Hans Journal of Ophthalmology
Vol.06 No.03(2017), Article ID:22146,6 pages
10.12677/HJO.2017.63015

Cataract Combined with Diabetic Non-Proliferative Retinopathy Reduced the Concentration of IL-12 in the Eye with Diclofenac

Sufang Zhu, Leifeng Wang, Xiaojuan Li, Qiuyan Dong, Shuqi Song

The Second Hospital of the Armed Police, Beijing

Received: Aug. 22nd, 2017; accepted: Sep. 16th, 2017; published: Sep. 25th, 2017

ABSTRACT

Objective: To investigate whether the partial use of diclofenac sodium in the treatment of cataract combined with diabetic non-proliferative retinopathy can reduce IL-12 concentration in the aqueous water. Methods: 38 cases of cataract patients with diabetes mellitus not hyperplastic retinopathy to accept the surgical treatment in our hospital, are randomly assigned for diclofenac sodium observation way and the placebo group, aqueous humor IL-12 levels are compared in research object of the two groups. There were 17 in diclofenac sodium and 21 in the placebo group. The patients of diclofenac sodium group were treated with 0.1% diclofenac 4/d and 30 days after surgery for 10 days before cataract surgery. In the placebo group, patients were given a placebo 10 days, 4/d, and postoperative standardized use of cataract surgery for 30 days. All patients were treated with antibiotic prophylaxis (tobramycin eye drops 4/d) after surgery and 30 days after surgery. Water samples collected before the operation of cataract was used to measure IL-12 concentration. Result: The concentration of IL-12 in the patients with diclofenac sodium was significantly lower than that in the placebo group. Conclusion: IL-12 was significantly elevated in diabetic patients with diabetic cataract. Such patients when get ultrasonic emulsification therapy gettering postoperative combined implantation of artificial crystal, should apply the preoperative diclofenac sodium, combine postoperative antibiotic drug therapy, which can effectively reduce the occurrence of macular edema, improve visual acuity.

Keywords:Cataract, Diabetes, Sodium Diclofenac, Interleukin 12

白内障合并糖尿病非增殖性视网膜病变患者术前局部使用双氯芬酸钠降低眼内IL-12浓度

朱素芳,王磊峰,李晓娟,董秋燕,宋殊琪

武警北京总队第二医院,北京

收稿日期:2017年8月22日;录用日期:2017年9月16日;发布日期:2017年9月25日

摘 要

目的:探讨白内障合并糖尿病非增殖性视网膜病变患者行白内障摘除手术前,局部使用双氯芬酸钠是否降低房水中IL-12浓度。方法:选取在我院拟接受手术治疗的38例白内障合并糖尿病非增殖性视网膜病变患者,随机分配为双氯芬酸钠观察组组和安慰剂对照组,对比分析两组研究对象房水中IL-12水平。其中双氯芬酸钠组17名,安慰剂组21名。双氯芬酸钠组患者在行白内障手术前10天,局部使用0.1%双氯芬酸钠4/日,术后继续用药30天。安慰剂组患者术前局部使用安慰剂10天,4/日,术后规范使用白内障术后用药共30天。所有患者术后均使用抗生素预防感染(妥布霉素滴眼液4/日),术后用药时间为30天。白内障手术术前收集房水样本用以测量IL-12浓度。结果:双氯芬酸钠组患者房水中IL-12浓度明显低于安慰剂组。结论:IL-12在发生黄斑水肿的糖尿病性白内障患者房水中明显升高。此类患者行超声乳化吸除术后联合植入人工晶体治疗时,于术前应用双氯芬酸钠,术后联合抗生素类药物治疗,可有效减少黄斑水肿的发生,提高术后视力。

关键词 :白内障,糖尿病,双氯芬酸钠,白介素-12

Copyright © 2017 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

1. 引言

我国有将近1.14亿糖尿病患者 [1] ,其中糖尿病视网膜病变是其主要的并发症之一,同时糖尿病也可加速白内障的进展 [2] 。白内障合并糖尿病非增殖性视网膜病变患者临床上以手术治疗为主,但术后患者多并发黄斑水肿的发病率在0.10%~2.30% [3] [4] ,严重时可影响患者术后视力,甚至有致盲的可能性 [5] 。

黄斑水肿初期视网膜黄斑区中心凹周围扩张的毛细血管内渗出血液成分而导致的黄斑增厚,之后逐渐在外丛状层和内丛状层积聚,形成黄斑囊样水肿 [6] 。目前认为,黄斑囊样水肿多与手术本身引起的血-房水屏障破坏释放以前列腺素为主的炎症介质有关 [7] 。

双氯芬酸钠可抑制眼内环氧化酶活性,而环氧化酶是前列腺素生物合成重要的酶 [8] 。双氯芬酸钠临床多用于控制白内障摘除术后炎症反应,缓解疼痛,还能减轻角膜切口引起的畏光反应 [9] 。

2. 对象与方法

2.1. 一般资料

选取2013年1月至2014年12月期间在我院眼科收治的38例白内障患者,合并非增殖性糖尿病视网膜病变,接受白内障摘除手术。患者接受口头及书面告知,对照组患者签知情同意书。

入组标准:年龄 > 60岁;依据ETDRS分级,糖尿病视网膜病变为轻中级;依据LOCS分级,LOCS III为2~3级。

排除标准:同时患有急性或慢性眼病的(葡萄膜炎、视网膜中央静脉阻塞、视网膜分支静脉阻塞、视网膜前膜);曾行视网膜激光光凝术;对双氯芬酸钠过敏的;口服抗凝药物的。

入组患者随机分为双氯芬酸钠观察组17人和安慰剂对照组21人,局部点眼药瓶无标签,以便保证患者与检查者对于治疗方案是双盲的。

2.2. 方法

入组患者施行统一的检查标准。首次接诊时签患者知情同意书,由同一名医师进行全面的眼科检查,包括最佳矫正视力、Goldmann压平眼压计测眼压、裂隙灯显微镜检查眼部前节、双目间接检眼镜查眼底、眼底照相、OCT测量黄斑厚度。之后在白内障手术前10天、手术当天以及术后1、7、30、90天均行眼科检查。

实验组患者术前10天开始局部点0.1%双氯芬酸钠,4/日,术后30天停药。对照组患者术前10天局部点安慰剂,术后按标准化治疗用药,即局部点0.1%氟美松4/日,妥布霉素滴眼液预防感染4/日,术后30天停药。

实验组和对照组患者均在白内障手术开始时,由术者进行前房穿刺,收集0.2 ml房水置于标本管冷藏待测。采用酶联免疫吸附法检测房水中IL-12水平含量。所有操作均按照试剂盒说明书进行。术后1 d、7 d、30 d,两组患者局部点复方托吡卡胺滴眼液散大瞳孔后,取坐位,由同一名医师行双目间接检眼镜检查眼底。然后利用光学相干断层扫描仪对患者进行黄斑检查,记录是否有水肿。

3. 结果

1) 本研究入组患者38名(23男、15女),平均年龄66.5 ± 8.4岁,平均病程15 (8~32)年。观察组和对照组在年龄、性别和糖尿病病程方面无明显差异(见表1)。术后1 d、7 d、30 d患者最佳矫正视力情况明显改善。

2) 作为反映炎症的指标,观察组和对照组房水中IL-12浓度。在观察组(27.4 ± 14.8 ug/ml)明显低于对照组(43.7 ± 19.6 ug/ml)。

3) 术后发生黄斑水肿情况:术后通过散瞳处理后在双目间接检眼镜下检查患者眼底,观察组发现2只患眼并发黄斑水肿,占11.8%,对照组为6只,占28.6%,差异有统计学意义(P < 0.05)。采用OCT检查发现,观察组发现3只患眼并发黄斑水肿,占17.6%,对照组为7只,占33.3%,差异有统计学意义(P < 0.05)。见表2

4. 讨论

白内障是糖尿病常见的并发症之一,其中以老年人居多,严重影响患者生活质量 [10] 。超声乳化吸除白内障并植入人工晶体是临床治疗白内障的主要方式 [11] 。Kim、Litvin [12] [13] 等针对糖尿病性白内障患者行超声乳化联合人工晶体植入治疗,术后患者并发黄斑水肿的概率为10%~15%。因此,如何防止术后并发黄斑囊样水肿是目前眼科亟待解决的重要问题。

Table 1. Comparison of two groups in general

表1. 两组研究对象一般情况比较

Table 2. Postoperative macular edema (eyes, (%))

表2. 两组研究对象术后发生黄斑水肿(眼,(%))

近年来,文献报道关于房水中细胞因子的研究越来越多,很多作者都在研究糖尿病患者房水中多种细胞因子,包括IL-6、IL-8 [3] [11] [14] [15] 、TGF-β2、FGF、MCP-4 [16] ,发现较非糖尿病患者明显升高。其中,IL-12由人类树突状细胞和巨噬细胞分泌,在损伤和伤口愈合时分泌增加 [15] 。其生物活性为增加NK细胞的杀伤力,增加CD8+T淋巴细胞特异性细胞毒活性 [15] 。在糖尿病患者房水中促炎症因子浓度增加提示患者有亚临床眼内炎症 [6] 。同样,我们发现房水中IL-12与白内障术后黄斑水肿的发生亦有关。术前局部应用双氯芬酸钠可明显降低房水中IL-12浓度,降低术前糖尿病视网膜病变引发的眼内炎症,也降低超乳术后黄斑水肿的发生。

黄斑囊样水肿的发病机制不明,可能因外科手术创伤使患者前列腺素类炎性物质增多 [17] ;也可能与术中眼压波动,晶体后囊破裂,玻璃体脱出牵拉黄斑区 [18] ;显微镜的光毒性 [19] [20] 等。临床针对白内障术后并发黄斑水肿患者常采用药物治疗、激光治疗以及外科手术治疗等。其中,林为华等 [21] [22] 学者报道,雷珠单抗作为高效血管内皮生长因子抑制剂,用于白内障术后降低黄斑水肿发生的概率为13.0%,显著低于常规治疗。

此外,临床较多学者研究报道非甾体类消炎镇痛药(NSAIDs),如双氯芬酸钠 [6] 、0.45%酮铬酸 [23] 、0.1%溴芬酸钠 [23] [24] 、0.3%奈帕芬胺 [25] [26] ,均有报道可用于预防简单白内障术后并发黄斑水肿。本文研究双氯芬酸钠通过抑制眼内环氧化酶活性,达到减少合成白三烯,预防术后黄斑水肿。0.1%溴芬酸钠、0.3%奈帕芬胺等作为新型NSAID制剂,具有渗透力更强、起效快的特点,其中0.3%奈帕芬胺对前列腺素有独特的靶向抑制作用 [27] ,Kern [28] Heier [29] 等都发现奈帕芬胺可有效治疗黄斑水肿。

综上所述,IL-12在发生黄斑水肿的糖尿病性白内障患者房水中明显升高。此类患者行超声乳化吸除术后联合植入人工晶体治疗时,于术前应用双氯芬酸钠,术后联合抗生素类药物治疗,可有效减少黄斑水肿的发生,提高术后视力。

文章引用

朱素芳,王磊峰,李晓娟,董秋燕,宋殊琪. 白内障合并糖尿病非增殖性视网膜病变患者术前局部使用双氯芬酸钠降低眼内IL-12浓度
Cataract Combined with Diabetic Non-Proliferative Retinopathy Reduced the Concentration of IL-12 in the Eye with Diclofenac[J]. 眼科学, 2017, 06(03): 88-93. http://dx.doi.org/10.12677/HJO.2017.63015

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