Meta-Analysis

. 2025 Nov;56(11):3175-3186.

doi: 10.1161/STROKEAHA.124.049955. Epub 2025 Aug 20.

Early Thrombolysis and Outcomes in Central Retinal Artery Occlusion: An Individual Participant Data Meta-Analysis

Jim S Xie^#¹, Kirill Zaslavsky^#², Yuri V Chaban¹, Adrien Lusterio¹, Hargun Kaur¹, Yasmin Motekalem¹, Dena Zeraatkar³, Marko M Popovic¹, Katharina Althaus⁴, Brett Malbin⁵, Christian H Nolte⁶, Jan F Scheitz⁶, Jacqueline A Pettersen^{7

8}, Ronen R Leker⁹, Joonhyung Kim¹⁰, Se Joon Woo¹¹, Celia Chen¹², Nicolas Feltgen¹³, Manya Khrlobyan¹⁴, Navdeep Sangha¹⁴, Elena A Jurado¹⁵, Marcel Arnold¹⁶, Heinrich Mattle¹⁶, Mirjam R Heldner¹⁶, Max G Nedelmann¹⁷, Charlotte Cordonnier¹⁸, Martin S Spitzer¹⁹, Sven Poli²⁰, Christian Hametner²¹, Philipp Baumgartner²², Susanne Wegener²², Lucas Kook²³, Shima Shahjouei²⁴, Oana M Dumitrascu²⁵, Edward M Margolin¹; Assessment Group for Interventional Lysis in Eye (AGILE)

Collaborators, Affiliations

Collaborators

Assessment Group for Interventional Lysis in Eye (AGILE):
Patrik Michel

Affiliations

¹ Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, ON, Canada (J.S.X., Y.V.C., A.L., H.K., Y.M., M.M.P., E.M.M.).
² Department of Ophthalmology and Vision Sciences (K.Z.), University of British Columbia, Vancouver, Canada.
³ Department of Anesthesiology, McMaster University, Hamilton, ON, Canada (D.Z.).
⁴ Department of Neurology, University Hospital Ulm, Germany (K.A.).
⁵ Department of Ophthalmology, Kresge Eye Institute, Detroit, MI (B.M.).
⁶ Department of Neurology with Experimental Neurology and Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Germany (C.H.N., J.F.S.).
⁷ Division of Neurology, Department of Medicine (J.A.P.), University of British Columbia, Vancouver, Canada.
⁸ Division of Medical Sciences, University of Northern British Columbia, Prince George, Canada (J.A.P.).
⁹ Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (R.R.L.).
¹⁰ Department of Ophthalmology, CHA Bundang Medical Center, CHA University School of Medicine, South Korea (J.K.).
¹¹ Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea (S.J.W.).
¹² Department of Ophthalmology, Flinders Medical Center and Flinders University, Adelaide, SA, Australia (C. Chen).
¹³ Department of Ophthalmology, University Hospital of Basel, Switzerland (N.F.).
¹⁴ Department of Neurology, Southern California Permanente Medical Group, Los Angeles Medical Center (M.K., N.S.).
¹⁵ Department of Neurology & Stroke Center, University Teaching & Research Hospital, Kantonsspital St. Gallen, Switzerland (E.A.J.).
¹⁶ Department of Neurology, Inselspital, University Hospital and University of Bern, Switzerland (M.A., H.M., M.R.H.).
¹⁷ Department of Neurology, Sana Regio Klinikum Pinneberg, Germany (M.G.N.).
¹⁸ University Lille, Inserm, CHU Lille, U1172, Lille Neuroscience and Cognition, France (C. Cordonnier).
¹⁹ Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Germany (M.S.S.).
²⁰ Department of Neurology, University Hospital Tübingen and Hertie Institute for Clinical Brain Research, University of Tübingen, Germany (S.P.).
²¹ Department of Neurology, Julius-Maximilian University of Würzburg, Germany (C.H.).
²² Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland (P.B., S.W.).
²³ Institute for Statistics and Mathematics, Vienna University of Economics and Business, Austria (L.K.).
²⁴ Department of Neurology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA (S.S.).
²⁵ Departments of Neurology and Ophthalmology, Mayo Clinic College of Medicine and Science, Scottsdale, AZ (O.M.D.).

^# Contributed equally.

PMID: 40832714
DOI: 10.1161/STROKEAHA.124.049955

Meta-Analysis

Early Thrombolysis and Outcomes in Central Retinal Artery Occlusion: An Individual Participant Data Meta-Analysis

Jim S Xie et al. Stroke. 2025 Nov.

. 2025 Nov;56(11):3175-3186.

doi: 10.1161/STROKEAHA.124.049955. Epub 2025 Aug 20.

Authors

Collaborators

Assessment Group for Interventional Lysis in Eye (AGILE):
Patrik Michel

Affiliations

¹ Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, ON, Canada (J.S.X., Y.V.C., A.L., H.K., Y.M., M.M.P., E.M.M.).
² Department of Ophthalmology and Vision Sciences (K.Z.), University of British Columbia, Vancouver, Canada.
³ Department of Anesthesiology, McMaster University, Hamilton, ON, Canada (D.Z.).
⁴ Department of Neurology, University Hospital Ulm, Germany (K.A.).
⁵ Department of Ophthalmology, Kresge Eye Institute, Detroit, MI (B.M.).
⁶ Department of Neurology with Experimental Neurology and Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Germany (C.H.N., J.F.S.).
⁷ Division of Neurology, Department of Medicine (J.A.P.), University of British Columbia, Vancouver, Canada.
⁸ Division of Medical Sciences, University of Northern British Columbia, Prince George, Canada (J.A.P.).
⁹ Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (R.R.L.).
¹⁰ Department of Ophthalmology, CHA Bundang Medical Center, CHA University School of Medicine, South Korea (J.K.).
¹¹ Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea (S.J.W.).
¹² Department of Ophthalmology, Flinders Medical Center and Flinders University, Adelaide, SA, Australia (C. Chen).
¹³ Department of Ophthalmology, University Hospital of Basel, Switzerland (N.F.).
¹⁴ Department of Neurology, Southern California Permanente Medical Group, Los Angeles Medical Center (M.K., N.S.).
¹⁵ Department of Neurology & Stroke Center, University Teaching & Research Hospital, Kantonsspital St. Gallen, Switzerland (E.A.J.).
¹⁶ Department of Neurology, Inselspital, University Hospital and University of Bern, Switzerland (M.A., H.M., M.R.H.).
¹⁷ Department of Neurology, Sana Regio Klinikum Pinneberg, Germany (M.G.N.).
¹⁸ University Lille, Inserm, CHU Lille, U1172, Lille Neuroscience and Cognition, France (C. Cordonnier).
¹⁹ Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Germany (M.S.S.).
²⁰ Department of Neurology, University Hospital Tübingen and Hertie Institute for Clinical Brain Research, University of Tübingen, Germany (S.P.).
²¹ Department of Neurology, Julius-Maximilian University of Würzburg, Germany (C.H.).
²² Department of Neurology, University Hospital Zurich and University of Zurich, Switzerland (P.B., S.W.).
²³ Institute for Statistics and Mathematics, Vienna University of Economics and Business, Austria (L.K.).
²⁴ Department of Neurology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA (S.S.).
²⁵ Departments of Neurology and Ophthalmology, Mayo Clinic College of Medicine and Science, Scottsdale, AZ (O.M.D.).

^# Contributed equally.

PMID: 40832714
DOI: 10.1161/STROKEAHA.124.049955

Abstract

Background: This individual participant data meta-analysis aimed to determine whether time to treatment influences the effect of intraarterial thrombolysis (IAT), intravenous thrombolysis, and conservative standard therapy on visual outcomes in nonarteritic central retinal artery occlusion.

Methods: We searched MEDLINE, CENTRAL, and Embase up to June 2023 for studies reporting treatment modality and peri-treatment best-corrected visual acuity (BCVA) for ≥5 participants, excluding patients with nonsevere vision loss (BCVA <1.0 logarithm of the minimum angle of resolution [logMAR]) or treated after 24 hours of symptom onset. The primary outcome was recovery from severe vision loss (final BCVA <1.0 logMAR). We used mixed-effect models and local polynomial regression to investigate nonlinear relationships between time to treatment and recovery from severe vision loss.

Results: Of 4074 screened studies, individual participant data were sought from 52, with 35 contributing individual participant data for 1038 participants. In total, 783 patients met inclusion criteria (age, 64.8±13.3 years; 35.5% female; baseline BCVA, 2.3±0.5 logMAR). For every hour decrease in time to treatment, thrombolysis was associated with greater improvement in BCVA (intraarterial, 0.02 logMAR [95% CI, 0-0.04]; intravenous, 0.04 logMAR [95% CI, 0.00-0.07]) than conservative standard therapy (0.01 logMAR [95% CI, 0-0.02]). A nonlinear relationship was detected for intraarterial thrombolysis with a changepoint at 8 hours (95% CI, 6.7-9.4). Thrombolysis was associated with increased recovery from severe vision loss compared with conservative standard therapy (intraarterial within 6 hours: odds ratio, 2.72 [95% CI, 1.02-7.28], 27.2% versus 12.0%; intravenous within 4.5 hours: odds ratio, 3.32 [95% CI, 1.24-8.92], 28.8% versus 11.1%). Findings were consistent in subgroup analysis restricted to patients receiving recombinant tissue-type plasminogen activator. Monte-Carlo simulations showed that a randomized controlled trial would require 95 participants per group to achieve 80% power to detect an odds ratio of 3.0 for recovery from severe vision loss.

Conclusions: Early intervention in nonarteritic central retinal artery occlusion is associated with improvement in visual recovery, with intraarterial thrombolysis and intravenous thrombolysis outperforming nonthrombolytic treatments. These findings warrant confirmation in sufficiently powered randomized controlled trials.

Keywords: ischemia; odds ratio; perfusion; plasminogen; retina; retinal artery; retinal artery occlusion.

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Conflict of interest statement

Dr Zaslavsky reports grants from Fighting Blindness Canada, Foundation Finding Blindness, and the American College of Medical Genetics (ACMG) Foundation for Genetic and Genomic Medicine. Dr Poli is the principal investigator of the investigator-initiated REVISION randomized trial investigating early thrombolysis in central retinal artery occlusion. The REVISION trial is funded by the German Federal Ministry of Education and Research (BMBF) and Boehringer Ingelheim. He has served as a consultant for Alexion Pharmaceuticals Inc, AstraZeneca, Portola Pharmaceuticals, LLC, and Werfen US LLC. He has received speaker honoraria from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo Company. He has received grants/contracts from BMBF, Boehringer Ingelheim, Daiichi Sankyo Company, the European Commission, Helena Laboratories Corporation, and Innovationsausschuss beim Gemeinsamen Bundesausschuss and has received funding for travel from Hybernia Medical. Dr Feltgen reports compensation from Novartis, Bayer, Roche, AbbVie, and Apellis for consultant and speaker services. Dr Baumgartner reports research funds by the Gottfried and Julia Bangerter-Rhyner Foundation and the Swiss Academy of Medical Sciences, and funding for travel and conference fees from Bristol-Myers Squibb and Pfizer Alliance and Novo Nordisk. Dr Spitzer is the coprincipal investigator of the investigator-initiated REVISION randomized trial investigating early thrombolysis in central retinal artery occlusion. The REVISION trial is funded by the BMBF and Boehringer Ingelheim. He has served as a consultant for 1stQ, AbbVie, Alcon, Atheneum Partners, Astellas, Bayer Healthcare, DORC, Nordic Pharma, Neurogene, Ocumeda, Roche, and SHS. He has received speaker honoraria from AbbVie, Apellis, Astellas, Bayer Healthcare, Novartis, Roche, and Zeiss. He has received grants/contracts from BMBF, EXIST, Else-Kroener Foundation, Danger Foundation, Claire-Jung Foundation, Stiftung Auge, Biomarin, IDxDR, Fielmann Company, and TelemedC. Dr Woo reports grants from the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSICT; RS-2023-00248480). He declares the following nonrelevant conflicts of interest: consulting fees from Samsung Bioepis, Curacle, Novelty Nobility, Pharmabcine, Sometech, Samil, Allergan, and Janssen; lecture fees from Bayer, Navartis, Allergan/AbbVie, Santen, and Samil; grants from Samsung Bioepis, Alcon, Alteogen, Curacle, Kyowa Kirin, Novelty Nobility, Novartis, Pharmabcine, and Roche; and owns equity of RetiMark and Panolos Bioscience. Dr Popovic reports grants from PSI Foundation and grants from Fighting Blindness Canada. He is also a consultant for Ainnova Tech. Dr Nolte reports compensation from Alexion, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Novartis, and Pfizer for consultant and other services; grants from the German Center for Neurodegenerative Disease (DZNE); and grants from the German Center for Cardiovascular Research (DZHK). Dr Scheitz reports compensation from Bristol-Myers Squibb and AstraZeneca for other services and reports compensation from Medtronic for consultant services. Dr Leker reports compensation from Filterlex for consultant services and reports compensation from Medtronic, Janssen Biotech, Biogen, Abbott Diabetes Care, Ischema View, Boehringer Ingelheim, and Bayer for other services. Dr Arnold reports grants from the Swiss National Science Foundation and reports compensation from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Novo Nordisk, Boehringer Ingelheim, and Covidien Medtronic for consultant services. Dr Heldner reports grants from the Swiss National Science Foundation; grants from SITEM Research Funds; and grants from the Swiss Heart Foundation. Dr Cordonnier reports compensation from the American Stroke Association for other services. Dr Wegener received research funds by the Swiss National Science Foundation, the Clinical Research Priority Program Precision for Stroke at Universitäts Spital Zürich, the Zürich Neuroscience Center (ZNZ), the Baugarten foundation, the Hartmann Müller Foundation, the Koetser Foundation, the Philas Foundation, and the Swiss Heart Foundation; received speaker honoraria from Amgen, Springer, Advisis AG, Teva Pharma, Boehringer Ingelheim, Lundbeck, Astra Zeneca, and Forum für medizinische Fortbildung (FoMF); and received a consultancy fee from Bayer and Novartis via an institution for research. The other authors report no conflicts.

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Early Thrombolysis and Outcomes in Central Retinal Artery Occlusion: An Individual Participant Data Meta-Analysis

Collaborators

Affiliations

Early Thrombolysis and Outcomes in Central Retinal Artery Occlusion: An Individual Participant Data Meta-Analysis

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous