD-OCT. Twenty-eight undiluted vitreous samples from patients with idiopathic, nonuveitis vitreous floaters served as the controls.
The mean IL-6 was 23.2 pg/mL (standard deviation, ±48.8), MCP-1 was 602.6 (±490.3), and VEGF-A was 161.8 (±314.3), and this was higher than in the control group, which had a mean IL-6 of 6.2 ± 3.4 pg/mL (P = 0.17), MCP-1 of 253.2 ± 73.5 (P < 0.0000001), and VEGF-A of 7.0 ± 4.9 (P < 0.003). In all BRVO samples, IL-6 correlated positively with MCP-1 and VEGF-A (correlation coefficient r = 0.79 and r = 0.46, respectively). VEGF-A was the only cytokine to correlate significantly with SD-OCT parameters (thickness of the neurosensory retina r = 0.31; disruption of the ellipsoid line r = 0.33). In the older BRVO group, there was a positive correlation between cytokines (IL-6 with MCP-1, r = 0.77; Il-6 with VEGF-A, r = 0.68; MCP-1 and VEGF-A, r = 0.68), whereas only IL-6 correlated with MCP-1 in the fresh group (r = 0.8).
The inflammatory markers and VEGF-A were elevated in the vitreous fluid of patients with BRVO, and these correlated with one another. VEGF-A was more often correlated with the morphologic changes assessed by SD-OCT, whereas the inflammatory markers had no significant influence on SD-OCT changes.
采用流式细胞仪微球阵列(CBA)评估未经治疗的非缺血性视网膜分支静脉阻塞(BRVO)继发黄斑水肿患者未稀释玻璃体中炎症和血管生成细胞因子的水平,并将结果与主观及多光谱域光学相干断层扫描(SD-OCT)参数相关联。
43例患者(平均年龄69.7岁,23例男性)的43只眼被分为新发“新鲜”BRVO组(n = 28;发病后平均病程4.1个月)和陈旧性BRVO组(n = 15;11.6个月)。由于黄斑水肿,这些患者接受了玻璃体腔内联合23G单通道核心玻璃体切除术、贝伐单抗和地塞米松的治疗。然后采用CBA分析未稀释玻璃体中的白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)和血管内皮生长因子A亚型(VEGF-A)水平,并将其与视力(VA)、BRVO的临床参数(类型和灌注状态)以及形态学参数相关联,这些形态学参数如中心黄斑厚度、中心视网膜厚度、神经感觉视网膜厚度、浆液性视网膜脱离厚度以及用SD-OCT测量的椭圆体线(光感受器内外节)和外界膜的破坏情况。来自特发性、非葡萄膜炎性玻璃体混浊患者的28份未稀释玻璃体样本作为对照。
IL-6平均为23.2 pg/mL(标准差,±48.8),MCP-1为602.6(±490.3),VEGF-A为161.8(±314.3),均高于对照组,对照组IL-6平均为6.2±3.4 pg/mL(P = 0.17),MCP-1为253.2±73.5(P < 0.0000001),VEGF-A为7.0±4.9(P < 0.003)。在所有BRVO样本中,IL-6与MCP-1和VEGF-A呈正相关(相关系数r分别为0.79和0.46)。VEGF-A是唯一与SD-OCT参数显著相关的细胞因子(神经感觉视网膜厚度r = 0.31;椭圆体线破坏r = 0.33)。在陈旧性BRVO组中,细胞因子之间呈正相关(IL-6与MCP-1,r = 0.77;IL-6与VEGF-A,r = 0.68;MCP-1与VEGF-A,r = 0.68),而在新鲜组中只有IL-6与MCP-1相关(r = 0.8)。
BRVO患者玻璃体中的炎症标志物和VEGF-A升高,且它们之间相互关联。VEGF-A更常与SD-OCT评估的形态学变化相关,而炎症标志物对SD-OCT变化无显著影响。