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陶继伟, 陈焕, 沈丽君, 俞雪婷, 陈亦棋, 毛剑波, 林丽. 玻璃体切割联合内界膜剥除和空气填充治疗特发性黄斑裂孔[J]. 中华眼视光学与视觉科学杂志, 2019,21(6): 439-443.
Jiwei Tao, Huan Chen, Lijun Shen, Xueting Yu, Yiqi Chen, Jianbo Mao, Li Lin. Clinical Outcomes of Vitrectomy and Internal Limiting Membrane Peeling with Air Tamponade for the Treatment of Idiopathic Macular Hole[J]. CHINESE JOURNAL OF OPTOMETRY OPHTHALMOLOGY AND VISUAL SCIENCE, 2019,21(6): 439-443.  
Doi: 10.3760/cma.j.issn.1674-845X.2019.06.007
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玻璃体切割联合内界膜剥除和空气填充治疗特发性黄斑裂孔
陶继伟, 陈焕, 沈丽君, 俞雪婷, 陈亦棋, 毛剑波, 林丽
温州医科大学附属眼视光医院杭州院区 310000
通信作者：沈丽君（ORCID：0000-0001-9106-5456）,Email：slj@mail.eye.ac.cn

第一作者：陶继伟（ORCID：0000-0002-9381-4462）,Email：512212585@qq.com

收稿日期: 2018-11-12
摘要

目的：观察玻璃体切割手术联合内界膜剥除和空气填充治疗特发性全层黄斑裂孔（IMH）的疗效。方法：回顾性系列病例研究。收集2017年1月至2018年1月在温州医科大学附属眼视光医院杭州院区确诊并行玻璃体切割术治疗的连续IMH患者32例（32眼）,年龄47~78（60.7±12.2）岁,其中男9例,女23例。术中均采用消毒空气进行眼内填充。根据术后早期首次光学相干断层扫描（OCT）提示裂孔是否闭合分为闭合组和未闭合组,对2组患者术前、术后的最佳矫正视力（BCVA）、裂孔直径等采用秩和检验及独立样本 t检验进行比较;2组患者裂孔闭合率及外界膜和光感受器连续性比较采用卡方检验。结果：术后末次随访时所有患者LogMAR BCVA为0.40（0.30,0.73）,较术前[0.80（0.70,1.00）]明显提高（ Z=-3.439, P<0.001）。术后早期OCT扫描显示24例黄斑裂孔闭合,8例黄斑裂孔未闭合,予再次玻璃体腔空气填充治疗,术后1个月及术后末次随访所有患者黄斑裂孔均闭合。术后1个月OCT扫描外界膜（ELM）连续的患者有16例,无一例椭圆体层（EZ）连续;末次随访时18例患者ELM连续,6例EZ连续。未闭合组术前黄斑裂孔直径为（532±104）μm,明显大于闭合组黄斑裂孔直径[（352±180）μm]（ t=-2.656, P=0.013）。闭合组术后1个月ELM均存在连续性,末次随访ELM和EZ连续性均高于未闭合组,2组差异具有显著的统计学意义（ χ2=4.23, P=0.040; χ2=3.89, P=0.048）。结论：玻璃体切割联合ILM剥除和空气填充治疗IMH具有较好的疗效,对于大于400 μm的裂孔部分患者需要再次玻璃体腔空气填充治疗。

关键词: 黄斑裂孔; 空气填充; 玻璃体切割
Clinical Outcomes of Vitrectomy and Internal Limiting Membrane Peeling with Air Tamponade for the Treatment of Idiopathic Macular Hole
Jiwei Tao, Huan Chen, Lijun Shen, Xueting Yu, Yiqi Chen, Jianbo Mao, Li Lin
Eye Hospital, Wenzhou Medical University, Hangzhou 310000, China
Corresponding author:Lijun Shen, Eye Hospital, Wenzhou Medical University, Hangzhou 310000, China (Email: slj@mail.eye.ac.cn)
Abstract

Objective: To evaluate the effect of vitrectomy and internal limiting membrane peeling with air tamponade for the treatment of idiopathic macular hole (MH).Methods:A retrospective study was performed on 32 eyes of 32 patients with idiopathic macular hole in our hospital from January 2017 to January 2018. There were 9 males (9 eyes) and 23 females (23 eyes), with amean age of 60.7±12.2 years (range from 47~78 years). Pars plana vitrectomy with internal limiting membrane peeling was performed, followed by fluid-air exchange. According to the results of OCT scanning in the first postoperative follow-up, all patients were divided into two groups: MH closed ornot closed. The preoperative and postoperative best corrected visual acuity (BCVA) and diameter of the MH were compared between the two groups, using a Wilcoxon test and independent sample t test. The MH closure rate, the continuity of the external limiting membranes and photoreceptors were compared using a chi square test.Results: At the last follow-up, the LogMAR BCVA was 0.40 (0.30, 0.73), which was significantly higher than the preoperative BCVA 0.80 (0.70, 1.00) ( Z=-3.439, P<0.001). Early postoperative OCT scansshowed that 24 macular holeswere closed, while the macular holes in the other 8 eyes were not closed sofluid-air exchange was performed again. The macular holeswereclosed in all 8 patients one month after the second treatment or the last follow-up. Sixteen patients hadcontinuous external limiting membrane (ELM) but none with a continuous external zone (EZ) in the OCT scansone month after the operation. However, 18 patients showed continuous ELM and 6 showed continuous EZ at the last follow-up. According to whether MH was closed or not at the first postoperative OCT scanning, all patients were divided into two groups. The mean pre-surgical diameter of the MH of the unclosed group was 532±104 um, which was significantly larger than that of the closed group (352±180 μm) ( t=-2.656, P=0.013). The continuity of the ELM of the MH closed group was higher than the unclosed group at one month after the operation and at the last follow-up ( P<0.05). The patients with continuous EZ at the last follow-up were all in the closed group, while the EZs in the unclosed group were discontinuous. There was a statistically significant difference between the two groups ( χ2=3.89, P=0.048).Conclusions:The results of this study indicate that vitrectomy combined with ILM peeling and air tamponade for the treatment of idiopathic macular hole has a good result. However, for those macular holes with more than a 400 um diameter, a second fluid-air exchange is needed. Early closure of the MH suggests a better prognosis after surgery.

Keyword: macular hole; air tamponade; vitrectomy

玻璃体切割联合内界膜剥除和眼内气体填充是目前治疗特发性黄斑裂孔（Idiopathic macular hole, IMH）的最常用手术方法, 大量的临床研究结果表明该手术方式的有效性, 但在剥膜范围、俯卧位及填充物选择方面仍存在争议[1, 2, 3]。消毒空气, 惰性气体如C3F8、S2F6是目前特发性黄斑裂孔术中最常用的填充物, 但惰性气体填充后体位限制时间长, 且存在青光眼、白内障等并发症, 而消毒空气相比惰性气体填充时间短, 但并发症少[4, 5, 6, 7]。目前文献关于空气与惰性气体治疗IMH的疗效存在争议, 且国内尚无可用的惰性气体填充物, 空气填充治疗IMH的报道较少。因此本研究收集一组连续的玻璃体切割联合内界膜（Internal limiting membrane, ILM）剥除并空气填充治疗的IMH患者, 观察术后裂孔愈合、外层结构恢复及视功能情况, 并分析影响预后的相关因素。

1 对象与方法
1.1 对象

收集2017年1月至2018年1月在温州医科大学附属眼视光医院杭州院区确诊并行玻璃体切割术治疗的连续IMH患者32例（32眼）, 年龄47~78（60.7± 12.2）岁, 其中男9例, 女23例。所有患者术前均签署手术知情同意书。术中均采用消毒空气进行眼内填充。术后随访时间大于3个月。

纳入标准：①OCT检查确诊为黄斑全层裂孔; ②球镜度> -6.00 D; ③无角膜病、青光眼和除MH外的其他眼底疾病。排除标准：①高度近视眼; ②外伤性黄斑裂孔; ③合并其他可能影响视力的眼部疾病, 包括青光眼、眼底其他疾病、视神经病变等; ④不能定期随诊或缺少相关资料的患者。

1.2 方法

1.2.1 手术前后相关检查 所有患者均行最佳矫正视力（BCVA）、眼压、裂隙灯显微镜、前置镜、眼底彩色照相及OCT（Spectralis OCT, 德国海德堡公司）检查。采用标准对数视力表行BCVA检查, 记录时换算为最小可分辨视角的对数（LogMAR）视力。

采用Spectralis OCT仪对黄斑部行线性水平扫描, 扫描深度2.0 mm, 轴向分辨率3.87 μ m, 横向分辨率11.40 μ m, 扫描模式512× 496, 扫描范围 5.8 mm× 5.8 mm, 探测深度2.3 mm, 手动操作测量黄斑裂孔直径, 测量均由同一检查者完成。每次扫描采用随访跟踪模式。

1.2.2 手术操作 手术由同一位经验丰富的眼底外科医师完成, 所有患者均接受标准三通道经睫状体平坦部23G玻璃体切割术, 年龄超过50岁且合并白内障者均行白内障微切口超声乳化吸除联合人工晶状体植入手术, 50岁以下患者行单纯23G玻璃体切割术。术中做玻璃体后脱离, 剥除玻璃体后皮质, 注入稀释的0.02 ml（5 mg/ml）吲哚青绿染色, 保留 30 s, 剥除黄斑区上下血管弓范围内界膜, 玻璃体腔行气液交换后, 填充消毒空气。所有患者术后均要求保持俯卧位, 俯卧时间根据裂孔的闭合情况决定。

术后3~4 d, 玻璃体腔气体填充小于50%后行OCT扫描, OCT提示裂孔闭合患者不再保持俯卧位; OCT提示裂孔未闭合患者, 于手术室再次进行玻璃体腔填充消毒空气。补气过程：患者取坐位, 表面麻醉, 常规碘伏冲洗消毒, 5 ml装满消毒空气针筒从距下方角膜缘3.5 mm处进针, 充分置换出玻璃体腔液。

1.2.3 术后随访 手术后随访时间3~16个月, 随访时采用与手术前相同的设备和方法行相关检查。以术后1个月及末次随访为疗效判定时间点, 观察并分析BCVA, OCT形态包括裂孔闭合情况、中心凹外层结构包括椭圆体层（Ellipsoid zone, EZ）和外界膜（External limiting membrane, ELM）的连续性。

1.3 统计学方法

回顾性系列病例研究。采用SPSS 20.0统计软件进行数据分析。患者手术前后的BCVA、裂孔相关参数等的比较采用秩和检验及独立样本t检验; 2组患者裂孔闭合率的比较采用卡方检验。以P< 0.05为差异有统计学意义。

2 结果
2.1 总体患者资料及手术疗效

本研究的32例患者黄斑裂孔直径为（397± 181）μ m, 其中11例伴有黄斑前膜, 13例伴有周边视网膜变性或裂孔。末次随访LogMAR BCVA为0.40（0.30, 0.73）, 较术前LogMAR BCVA[0.80 （0.70, 1.00）]明显改善（Z=-3.439, P< 0.001）。术后3~4 d玻璃体腔空气吸收超过50%后行OCT扫描显示24例黄斑裂孔闭合; 另外8例黄斑裂孔未闭 合, 予再次玻璃体腔填充空气, 其中1例患者予2次 补气, 7例患者予单次补气, 术后1个月及术后末次随访所有患者黄斑裂孔均闭合。术后1个月OCT扫描ELM连续的患者有16例, EZ连续0例; 末次随访时ELM连续18例, EZ连续6例。闭合组和未闭合组典型病例见图1-2。

图1. 病例1, 女性, 50岁, 裂孔直径小于400 μ m, 首次OCT扫描裂孔闭合
A：术前裂孔直径107 μ m, BCVA（LogMAR）为0.40; B：术后3 d OCT提示黄斑裂孔闭合; C：术后1个月, OCT扫描提示裂孔闭合, ELM连续, EZ不连续, BCVA（LogMAR）为0.22; D：术后末次随访, OCT扫描提示ELM层及EZ层均连续, BCVA（LogMAR）为0.15Figure 1. Case 1: Female, 50 years old, with a hole diameter less than 400 μ m. The first OCT scan after the operation shows that the MH is repaired.
A: Preoperative: Hole diameter 107 μ m, BCVA: 0.4. B: Postoperative OCT scan at 3 days indicatesthe closure of the macular hole. C: One month after surgery, the OCT scan indicatesthat the MH isclosed, ELM iscontinuous, EZ isdiscontinuous, BCVA: 0.6. D: At the last follow-up, the OCT scan showsthat the ELM layer and the EZ layer arecontinuous, BCVA: 0.7.

图2. 病例2, 女性, 57岁, 裂孔直径大于400 μ m, 首次OCT扫描裂孔未闭合, 再次填气后裂孔闭合
A：术前裂孔直径659 μ m; BCVA（LogMAR）为2.30; B：术后3 d OCT提示黄斑裂孔未闭合, 予再次玻璃体腔填充空气治疗; C：术后1个月, OCT提示黄斑裂孔闭合, ELM及EZ层不连续, BCVA（LogMAR）为0.82; D：术后末次随访, OCT提示黄斑裂孔闭合, ELM及EZ层不连续, BCVA（LogMAR）为0.52Figure 2. Case 2: Female, 57 years old, with a hole diameter over 400 μ m. The first OCT scans shows the MH isnot closed, however, it isclosed after another fluid-air exchange was performed.
A: Preoperative: Hole diameter 659 μ m, BCVA: FC/50CM. B: 3 days after sugery, the OCT scan indicatesthe macular hole is not closed, then another fluid-air exchange was performed. C: One month after surgery, OCT scan indicatesthe closure of macular hole; ELM and the EZ layer are discontinuous, BCVA: 0.15. D: The last follow-up after the operation, OCT scan indicates the macular hole is closed; ELM and EZ layer are discontinuous, BCVA: 0.3.

2.2 分组的基线资料和手术疗效比较

根据术后首次OCT扫描裂孔是否闭合进行分组, 2组的年龄、性别、病程等其他基线资料差异均无统计学意义。未闭合组术前黄斑裂孔直径为（532± 104）μ m, 明显大于闭合组黄斑裂孔直径[（352± 180）μ m]（t=-2.656, P=0.013）。术后1个月及末次的ELM连续性闭合组均高于未闭合组（χ 2=6.00, P=0.037; χ 2=4.23, P=0.040）, 术后末次随访EZ连续的患者均在闭合组, 而未闭合组术后EZ均不连续, 2组差异存在明显的统计学意义（χ 2=3.89, P=0.048）。闭合组的术后BCVA高于未闭合组, 但组间差异不存在统计学意义（Z=65.50, P=0.18）。

3 讨论

为探索玻璃体切割联合ILM剥除并消毒空气填充治疗IMH的有效性, 本研究回顾性分析了一组在我院手术治疗的特发性黄斑裂孔的连续病例, 结果表明玻璃体切割联合ILM剥除和空气填充治疗黄斑裂孔具有较好的长期疗效, 术后末次随访所有患者黄斑裂孔均闭合, 矫正视力明显提高, 中心凹外层结构改善。

惰性气体是IMH最常用的眼内填充物, 但既往也有消毒空气用于填充眼内的文献报道。Eckardt 等[4]使用空气作为填充物, 手术后前3 d的MH闭合率分别为54.5%、75.7%、78.8%。空气对比惰性气体治疗黄斑裂孔的疗效存在争议, Briand等[6]认为空气与S2F6填充治疗IMH疗效相当, 2组MH闭合率分别为92.3%和90.1%。Gesser等[5]研究发现, 首次空气填充后MH闭合率为79%, 低于其他长效气体, 但二次空气填充后MH闭合率可达96%。本研究结果表明空气可作为IMH的有效眼内填充物, 消毒空气进行眼内填充, 将能够更早地明确黄斑裂孔的闭合情况, 从而更早结束俯卧位, 许多继发于膨胀气体玻璃体腔填充的并发症, 如继发性白内障、继发性青光眼等也能够明显减少。

虽然本研究IMH患者末次裂孔均闭合, 但术后早期首次行OCT扫描时有8例IMH裂孔显示未闭合, 患者行二次空气填充后裂孔均闭合。分析原因可能与消毒空气眼内填充时间不足相关, 气体在IMH患者眼内填充的原理是通过气泡表面张力使黄斑裂孔表面保持干燥, 从而促进裂孔闭合及视细胞的愈合[4, 5, 6], 消毒空气相对惰性气体眼内填充时间短, 可能是导致部分患者裂孔没闭合的因素。所有患者在补充空气后裂孔均闭合, 也从另一个角度验证本研究病例患者裂孔早期未闭合的原因主要是眼内填充因素, 而不是ILM剥除不完整等其他因素。玻璃体腔补充空气只需表面麻醉下取坐位进行气液交换即可完成, 操作简便, 手术时间较短, 费用低, 可在临床上推广使用。

既往研究报道空气填充后90%以上的裂孔均在术后3 d内闭合[4], 但本研究患者术后3 d空气消退近50%后OCT扫描提示近1/3患者裂孔未闭合, 与既往研究报道不同, 可能与本研究黄斑裂孔直径大小有关。IVST研究表明黄斑裂孔直径是预测黄斑裂孔预后的重要指标, 循证医学证据也表明对于小于400 μ m的裂孔可以不进行严格的面朝下体 位[8, 9]。Ch'ng等[10]研究表明小于650 μ m的裂孔手术治疗一期裂孔闭合率较高。但目前关于裂孔直径对空气填充治疗黄斑裂孔疗效影响的报道较少, 本研究根据首次术后OCT扫描裂孔是否闭合进行分组比较, 发现闭合组的术前黄斑裂孔直径明显小于未闭合组, 且未闭合组的术前黄斑裂孔直径均大于400 μ m。因此本研究结果提示直径小于400 μ m的MH行空气填充可取得较好的裂孔闭合率, 但对于大于400 μ m的裂孔空气填充首次裂孔闭合率相对不高, 部分需要再次空气填充, 最终均能取得较好的疗效。

目前对于IMH的预后预测因素尚无确切定论[11, 12]。本研究结果表明黄斑裂孔空气填充早期OCT扫描裂孔闭合的患者术后ELM连续性比例较高。ELM连续性的恢复对黄斑裂孔感光细胞的恢复和视功能的提高至关重要[13, 14, 15]。本研究结果提示IMH闭合的时间也可能是影响手术预后的相关因素, 但需要进一步大样本研究证实。

本研究结果表明玻璃体切割联合ILM剥除和空气填充治疗IMH具有较好的疗效, 对于大于 400 μ m的裂孔部分需要再次玻璃体腔空气填充治疗, 早期裂孔闭合提示更好的预后。但本研究为回顾性系列病例研究, 与惰性气体治疗黄斑裂孔的疗效对比尚需大样本的前瞻性对照试验来验证。

利益冲突申明 本研究无任何利益冲突

作者贡献声明 陶继伟：课题设计, 收集数据, 资料分析与解释, 撰写论文, 对编辑部的修改意见进行修改。陈焕、俞雪婷：参与收集数据。沈丽君：指导课题设计, 修改论文。毛剑波、陈亦棋、林丽：参与课题设计, 修改论文并参与编辑部修改意见的修改

The authors have declared that no competing interests exist.

参考文献
[1] Chatziralli IP, Theodossiadis PG, Steel D. Internal limiting membrane peeling in macular hole surgery; why, when, and how? Retina, 2018, 38(5): 870-882. DOI:10.1097/IAE.0000000000001959. [本文引用:1]
[2] Haritoglou C, Reiniger IW, Schaumberger M, et al. Five-year follow-up of macular hole surgery with peeling of the internal limiting membrane: Update of a prospective study. Retina, 2006, 26(6): 618-622. DOI:10.1097/01.iae.0000236474.63819.3a. [本文引用:1]
[3] Tognetto D, Grand in R, Sanguinetti G, et al. Internal limiting membrane removal during macular hole surgery: Results of a multicenter retrospective study. Ophthalmology, 2006, 113(8): 1401-1410. DOI:10.1016/j.ophtha.2006.02.061. [本文引用:1]
[4] Eckardt C, Eckert T, Eckardt U, et al. Macular hole surgery with air tamponade and optical coherence tomography-based duration of face-down positioning. Retina, 2008, 28(8): 1087-1096. DOI:10.1097/iae.0b013e318185fb5f. [本文引用:4]
[5] Gesser C, Eckert T, Eckardt U, et al. Macular hole surgery with air tamponade. Does air suffice for short-term tamponade? Ophthalmologe, 2010, 107(11): 1043-1050. DOI:10.1007/s00347-010-2171-2. [本文引用:3]
[6] Briand S, Chalifoux E, Tourville E, et al. Prospective rand omized trial: Outcomes of SF6 versus C3F8 in macular hole surgery. Can J Ophthalmol, 2015, 50(2): 95-100. DOI:10.1016/j.jcjo.2014.12.006. [本文引用:3]
[7] Usui H, Yasukawa T, Hirano Y, et al. Comparative study of the effects of room air and sulfur hexafluoride gas tamponade on functional and morphological recovery after macular hole surgery: A retrospective study. Ophthalmic Res, 2013, 50(4): 227-230. DOI:10.1159/000354324. [本文引用:1]
[8] Duker JS, Kaiser PK, Binder S, et al. The international vitreomacular traction study group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology, 2013, 120(12): 2611-2619. DOI:10.1016/j.ophtha.2013.07.042. [本文引用:1]
[9] Liu L, Enkh-Amgalan I, Wang NK, et al. Results of macular hole surgery: Evaluation based on the international vitreomacular traction study classification. Retina, 2018, 38(5): 900-906. DOI:10.1097/IAE.0000000000001647. [本文引用:1]
[10] Ch'ng SW, Patton N, Ahmed M, et al. The manchester large macular hole study: Is it time to reclassify large macular holes? Am J Ophthalmol, 2018, 195: 36-42. DOI:10.1016/j.ajo.2018.07.027. [本文引用:1]
[11] Kusuhara S, Teraoka Escaño MF, Fujii S, et al. Prediction of postoperative visual outcome based on hole configuration by optical coherence tomography in eyes with idiopathic macular holes. Am J Ophthalmol, 2004, 138(5): 709-716. DOI:10.1016/j.ajo.2004.04.063. [本文引用:1]
[12] Liu P, Sun Y, Dong C, et al. A new method to predict anatomical outcome after idiopathic macular hole surgery. Graefes Arch Clin Exp Ophthalmol, 2016, 254(4): 683-688. DOI:10.1007/s00417-015-3116-x. [本文引用:1]
[13] Kim NM, Park HJ, Koo GH, et al. Photoreceptor layer assessed in tissue layer image using spectral-domain optical coherence tomography after surgical closure of macular hole. Retina, 2011, 31(8): 1483-1492. DOI:10.1097/IAE.0b013e3182083de0. [本文引用:1]
[14] Oh J, Smiddy WE, Flynn HW Jr, et al. Photoreceptor inner/outer segment defect imaging by spectral domain OCT and visual prognosis after macular hole surgery. Invest Ophthalmol Vis Sci, 2010, 51(3): 1651-1658. DOI:10.1167/iovs.09-4420. [本文引用:1]
[15] Theodossiadis PG, Grigoropoulos VG, Theodossiadis GP. The significance of the external limiting membrane in the recovery of photoreceptor layer after successful macular hole closure: A study by spectral domain optical coherence tomography. Ophthalmologica, 2011, 225(3): 176-184. DOI:10.1159/000323322. [本文引用:1]