影像科学与光化学  2020, Vol. 38 Issue (1): 87-93  DOI: 10.7517/issn.1674-0475.190716   PDF    
全视网膜激光光凝术联合玻璃体腔内注射康柏西普对增生性糖尿病视网膜病变患者视功能恢复的影响
陈辑     
重庆市大足区人民医院 眼科, 重庆 402360
摘要: 本文分析了全视网膜激光光凝术(PRP)联合玻璃体腔内注射康柏西普对增生性糖尿病视网膜病变(PDR)患者视功能恢复的影响。选取大足区人民医院2016年8月~2018年8月收治的PDR患者86例(86眼),按照治疗方法分为手术组和联合组,各43例。手术组采用Carl Zeiss Meditec AG激光治疗仪在眼底荧光血管造影(FFA)引导下行PRP治疗,联合组则术前72 h于玻璃体腔内注射康柏西普0.1 mL,再行PRP治疗。采用ETDRS视力表测量两组患者术前和术后4个月的视力,非接触式眼压计测量眼压,光学相干断层扫描(OCT)检查黄斑中心凹视网膜厚度(CMT),FFA检查眼底视网膜无灌注区和新生血管消退情况,统计两组患者术后并发症发生情况。术后4个月,两组视力、CMT较术前均有变化,且联合组视力较手术组明显提高,CMT较手术组明显下降,差异有统计学意义(P < 0.05)。联合组视网膜无灌注区和新生血管消退率均明显高于手术组,差异有统计学意义(P < 0.05)。联合组术后视网膜脱离、眼高压及视网膜出血等并发症发生率为4.65%,明显低于手术组的23.26%,差异有统计学意义(P < 0.05)。研究结果显示,PRP联合玻璃体腔内注射康柏西普治疗PDR,可明显提高患者视力,降低CMT,促进已形成的无灌注区或新生血管消退,延缓视网膜新生血管增殖,改善视功能,且安全性较高,值得临床推广应用。
关键词: 增生性糖尿病视网膜病变    全视网膜激光光凝术    康柏西普    视功能    
Effect of Panretinal Laser Photocoagulation Combined with Intravitreal Injection of Conbercept on Visual Function Recovery in Patients with Proliferative Diabetic Retinopathy
CHEN Ji     
Department of Ophthalmology, Dazu District People's Hospital, Chongqing 402360, P. R. China
Abstract: To investigate the effect of PRP combined with intravitreal injection of Conbercept on visual function recovery in patients with proliferative diabetic retinopathy (PDR), 86 patients (86 eyes) with PDR were selected from August 2016 to August 2018. According to the treatment methods, they were divided into operation group and combination group, 43 cases each. The operation group was treated with PRP guided by fundus fluorescein angiography (FFA) with Carl Zeiss Meditec AG laser therapy instrument, while the combined group was treated with 0.1 mL of Conbercept injected into vitreous cavity 72 hours before operation. The visual acuity of the two groups was measured by ETDRS visual acuity meter, non-contact tonometer, optical coherence tomography (OCT) and FFA before and 4 months after operation. The incidence of postoperative complications in the two groups was analyzed. Four months after operation, the visual acuity and CMT of the two groups were changed compared with those before operation, and the vision of the combined group was significantly improved compared with that of the operation group, while CMT was significantly decreased compared with the operation group, with statistical significance (P < 0.05). Retinal non-perfusion area and the disappearance rate of neovascularization in the combined group were significantly higher than those in the operation group (P < 0.05). The incidence of complications such as retinal detachment, ocular hypertension and retinal hemorrhage was 4.65% in the combined group, which was significantly lower than 23.26% in the operation group (P < 0.05). PRP combined with intravitreal injection of Conbercept in the treatment of PDR can significantly improve the visual acuity of patients, reduce CMT, promote the formation of no perfusion area or the regression of neovascularization, delay the proliferation of retinal neovascularization, improve visual function, and has high safety, which is worthy of clinical application.
Key words: proliferative diabetic retinopathy    panretinal laser photocoagulation    Conbercept    visual function    

增生性糖尿病视网膜病变(PDR)是糖尿病常见的微血管并发症,病变表现为棉绒斑、动脉瘤、黄斑水肿、硬性渗出、出血斑点、静脉串珠状等,是致盲的主要原因之一[1]。因PDR患者视网膜内血管快速新生,可导致纤维增生,或长入玻璃体,造成玻璃体出血,或存在视网膜脱离,并且大部分患者伴有多种并发症,如视神经萎缩、视网膜血管闭塞、侵袭黄斑区牵引性等,严重损伤视神经功能,最终造成眼盲的发生,严重影响患者日常生活、工作和学习[2]。全视网膜激光光凝术(PRP)是目前临床治疗PDR的常用方法,具有良好的疗效,且对周围组织影响较小,但仍存在部分患者术后视力恢复较差等不足[3],故临床常联合抑制血管新生类药物辅助治疗[4]。康柏西普是目前临床常用的玻璃腔注射药物,它是一种重组融合蛋白,具有抗血管内皮生长因子(VEGF)作用,可特异性结合VEGF,抑制血管新生[5],但目前关于康柏西普辅助PRP治疗的研究报道并不多见。为此,本研究选取我院收治的PDR患者86例(86眼)作为研究对象,旨在探讨PRP联合玻璃体腔内注射康柏西普对患者视功能恢复的影响。

1 资料与方法 1.1 一般资料

选取大足区人民医院2016年8月~2018年8月收治的PDR患者86例(86眼),按照治疗方法分为手术组和联合组,各43例。其中,手术组:男24例、女性19例,年龄36~75岁,平均(55.48±6.14)岁;糖尿病病程2~22年,平均(12.13±3.28)年。联合组:男26例、女17例,年龄37~74岁,平均(55.69±6.03)岁;糖尿病病程2~21年,平均(11.84±3.05)年。本研究经我院医学伦理委员会批准,两组患者性别、年龄、糖尿病病程等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 入选标准

纳入标准:①符合PDR临床诊断标准[6];②单眼患病,散瞳后经眼底照相、眼底镜、视网膜电图检查确诊;③具备手术适应证;④术前最佳矫正视力(BCVA) < 0.1;⑤患者及家属均知情同意。排除标准:①既往眼部手术史;②眼部感染、青光眼、视网膜脱落;③伴有重要脏器功能不全;④伴有精神性疾病,治疗依从性较差者;⑤妊娠、哺乳期女性。

1.3 治疗方法 1.3.1 手术组

采用Carl Zeiss Meditec AG激光治疗仪在FFA引导下行PRP治疗。术前行视力、视野、眼压、光学相干断层扫描(OCT)、眼底荧光血管造影(FFA)、视觉电生理等检查,术前3 h复方托吡卡胺滴眼液散瞳;奥布卡因滴眼液表面麻醉。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[7]。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PRP向周边多出2行激光斑[8]。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。

1.3.2 联合组

术前72 h于玻璃体腔内注射康柏西普眼用注射液(成都康弘生物科技有限公司,国药准字S20130012)0.1 mL,再行PRP治疗,手术操作同手术组。两组治疗均由同一临床医师进行并负责。

1.4 观察指标

记录两组患者术前和术后4个月视力、眼压、黄斑中心凹视网膜厚度(CMT)、眼底情况及术后并发症发生情况,如视网膜脱离、眼高压及视网膜出血等。采用ETDRS视力表测量视力,非接触式眼压计测量眼压,OCT检查CMT,FFA检查眼底视网膜无灌注区和新生血管消退情况。

1.5 统计学方法

采用SPSS 22.0统计软件进行数据处理,计量资料用(x±s)表示,行t检验,计数资料用[n(%)]表示,采用χ2检验,P < 0.05表示差异有统计学意义。

2 结果 2.1 两组患者治疗前后视力、眼压、CMT比较

术前,两组视力、眼压、CMT比较差异均无统计学意义(P>0.05);术后4个月,两组视力、CMT均有变化,且联合组视力较手术组明显提高,CMT较手术组明显下降,差异有统计学意义(P < 0.05),相关数据见表 1

表 1 两组患者治疗前后视力、眼压、CMT比较(x±s)
2.2 两组患者眼底情况及术后并发症发生情况比较

术后4个月,联合组视网膜无灌注区和新生血管消退率均明显高于手术组,差异有统计学意义(P < 0.05),见图 1图 2;联合组术后并发症发生率明显低于手术组,差异有统计学意义(P < 0.05),见表 2

图 1 联合组术后4个月眼底彩照(a)和FFA图(b)

图 2 手术组术后4个月眼底彩照(a)和FFA图(b)

表 2 两组患者眼底情况及术后并发症发生情况比较[n(%)]
3 讨论

PDR是糖尿病患者常见的致盲眼病,由于糖尿病患者血液成分变化,导致血管内皮细胞功能异常,损伤血-视网膜屏障。PDR患者玻璃体出现积血、纤维增生,视网膜血管增生,引起新生血管性青光眼或视网膜脱离[9]。如果未能及时采取有效措施进行治疗,则容易造成视网膜细胞死亡、出现纤维化,使患者永久性丧失视力。

PRP手术是目前临床治疗PDR的主要方法,但在术中可能存在视网膜增殖膜、新生血管膜等与视网膜紧密连接的情况,使手术彻底剥除的难度较大,并且在手术剥除过程中可能出现医源性裂孔、视网膜出血等严重并发症,使手术风险性升高,影响手术治疗效果,甚至可导致继发性青光眼等情况[10]。因此,积极探索一种合适、有效且安全的治疗方法,对增强PDR患者的治疗效果,促进患者视力恢复具有重要意义。

有研究表明[11],VEGF是引发视网膜渗漏的常见原因。此外,因糖尿病促使视网膜广泛无灌注和缺血,可刺激VEGF的激活[12]。康柏西普是基于生物技术所产生的重组VEGF受体,可与VEGF进行特异性结合,从而发挥阻滞VEGF、抑制其信号传导、阻断视网膜新生血管生成的作用[13]。曾广川等[14]的研究表明,于激光光凝手术治疗前,玻璃体腔注射康柏西普,具有缩短手术时间和减少术后并发症等作用。有研究报道[15],于激光光凝术前,采取玻璃腔内注射康柏西普的方式可使药物直接作用于患处,从而起到恢复视力,消除血-眼屏障的作用。另有Meta分析[16]认为,于玻璃腔内注射抗VEGF类药物,可降低PDR患者玻璃体出血和黄斑水肿发生率,有助于减轻患者PRP术后视网膜功能损伤。

本研究结果显示,联合组术后4个月的视力明显高于术前和手术组(P < 0.05),CMT明显低于术前和手术组(P < 0.05),视网膜无灌注区和新生血管消退率均明显高于手术组(P < 0.05),与既往研究报道[17]相符。表明PRP联合玻璃体腔内注射康柏西普治疗PDR,可明显改善患者视力,降低CMT,促进已形成的无灌注区或新生血管消退,延缓视网膜新生血管增殖,控制病变进一步发展。其原因可能与术前玻璃体腔注射康柏西普,抑制血管新生有关。其次,联合组术后视网膜脱离、眼高压及视网膜出血等并发症发生率为4.65%,明显低于手术组的23.26%(P < 0.05),与既往研究报道[18]相符。表明PRP联合玻璃体腔内注射康柏西普治疗PDR,可有效降低术后并发症发生率,具有较高的安全性。

综上所述,PRP联合玻璃体腔内注射康柏西普治疗PDR,可明显提高患者视力,降低CMT,促进已形成的无灌注区或新生血管消退,延缓视网膜新生血管增殖,改善视功能,且安全性较高,值得临床推广应用。但本研究的样本量偏少,随访时间较短,下一步将扩大样本量、量延长随访时间进行研究。

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