临床难题——溶栓在急性视网膜中央动脉阻塞中的作用是什么？
本文讨论急性视网膜中央动脉阻塞（CRAO）是否应静脉溶栓。既往观察性研究和患者水平荟萃分析提示溶栓可能有益，2021年AHA科学声明建议对4.5小时内的特定患者考虑溶栓。但近期两项高质量随机对照试验THEIA和TenCRAOS显示，阿替普酶或替奈普酶相比阿司匹林未改善视力恢复，且溶栓组不良事件有增加趋势或出现症状性颅内出血。因此当前证据不支持对急性非动脉炎性CRAO常规静脉溶栓，应优先快速诊断、眼科与神经科会诊、卒中性评估和二级卒中预防。
要点
- 对发病2.5小时内的急性CRAO患者，即使处于传统4.5小时溶栓时间窗内，当前证据也不支持常规静脉溶栓。
- THEIA试验显示静脉阿替普酶相比阿司匹林未改善视力恢复，且不良事件有增加趋势（Preterre 2025）。
- TenCRAOS试验显示替奈普酶与阿司匹林在视力恢复方面无显著差异，溶栓组报告1例症状性颅内出血（Ryan 2026）。
- 急诊处理应优先快速诊断、眼科和神经科会诊、卒中性评估及二级卒中预防，CRAO仍属血管急症。
- 2021年AHA科学声明曾建议对4.5小时内特定患者考虑溶栓，但其依据缺乏随机试验证据（Mac Grory 2021）。
适用人群与场景
- 本文讨论急性视网膜中央动脉阻塞（CRAO）患者，病例为71岁女性，有高血压和心房颤动，突发左眼视力丧失2.5小时。
- 临床问题聚焦急性非动脉炎性CRAO患者，尤其是发病4.5小时内的患者。
- 适用场景为急诊科或ICU床旁遇到急性单眼视力丧失、考虑静脉溶栓的决策情境。
- 原文提及视网膜循环与脑循环有共同血管起源，CRAO最常由视网膜中央动脉或其分支的栓塞性闭塞引起。
- 原文指出视网膜侧支循环极少，缺血损伤快速且不可逆；视网膜血管管径小及CRAO病因异质性可能降低全身溶栓效果。
诊断标准与关键阈值
- 原文提到的诊断方法包括：临床表现为严重单眼视力丧失，CTA阴性但床旁POCUS显示球后斑点征可确诊急性CRAO。
- 传统溶栓时间窗为发病4.5小时内，但原文指出该时间窗并非支持CRAO溶栓的充分依据。
- 2021年AHA科学声明建议在发病4.5小时内、经仔细筛选的患者中考虑溶栓，同时承认缺乏随机证据（Mac Grory 2021）。
- 原文未提及急性动脉炎性CRAO的诊断标准或界值。
处置流程与药物剂量
- 原文临床底线：对急性非动脉炎性CRAO患者，不支持常规静脉溶栓。
- 原文建议的急诊处理优先级为：快速诊断、眼科会诊、神经科会诊、卒中性评估、二级卒中预防。
- THEIA试验中静脉阿替普酶对照口服阿司匹林，未改善视力恢复；原文未提供具体剂量、单位、频次或疗程。
- TenCRAOS试验中替奈普酶对照阿司匹林，视力恢复无显著差异；原文未提供具体剂量、单位、频次或疗程。
- 原文未提及具体的抗血小板剂量、降压目标、血糖管理或其他床旁操作流程。
红旗征与不能漏的情况
- CRAO需按血管急症处理，不能因不推荐溶栓而延误卒中性评估和二级预防。
- 溶栓组报告1例症状性颅内出血（TenCRAOS试验，Ryan 2026），提示溶栓可能增加颅内出血风险。
- THEIA试验显示静脉阿替普酶相比阿司匹林不良事件有增加趋势（Preterre 2025），需警惕溶栓相关危害。
- 原文提及急性动脉炎性CRAO与非动脉炎性CRAO的区分在临床决策中重要，但未给出动脉炎性的诊断标准或具体处理。
研究设计与关键结果
- THEIA试验：静脉阿替普酶对比口服阿司匹林治疗发病4.5小时内严重视力丧失的急性CRAO，未改善视力恢复，不良事件有增加趋势（Preterre 2025）。
- TenCRAOS试验：替奈普酶对比阿司匹林的随机试验，视力恢复无显著差异，溶栓组报告1例症状性颅内出血（Ryan 2026）。
- 早期支持溶栓的证据主要来自观察性研究和患者水平荟萃分析（Dumitrascu 2020; Schrag 2015）。
- 患者水平荟萃分析显示静脉纤溶治疗与CRAO结局的关系（Schrag 2015）。
- 两项随机试验减少非随机设计的选择偏倚和混杂，提供了目前最强证据。
证据类型、等级与局限
- 证据类型：主要包括两项随机对照试验（THEIA、TenCRAOS）、观察性研究、患者水平荟萃分析、AHA科学声明及综述。
- 原文指出早前证据主要来自观察性研究和患者水平荟萃分析，存在选择偏倚和混杂等固有偏倚。
- 两项RCT减少非随机设计的偏倚，提供了目前最强证据，但原文未给出GRADE等级或具体推荐强度。
- 原文未报告两项RCT的样本量、中心数、失访率、效应量数值或95%置信区间。
- 2021年AHA科学声明建议考虑溶栓时明确承认缺乏随机证据（Mac Grory 2021）。
对床旁实践的改变
- 改变的做法：对急性CRAO患者不再将常规静脉溶栓作为默认策略，即使处于4.5小时时间窗内。
- 保留的做法：CRAO仍按血管急症处理，完成快速诊断、眼科与神经科会诊、卒中性评估和二级卒中预防。
- 常见陷阱：把CRAO等同于脑卒中而直接套用4.5小时溶栓时间窗，忽视CRAO溶栓缺乏随机获益证据且有出血风险。
- 适用人群：临床底线明确限于急性非动脉炎性CRAO患者，原文未讨论动脉炎性CRAO的溶栓问题。
- 不适用人群：原文未提供其他可能适用或不适用溶栓的亚组划分。
指南或共识出处
- 2021年AHA科学声明：Management of central retinal artery occlusion: A scientific statement from the American Heart Association（Mac Grory 2021）。
- THEIA试验：Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4.5 hours of severe vision loss（Preterre 2025）。
- TenCRAOS试验：A randomized trial of tenecteplase in acute central retinal artery occlusion（Ryan 2026）。
- 患者水平荟萃分析：Intravenous fibrinolytic therapy in central retinal artery occlusion: A patient level meta analysis（Schrag 2015）。
- 综述：Thrombolysis for central retinal artery occlusion in 2020: Time is vision!（Dumitrascu 2020）；Ocular vascular occlusive disorders: Natural history of visual outcome（Hayreh 2011）。
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原文图文 · 图 8 张
Bottom Line Up Top
Current evidence does not support the routine use of intravenous thrombolysis for acute central retinal artery occlusion (CRAO).
Case
A 71 year old woman with hypertension and atrial fibrillation presents 2.5 hours after the sudden onset of vision loss in her left eye. Examination demonstrates profound monocular vision loss, CTA is negative but bedside POCUS shows a retrobulbar spot sign, confirming the diagnosis of acute CRAO. Because she presents within the traditional 4.5 hour thrombolytic window, you consider whether intravenous thrombolysis should be administered.
What Your Gut Says
CRAO is commonly referred to as an “eye stroke.” If thrombolytics improve outcomes in acute ischemic stroke, they should similarly be helpful in restoring vision in CRAO.
What The Evidence Says
CRAO is an acute ischemic injury of the retina, most commonly caused by an embolic occlusion of the central retinal artery or one of its branches. Because the retinal and cerebral circulations share a common vascular origin, thrombolysis has long been considered a potential treatment strategy (Dumitrascu 2020; Mac Grory 2021). Important anatomical differences distinguish CRAO from cerebral stroke. The retina has minimal collateral circulation, resulting in rapid, irreversible ischemic injury. In addition, the small caliber of the retinal vasculature and the heterogeneous causes of CRAO may reduce the effectiveness of systemic thrombolysis (Hayreh 2011).
Early evidence supporting thrombolysis came primarily from observational studies and patient level meta analyses. This led to the 2021 American Heart Association Scientific Statement to recommend considering thrombolysis in carefully selected patients presenting within 4.5 hours while acknowledging the absence of randomized evidence (Mac Grory 2021; Schrag 2015).
More recently, two high quality randomized controlled trials have challenged this practice. In contrast to the earlier observational studies and patient level meta analyses, these trials reduce important sources of bias inherent to non-randomized designs including selection bias and confounding, and therefore provide the strongest evidence available to date. The THEIA trial found no improvement in visual recovery with intravenous alteplase compared with aspirin and demonstrated a trend toward more adverse events (Preterre 2025). Likewise, the TenCRAOS trial showed no significant difference in vision recovery between tenecteplase and aspirin while reporting one symptomatic intracranial hemorrhage in the thrombolysis group (Ryan 2026). Together, these studies suggest that the potential risks of thrombolysis outweigh any unproven benefit.
Clinical Bottom Line
Routine intravenous thrombolysis is not supported for patients with acute nonarteritic CRAO. Emergency physicians should instead prioritize rapid diagnosis, ophthalmology and neurology consultation, stroke evaluation, and secondary stroke prevention. Although CRAO remains a vascular emergency, current evidence suggests that thrombolytic therapy does not improve visual outcomes and may expose patients to unnecessary harm (Preterre 2025; Ryan 2026).
References
Dumitrascu, O. M., Newman, N. J., & Biousse, V. (2020).
Thrombolysis for central retinal artery occlusion in 2020: Time is vision! Journal of Neuro-Ophthalmology, 40(3), 333–345.
PMID: 32739995
Hayreh, S. S. (2011).
Ocular vascular occlusive disorders: Natural history of visual outcome. Progress in Retinal and Eye Research, 30(5), 359–394.
PMID: 24769221
Mac Grory, B., et al. (2021)
Management of central retinal artery occlusion: A scientific statement from the American Heart Association. Stroke.
PMID: 33677974
Preterre, C., Gaultier, A., Obadia, M., et al. (2025).
Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4.5 hours of severe vision loss (THEIA): The Lancet Neurology.
PMID: 41109232
Ryan, S. J. et al.
A randomized trial of tenecteplase in acute central retinal artery occlusion. New England Journal of Medicine, 394(5), 442–450.
PMID: 41604638
Schrag, M., et al.
Intravenous fibrinolytic therapy in central retinal artery occlusion: A patient level meta analysis. JAMA Neurology, 72(10), 1148–1154.
PMID: 26258861
Post Peer Reviewed By: Mark Ramzy, DO (X: @MRamzyDO), and Marco Propersi, DO (X: @Marco_Propersi)
Authors
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The post Clinical Conundrum — What is the Role of Thrombolysis in Central Retinal Artery Occlusion? appeared first on REBEL EM - Emergency Medicine Blog.
参考来源
- REBEL EM：Clinical Conundrum — What is the Role of Thrombolysis in Central Retinal Artery Occlusion?
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