Gewaily Dina, Muthuswamy Karthikeyan, Greenberg Paul B
Deglin and Greene Retinal Center, Wynnewood, Pennsylvania, USA, 19096.
Cochrane Database Syst Rev. 2015 Sep 9;2015(9):CD007324. doi: 10.1002/14651858.CD007324.pub3.
BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular abnormality associated with conditions such as hypertension, diabetes, glaucoma, and a wide variety of hematologic disorders. Macular edema (ME) represents an important vision-threatening complication of CRVO. Intravitreal steroids (IVS), such as triamcinolone acetonide, have been utilized to treat macular edema stemming from a variety of etiologies and may be a treatment option for CRVO-ME. OBJECTIVES: To explore the effectiveness and safety of intravitreal steroids in the treatment of CRVO-ME. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014 Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2014), EMBASE (January 1980 to November 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), 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 searches for trials. We last searched the electronic databases on 13 November 2014. For all included primary studies, we used The Science Citation Index (3 December 2014) and manually reviewed reference lists to identify other possible relevant trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared intravitreal steroids, of any dosage and duration of treatment of at least six months, with observation for the treatment of CRVO-ME. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified from the electronic searches and assessed full-text articles from potentially eligible trials. Two review authors independently assessed trial characteristics, risk of bias, and extracted data from included trials. We contacted investigators of included trials for desired data not provided in the trial reports. MAIN RESULTS: We included two RCTs that enrolled a total of 708 participants with CRVO-ME. SCORE compared triamcinolone acetonide intravitreal injections (n = 165) with observation (n = 72); GENEVA compared dexamethasone intravitreal implants (n = 290) with sham injections (n = 147). We observed characteristics indicative of high risk of bias due to incomplete outcome data in SCORE and selective outcome reporting in GENEVA. Loss to follow-up was high with 10% in the steroid groups and almost twice as much (17%) in the observation group. GENEVA enrolled participants with both branch and central retinal vein occlusion, but did not present subgroup data for the CRVO-ME population. A qualitative assessment of the results from GENEVA indicated that the dexamethasone implant was not associated with improvement in visual acuity after six months among participants with CRVO-ME. Although the SCORE investigators reported that participants treated with 1 mg (n = 82) or 4 mg (n = 83) triamcinolone intravitreal injections were five times more likely to have gained 15 letters or more in visual acuity compared with participants in the observation group (1 mg; risk ratio (RR): 5.27; 95% confidence interval (CI) 1.62 to 17.15; 4 mg RR 4.92; 95% CI 1.50 to 16.10) by the eighth-month follow-up examination, the average visual acuity decreased in all three groups. However, eyes treated with triamcinolone lost fewer letters than participants in the observation group at 8 months (1 mg mean difference (MD): 8.70 letters, 95% CI 1.86 to 15.54; 4 mg MD: 9.80 letters, 95% CI 3.32 to 16.28). A higher incidence of adverse events was noted with IVS therapy when compared with observation alone. As many as 20% to 35% of participants experienced an adverse event in the IVS groups compared with 8% of participants in the observation group of the SCORE study. The GENEVA investigators reported 63% in the treatment arm versus 43% in the observation arm experienced an adverse event. The most commonly encountered adverse events were elevated intraocular pressure, progression of cataracts, and retinal neovascularization. We graded the quality of evidence as low due to study limitations, imprecision of treatment estimates, and selective outcome reporting. AUTHORS' CONCLUSIONS: The two RCTs reviewed herein provide insufficient evidence to determine the benefits of IVS for individuals with CRVO-ME. The improvement in visual acuity noted in the SCORE trial should be interpreted with caution as outcome data were missing for a large proportion of the observation group. Adverse events were observed more often with IVS treatment compared with observation/no treatment.
背景:视网膜中央静脉阻塞(CRVO)是一种常见的视网膜血管异常疾病,与高血压、糖尿病、青光眼以及多种血液系统疾病相关。黄斑水肿(ME)是CRVO的一种重要的视力威胁性并发症。玻璃体内注射类固醇(IVS),如曲安奈德,已被用于治疗多种病因引起的黄斑水肿,可能是治疗CRVO-ME的一种选择。 目的:探讨玻璃体内注射类固醇治疗CRVO-ME的有效性和安全性。 检索方法:我们检索了Cochrane中心对照试验注册库(CENTRAL)(2014年第10期,其中包含Cochrane眼科和视力组试验注册库)、Ovid MEDLINE、Ovid MEDLINE在研及其他未索引的文献、Ovid MEDLINE每日更新版、Ovid OLDMEDLINE(1946年1月至2014年11月)、EMBASE(1980年1月至2014年11月)、对照试验元注册库(mRCT)(www.controlled-trials.com)、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,我们未设置任何日期或语言限制。我们最后一次检索电子数据库是在2014年11月13日。对于所有纳入的原始研究,我们使用科学引文索引(2014年12月3日)并手动查阅参考文献列表,以识别其他可能相关的试验。 选择标准:我们纳入了随机对照试验(RCT) , 这些试验比较了任何剂量和至少六个月治疗期的玻璃体内注射类固醇与观察治疗CRVO-ME的效果。 数据收集与分析:两名综述作者独立筛选电子检索中识别出的标题和摘要,并评估潜在合格试验的全文。两名综述作者独立评估试验特征、偏倚风险,并从纳入试验中提取数据。对于试验报告中未提供的所需数据,我们联系了纳入试验的研究者。 主要结果:我们纳入了两项RCT,共708名CRVO-ME参与者。SCORE试验比较了玻璃体内注射曲安奈德(n = 165)与观察(n = 72);GENEVA试验比较了玻璃体内植入地塞米松(n = 290)与假注射(n = 147)。我们观察到SCORE试验因结局数据不完整以及GENEVA试验因选择性报告结局而存在高偏倚风险的特征。失访率很高,类固醇组为10%,观察组几乎是其两倍(17%)。GENEVA试验纳入了视网膜分支静脉阻塞和中央静脉阻塞的参与者,但未提供CRVO-ME人群的亚组数据。对GENEVA试验结果的定性评估表明,地塞米松植入物与CRVO-ME参与者六个月后的视力改善无关。尽管SCORE试验的研究者报告,与观察组相比,接受1 mg(n = 82)或4 mg(n = 83)曲安奈德玻璃体内注射的参与者在第八个月随访检查时视力提高15个字母或更多的可能性高出五倍(1 mg;风险比(RR):5.27;95%置信区间(CI)1.62至17.15;4 mg RR 4.92;95%CI 1.50至16.10),但所有三组的平均视力均下降。然而,在8个月时,接受曲安奈德治疗的眼睛比观察组参与者视力下降的字母数更少(1 mg平均差(MD):8.70个字母,95%CI 1.86至15.54;4 mg MD:9.80个字母,95%CI 3.32至16.28)。与单独观察相比,IVS治疗的不良事件发生率更高。SCORE研究中,IVS组多达20%至35%的参与者经历了不良事件,而观察组为8%。GENEVA试验的研究者报告,治疗组有63%的参与者经历了不良事件,而观察组为43%。最常见的不良事件是眼压升高、白内障进展和视网膜新生血管形成。由于研究局限性、治疗估计的不精确性以及选择性报告结局,我们将证据质量评为低质量。 作者结论:本文综述的两项RCT提供的证据不足,无法确定IVS对CRVO-ME患者的益处。SCORE试验中观察到的视力改善应谨慎解读,因为观察组很大一部分的结局数据缺失。与观察/未治疗相比,IVS治疗观察到的不良事件更频繁。
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