玻璃体腔注射雷珠单抗联合筋膜囊注射曲安奈德治疗视网膜静脉阻塞继发黄斑水肿

李婷婷 牛彤彤

玻璃体腔注射雷珠单抗联合筋膜囊注射曲安奈德治疗视网膜静脉阻塞继发黄斑水肿

李婷婷 牛彤彤

目的 评价玻璃体腔注射雷珠单抗(ranibizumab)联合筋膜囊下注射曲安奈德(TA)治疗视网膜静脉阻塞(RVO)继发黄斑水肿(ME)的临床疗效。方法经眼底荧光血管造影(FFA)及光学相干断层扫描(OCT)检查确诊为RVO合并黄斑水肿的患者30例,30眼。对比分析单次玻璃体腔注射雷珠单抗联合筋膜囊下注射TA治疗前后最佳矫正视力(BCVA)、OCT的变化。结果治疗前与治疗后1周、1、3个月BCVA分别为(0.727±0.115)、(0.591±0.062)、(0.528±0.083)、(0.494±0.082)；黄斑中心厚度(CMT)分别为(482.6±75.9)μm、(402.7±77.2)μm、(344.6±72.7)μm、(310.6±68.7)μm。治疗后1周、1、3个月BCVA显著提高, CMT显著降低, 与治疗前相比差异均具有统计学意义(P＜0.05)；治疗后1、3个月分别与治疗后1周相比, BCVA显著提高, CMT显著降低, 差异均具有统计学意义(P＜0.05)；治疗后3个月和1个月相比, BCVA提高, CMT降低, 但差异无统计学意义(P＞0.05)。结论玻璃体腔注射雷珠单抗联合筋膜囊下注射TA可以在短期内减轻黄斑水肿、提高BCVA, 为RVO继发黄斑水肿治疗提供了新的思路, 但长期效果有待进一步观察。

雷珠单抗；玻璃体腔注射；曲安奈德；视网膜静脉阻塞；黄斑水肿

黄斑水肿是黄斑中心凹部位视网膜毛细血管发生微血管异常, 视网膜色素上皮(retinal pigment epithelium, RPE)细胞离子泵功能损害导致液体渗漏的结果[1］。视网膜静脉阻塞是一种可引起明显视觉障碍的视网膜血管病, 主要发生于65岁以上人群[2-4］, 视网膜静脉阻塞(retinal venous occlusions, RVO)并发症较多, 其中黄斑水肿最为常见, 是RVO患者视力丧失的一个主要原因[5］。传统的视网膜光凝是治疗RVO所致黄斑水肿(macular edema, ME)的主要手段, 但效果不理想。近年来, 越来越多的糖皮质激素治疗[6-8］及抗血管内皮生长因子(vascular endothelial growth factor, VEGF)药物被应用于治疗黄斑水肿相关疾病[9］。糖皮质激素在RVO所致黄斑水肿中稳定血视网膜屏障减少血管通透性。抗VEGF治疗如雷珠单抗可拮抗VEGF促血管内皮增殖作用, 降低血管通透性, 从而使黄斑水肿患者视网膜内渗液减少, 并促进其吸收, 达到消除水肿, 减轻症状的目的[10］。由于雷珠单抗在玻璃体腔内存在的半衰期较短, 往往需要重复注射以维持疗效,不但增加患者的经济负担, 更增加了玻璃体腔注药致眼内炎等并发症发生的风险。故本研究通过采取玻璃体腔注射雷珠单抗联合筋膜囊注射曲安奈德(triamcinolone acetonide, TA)治疗RVO继发黄斑水肿, 取得了良好的治疗效果, 现报告如下。

1 资料与方法

1.1 一般资料 选取2012年10月～2013年5月于本院眼科收治的经常规检查、眼底荧光血管造影(fundus fluorescence angiography, FFA)及光学相干断层扫描(optical coherence tomography, OCT)检查确诊为RVO继发黄斑水肿的患者30例30眼, 其中男17例17眼, 女13例13眼, 年龄37～66岁。病程1周～3个月。最佳矫正视力(0.727±0.115)；OCT测得黄斑中心厚度(482.6±75.9)μm。病例纳入标准：①继发于RVO的黄斑水肿；②病程不超过3个月；③全部患者既往无其他眼底激光光凝或球内注射药物等侵入性治疗或眼部手术史。排除标准：①合并严重的白内障、角膜病、玻璃体积血等严重屈光间质浑浊影响治疗及检查者；②合并其他视网膜及视神经病变, 如糖尿病性视网膜病变、脉络膜新生血管(CNV)、视网膜脱离等；③严重高血压, 糖尿病, 心、肺、肾功能不全者。

1.2 方法 注药前3 d左氧氟沙星滴眼液6次/d清洁结膜囊；注药前冲洗泪道, 清洁结膜囊。注药前30 min复方托吡卡胺滴眼液散瞳。玻璃体腔注射按照内眼手术规范, 且于手术室内完成。盐酸奥布卡因滴眼液表面麻醉, 聚维酮碘消毒结膜囊, 于眼球颞下象限角膜缘后4 mm, 以30 G针头垂直眼球壁刺入眼内, 缓慢注入0.05 ml雷珠单抗药液, 小心抽出注射针, 无菌棉签按压防止返流, 查术眼光感, 指测眼压正常,后于颞上象限, 上、外直肌间, 纤维剪刀剪开球结膜、分离筋膜, 以泪道冲洗针头顺巩膜表面进入后筋膜囊, 注入曲安奈德注射液40 mg/ml, 抽取针头, 妥布霉素地塞米松眼膏涂术眼, 包扎术眼。术后左氧氟沙星滴眼液6次/d点眼, 连续用7 d。

随访时间为治疗后1周、1、3个月。于治疗前及每次随访时行最佳矫正视力(best corrected visual acuity, BCVA)、眼压、裂隙灯、间接检眼镜眼底检查、OCT检查。BCVA 转化成标准化LogMAR视力进行比较。OCT检查采用黄斑厚度图方式进行扫描, 所有检查均采用同一个扫描模式, 重复性好。所有OCT检查均由同一位经验丰富的技师完成。黄斑中心厚度(central macular thickness, CMT)测量采用手动测量从内界膜表面至视网膜色素上皮层表面之间的距离。

1.3 统计学方法 采用SPSS19.0统计学软件对数据进行统计学分析。计量资料以均数±标准差(±s)表示, 采用t检验。P＜0.05为差异具有统计学意义。

2 结果

2.1 治疗前后BCVA变化 玻璃体腔注射雷珠单抗联合筋膜囊下注射曲安奈德治疗后1周、1、3个月, 分别与治疗前相比, BCVA显著提高, 差异均具有统计学意义(P＜0.05)；治疗后1、3个月分别与治疗后1周相比, BCVA显著提高, 差异均具有统计学意义(P＜0.05)；治疗后3个月与1个月相比, BCVA提高, 但差异无统计学意义(P＞0.05)。见表1。

2.2 治疗前后CMT变化 与治疗前相比, 玻璃体腔注射雷珠单抗联合筋膜囊下注射曲安奈德治疗后1周、1、3个月, CMT显著降低, 差异均具有统计学意义(P＜0.05)；治疗后1、3个月分别与治疗后1周相比, CMT均降低, 差异均具有统计学意义(P＜0.05)；治疗后3个月与1个月相比, CMT降低,但差异无统计学意义(P＞0.05)。见表1。

表1 治疗前后标准化LogMAR视力与CMT变化(±s, n=30)

表1 治疗前后标准化LogMAR视力与CMT变化(±s, n=30)

注：与治疗前比较,aP<0.05；与治疗后1周比较,bP<0.05

时间 标准化LogMAR 视力 CMT(μm)治疗前 0.727±0.115 482.6±75.9治疗后1周 0.591±0.062a 402.7±77.2a治疗后1个月 0.528±0.083ab 344.6±72.7ab治疗后3个月 0.494±0.082ab 310.6±68.7ab

3 讨论

RVO是常见的可致盲的视网膜血管疾病, 随着激光、眼底照影、照相等技术的发展, 对本病的病因、分类、并发症、预后和治疗有了进一步的认识和提高, 研究肯定了RVO的视力预后与初诊视力有关[11］, RVO患者视力随时间延长可逐渐下降[12］。结合临床实践体会到, 如果RVO黄斑水肿长时间不纠正, 发生黄斑囊样变性会导致患者丧失有用视力。因此出于对患者现有视力的保护及提高, 对患者采取联合治疗, 尽早纠正黄斑水肿保护视功能, 并得到较为满意的临床效果。目前, VEGF导致血管通透性增加的作用已得到广泛的认可, 缺血导致视网膜产生VEGF, 而VEGF抑制剂通过拮抗作用, 降低血管通透性, 促进水肿吸收已成为目前治疗黄斑水肿的有效手段之一。玻璃体腔注射雷珠单抗可以较好的改变闭塞的过程, 快速并长期的封锁血管内皮生长因子以恢复血-视网膜屏障的完整性, 减少黄斑水肿且具有较好的安全性[13］。曲安奈德主要为人工合成的一种糖皮质激素, 可以使VEGF表达得到有效抑制, 具有降低毛细血管通透性, 减少渗出等作用。大量临床研究认为曲安奈德能稳定血-视网膜屏障, 明显减轻ME程度并提高视力[14,15］。而筋膜囊注射曲安奈德不需进入眼内, 避免了玻璃体腔注射曲安奈德导致高眼压及白内障等并发症的发生率, 易被患者接受, 且其可以加快ME消退, 有助于保护视功能, 同时也避免了玻璃体腔频繁注射雷珠单抗, 减轻了患者的经济负担。同时也降低了玻璃体腔注药致玻璃体出血、网脱、眼内炎等风险。故应对RVO患者采取早期积极治疗, 使黄斑水肿尽快消退, 为患者保有较好视力。

抗VEGF药[16,17］及糖皮质激素[18,19］, 以其安全、有效且简单易行的优点, 成了治疗黄斑水肿的主流, 对RVO致黄斑水肿时, 采用联合治疗, 从而挽救患者视力。本研究为短期研究, 而且患者例数偏少, 结果的可靠性、远期疗效还有待于大样本远期观察。

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Intravitreal injection of ranibizumab combined with membrane sac injection of triamcinolone acetonide in the treatment of retinal vein occlusion complicated with macular edema

LI Ting-ting, NIU Tong-tong. Department of Ophtalmology, Shenyang City the Fourth People’s Hospital, Shenyang110031, China

ObjectiveTo evaluate the clinial effect of intravitreal injection of ranibizumab combinedwith membrane sac injection of triamcinolone acetonide (TA) in the treatment of retinal vein occlusion (RVO) complicated with macular edema (ME). Methods There were30 patients (30 eyes) who were diagnosed as RVO with macular edema by fundus fluorescence angiography (FFA) and optical coherence tomography (OCT). The changes of best corrected visual acuity (BCVA) and OCT were compared before and after the treatment by intravitreal injection of ranibizumab combined with membrane sac injection of TA.ResultsThe BCVA before injection and after1 week,1 month, and3 months of injection were (0.727±0.115), (0.591±0.062), (0.528±0.083), and (0.494±0.082). Central macular thickness (CMT) were (482.6±75.9) μm, (402.7±77.2) μm, (344.6±72.7)μm, and (310.6±68.7) μm respectively. BCVA was remarkably increased and CMT decreased after1 month,3 months, and1 week of treatment, and the difference with those before treatment had statistical significance (P<0.05). Compared with those in1 week after treatment BCVA increased and CMT decreased in1 month and3 months after treatment, and the difference had statistical significance (P<0.05). The difference between1 month and3 month after treatment of increased BCVA and decreased CMT had no statistical significance (P>0.05).ConclusionThe treatment by intravitreal injection of ranibizumab combined with membrane sac injection of TA can reduce macular edema in short time and increase BCVA. It provides a new idea for treating RVO complicated with macular edema, however, its long-term effect requires further observation.

Ranibizumab; Intravitreal injection; Triamcinolone acetonide; Retinal vein occlusion; Macular edema

10.14164/j.cnki.cn11-5581/r.2015.02.002

2014-10-24］

110031 沈阳市第四人民医院眼科