泪液MMP-2、TGF-β1水平变化与白内障超声乳化术后干眼的关系

Relationship between changes in tear MMP-2 and TGF-β1 levels and dry eye after phacoemulsification for cataract surgery

摘要

目的 分析泪液基质金属蛋白酶-2(matrix metalloproteinase-2, MMP-2)、转化生长因子-β1(transforming growth factor-β1, TGF-β1)水平变化与白内障超声乳化术后干眼的关系。方法 以进行超声乳化术治疗的156例白内障患者为研究对象,对所有研究对象进行为期3个月的随访,并根据随访结果分为干眼组(36例)和非干眼组(120例)。收集研究对象的临床资料,采用酶联免疫吸附法监测泪液MMP-2、TGF-β1水平,通过t检验、χ²检验及非条件logistic回归分析筛选影响白内障超声乳化术后干眼发生的危险因素。绘制受试者工作特征(receiver operating characteristic, ROC)曲线分析泪液MMP-2、TGF-β1水平对白内障超声乳化术后发生干眼的预测价值。结果 156例均获得完全随访,36例发生干眼,干眼发生率为23.08%(36/156)。干眼组睑板腺功能障碍占比高于非干眼组(P=0.002)。与术前相比,干眼组患者术后第3天、术后2周、术后1个月泪液MMP-2、TGF-β1水平明显升高(均P<0.001),非干眼组术后上述指标总体呈下降趋势。校正后两组患者术后第3d泪液MMP-2、TGF-β1经Bonferroni检验差异有统计学意义(P<0.001)。Logistic回归分析结果显示,影响患者术后发生干眼的危险因素有睑板腺功能障碍[OR(95%CI):2.408(1.138~3.679)]、术后第3天泪液MMP-2[OR(95%CI):4.943(2.468~7.418)]、TGF-β1[OR(95%CI):3.025(1.672~4.379)](P<0.05)。ROC曲线结果显示,术后第3d泪液MMP-2、TGF-β1联合检测预测白内障超声乳化术后发生干眼的ROC曲线下面积(AUC)95%CI、敏感度、特异度分别为0.917(0.874~0.960)、97.20%、83.30%,均高于上述指标单独检测(DeLong检验:Z=2.867、3.215,P=0.023、<0.001)。结论 泪液MMP-2、TGF-β1水平高表达与白内障超声乳化术后发生干眼密切相关,二者联合检测对白内障超声乳化术后发生干眼的预测价值更高,有望成为评估白内障超声乳化术后发生干眼的潜在标志物,且可为干眼的预防提供新的研究方向。

Abstract

Objective To investigate the relationship between changes in the levels of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β1 (TGF-β1) in tear fluid and dry eye following phacoemulsification for cataracts. Methods This study included 156 patients who underwent phacoemulsification for cataract surgery. All participants were followed up for 3 months and were classified into a dry eye group (36 patients) and a non-dry eye group (120 patients) based on the follow-up results. Clinical data were collected from the study participants, and level of MMP-2 and TGF-β1 in tears were measured using an enzyme-linked immunosorbent assay (ELISA). T-tests, chi-square tests, and unconditional logistic regression analysis were used to identify risk factors for the development of dry eye following phacoemulsification for cataracts. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of tear MMP-2 and TGF-β1 levels for the development of dry eye following phacoemulsification. Results All 156 patients were fully followed up; 36 patients developed dry eye, resulting in an incidence rate of 23.08% (36/156). The prevalence of meibomian gland dysfunction was higher in the dry eye group than in the non-dry eye group (P=0.002). Compared with preoperative levels, at postoperative day 3, week 2, and month 1, tear fluid levels of MMP-2 and TGF-β1 were significantly elevated in the dry eye group (P<0.001), while these markers generally showed a downward trend in the non-dry eye group. After adjustment, the postoperative levels of MMP-2 and TGF-β1 in tear fluid on day 3 were found to differ significantly between the two groups following a Bonferroni test (P<0.001). Logistic regression analysis revealed that risk factors for postoperative dry eye in patients included meibomian gland dysfunction [OR (95%CI): 2.408(1.138-3.679)], postoperative day 3 tear MMP-2 [OR (95%CI): 4.943(2.468-7.418)], and TGF-β1 [OR (95%CI): 3.025(1.672-4.379)] (P<0.05). The ROC curve results showed that the area under the ROC curve (AUC), 95%CI, sensitivity, and specificity for predicting the occurrence of dry eye after phacoemulsification cataract surgery using combined postoperative day 3 tear MMP-2 and TGF-β1 testing were 0.917(0.874-0.960), 97.20%, and 83.30%, respectively, all of which were higher than those obtained when these markers were tested individually (DeLong test: Z-values=2.867 and 3.215, P=0.023 and <0.001). Conclusion Elevated levels of MMP-2 and TGF-β1 in tears are closely associated with the development of dry eye following phacoemulsification. Combined testing of these two markers demonstrates greater predictive value for dry eye following phacoemulsification, suggesting they may serve as potential biomarkers for assessing the risk of dry eye after this procedure and offering a new direction for research into the prevention of dry eye.

关键词

基质金属蛋白酶-2 / 转化生长因子-β1 / 白内障 / 超声乳化术 / 干眼

Key words

Matrix metalloproteinase-2 / Transforming growth factor-β1 / Cataracts / Ultrasonic emulsification / Dry eye syndrome

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基金资助

国家自然科学基金(82000866)

南京市卫生科技发展项目(YKK24121)