Kim Jong Ho, Shin Jae Pil, Kim In Taek, Park Dong Ho
Invest Ophthalmol Vis Sci. 2016 Jan 1;57(1):6-11. doi: 10.1167/iovs.15-18304.
To investigate whether macular edema (ME) due to branch retinal vein occlusion (BRVO) associates with retinal overexpression of angiopoietin-like 4 (ANGPTL4). The aqueous ANGPTL4 and vascular endothelial growth factor (VEGF) levels in patients with ME due to BRVO were measured, and the relationships between ANGPTL4 levels and the degree of retinal ischemia and edema were determined.
The study and control groups consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve BRVO with ME and senile cataract surgery, respectively. The study group was divided into the major BRVO and macular BRVO subgroups on the basis of the involved retinal area. The aqueous ANGPTL4 and VEGF levels were measured by enzyme-linked immunosorbent assay. In the patients with BRVO, capillary nonperfusion area by fluorescein angiography and central subfield macular thickness (CSMT) and total macular volume (TMV) by spectral-domain optical coherence tomography were determined.
Patients with ME due to BRVO (50 eyes) had higher aqueous ANGPTL4 and VEGF levels than the controls (61 eyes) (both P < 0.001). The major BRVO had higher ANGPTL4 and VEGF levels than the macular BRVO (both P < 0.001). The aqueous ANGPTL4 levels of all BRVO patients correlated positively with nonperfusion area (r = 0.901, P < 0.001), CSMT (r = 0.574, P < 0.001), and TMV (r = 0.453, P = 0.001), even after adjustment for VEGF levels.
The aqueous ANGPTL4 levels correlated significantly with phenotypes of BRVO with ME. This suggests that ANGPTL4 may be a candidate biomarker and treatment target in ischemia-induced retinopathies, including BRVO.
研究视网膜分支静脉阻塞(BRVO)所致黄斑水肿(ME)是否与血管生成素样4(ANGPTL4)在视网膜的过表达相关。测量BRVO所致ME患者房水中ANGPTL4和血管内皮生长因子(VEGF)水平,并确定ANGPTL4水平与视网膜缺血和水肿程度之间的关系。
研究组和对照组分别由所有计划接受玻璃体腔注射贝伐单抗治疗初治的BRVO合并ME患者和老年性白内障手术患者组成。研究组根据受累视网膜区域分为主要BRVO和黄斑BRVO亚组。采用酶联免疫吸附测定法测量房水中ANGPTL4和VEGF水平。对于BRVO患者,通过荧光素血管造影确定毛细血管无灌注区,通过光谱域光学相干断层扫描确定黄斑中心子区域厚度(CSMT)和黄斑总体积(TMV)。
BRVO所致ME患者(50只眼)房水中ANGPTL4和VEGF水平高于对照组(61只眼)(均P<0.001)。主要BRVO患者的ANGPTL4和VEGF水平高于黄斑BRVO患者(均P<0.001)。即使在调整VEGF水平后,所有BRVO患者的房水ANGPTL4水平与无灌注区(r=0.901,P<0.001)、CSMT(r=0.574,P<;0.001)和TMV(r=0.453,P=0.001)呈正相关。
房水ANGPTL4水平与BRVO合并ME的表型显著相关。这表明ANGPTL4可能是包括BRVO在内的缺血性视网膜病变的候选生物标志物和治疗靶点。