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血清促炎因子作为抗VEGF治疗解剖学反应有限的持续性糖尿病性黄斑水肿的预测指标:与现实环境中玻璃体内注射治疗情况的关联

Serum pro-inflammatory factors as predictors of persistent diabetic macular oedema with limited anatomic response to anti-VEGF: association with intravitreal injection treatment profiles in real-world setting.

作者信息

Brito Pedro, Costa Jorge, Gomes Nuno, Costa Sandra, Correia-Pinto Jorge, Silva Rufino

机构信息

Opthalmology Department, Hospital de Braga, Braga, Portugal.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, Braga, Portugal.

出版信息

Acta Ophthalmol. 2020 Jun;98(4):e421-e427. doi: 10.1111/aos.14308. Epub 2019 Nov 19.

Abstract

PURPOSE

To study the role of serum levels of pro-inflammatory factors in the identification of persistent diabetic macular oedema (DME) cases with limited anatomic response to anti-VEGF. Additionally, possible predictive associations between serum factors and intravitreal treatment profiles were analysed.

METHODS

Cases with DME were treated with monthly bevacizumab (BVZ). After the sixth month of follow-up, if the change in central foveal thickness (CFT) was <20% of baseline, combination treatment with triamcinolone was initiated. All cases underwent a baseline laboratory workup including inflammatory, metabolic and prothrombotic factors. The following outcome parameters were evaluated: percentage of CFT change from baseline, occurrence of persistent DME with <20% change in CFT, achieving CFT <330 μm with ≤6 BVZ injections, total number of intravitreal injections (IVI), number of IVI after the 6th month and number of triamcinolone acetonide (TCA) injections.

RESULTS

A total of 58 cases were included receiving a mean of 7.23 ± 1.55 IVI in 12 months, resulting in a significant improvement of visual acuity (VA) and CFT. No significant differences were found for baseline CFT, baseline LogMAR VA, diabetic retinopathy grade, age or duration of DM2 between cases initiating TCA and those treated only with anti-VEGF. Significant correlations were found between total number of IVI and the following serum factors: high-sensitivity C-reactive protein (hsCRP) (p = 0.004, r = 0.395), creatinine (p = 0.023, r = 0.338) and homocysteine (p = 0.037, r = 0.309). Regression analysis revealed that hsCRP was a significant predictor of TCA treatment (p = 0.028, r  = 0.350). Cases requiring ≤6 IVI had significantly lower values of hsCRP (1.33 ± 1.07 versus 2.46 ± 2.18 mg/l, p = 0.016) and creatinine (0.71 ± 0.28 versus 0.94 ± 0.19 mg/dl, p = 0.003).

CONCLUSIONS

Serum markers of microvascular damage (hsCRP, homocysteine and creatinine) were associated with a higher frequency of IVI due to persistent DME, suggesting a role for such biomarkers in the identification of limited responders to anti-VEGF monotherapy.

摘要

目的

研究血清促炎因子水平在鉴别对抗血管内皮生长因子(anti-VEGF)治疗解剖学反应有限的持续性糖尿病性黄斑水肿(DME)病例中的作用。此外,分析血清因子与玻璃体内治疗情况之间可能的预测关联。

方法

DME病例每月接受贝伐单抗(BVZ)治疗。随访6个月后,如果中心凹厚度(CFT)变化小于基线的20%,则开始联合曲安奈德治疗。所有病例均进行了包括炎症、代谢和血栓前状态因子在内的基线实验室检查。评估以下结局参数:CFT相对于基线的变化百分比、CFT变化小于20%的持续性DME的发生情况、接受≤6次BVZ注射后CFT达到<330μm、玻璃体内注射(IVI)总数、第6个月后的IVI次数以及曲安奈德(TCA)注射次数。

结果

共纳入58例病例,12个月内平均接受7.23±1.55次IVI,视力(VA)和CFT有显著改善。开始使用TCA的病例与仅接受抗VEGF治疗的病例在基线CFT、基线LogMAR VA、糖尿病视网膜病变分级、年龄或2型糖尿病病程方面未发现显著差异。IVI总数与以下血清因子之间存在显著相关性:高敏C反应蛋白(hsCRP)(p = 0.004,r = 0.395)、肌酐(p = 0.023,r = 0.338)和同型半胱氨酸(p = 0.037,r = 0.309)。回归分析显示,hsCRP是TCA治疗的显著预测因子(p = 0.028,r = 0.350)。需要≤6次IVI的病例hsCRP(1.33±1.07 vs 2.46±2.18mg/L,p = 0.016)和肌酐(0.71±0.28 vs 0.94±0.19mg/dl,p = 0.003)值显著更低。

结论

微血管损伤的血清标志物(hsCRP、同型半胱氨酸和肌酐)与持续性DME导致的较高IVI频率相关,表明此类生物标志物在鉴别抗VEGF单药治疗反应有限的患者中具有一定作用。

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