影像科学与光化学  2020, Vol. 38 Issue (2): 301-306  DOI: 10.7517/issn.1674-0475.190916   PDF    
改良全视网膜激光光凝术治疗糖尿病性视网膜病变的临床效果及对血清VEGF水平的影响
徐建龙1, 马青2     
1. 邢台医学高等专科学校第二附属医院 眼科, 河北 邢台 054000;
2. 邢台医学高等专科学校 检验教研室, 河北 邢台 054000
摘要: 为探讨改良全视网膜激光光凝术治疗糖尿病性视网膜病变(DR)的临床效果,以及对患者血清血管内皮生长因子(VEGF)水平的影响,本研究选取2018年1月~2019年1月我院收治的DR患者168例(212眼),随机分为对照组和观察组,各84例(106眼)。对照组给予常规全视网膜激光光凝术治疗,观察组给予改良全视网膜激光光凝术治疗,光凝治疗间隔为1周,持续4周完成治疗。随访6个月,观察两组患者的临床疗效,比较治疗前后患者的最佳矫正视力、眼压、视网膜毛细血管无灌注区和新生血管消退情况,以及血清VEGF和ET-1水平。治疗后6个月,观察组治疗总有效率为92.45%,明显高于对照组的75.47%,差异有统计学意义(P < 0.05)。两组最佳矫正视力、眼压,与治疗前及组间比较差异均无统计学意义(P>0.05)。观察组视网膜毛细血管无灌注区和新生血管消退率均明显高于对照组,差异有统计学意义(P < 0.05)。两组血清VEGF、ET-1水平较治疗前均降低,且观察组血清VEGF、ET-1水平均明显低于对照组,差异有统计学意义(P < 0.05)。两组随访期间均未出现视力严重下降、眼压升高、黄斑水肿明显增加或玻璃体出血等严重并发症。表明改良全视网膜激光光凝术治疗DR安全有效,有助于促进视网膜无灌注区和新生血管消退,降低VEGF水平,改善视网膜缺血缺氧状态,控制病变的进一步发展。
关键词: 糖尿病性视网膜病变(DR)    改良全视网膜激光光凝术    血管内皮生长因子(VEGF)    
Clinical Effect of Modified Panretinal Photocoagulation on Diabetic Retinopathy and Its Effect on Serum Level of Vascular Endothelial Growth Factor
XU Jianlong1, MA Qing2     
1. Department of Ophthalmology, The Second Affiliated Hospital of Xingtai Medical College, Xingtai 054000, Hebei, P. R. China;
2. Department of Laboratory Teaching and Research Section, Xingtai Medical College, Xingtai 054000, Hebei, P. R. China
Abstract: To investigate the clinical effect of modified panretinal photocoagulation in the treatment of diabetic retinopathy (DR) and its effect on serum vascular endothelial growth factor (VEGF), this study selected 168 DR patients (212 eyes) admitted to our hospital from January 2018 to January 2019 were randomly divided into control group and observation group, 84 cases (106 eyes) in each group. The control group was treated with whole retina laser photocoagulation, while the observation group was treated with improved whole retina laser photocoagulation. The interval of photocoagulation therapy was 1 week, the treatment lasted 4 weeks. Following up for 6 months, the clinical effects of the two groups were observed; Before and after treatment, the best corrected visual acuity, intraocular pressure, retinal capillary non-perfusion area and regression of neovascularization were compared, and serum levels of vascular endothelial growth factor and ET-1 were compared. 6 months after treatment, the total effective rate of the observation group (92.45%) was significantly higher than that of the control group (75.47%), and the difference was statistically significant (P < 0.05). There was no significant difference in the best corrected visual acuity and intraocular pressure between the two groups before and after treatment (P>0.05). Retinal capillary non-perfusion area and the regression rate of neovascularization in the observation group were significantly higher than those in the control group (P < 0.05). The levels of serum VEGF and ET-1 in both groups were lower than those before treatment, and the levels of serum VEGF and ET-1 in the observation group were significantly lower than those in the control group (P < 0.05). During the follow-up period, no serious complications such as visual acuity decrease, intraocular pressure increase, macular edema increase or vitreous hemorrhage occurred in both groups. The results show that, the modified panretinal photocoagulation is safe and effective in the treatment of DR. It is helpful to promote the regression of retinal non-perfusion area and neovascularization, reduce the level of vascular endothelial growth factor, improve the status of retinal ischemia and hypoxia, and control the further development of retinal lesions.
Key words: diabetic retinopathy(DR)    modified panretinal photocoagulation    vascular endothelial growth factor    

糖尿病性视网膜病变(DR)是糖尿病微血管病变的重要表现,是一种具有特异性改变的眼底病变,临床常表现为视物模糊、视力下降、失明等,是中老年常见的致盲眼病,临床上以是否出现视网膜新生血管为标志,将没有视网膜新生血管形成的DR称为非增殖性DR (NPDR),将有视网膜新生血管形成的DR称为增殖性DR(PDR)[1]。目前DR的发病机制尚未明确,诸多研究认为与自然免疫和炎症损伤密切相关[2]。多种细胞因子可以激活DR病理方面的信号通路,包括视网膜新生血管的形成和黄斑水肿,其中血管内皮生长因子(VEGF)会诱导血管的通透性增加,促进新生血管的生成,在DR的发病机制中起着重要作用[3]。及时激光光凝治疗可以有效防止DR向重度增殖期发展,降低失明的风险[4]。目前,常规全视网膜光凝术的治疗范围包括视盘上下、鼻侧各1个视盘直径,黄斑中心凹上下与颞侧各2个视盘直径,保留视盘黄斑束及颞侧上下血管弓之间的后极部,向周边至赤道部或略超过赤道,光凝斑反应为Ⅲ级光斑[5]。但对于重度NPDR和轻度PDR,其治疗效果不稳定,需要多次追加视网膜光凝[6]。本研究旨在探讨改良全视网膜激光光凝术治疗DR的临床效果及对患者血清VEGF、内皮素-1(ET-1)水平的影响。

1 资料与方法 1.1 一般资料

选取2018年1月~2019年1月我院收治的DR患者168例(212眼),按随机数字表法将患者分为对照组和观察组,各84例(106眼)。对照组:男38例、女46例,年龄36~76岁,平均(59.64±7.81)岁;病变类型:重度NPDR 50眼,轻度PDR 56眼;糖尿病病程6~22年,平均(16.29±3.87)年;眼压11~21 mmHg,平均(16.28±3.19) mmHg。观察组:男42例、女42例,年龄35~76岁,平均(57.47±8.79)岁;病变类型:重度NPDR 48眼,轻度PDR 58眼;糖尿病病程5~23年,平均(16.85±3.21)年;眼压10~20 mmHg,平均(16.13±2.71) mmHg。本研究经医院医学伦理委员会批准,患者及家属均知情同意。两组患者一般资料比较差异均无统计学意义(P>0.05),具有可比性。

1.2 纳入和排除标准

纳入标准:(1)符合中华医学会糖尿病学分会《中国2型糖尿病防治指南(2013年版)》[7]相关诊断标准;(2)经眼科常规检查、眼底荧光血管造影(FFA)和光学相干断层扫描(OCT)检查确诊,符合中华医学会眼科学分会眼底病学组《我国糖尿病视网膜病变临床诊疗指南》[8]中的分期标准;(3)入院前无眼部外伤和视网膜激光光凝手术史;(4)血糖、血脂、血压控制良好。

排除标准:(1)合并严重肝肾功能不全、急慢性感染、风湿结缔组织疾病、其他恶性肿瘤、大血管和微血管病变者;(2)接受新生血管药物治疗及有眼部手术史者;(3)合并其他眼科疾病者;(4)中途退出研究,导致临床数据缺失者。

1.3 治疗方法

所有患者使用标准对数视力表检查裸眼视力和矫正视力,用非接触眼压计测量眼压,并行裂隙灯、OCT及FFA检查。治疗前使用复方托吡卡胺滴眼液充分散瞳,每5 min滴1次。两组均采用德国蔡司MEL-80激光系统进行治疗,光凝治疗间隔为1周,持续4周完成治疗,所有患者均由同一医师完成激光光凝治疗。

对照组给予常规全视网膜激光光凝术治疗。光凝范围向后距视神经盘1个视盘直径,距黄斑中心凹颞侧2个视盘直径,上下以血管弓为界,向前至赤道部或略超过赤道,光斑直径300 μm,能量180~260 mW,曝光时间0.1~0.2 s,光凝斑为Ⅲ级,光斑间隔1个光斑直径,每次光凝点数约400个,总激光点数约1600个。

观察组给予改良全视网膜激光光凝术治疗。黄斑区格栅状光凝:距黄斑中心凹500~600 μm开始向外做“C”形光凝,保留盘斑束,用直径100 μm的光斑围绕中心凹做2~3排环形光凝,能量120~200 mW,曝光时间0.1~0.2 s,产生Ⅰ~Ⅱ级光斑,光斑间隔1个光斑直径。后极部、赤道部及远周边光凝:光斑直径300 μm,能量160~280 mW,曝光时间0.2~0.3 s,产生Ⅱ~Ⅲ级光斑,光斑间隔1个光斑直径,按照颞下、鼻下、颞上、鼻上的顺序完成光凝。远周边视网膜光凝时通过嘱咐患者向相应方向转动眼球及调整激光机裂隙灯光照方向,使光凝位置较常规全视网膜激光光凝术向周边多出2行激光斑[9]。对FFA显示的无灌注区和新生血管区做重点光凝,适当增加光斑能量,产生Ⅲ级光斑反应,缩小光斑间隔至0.5个光斑直径。每周1次,每次光凝的点数为500~600,光凝总量达2000~2400个激光点,分4次完成。

1.4 观察指标

(1) 视力和眼底情况:每月随访1次,记录两组患者治疗后3个月、6个月的最佳矫正视力、眼压及眼底情况。通过FFA检查眼底,记录视网膜毛细血管无灌注区和新生血管消退情况;(2)生化指标检测:收集所有患者治疗前和治疗后6个月晨起空腹静脉血5 mL,经离心后分离血清,采用酶联免疫吸附试验测定血清VEGF和ET-1水平;(3)临床疗效:治疗后6个月的FFA显示视网膜毛细血管无灌注区和新生血管消退为有效;新生血管虽未消退,但无新的新生血管出现、眼底稳定为显效;新生血管未消退,新的新生血管出现为无效。治疗总有效率=(有效眼数+显效眼数)/总眼数×100%。

1.5 统计学分析

采用SSPS 20.0软件进行数据分析。计量资料以(x±s)表示,行t检验,计数资料以(%)表示,行χ2检验,P < 0.05表示差异有统计学意义。

2 结果 2.1 两组治疗前后最佳矫正视力、眼压及眼底情况比较

治疗后3个月、6个月,两组患者最佳矫正视力、眼压与治疗前及组间比较差异均无统计学意义(P>0.05),治疗后6个月,观察组患者视网膜毛细血管无灌注区和新生血管消退率均明显高于对照组,差异有统计学意义(P < 0.05),数据见表 1

表 1 两组治疗前后最佳矫正视力、眼压及眼底情况比较(x±s)
2.2 两组治疗前后血清VEGF、ET-1水平比较

治疗后6个月,两组患者血清VEGF、ET-1水平较治疗前均降低,且观察组血清VEGF、ET-1水平均明显低于对照组,差异有统计学意义(P < 0.05),数据见表 2

表 2 两组患者治疗前后血清VEGF、ET-1水平比较(x±s)
2.3 两组临床疗效比较

治疗后6个月,观察组患者治疗总有效率为92.45%,明显高于对照组的75.47%,差异有统计学意义(P < 0.05),见表 3。两组患者随访期间均未出现视力严重下降、眼压升高、黄斑水肿明显增加或玻璃体出血等严重并发症。

表 3 两组患者临床疗效比较[眼(%)]
3 讨论

DR是糖尿病最常见的并发症之一,可导致糖尿病性黄斑水肿的发生和视力的丧失[10]。视网膜血管对高血糖最早的反应是血管扩张和血流改变,这种变化引起视网膜代谢自动调节,增加糖尿病患者的视网膜代谢,随着疾病的进展,毛细血管无灌注区的产生可导致视网膜新生血管开始生长,发展成为PDR[11]。而DR的这些病理改变是通过缺氧、慢性炎症、氧化应激、糖基化终末产物(AGEs)形成、肾素-血管紧张素通路、生长因子、脂质氧化及其产物等多种机制激活的[12]。人体组织和细胞中广泛存在蛋白激酶C(PKC),并参与生命活动,高血糖使PKC活化,活化的PKC不但可以使具有强烈缩血管作用的ET-1释放增加,也可以促进血管内皮生长因子VECF的表达[13]。VEGF是目前发现的最强的促血管生成因子,刺激血管内皮细胞增殖,上调血浆纤溶酶原激活物的表达,导致细胞外基质发生变性,诱导新生血管形成[14]。ET-1能强烈收缩血管、刺激血管平滑肌细胞增殖,亦可诱导VEGF大量表达,形成新生血管等增殖性病变,最终发展为玻璃体积血、继发性视网膜脱离和新生血管性青光眼,严重时可导致眼盲[15]

目前,全视网膜激光光凝术是治疗重度NPDR和轻度PDR的有效手段,其基本原理是破坏高耗氧视网膜色素上皮组织,使其瘢痕化,以改善视网膜缺血状态,使新生血管生长因子产生减少[16];减弱视网膜的外屏障,增加脉络膜的氧供应至视网膜,使供氧渠道改善[17];视网膜周边的区域被光凝后,改变了血流分布,使有限的血流更多地供应黄斑区,阻止病变进展,缓解视力下降,从而保护视功能[18]。本研究结果显示,治疗后6个月复查,两组视力均呈轻度上升趋势,组间比较差异无统计学意义(P>0.05),但观察组视网膜毛细血管无灌注区和新生血管消退率均明显高于对照组(P < 0.05),总有效率也明显高于对照组(P < 0.05),且观察组血清VEGF、ET-1水平均明显低于对照组(P < 0.05),其原因可能为:(1)先行黄斑区格栅样光凝,在进行全视网膜光凝前激光斑先将视网膜分隔成两部分,使后极部视网膜处于相对独立的区域,形成类似“堤坝”效应,有助于封闭后极部的无灌注区,从而抑制后极部视网膜新生血管的发展,减少黄斑水肿的发生几率,促进患者视力的提高[19];(2)改良全视网膜激光光凝术使周边视网膜无灌注区或新生血管部位光凝的更为充分,减少新生血管发生的几率,也有助于促进已形成的新生血管消退。同时,对FFA显示的视网膜无灌注区和新生血管区进行重点光凝,增加光凝能量,缩小光斑间距,从而快速、彻底缓解视网膜缺氧,减少VEGF的生成,去除新生血管生成的始动因素,促使新生血管消退。而对于无灌注区和新生血管之外的视网膜,光斑密度和光凝能量适当减小,避免了不必要的视网膜损伤,更好地保留了视网膜功能[20]。本研究还发现,两组患者随访期间均未出现视力严重下降、眼压升高、黄斑水肿明显增加或玻璃体出血等严重并发症,表明改良全视网膜激光光凝术治疗DR具有较高的安全性。

综上所述,改良全视网膜激光光凝术治疗DR安全有效,有助于促进视网膜无灌注区和新生血管消退,降低VEGF水平,改善视网膜缺血缺氧状态,可控制病变的进一步发展。

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