Pradhan Eli, Bhandari Sanjeeb, Gilbert Ruth E, Stanford Miles
Tilganga Institute of Ophthalmology, Kathmandu, Nepal.
Cochrane Database Syst Rev. 2016 May 20;2016(5):CD002218. doi: 10.1002/14651858.CD002218.pub2.
Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment.
To compare the effects of antibiotic treatment versus placebo or no treatment for toxoplasma retinochoroiditis.
We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 22 February 2016. We searched the reference lists of identified articles and contacted pharmaceutical companies for unpublished trials.
We included randomised controlled trials that compared any antibiotic treatment against placebo or no treatment. We excluded trials that included immunocompromised participants. We considered any antibiotic treatment known to be active against Toxoplasma gondii. Antibiotic treatment could be given in any dose orally, by intramuscular injection, by intravenous infusion, or by intravitreal injection.
The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion, and adverse events. We used standard methodological procedures expected by Cochrane.
Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally.One study conducted in Brazil in both adults and children compared trimethoprim-sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim-sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo.Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence).Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I(2) = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis.The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim-sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine-trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment.Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia.
AUTHORS' CONCLUSIONS: Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes.
急性弓形虫视网膜脉络膜炎会引发眼部不适的短暂症状，并可能导致永久性视力丧失。抗生素治疗主要旨在降低永久性视力丧失、复发性视网膜脉络膜炎的风险，以及减轻急性症状的严重程度和缩短其持续时间。抗生素治疗的有效性尚不确定。
比较抗生素治疗与安慰剂或不治疗对弓形虫视网膜脉络膜炎的效果。
我们检索了Cochrane中心对照试验注册库（CENTRAL）（其中包含Cochrane眼科和视力组试验注册库）（2016年第1期）、Ovid MEDLINE、Ovid MEDLINE在研及其他未索引引文、Ovid MEDLINE每日更新、Ovid OLDMEDLINE（1946年1月至2016年2月）、EMBASE（1980年1月至2016年2月）、拉丁美洲和加勒比健康科学文献数据库（LILACS）（1982年1月至2016年2月）、国际标准随机对照试验编号注册库（ISRCTN registry）（www.isrctn.com/editAdvancedSearch）、美国国立医学图书馆临床试验数据库（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2016年2月22日。我们检索了已识别文章的参考文献列表，并联系了制药公司以获取未发表的试验。
我们纳入了比较任何抗生素治疗与安慰剂或不治疗的随机对照试验。我们排除了纳入免疫功能低下参与者的试验。我们考虑任何已知对弓形虫有效的抗生素治疗。抗生素治疗可以通过口服、肌肉注射、静脉输注或玻璃体内注射等任何剂量给药。
本综述的主要结局是治疗后至少三个月的视力以及复发性视网膜脉络膜炎的风险。次要结局是眼内炎症症状和体征的改善、病变大小以及不良事件。我们采用了Cochrane预期的标准方法程序。
四项共随机分配268名参与者的试验符合纳入标准。在所有四项研究中，抗生素均通过口服给药。在巴西进行的一项针对成人和儿童的研究中，将复方新诺明治疗20个月与不治疗进行了比较，该研究被判定在实施、检测和失访偏倚方面风险较高。其他三项研究将抗生素治疗与安慰剂进行了比较。由于报告不佳，我们判定这三项研究存在低或不明确的偏倚风险。在美国进行的一项针对成人的研究中，研究了乙胺嘧啶 - 三磺胺嘧啶治疗八周；在英国进行的一项针对儿童和成人的研究中，评估了乙胺嘧啶治疗四周；在巴西进行的一项针对成人的研究中，研究了复方新诺明治疗12个月。在最后一项研究中，所有参与者均患有活动性视网膜脉络膜炎，在随机分配至复方新诺明组与安慰剂组之前，均接受了45天的抗生素治疗。只有巴西进行的为期12个月的复方新诺明研究，在病变已愈合的参与者中，报告了治疗对视力的影响。与接受安慰剂治疗的人相比，接受抗生素治疗的人在一年时视力变化可能相似（平均差 -1.00字母；95%置信区间（CI）-7.93至5.93字母；93名参与者；低质量证据）。与安慰剂相比，抗生素治疗可能会降低复发性视网膜脉络膜炎的风险（风险比（RR）0.26，95%CI 0.11至0.63；227名参与者；3项研究；I² = 0%；中等质量证据）；急性和慢性视网膜脉络膜炎均观察到类似结果。英国进行的乙胺嘧啶治疗四周的研究报告称，与对照参与者相比，治疗组的眼内炎症有所改善（RR 1.76，95%CI 0.98至3.19；29名参与者；低质量证据）。巴西进行的复方新诺明治疗12个月的研究称，与抗生素治疗组相比，对照组的炎症严重程度更高，但未提供进一步细节。在美国进行的乙胺嘧啶 - 三磺胺嘧啶治疗八周的研究中，所有参与者在八周时眼内炎症几乎完全消退，然而在该研究中所有参与者均接受了类固醇治疗。两项研究（英国和美国的研究）报告称，治疗参与者的不良事件风险增加。这些不良事件包括血红蛋白、白细胞和血小板计数下降、恶心、食欲不振、皮疹和关节痛。
抗生素治疗可能会降低复发性弓形虫视网膜脉络膜炎的风险，但目前尚无充分证据表明这会带来更好的视力结果。然而，缺乏疗效证据并不等同于无效果证据。需要对影响视网膜任何部位的急性和慢性弓形虫视网膜脉络膜炎患者进行进一步试验，以确定抗生素治疗对视力结果的影响。
