Gharaibeh Almutez, Savage Howard I, Scherer Roberta W, Goldberg Morton F, Lindsley Kristina
Department of Special Surgery-Ophthalmology, Faculty of Medicine, The University of Jordan, P.O. Box 13046, Amman, Jordan.
Cochrane Database Syst Rev. 2019 Jan 14;1(1):CD005431. doi: 10.1002/14651858.CD005431.pub4.
Traumatic hyphema is the entry of blood into the anterior chamber (the space between the cornea and iris) subsequent to a blow or a projectile striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma, optic atrophy, etc.) may seriously affect vision. Such complications can lead to permanent impairment of vision. People with sickle cell trait/disease may be particularly susceptible to increases of elevated intraocular pressure. If rebleeding occurs, the rates and severity of complications increase.
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase.com; PubMed (1948 to June 2018); the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 28 June 2018.
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. In this review, we included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical intervention or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions regarding age, gender, severity of the closed-globe trauma, or level of visual acuity at the time of enrollment.
Two review authors independently extracted the data for the primary outcomes, visual acuity and time to resolution of primary hemorrhage, and secondary outcomes including: secondary hemorrhage and time to rebleed; risk of corneal blood staining, glaucoma or elevated intraocular pressure, optic atrophy, or peripheral anterior synechiae; adverse events; and duration of hospitalization. We entered and analyzed data using Review Manager 5. We performed meta-analyses using a fixed-effect model and reported dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD).
We included 20 randomized and seven quasi-randomized studies with a total of 2643 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest.We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Eight trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty.Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60) as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two studies with 121 participants. We assessed the certainty of these findings as low and very low, respectively. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.31, 95% CI 0.17 to 0.55) in five trials with 578 participants, as did aminomethylbenzoic acid as reported in one study (RR 0.10, 95% CI 0.02 to 0.41). The evidence to support an associated reduction in the risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect in the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention.The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials.We found no evidence of an effect between a single versus binocular patch or ambulation versus complete bed rest on the risk of secondary hemorrhage or time to rebleed.
AUTHORS' CONCLUSIONS: We found no evidence of an effect on visual acuity by any of the interventions evaluated in this review. Although evidence was limited, it appears that people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema took longer clear in people treated with systemic aminocaproic acid.There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
外伤性前房积血是指眼球受到撞击或弹丸击中后，血液进入前房（角膜和虹膜之间的间隙）。前房积血很少导致永久性视力丧失。相关创伤（如角膜染色、外伤性白内障、房角后退性青光眼、视神经萎缩等）可能严重影响视力。此类并发症可导致永久性视力损害。患有镰状细胞性状/疾病的人可能特别容易出现眼压升高。如果发生再次出血，并发症的发生率和严重程度会增加。
评估各种药物干预措施治疗外伤性前房积血的效果。
我们检索了Cochrane对照试验中心注册库（CENTRAL）（其中包含Cochrane眼科和视力试验注册库）（2018年第6期）；MEDLINE Ovid；Embase.com；PubMed（1948年至2018年6月）；ISRCTN注册库；ClinicalTrials.gov以及世界卫生组织（WHO）国际临床试验注册平台（ICTRP）。检索日期为2018年6月28日。
两名综述作者独立评估了通过电子和手动检索确定的所有报告的标题和摘要。在本综述中，我们纳入了随机和半随机试验，这些试验比较了各种药物（非手术）干预措施与其他药物干预措施或对照组，用于治疗闭合性眼球外伤后的外伤性前房积血。我们对年龄、性别、闭合性眼球外伤的严重程度或入组时的视力水平没有限制。
两名综述作者独立提取了主要结局的数据，即视力和原发性出血的消退时间，以及次要结局的数据，包括：继发性出血和再次出血的时间；角膜血染、青光眼或眼压升高、视神经萎缩或周边前粘连的风险；不良事件；以及住院时间。我们使用Review Manager 5录入和分析数据。我们采用固定效应模型进行荟萃分析，并将二分法结局报告为风险比（RR），将连续结局报告为平均差（MD）。
我们纳入了20项随机试验和7项半随机试验，共有2643名参与者。干预措施包括抗纤维蛋白溶解剂（全身和局部应用氨基己酸、氨甲环酸和氨甲苯酸）、皮质类固醇（全身和局部）、睫状肌麻痹剂、缩瞳剂、阿司匹林、结合雌激素、中药、单眼与双眼包扎、头部抬高和卧床休息。我们没有发现任何干预措施对视力有影响的证据，无论是在两周内（短期）还是更长时间内测量。在两项试验的荟萃分析中，我们没有发现氨基己酸对长期视力有影响的证据（RR = 1.03，95%置信区间（CI）0.82至1.29），也没有发现前房积血后长达三年测量的最终视力有影响的证据（RR = 1.05，95%CI 0.93至1.18）。八项试验评估了各种干预措施对短期视力的影响；这些干预措施在不止一项试验中进行了测量。没有干预措施显示出统计学上的显著效果（RR范围为0.75至1.10）。同样，在四项评估不同干预措施的试验中，较长时间测量的视力也没有统计学意义（RR范围为0.82至1.02）。支持这些发现的证据的确定性较低或非常低。在六项涉及330名参与者的试验中评估发现，全身应用氨基己酸可降低再出血率（RR = 0.28，95%CI 0.13至0.60）。一项敏感性分析排除了两项未采用意向性治疗分析的研究，降低了证据的强度（RR = 0.43，95%CI 0.17至1.08）。在两项涉及121名参与者的研究中，我们对局部应用氨基己酸也得到了类似的结果（RR = 0.48，95%CI 0.20至1.10）。我们分别将这些发现的确定性评估为低和非常低。在五项涉及578名参与者的试验中，全身应用氨甲环酸对降低继发性出血率有显著效果（RR = 0.31，95%CI 0.17至0.55），一项研究报告的氨甲苯酸也有同样效果（RR = 0.10，95%CI 0.02至0.41）。抗纤维蛋白溶解剂相关的继发性出血并发症（即角膜血染、周边前粘连、眼压升高和视神经萎缩的发生）风险降低的证据受到这些事件数量较少的限制。与安慰剂相比，使用氨基己酸会增加恶心、呕吐和其他不良事件。我们没有发现全身与局部应用氨基己酸或标准与低剂量药物在不良事件数量上有影响的证据。与未使用相比，全身应用氨基己酸时原发性前房积血消退的天数似乎更长，但任何其他干预措施都没有改变这一结果。由于试验中的参与者和事件数量较少，关于全身或局部应用皮质类固醇、睫状肌麻痹剂或阿司匹林治疗外伤性前房积血的现有证据有限。我们没有发现单眼与双眼包扎或活动与完全卧床休息对继发性出血风险或再次出血时间有影响的证据。
我们没有发现本综述中评估的任何干预措施对视力有影响的证据。尽管证据有限，但似乎接受氨基己酸或氨甲环酸治疗的外伤性前房积血患者继发性出血的可能性较小。然而，全身应用氨基己酸治疗的患者前房积血清除时间更长。除了可能降低继发性出血率外，没有充分的证据支持在治疗外伤性前房积血时使用抗纤维蛋白溶解剂。同样，也没有证据支持在治疗外伤性前房积血时使用皮质类固醇、睫状肌麻痹剂或非药物干预措施（如双眼包扎、卧床休息或头部抬高）。由于这些多种干预措施很少单独使用，进一步研究评估这些干预措施的叠加效果可能会有价值。
