病毒引起约80%的急性结膜炎病例。人类腺病毒被认为占65%至90%的病毒性结膜炎病例,或全球感染性角膜结膜炎的所有原因的20%至75%。流行性角膜结膜炎(EKC)是腺病毒结膜炎的高度传染性子集,与军事设施和医疗设施的大规模暴发有关。它伴有严重的结膜炎症,水性放电,和光敏性,并可能导致慢性并发症,如角膜和结膜疤痕,不适和视力质量差。由于对任何改变EKC临床病程的药物疗法的疗效缺乏共识,没有护理标准,因此,许多临床医生只提供支持治疗。
为了评估局部药物治疗与安慰剂的疗效和安全性,一个主动控制,或不治疗成人EKC。
我们搜索了Cochrane中央对照试验登记册(中央,其中包含Cochrane眼睛和视力试验登记册;2021年,第4期);OvidMEDLINE;OvidEmbase;拉丁美洲和加勒比健康科学数据库(LILACS);ClinicalTrials.gov;和世界卫生组织(WHO)国际临床试验注册平台(ICTRP),没有语言或出版年份的限制。最后一次搜索的日期是2021年4月27日。
我们纳入了随机对照试验,病毒抑制剂,或将局部免疫调节疗法与安慰剂进行比较,一个主动控制,或者没有治疗。
我们使用了标准的Cochrane方法。
我们确定了在亚洲进行的10项研究,欧洲,中东,和北非,共有892名参与者接受了7天至6个月的治疗,并随访了7天至1.5年。研究特征和偏倚风险在大多数研究中,参与者主要是男性(范围:44%至90%),年龄从9岁到82岁。三项研究报告了有关试验登记的信息,但我们没有发现发表的研究方案.大多数试验的样本量都很小,每个研究纳入18~90名参与者;唯一的例外是一项纳入350名参与者的试验.我们认为大多数研究在偏倚风险域中存在高或不清楚的偏倚风险。研究结果我们纳入了10项研究,包括892名EKC参与者,并通过含类固醇对照治疗或人工泪液进行分层分析,估计综合干预效果。六项试验有助于局部干预措施的比较(聚维酮碘[PVP-I],三氟尿苷,更昔洛韦,地塞米松加新霉素)与人工泪液(或盐水)。来自两项比较氟尿苷或更昔洛韦与人工泪液的试验的确定性非常低的证据表明,对缩短EKC的主要症状或体征的平均持续时间的影响不一致。基于两项研究(409名参与者)的低确定性证据表明,与使用人工泪液治疗的参与者相比,仅使用PVP-I治疗的参与者在治疗的第一周更经常出现症状缓解(风险比(RR)1.15,95%置信区间(CI)1.07至1.24)和体征缓解(RR3.19,95%CI2.29至4.45)。来自两项研究(77名参与者)的极低确定性证据表明,PVP-I或更昔洛韦在治疗后30天内与人工泪液相比可预防上皮下浸润(SEI)的发展(RR0.24,95%CI0.10至0.56)。四项研究比较了局部干预(他克莫司,环孢菌素A[CsA],三氟尿苷,PVP-I+地塞米松)与局部类固醇,一项试验比较了氟米龙(FML)加聚乙烯醇碘(PVA-I)与FML加左氧氟沙星。一项试验的证据表明,与单独接受地塞米松的患者相比,接受PVP-I1.0%加地塞米松0.1%的患者在第7天有更多的症状缓解(RR9.00,95%CI1.23至66.05;52只眼)。在两次审判中,与单独使用类固醇或类固醇加左氧氟沙星相比,PVP-I或PVA-I加类固醇治疗后15天内出现SEI的眼睛较少(RR0.08,95%CI0.01~0.55;69只眼).一项研究发现,CsA在治疗四周内解决SEI方面并不比类固醇更有效(RR0.84,95%CI0.67至1.06;N=88)。比较局部干预与类固醇的试验证据总体上具有非常低的确定性。不良反应在滴注时的眼部不适方面,抗病毒或抗菌药物加类固醇与人工泪液没有差异(RR9.23,95%CI0.61至140.67;N=19)。CsA和他克莫司滴眼液与更多的严重眼部不适病例相关,有时是不宽容,与类固醇相比(RR4.64,95%CI1.15至18.71;2项研究;N=141)。与类固醇相比,他克莫司并不增加眼压升高的风险(RR0.07,95%CI0至1.13;1项研究;N=80),而与泪液替代物相比,氟尿苷没有增加风险(RR5.50,95%CI0.31~96.49;1项研究;N=97)。总的来说,细菌重复感染很少见(23例CsA用户中有1例),与使用干预类固醇无关(RR3.63,95%CI0.15~84.98;N=51).所有估计的证据都具有很低或非常低的确定性。
由于不精确和高偏倚风险,七个特定结果的证据具有低或非常低的确定性。与人工泪液相比,抗病毒药物缩短症状或体征持续时间的证据尚无定论。低确定性证据表明,相对于人工泪液,PVP-I单独可以解决7天的体征和症状。PVP-I或PVA-I,单独或与类固醇,与人工泪液或类固醇相比,SEI发展的风险较低(确定性非常低的证据)。目前可用的证据不足以确定任何评估的干预措施是否在根除病毒或将其传播到最初未涉及的眼睛方面比类固醇或人工泪液更具优势。本综述的未来更新应提供来自较大样本量的试验的高水平确定性的证据,具有相似体征和症状持续时间的参与者的招募,以及评估短期和长期结果的有效方法。
Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.
To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.
We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.
We used standard Cochrane methodology.
We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.
The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.