Advances in Clinical Medicine
Vol. 11  No. 03 ( 2021 ), Article ID: 41325 , 10 pages
10.12677/ACM.2021.113192

地塞米松玻璃体植入剂治疗不同OCT分型RVO继发ME的疗效对比

邴荣登,姜涛*,胥美琦,于志颖,刘鹏辉

青岛大学附属医院眼科,山东 青岛

收稿日期:2021年2月23日;录用日期:2021年3月11日;发布日期:2021年3月30日

摘要

目的:观察地塞米松玻璃体植入剂(Ozurdex)对视网膜静脉阻塞(retinal vein occlusion, RVO)继发黄斑水肿(macular edema, ME)的疗效,对比在不同OCT分型中的疗效并探究RVO患者预后影响因素。方法:回顾性研究。选取2018-6/2019-12于我院诊断为RVO继发ME的31例31眼作为研究对象。根据黄斑中心凹厚度(central macular thickness, CMT)分为:CMT ≤ 600 um组(15眼),CMT > 600 um组(16眼);根据是否存在浆液性视网膜脱离(serous retinal detachment, SRD)分为:SRD组(13眼),非SRD组(18眼)。31眼均行玻璃体腔内Ozurdex植入。观察并对比各组治疗前后各时间点(植入前、植入后14 d、1 mo、2 mo、3 mo、4 mo、5 mo、6 mo)的最佳矫正视力(best corrected visual acuity, BCVA)、CMT、眼压、复发率、不良反应。结果:与植入前比较,植入后14 d至6 mo患者的BCVA提高、CMT下降(P < 0.001)。CMT ≤ 600 um组BCVA优于CMT > 600 um组(P < 0.05)。植入前、植入后14 d、5 mo及6 mo CMT ≤ 600 um组CMT低于CMT > 600 um组(P < 0.05)。植入后4 mo、5 mo及6 mo,非SRD组BCVA优于SRD组、CMT小于SRD组(P < 0.05)。与植入前进行比较,植入后14 d至4 mo患者眼压升高(P < 0.05)。CMT > 600 um及合并SRD的患者复发率高于CMT ≤ 600 um及不合并SRD者(P < 0.05)。结论:Ozurdex可以在6月内提高RVO继发ME患者BCVA,降低CMT。部分患者ME会复发,CMT > 600 um及合并SRD的患者更容易复发。初始ME的轻重以及有无SRD是RVO患者的预后影响因素。

关键词

视网膜静脉阻塞,黄斑水肿,地塞米松玻璃体内植入剂,光学相干断层扫描

Comparison of the Efficacy of Intravitreal Dexamethasone Implant for the Treatment of Macular Edema Secondary to RVO with Different OCT Types

Rongdeng Bing, Tao Jiang*, Meiqi Xu, Zhiying Yu, Penghui Liu

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao Shandong

Received: Feb. 23rd, 2021; accepted: Mar. 11th, 2021; published: Mar. 30th, 2021

ABSTRACT

Aim: To observe the efficacy of intravitreal dexamethasone implant (Ozurdex) for the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO), compare the efficacy in different OCT types and explore the prognostic factors of RVO patients. Methods: Retrospective Study. A total of 31 cases of ME secondary to RVO diagnosed in our hospital from June 2018 to December 2019 were selected as the research subjects. According to the central macular thickness (CMT), they were divided into two groups: the CMT ≤ 600 um group (15 eyes) and the CMT > 600 um group (16 eyes); according to the existence of serous retinal detachment (SRD), the patients were divided into the SRD group (13 eyes) and the non-SRD group (18 eyes). All patients were intravitreally injected with Ozurdex. The best corrected visual acuity (BCVA), CMT, intraocular pressure, recurrence rate and adverse reactions were observed and compared at each time point (before implantation, 14 d, 1, 2, 3, 4, 5 and 6 mo after implantation). Results: Compared with pre-injection, BCVA was increased and CMT was decreased from 14 d to 6 mo after injection (P < 0.001). BCVA in the CMT ≤ 600 um group was better than that in the CMT > 600 um group (P < 0.05). Before implantation, 14 d, 5 mo and 6 mo after implantation, CMT of the CMT ≤ 600 um group was lower than that of the CMT > 600 um group (P < 0.05). At 4 mo, 5 mo and 6 mo after implantation, BCVA in the non-SRD group was greater than that in the SRD group, while CMT was lower than that in the combined SRD group (P < 0.05). Compared with pre-implantation, intraocular pressure increased from 14 d to 4 mo after implantation (P < 0.05). RVO patients with CMT > 600 um and SRD were more prone to relapse (P < 0.05). Conclusion: Ozurdex increased BCVA and decreased CMT in patients with ME secondary to RVO within 6 months. However, some patients with ME will relapse. Patients with CMT > 600 um and SRD were more likely to relapse. The severity of the baseline ME and the presence of SRD are prognostic factors in patients with RVO.

Keywords:Retinal Vein Occlusion, Macular Edema, Intravitreal Dexamethasone Implant, Optical Coherence Tomography

Copyright © 2021 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

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

1. 引言

视网膜静脉阻塞(retinal vein occlusion, RVO)是仅次于糖尿病视网膜病变的第二大视网膜血管疾病 [1]。RVO影响视力的最主要因素是黄斑水肿(macular edema, ME) [2]。炎症反应在RVO继发ME发生发展中发挥重要作用 [3]。地塞米松玻璃体植入剂(Ozurdex®;Allergan公司)作为一种糖皮质激素类抗炎药物于2017年被中国药品监督管理局批准用于RVO继发ME患者的治疗。本研究应用Ozurdex治疗RVO继发ME,应用不同OCT特征分组,对其6个月内的疗效进行对比研究,探讨预后相关因素。

2. 对象与方法

2.1. 对象

回顾性研究。选取2018-6/2019-12就诊于我院的31例RVO患者31眼作为研究对象。纳入标准:1)年龄 > 18岁;2) 结合眼底照相、光学相干断层扫描仪(optical coherence tomography,OCT,采用海德堡Spectralis SD-OCT)与眼底荧光素血管造影检查,诊断为RVO继发ME;3) 黄斑中心凹厚度(central macular thickness, CMT) > 250 um。排除标准:1) 治疗前玻璃体腔注射过糖皮质激素类药物或抗血管内皮生长因子(vascular endothelial growth factor, VEGF)药物;2) 治疗前1 mo全身应用过糖皮质激素;3) 治疗前进行过玻璃体切除手术或进行了白内障手术;4) 有青光眼病史或者青光眼危险因素;5) 合并其他影响BCVA的疾病。

患者根据基线CMT分为:CMT ≤ 600 um组(15眼),CMT > 600 um组(16眼);根据是否合并浆液性视网膜脱离(serous retinal detachment, SRD)分为:SRD组(13眼),非SRD组(18眼)。所有患者均行玻璃体腔植入Ozurdex治疗。本研究通过了医院伦理委员会审批。

Figure 1. Data of 1 CRVO patient. (a), (b) and (c) were the fundus photography, OCT and FFA of the patient before treatment. (d) and (e) were the fundus photography and OCT of the patients after Ozurdex implantation at 1 mo

图1. 1名CRVO患者的资料,(a)、(b)、(c)分别为患者治疗前的眼底照相、OCT、FFA;(d)、(e)分别为患者植入Ozurdex治疗1mo后的眼底照相、OCT

2.2. 方法

2.2.1. 手术方法

1) 所有患者签署知情同意书。2) 植入前3天开始滴用0.5%左氧氟沙星滴眼液,每天4次,每次l滴。3) 取仰卧位,使用盐酸奥布卡因滴眼液行表面麻醉3次,用0.09%~0.11%聚维酮碘消毒液清洁结膜囊。4) 常规消毒铺巾,显微镜下采用Ozurdex自带的22G无菌专用植入器,在距离角巩膜缘3.5~4.0 mm巩膜处穿刺后,按压植入按钮听到“咔”的一声,Ozurdex植入玻璃体腔。5) 无菌棉签按压穿刺口。6) 植入完成,涂氧氟沙星眼膏,无菌敷料包扎术眼。术后继续用左氧氟沙星滴眼液预防感染,每天4次,持续一周。

2.2.2. 观察指标

所有患者植入前及植入后14 d、1 mo、2 mo、3 mo、4 mo、5 mo、6 mo均行裂隙灯、BCVA (ETDRS视力表)、眼压(Goldman眼压计)与CMT(采用海德堡Spectralis SD-OCT)检查,同时观察有无眼部不良反应及全身并发症。复发定义:CMT较以往任何一次检查中测得最低值相比增加100 um以上或BCVA与最高值相比下降10个字母以上。

2.3. 统计学方法

采用SPSS 23.0软件进行统计学分析。所得计量资料符合正态分布且方差齐,以 x ¯ ± s表示;计数资料以n (%)表示。采用卡方检验比较患者一般特征中的计数资料以及不同分组之间的复发率。采用独立样本t检验比较患者一般特征中的计量资料。采用单因素重复测量方差分析比较治疗前后BCVA、CMT以及眼压,采用两因素重复测量方差分析比较不同分组间治疗前后的BCVA、CMT,组内两两比较采用LSD-t检验,组间比较采用独立样本t检验。P < 0.05为差异有统计学意义。

3. 结果

3.1. 患者一般信息

RVO患者共31例,其中BRVO:CRVO为13:18;男:女为14:17;缺血型:非缺血型为10:21。患者平均年龄54.84 ± 10.68岁,平均病程6.61 ± 6.28 mo。

3.2. 植入后患者BCVA、CMT及眼压变化

患者治疗前后BCVA进行比较,时间效应具有统计学意义(F = 23.356, P < 0.001)。与植入前进行比较,植入后各个随访时间BCVA均提高,差异有统计学意义(均P < 0.001)。植入后2 mo,BCVA提高幅度最大(平均提高28.52个字母),见表1

患者治疗前后CMT进行比较,时间效应具有统计学意义(F = 31.901, P < 0.001)。与植入前进行比较,植入后各个随访时间CMT下降,差异有统计学意义(均P < 0.001)。植入后2 mo,CMT下降幅度最大(平均下降377.21 um),见表1

患者治疗前后眼压进行比较,时间效应具有统计学意义(F = 9.721, P < 0.001)。与植入前进行比较,植入后14 d至4 mo患者眼压升高,差异有统计学意义(均P < 0.05),其中植入后1 mo眼压升高最明显(平均升高4.20 mmHg),见表1

Table 1. Changes of observation indexes after Ozurdex implantation

表1. Ozurdex植入后各观察指标的变化( x ¯ ± S)

注:FBCVA = 23.356,P < 0.001;FCMT = 31.901,P < 0.001;F眼压 = 9.721,P < 0.001。表格中的P为与植入前比较所得。

3.3. CMT ≤ 600 um组与CMT > 600 um组

3.3.1. CMT ≤ 600 um组与CMT > 600 um组一般资料比较

两组一般资料的差异均无统计学意义(P > 0.05),具有可比性,详见表2

Table 2. Comparison of general data between the CMT ≤ 600 um group and the CMT > 600 um group

表2. CMT ≤ 600 um组与CMT > 600 um组一般资料对比

3.3.2. CMT ≤ 600 um组与CMT > 600 um组BCVA比较

两组BCVA比较,组间和时间效应有统计学意义(F组间 = 8.937, P < 0.05; F时间 = 23.709, P < 0.001),交互效应没有统计学意义(F交互 = 1.500, P > 0.05)。CMT ≤ 600 um组BCVA优于CMT > 600 um组(P < 0.05)。CMT ≤ 600 um组与CMT > 600 um组植入后各时间点BCVA均较植入前提高(均P < 0.05),见表3图2

Table 3. Comparison of BCVA between the CMT ≤ 600 um group and the CMT > 600 um group

表3. CMT ≤ 600 um组与CMT > 600 um组BCVA比较( x ¯ ± S,个字母)

注:aP < 0.05 VS同组植入前,bP > 0.05 VS同组植入前。

Figure 2. Comparison of BCVA between the CMT ≤ 600 um group and the CMT > 600 um group (*P < 0.05 VS before implantation in the same group)

图2. CMT ≤ 600 um组与CMT > 600 um组BCVA比较(*P < 0.05 VS同组植入前)

3.3.3. CMT ≤ 600 um组与CMT > 600 um组CMT比较

两组CMT比较,组间、时间、交互效应有统计学意义(F组间 = 16.841, P < 0.001; F时间 = 39.042, P < 0.001; F交互 = 8.386, P < 0.001)。两组植入后各个随访时间点CMT均较同组植入前下降(均P < 0.05)。植入前、植入后14 d、5 mo及6 mo CMT ≤ 600 um组CMT低于CMT > 600 um组(均P < 0.05)。植入后1 mo、2 mo、3 mo及4 mo两组CMT之间差异无统计学意义(均P > 0.05),见表4图3

Table 4. Comparison of CMT between the CMT ≤ 600 um group and the CMT > 600 um group

表4. CMT ≤ 600 um组与CMT > 600 um组CMT比较( x ¯ ± S, um)

注:aP < 0.05 VS同组植入前,bP > 0.05 VS同组植入前。

Figure 3. Comparison of CMT between the CMT ≤ 600 um group and the CMT > 600 um (*P < 0.05 VS before implantation in the same group, +P < 0.05 VS another group at the same time)

图3. CMT ≤ 600 um组与CMT > 600 um组CMT比较(*P < 0.05 VS同组植入前,P < 0.05 VS组间同一时间)

3.3.4. CMT ≤ 600 um组与CMT > 600 um组复发率比较

CMT ≤ 600 um组有4眼(26.67%)复发,CMT > 600 um组有11眼(68.75%)复发。CMT ≤ 600 um组复发率低于CMT > 600 um组(χ2 = 5.490, P < 0.05)。

3.4. 非SRD组与SRD组

3.4.1. 非SRD组与SRD组一般资料比较

两组一般资料差异均无统计学意义(均P > 0.05),具有可比性,详见表5

Table 5. Comparison of general data between the non-SRD group and the SRD group

表5. 非SRD组与SRD组一般资料比较

3.4.2. 非SRD组与SRD组BCVA比较

两组BCVA比较,时间、交互效应有统计学意义(F时间 = 27.439, P < 0.05; F交互 = 7.091, P < 0.05),组间效应无统计学意义(F组间 = 1.946, P > 0.05)。非SRD组植入后14 d至6 mo BCVA均较植入前提高(均P < 0.05)。SRD组植入后14 d至4 mo BCVA均较植入前提高(均P < 0.05),植入后5 mo及6 mo BCVA与植入前比较差异无统计学意义(均P > 0.05)。植入前及植入后14 d至3 mo,两组BCVA无统计学差异。植入后4 mo、5 mo及6 mo,非SRD组BCVA优于SRD组(均P < 0.05),见表6图4

Table 6. Comparison of BCVA between the non-SRD group and the SRD group

表6. 非SRD组与SRD组BCVA比较( x ¯ ± S,个字母)

注:aP < 0.05 VS同组植入前,bP > 0.05 VS同组植入前。

Figure 4. Comparison of BCVA between the non-SRD group and the SRD group (*P < 0.05 VS before implantation in the same group, +P < 0.05 VS another group at the same time)

图4. 非SRD组与SRD组BCVA比较(*P < 0.05 VS同组植入前,P < 0.05 VS组间同一时间)

3.4.3. 非SRD组与SRD组CMT比较

两组CMT比较,组间、时间、交互效应有统计学意义(F组间 = 6.317, P < 0.05; F时间 = 37.102, P < 0.001; F交互 = 5.314, P < 0.001)。非SRD组与SRD组植入后14 d至6 mo CMT均较同组植入前下降(均P < 0.05)。植入前及植入后14 d、1 mo、2 mo及3 mo,两组CMT差异无统计学意义(均P > 0.05)。植入后4 mo、5 mo及6 mo,非SRD组CMT低于SRD组(均P < 0.05),见表7图5

Table 7. Comparison of CMT between the non-SRD group and the SRD group

表7. 非SRD组与SRD组CMT比较( x ¯ ± S, um)

注:aP < 0.05 VS同组植入前,bP > 0.05 VS同组植入前。

Figure 5. Comparison of CMT between the non-SRD group and the SRD group (*P < 0.05 VS before implantation in the same group, +P < 0.05 VS another group at the same time)

图5. 非SRD组与SRD组CMT比较(*P < 0.05 VS同组植入前,P < 0.05 VS组间同一时间)

3.4.4. 非SRD组与SRD组复发率比较

非SRD组有5眼(27.78%)复发,SRD组有10眼(76.92%)复发。非SRD组复发率低于SRD组(χ2 = 7.300,P < 0.05)。

3.5. 不良反应

所有患者在植入后没有出现白内障进展、视网膜脱离、眼内炎等严重并发症。有4眼(12.90%)出现球结膜下出血,均自行吸收。

4. 讨论

RVO继发ME可能与前列腺素、白细胞介素等炎性因子及促血管生成因子如VEGF增加有关 [3] [4]。糖皮质激素可同时抑制上述两类因子增加,从而降低ME [5] [6]。Ozurdex是一种糖皮质激素类持续性植入物,植入玻璃体内后可在6 mo内释放地塞米松,并完全降解为二氧化碳和水 [7]。图1为1名RVO患者植入Ozurdex后的变化,可以看到静脉迂曲扩张减轻、火焰状出血吸收、黄斑水肿消退。本研究发现:Ozurdex可在6 mo内有效治疗RVO继发ME,降低CMT,提高BCVA,这与Haller等 [8] 的研究相一致。有关Ozurdex的药代动力学研究发现:植入2 mo时,玻璃体腔内地塞米松浓度约为213 ng/ml,植入3 mo时浓度约为前者1/200,后期浓度继续下降 [9]。本研究发现,Ozurdex植入后2 mo时患者BCVA提高最为显著,CMT下降最为显著,这与药代动力学的研究发现相吻合 [9]。

既往有研究以400 um为基线ME严重程度进行分组,以探究RVO患者治疗后的病情变化 [10]。本研究中有28眼(90.32%) CMT > 400 um,CMT中位数和平均值同时接近600 um (中位数:606 um,平均值:635.26 um)。因此,本研究选取600 um作为分界线为基线ME严重程度进行分组。本研究发现:植入后3 mo内Ozurdex可有效降低CMT ≤ 600 um和CMT > 600 um患者CMT。Noma等 [11] 研究发现RVO患者玻璃体液中VEGF和白细胞介素-6水平与ME严重程度显著相关,这提示基线CMT较高的患者可能伴有更严重炎症反应。我们推测Ozurdex植入3 mo后释放出的地塞米松减少,不足以抑制基线ME较高患者严重的炎症反应,引起部分患者CMT逐渐升高,ME复发。本研究发现CMT > 600 um组BCVA低于CMT ≤ 600 um组,这提示初始CMT可能是影响RVO患者预后影响因素之一,这与Lin等 [12] 人的研究结果相同。

SRD在RVO患者中常见,本研究中共有13眼(41.94%)患者合并SRD。关于SRD是否影响RVO患者预后仍然存在争议。Poon等 [13] 研究发现RVO合并SRD患者初次植入贝伐单抗6 mo后有较大的形态和功能改善,作者认为存在SRD可能是RVO预后良好的一个指标。而Maggio等 [14] 研究发现,未合并SRD患者最终BCVA和CMT改善程度要比合并SRD患者高。本研究结果表明:在植入后3 mo内,SRD组与非SRD组取得了无统计学差异的形态和功能恢复。从植入后4 mo开始,SRD组的形态和功能恢复显著低于非SRD组。有研究表明:合并SRD患者常伴有严重的炎症反应,玻璃体液中有较高浓度VEGF及可溶性细胞间粘附分子-1 [15]。Ozurdex植入3mo后释放出的地塞米松减少,不足以抑制合并SRD患者严重的炎症反应,导致了合并SRD患者预后较差。脉络膜毛细血管是黄斑中心凹唯一的营养支持来源,SRD阻止了光感受器与视网膜色素上皮和脉络膜毛细血管接触 [14]。这也是合并SRD患者预后较差的原因之一。

本研究中有15眼(48.39%) ME出现了复发,平均复发时间为4.33 mo。我们对比了不同组间复发率,发现初始ME较严重及存在SRD的患者更容易复发。对于这些容易复发的患者在植入3个月以后需要更加频繁的随访,必要时需要再次植入Ozurdex来治疗。

Ozurdex最主要的并发症是眼压升高 [16] [17]。本研究中,9眼(29.3%)出现了眼压 > 25 mmHg的改变,局部滴用降眼压药后,眼压均可恢复至正常水平。因此应用Ozurdex治疗后,需要密切观察患者眼压情况,眼压升高患者需要及时使用降眼压药物来控制眼压。

由于本研究是样本量少的回顾性研究,存在一定局限性。同时本研究分组不能完全匹配,可能存在一定偏倚。在未来的研究中,需要加大规模并且延长随访时间来探究影响RVO患者预后的因素。视网膜外周血管灌注状态也可能是RVO患者预后影响因素之一,这是我们下一步的研究方向。

5. 结论

Ozurdex可在6个月内提高RVO继发ME患者BCVA,降低CMT。Ozurdex植入后部分患者ME会复发,平均复发时间为4.33 mo。初始ME较严重及存在SRD的患者更容易复发。复发患者需要再次植入Ozurdex来维持疗效。初始ME的轻重及有无SRD是RVO患者预后影响因素。

文章引用

邴荣登,姜 涛,胥美琦,于志颖,刘鹏辉. 地塞米松玻璃体植入剂治疗不同OCT分型RVO继发ME的疗效对比
Comparison of the Efficacy of Intravitreal Dexamethasone Implant for the Treatment of Macular Edema Secondary to RVO with Different OCT Types[J]. 临床医学进展, 2021, 11(03): 1343-1352. https://doi.org/10.12677/ACM.2021.113192

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  18. NOTES

    *通讯作者。

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