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地塞米松植入治疗视网膜静脉阻塞后的促通透性因子;Ozurdex治疗视网膜静脉阻塞(ORVO)研究

Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study.

作者信息

Campochiaro Peter A, Hafiz Gulnar, Mir Tahreem A, Scott Adrienne W, Sophie Raafay, Shah Syed M, Ying Howard S, Lu Lili, Chen Connie, Campbell J Peter, Kherani Saleema, Zimmer-Galler Ingrid, Wenick Adam, Han Ian, Paulus Yannis, Sodhi Akrit, Wang Guohua, Qian Jiang

机构信息

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

出版信息

Am J Ophthalmol. 2015 Aug;160(2):313-321.e19. doi: 10.1016/j.ajo.2015.04.025. Epub 2015 Apr 20.

Abstract

PURPOSE

To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO).

DESIGN

Prospective, interventional case series.

METHODS

Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay.

RESULTS

Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P = .014 and P = .003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant.

CONCLUSIONS

Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

摘要

目的

探讨视网膜静脉阻塞(RVO)患者地塞米松植入术后房水血管活性蛋白变化与黄斑水肿的相关性。

设计

前瞻性干预性病例系列研究。

方法

23例中心性视网膜静脉阻塞(CRVO)和17例分支性视网膜静脉阻塞(BRVO)患者,尽管先前接受了抗血管内皮生长因子(VEGF)治疗仍存在水肿,在基线、地塞米松植入后4周和16周进行房水穿刺。每4周测量最佳矫正视力(BCVA)和中心子野厚度。通过蛋白质芯片或酶联免疫吸附测定法测量房水血管活性蛋白水平。

结果

在因RVO导致黄斑水肿的未治疗眼中,检测到32种房水血管活性蛋白。地塞米松植入后黄斑中心凹厚度的减少与Persephin和五聚素3的减少相关(Pearson相关系数分别为0.682和0.638,P = 0.014和P = 0.003)。随着水肿减轻,其他蛋白变化在RVO患者中有所不同,但≥50%的患者肝细胞生长因子、内分泌腺VEGF、胰岛素样生长因子结合蛋白或内皮抑素减少≥30%。对18只眼(12例CRVO,6例BRVO)进行的酶联免疫吸附测定显示,肝细胞生长因子和VEGF的基线水平分别为168.2±20.1 pg/mL和78.7±10.0 pg/mL,地塞米松植入后12只眼中这两种蛋白水平均降低。

结论

地塞米松植入物可降低多种促通透性蛋白,为RVO提供了一种多靶点治疗方法。除VEGF外,没有单一蛋白可被认为是所有患者黄斑水肿的促成因素。值得进一步研究的可能导致部分患者慢性水肿的蛋白包括Persephin、肝细胞生长因子和内分泌腺VEGF。

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