Lim Blanche X, Lim Chris Hl, Lim Dawn K, Evans Jennifer R, Bunce Catey, Wormald Richard
Department of Ophthalmology, National University Health System, 1E Kent Ridge Rd, Singapore 119228, Singapore, Singapore.
Cochrane Database Syst Rev. 2016 Nov 1;11(11):CD006683. doi: 10.1002/14651858.CD006683.pub3.
BACKGROUND: Macular oedema (MO) is the accumulation of extracellular fluid in the central retina (the macula). It may occur after cataract surgery and may give rise to poor visual outcome, with reduced visual acuity and distortion of the central vision. MO is often self-limiting with spontaneous resolution, but a small proportion of people with chronic persistent MO may be difficult to treat. Chronic oedema may lead to the formation of cystic spaces in the retina termed 'cystoid macular oedema' (CMO). Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in cataract surgery and may reduce the chances of developing MO. OBJECTIVES: The aim of this review is to answer the question: is there evidence to support the prophylactic use of topical NSAIDs either in addition to, or instead of, topical steroids postoperatively to reduce the incidence of macular oedema (MO) and associated visual morbidity. SEARCH METHODS: We searched a number of electronic databases including CENTRAL, MEDLINE and Embase. Date last searched 2 September 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which adult participants had undergone surgery for age-related cataract. We included participants irrespective of their baseline risk of MO, in particular we included people with diabetes and uveitis. We included trials of preoperative and/or postoperative topical NSAIDs in conjunction with postoperative topical steroids. The comparator was postoperative topical steroids alone. A secondary comparison was preoperative and/or postoperative topical NSAIDs alone versus postoperative topical steroids alone. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed risk of bias and extracted data using standard methods expected by Cochrane. We pooled data using a random-effects model. We graded the certainty of the evidence using GRADE and considered the following: risk of bias of included studies, precision of the effect estimate, consistency of effects between studies, directness of the outcome measure and publication bias. MAIN RESULTS: We identified 34 studies that were conducted in the Americas, Europe, the Eastern Mediterranean region and South-East Asia. Over 5000 people were randomised in these trials. The majority of studies enrolled one eye per participant; a small subset (4 trials) enrolled a proportion of people with bilateral surgery. Twenty-eight studies compared NSAIDs plus steroids with steroids alone. Six studies compared NSAIDs with steroids. A variety of NSAIDs were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, flurbiprofen and pranopfen. Follow-up ranged from one to 12 months. In general, the studies were poorly reported. We did not judge any of the studies at low risk of bias in all domains. Six studies were funded by industry, seven studies were funded from non-industry sources, and the rest of the studies did not report the source of funding.There was low-certainty evidence that people receiving topical NSAIDs in combination with steroids may have a lower risk of poor vision due to MO at three months after cataract surgery compared with people receiving steroids alone (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.23 to 0.76; eyes = 1360; studies = 5; I = 5%). We judged this to be low-certainty evidence because of risk of bias in the included studies and indirectness, as the extent of visual loss was not always clear. Only one study reported poor vision due to MO at 12 months and we judged this to be very low-certainty evidence as there were only two events. Quality of life was only reported in one of the 34 studies comparing NSAIDs plus steroids versus steroids alone, and it was not fully reported, other than to comment on lack of differences between groups. There was evidence of a reduced risk of MO with NSAIDs at three months after surgery, but we judged this to be low-certainty due to risk of bias and publication bias (RR 0.40, 95% CI 0.32 to 0.49; eyes = 3638; studies = 21). There was inconsistent evidence on central retinal thickness at three months (I = 87%). Results ranged from -30.9 µm in favour of NSAIDs plus steroids to 7.44 µm in favour of steroids alone. Similarly, data on best corrected visual acuity (BCVA) were inconsistent, but nine out of 10 trials reporting this outcome found between-group differences in visual acuity of less than 0.1 logMAR.None of the six studies comparing NSAIDs alone with steroids reported on poor vision due to MO at three or 12 months. There was low-certainty evidence that central retinal thickness was lower in the NSAIDs group at three months (mean difference (MD) -22.64 µm, 95% CI -38.86 to -6.43; eyes = 121; studies = 2). Five studies reported on MO and showed a reduced risk with NSAIDs, but we judged this evidence to be of low-certainty (RR 0.27, 95% CI 0.18 to 0.41; eyes = 520). Three studies reported BCVA at three months and the results of these trials were inconsistent, but all three studies found differences of less than 0.1 logMAR between groups.We did not note any major adverse events - the main consistent observation was burning or stinging sensation with the use of NSAIDs. AUTHORS' CONCLUSIONS: Using topical NSAIDs may reduce the risk of developing macular oedema after cataract surgery, although it is possible that current estimates as to the size of this reduction are exaggerated. It is unclear the extent to which this reduction has an impact on the visual function and quality of life of patients. There is little evidence to suggest any important effect on vision after surgery. The value of adding topical NSAIDs to steroids, or using them as an alternative to topical steroids, with a view to reducing the risk of poor visual outcome after cataract surgery is therefore uncertain. Future trials should address the remaining clinical uncertainty of whether prophylactic topical NSAIDs are of benefit, particularly with respect to longer-term follow-up (at least to 12 months), and should be large enough to detect reduction in the risk of the outcome of most interest to patients, which is chronic macular oedema leading to visual loss.
背景:黄斑水肿(MO)是指中央视网膜(黄斑)处细胞外液的积聚。它可能在白内障手术后发生,并可能导致视力不佳,表现为视力下降和中央视力扭曲。MO通常具有自限性,可自行消退,但一小部分慢性持续性MO患者可能难以治疗。慢性水肿可能导致视网膜中形成囊样间隙,称为“囊样黄斑水肿”(CMO)。非甾体抗炎药(NSAIDs)常用于白内障手术,可能会降低发生MO的几率。 目的:本综述的目的是回答以下问题:是否有证据支持在白内障手术后预防性使用局部NSAIDs,作为局部类固醇的补充或替代,以降低黄斑水肿(MO)的发生率及相关视觉损害。 检索方法:我们检索了多个电子数据库,包括Cochrane系统评价数据库、医学期刊数据库(MEDLINE)和荷兰医学文摘数据库(Embase)。最后检索日期为2016年9月2日。 选择标准:我们纳入了成年参与者接受年龄相关性白内障手术的随机对照试验(RCT)。无论参与者MO的基线风险如何,我们均纳入研究,尤其纳入了患有糖尿病和葡萄膜炎的患者。我们纳入了术前和/或术后局部使用NSAIDs联合术后局部使用类固醇的试验。对照为单纯术后局部使用类固醇。次要比较为术前和/或术后单独使用局部NSAIDs与术后单独使用局部类固醇。 数据收集与分析:两位综述作者独立选择纳入研究,评估偏倚风险并使用Cochrane期望的标准方法提取数据。我们使用随机效应模型合并数据。我们使用GRADE对证据的确定性进行分级,并考虑以下因素:纳入研究的偏倚风险、效应估计的精确性、研究间效应的一致性、结局测量的直接性和发表偏倚。 主要结果:我们识别出在美洲、欧洲、东地中海地区和东南亚开展的34项研究。超过5000人参与了这些试验。大多数研究为每位参与者的一只眼睛进行随机分组;一小部分(4项试验)纳入了部分接受双侧手术的患者。28项研究比较了NSAIDs加类固醇与单独使用类固醇。6项研究比较了NSAIDs与类固醇。使用了多种NSAIDs,包括酮咯酸、双氯芬酸、奈帕芬酸、吲哚美辛、溴芬酸、氟比洛芬和普拉洛芬。随访时间为1至12个月。总体而言,研究报告质量较差。我们未判定任何一项研究在所有领域均为低偏倚风险。6项研究由行业资助,7项研究由非行业来源资助,其余研究未报告资金来源。有低确定性证据表明,与单独接受类固醇的患者相比,接受局部NSAIDs联合类固醇的患者在白内障手术后三个月因MO导致视力不佳的风险可能更低(风险比(RR)0.41,95%置信区间(CI)0.23至0.76;眼睛数量 = 1360;研究数量 = 5;I² = 5%)。由于纳入研究存在偏倚风险且证据不直接,因为视力丧失程度并不总是明确的,我们将此判定为低确定性证据。仅有一项研究报告了12个月时因MO导致的视力不佳情况,我们将其判定为极低确定性证据,因为仅有两例事件。在比较NSAIDs加类固醇与单独使用类固醇的34项研究中,仅有一项研究报告了生活质量,且报告不完整,仅提及两组之间无差异。有证据表明术后三个月使用NSAIDs可降低MO的风险,但由于偏倚风险和发表偏倚,我们将此判定为低确定性证据(RR 0.40,95% CI 0.32至0.49;眼睛数量 = 3638;研究数量 = 21)。关于三个月时的中央视网膜厚度,证据不一致(I² = 87%)。结果从有利于NSAIDs加类固醇的 -30.9 µm到有利于单独使用类固醇的7.44 µm不等。同样,关于最佳矫正视力(BCVA)的数据也不一致,但报告此结局的10项试验中有9项发现两组之间的视力差异小于0.1 logMAR。比较单独使用NSAIDs与类固醇的6项研究中,无一报告三个月或12个月时因MO导致的视力不佳情况。有低确定性证据表明,三个月时NSAIDs组的中央视网膜厚度更低(平均差(MD) -22.64 µm,95% CI -38.86至 -6.43;眼睛数量 = 121;研究数量 = 2)。5项研究报告了MO情况,显示使用NSAIDs可降低风险,但我们将此证据判定为低确定性(RR 0.27,95% CI 0.18至0.41;眼睛数量 = 520)。3项研究报告了三个月时的BCVA,这些试验结果不一致,但所有三项研究均发现两组之间的差异小于0.1 logMAR。我们未注意到任何重大不良事件 - 主要一致的观察结果是使用NSAIDs时出现烧灼感或刺痛感。 作者结论:使用局部NSAIDs可能会降低白内障手术后发生黄斑水肿的风险,尽管目前关于这种降低幅度的估计可能存在夸大。目前尚不清楚这种降低对患者视觉功能和生活质量的影响程度。几乎没有证据表明对术后视力有任何重要影响。因此,为降低白内障手术后视力不佳风险而在类固醇中添加局部NSAIDs或用其替代局部类固醇的价值尚不确定。未来的试验应解决预防性局部使用NSAIDs是否有益这一剩余的临床不确定性,特别是关于长期随访(至少至12个月),并且试验规模应足够大,以检测对患者最感兴趣的结局(即导致视力丧失的慢性黄斑水肿)风险的降低情况。
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