Clearfield Elizabeth, Muthappan Valliammai, Wang Xue, Kuo Irene C
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room 6014, Baltimore, Maryland, USA, 21205.
Cochrane Database Syst Rev. 2016 Feb 11;2(2):CD011349. doi: 10.1002/14651858.CD011349.pub2.
A pterygium is a fleshy, wing-shaped growth from the conjunctiva, crossing over the limbus onto the cornea. Prevalence ranges widely around the world. Evidence suggests that ultraviolet light is a major contributor in the formation of pterygia. Pterygia impair vision, limit eye movements, and can cause eye irritation, foreign body sensation, and dryness. In some susceptible patients, the pterygium can grow over the entire corneal surface, blocking the visual axis.Surgery is the only effective treatment for pterygium, though recurrences are common. With simple excision techniques (that is, excising the pterygium and leaving bare sclera), the risk of recurrence has been reported to be upwards of 80%. Pterygium excision combined with a tissue graft has a lower risk of recurrence. In conjunctival autograft surgery, conjunctival tissue from another part of the person's eye along with limbal tissue is resected in one piece and used to cover the area from which the pterygium was excised. Another type of tissue graft surgery for pterygium is amniotic membrane graft, whereby a piece of donor amniotic membrane is fixed to the remaining limbus and bare sclera area after the pterygium has been excised.
The objective of this review was to assess the safety and effectiveness of conjunctival autograft (with or without adjunctive therapy) compared with amniotic membrane graft (with or without adjunctive therapy) for pterygium. We also planned to determine whether use of MMC yielded better surgical results and to assess the direct and indirect comparative costs of these procedures.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 21 November 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 23 November 2015.
We included in this review randomized controlled trials that had compared conjunctival autograft surgery (with or without adjunctive therapy) with amniotic membrane graft surgery (with or without adjunctive therapy) in people with primary or recurrent pterygium.
Two review authors independently screened search results and assessed full-text reports from among the potentially eligible trials. Two review authors independently extracted data from the included trials and assessed the trial characteristics and risk of bias. The primary outcome was the risk of recurrence of pterygium at 3 months and 6 months after surgery. We combined results from individual studies in meta-analyses using random-effects models. Risk of recurrence of pterygium was reported using risk ratios to compare conjunctival autograft with amniotic membrane transplant.
We identified 20 studies that had analyzed a total of 1947 eyes of 1866 participants (individual studies ranged from 8 to 346 participants who were randomized). The studies were conducted in eight different countries: one in Brazil, three in China, three in Cuba, one in Egypt, two in Iran, two in Thailand, seven in Turkey, and one in Venezuela. Overall risk of bias was unclear, as many studies did not provide information on randomization methods or masking to prevent performance and detection bias.The risk ratio for recurrence of pterygium using conjunctival autograft versus amniotic membrane transplant was 0.87 (95% confidence interval (CI) 0.43 to 1.77) and 0.53 (95% CI 0.33 to 0.85) at 3 months and 6 months, respectively. These estimates include participants with primary and recurrent pterygia. We performed a subgroup analysis to compare participants with primary pterygia with participants with recurrent pterygia. For participants with primary pterygia, the risk ratio was 0.92 (95% CI 0.37 to 2.30) and 0.58 (95% CI 0.27 to 1.27) at 3 months and 6 months, respectively. We were only able to estimate the recurrence of pterygia at 6 months for participants with recurrent pterygia, and the risk ratio comparing conjunctival autograft with amniotic membrane transplant was 0.45 (95% CI 0.21 to 0.99). One included study was a doctoral thesis and did not use allocation concealment. When this study was excluded in a sensitivity analysis, the risk ratio for pterygium recurrence at 6 months' follow-up was 0.43 (95% CI 0.30 to 0.62) for participants with primary and recurrent pterygium. One of the secondary outcomes, the proportion of participants with clinical improvement, was analyzed in only one study. This study reported clinical outcome as the risk of non-recurrence, which was seen in 93.8% of participants in the conjunctival limbal autograft group and 93.3% in the amniotic membrane transplant group at 3 months after surgery.We did not analyze data on the need for repeat surgery, vision-related quality of life, and direct and indirect costs of surgery due to an insufficient number of studies reporting these outcomes.Thirteen studies reported adverse events associated with conjunctival autograft surgery and amniotic membrane transplant surgery. Adverse events that occurred in more than one study were granuloma and pyogenic granuloma and increased intraocular pressure. None of the included studies reported that participants had developed induced astigmatism.
AUTHORS' CONCLUSIONS: In association with pterygium excision, conjunctival autograft is associated with a lower risk of recurrence at six months' after surgery than amniotic membrane transplant. Participants with recurrent pterygia in particular have a lower risk of recurrence when they receive conjunctival autograft surgery compared with amniotic membrane transplant. There are few studies comparing the two techniques with respect to visual acuity outcomes, and we identified no studies that reported on vision-related quality of life or direct or indirect costs. Comparison of these two procedures in such outcome measures bears further investigation. There were an insufficient number of studies that used adjunctive mitomycin C to estimate the effects on pterygium recurrence following conjunctival autograft or amniotic membrane transplant.
翼状胬肉是一种从结膜长出的肉质、翼状肿物，越过角膜缘延伸至角膜。其患病率在全球范围内差异很大。有证据表明，紫外线是翼状胬肉形成的主要因素。翼状胬肉会损害视力、限制眼球运动，并可导致眼部刺激、异物感和干涩感。在一些易感患者中，翼状胬肉可生长覆盖整个角膜表面，遮挡视轴。手术是治疗翼状胬肉的唯一有效方法，不过复发很常见。采用简单切除技术（即切除翼状胬肉并留下裸露的巩膜），复发风险据报道高达80%以上。翼状胬肉切除联合组织移植复发风险较低。在结膜自体移植手术中，从患者眼部的另一部位切取包括角膜缘组织的结膜组织，整块用于覆盖切除翼状胬肉的区域。另一种用于翼状胬肉的组织移植手术是羊膜移植，即切除翼状胬肉后，将一片供体羊膜固定于剩余的角膜缘和裸露的巩膜区域。
本综述的目的是评估结膜自体移植（无论是否联合辅助治疗）与羊膜移植（无论是否联合辅助治疗）治疗翼状胬肉的安全性和有效性。我们还计划确定使用丝裂霉素C是否能产生更好的手术效果，并评估这些手术的直接和间接比较成本。
我们检索了CENTRAL（包括Cochrane眼科和视力试验注册库）（2015年第10期）、Ovid MEDLINE、Ovid MEDLINE在研及其他未索引引文、Ovid MEDLINE日报、Ovid OLDMEDLINE（1946年1月至2015年11月）、EMBASE（1980年1月至2015年11月）、PubMed（1948年至2015年11月）、拉丁美洲和加勒比卫生科学文献数据库（LILACS）（1982年至2015年11月）、对照试验元注册库（mRCT）（www.controlled-trials.com）（最后检索日期为2014年11月21日）、ClinicalTrials.gov（www.clinicaltrials.gov）以及世界卫生组织（WHO）国际临床试验注册平台（ICTRP）（www.who.int/ictrp/search/en）。在电子检索试验时，我们未使用任何日期或语言限制。我们最后一次检索电子数据库的时间为2015年11月23日。
我们纳入了本综述中比较结膜自体移植手术（无论是否联合辅助治疗）与羊膜移植手术（无论是否联合辅助治疗）治疗原发性或复发性翼状胬肉患者的随机对照试验。
两位综述作者独立筛选检索结果，并评估潜在合格试验中的全文报告。两位综述作者独立从纳入的试验中提取数据，并评估试验特征和偏倚风险。主要结局是术后3个月和6个月翼状胬肉复发的风险。我们使用随机效应模型在荟萃分析中合并了个体研究的结果。使用风险比来比较结膜自体移植与羊膜移植，报告翼状胬肉复发的风险。
我们确定了20项研究，共分析了1866名参与者的1947只眼睛（个体研究的随机参与者人数从8至346不等）。这些研究在八个不同国家进行：巴西1项、中国3项、古巴3项、埃及1项、伊朗2项、泰国2项、土耳其7项、委内瑞拉1项。总体偏倚风险尚不清楚，因为许多研究未提供关于随机化方法或用于防止执行和检测偏倚的盲法的信息。使用结膜自体移植与羊膜移植相比，翼状胬肉复发的风险比在3个月时为0.87（95%置信区间（CI）0.43至1.77），在6个月时为0.53（95%CI 0.33至0.85）。这些估计包括原发性和复发性翼状胬肉患者。我们进行了亚组分析，以比较原发性翼状胬肉患者与复发性翼状胬肉患者。对于原发性翼状胬肉患者，3个月和6个月时的风险比分别为0.92（95%CI 0.37至2.30）和0.58（95%CI 0.27至1.27）。对于复发性翼状胬肉患者，我们仅能估计6个月时翼状胬肉的复发情况，结膜自体移植与羊膜移植相比的风险比为0.45（95%CI 0.21至0.99）。一项纳入研究是博士论文，未使用分配隐藏。在敏感性分析中排除该研究后，原发性和复发性翼状胬肉患者在6个月随访时翼状胬肉复发的风险比为0.43（95%CI 0.30至0.62）。次要结局之一，临床改善的参与者比例，仅在一项研究中进行了分析。该研究将临床结局报告为不复发的风险，术后3个月结膜角膜缘自体移植组93.8%的参与者和羊膜移植组93.3%的参与者出现了这种情况。由于报告这些结局的研究数量不足，我们未分析关于再次手术需求、视力相关生活质量以及手术直接和间接成本的数据。13项研究报告了与结膜自体移植手术和羊膜移植手术相关的不良事件。在不止一项研究中出现的不良事件是肉芽肿、化脓性肉芽肿和眼压升高。纳入的研究均未报告参与者出现诱导性散光。
与翼状胬肉切除相关，结膜自体移植术后6个月的复发风险低于羊膜移植。特别是复发性翼状胬肉患者，与羊膜移植相比，接受结膜自体移植手术时复发风险较低。关于视力结果比较这两种技术的研究很少，我们未发现报告视力相关生活质量或直接或间接成本的研究。在这些结局指标方面比较这两种手术值得进一步研究。使用辅助丝裂霉素C的研究数量不足，无法估计其对结膜自体移植或羊膜移植后翼状胬肉复发的影响。
