Non-arteritic, thromboembolic central retinal artery occlusion (CRAO) is an acute neurovascular-ophthalmological emergency which leads to severe and permanent vision loss; no evidence-based therapy does exist. Two recent meta-analyses indicate early intravenous thrombolysis to be beneficial in CRAO. Therefore, the REVISION randomized placebo-controlled interventional trial will investigate intravenous alteplase in CRAO as it is practiced in acute ischemic stroke, i.e. within 4.5 hours after symptom onset. The REVISION observational study will evaluate retinal changes on optical coherence tomography (OCT) in patients within 12 hours of CRAO onset, and the REVISION substudy, which will be conducted adjunct to either the interventional or the observational study, will evaluate the value of the retrobulbar spot sign for prediction of outcome and treatment response.
Non-arteritic, thromboembolic central retinal artery occlusion (CRAO) is an acute neurovascular-ophthalmological emergency which leads to severe and permanent vision loss in the affected eye in \~ 95% of cases. Despite a variety of widely practiced "conservative standard treatments", such as hemodilution, ocular massage, and paracentesis, there is no evidence-based therapy for non-arteritic CRAO. Animal models have proven a limited ischemic tolerance of the retina with irreversible damage occurring within only four hours after disruption of blood flow. This is why rapid reperfusion represents THE logical therapeutic approach. Two recent meta-analyses indicate early intravenous thrombolysis to be beneficial in CRAO. Therefore, the REVISION trial will investigate intravenous alteplase in CRAO as it is practiced in acute ischemic stroke, i.e. within 4.5 hours after symptom onset. Sequential evaluation by optical coherence tomography (OCT) will visualize dynamic ischemic changes of the retina during and after CRAO. The REVISION observational study will enroll patients within 12 hours of symptom onset and aims at comparing late time window retinal findings to early ischemic changes found in patients of the randomized REVISION interventional trial. Ultimately, OCT may become the preferred tool when it comes to assess retinal tissue viability in patients with an unknown CRAO onset (e.g. wake-up CRAO), and CRAO patients who present in an extended time window beyond 4.5 hours. The REVISION substudy, which will be conducted adjunct to either the interventional or the observational study, will evaluate the value of the retrobulbar spot sign for prediction of outcome and treatment response.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
422
Intravenous thrombolysis within 4.5 hours of symptom onset
University Hospital Tuebingen
Tübingen, Germany
RECRUITINGFunctional recovery at visit 3
Functional recovery to best corrected visual acuity of logarithm of the minimum angle of resolution ≤ 0.5 in the affected eye, which corresponds to normal to mild vision impairment (intention-to-treat analysis).
Time frame: 30 days
best corrected visual acuity (BCVA) at visits 2, 3, and 4
Functional recovery to best corrected visual acuity of logarithm of the minimum angle of resolution ≤ 0.5 in the affected eye, which corresponds to normal to mild vision impairment (intention-to-treat and per-protocol analyses).
Time frame: 90 days
Shift in visual outcome categories at visits 2, 3, and 4
Shift in visual outcome categories: normal vision (logarithm of the minimum angle of resolution (LogMAR) ≤ 0), mild vision impairment (LogMAR \> 0 and ≤ 0.5), moderate vision impairment (LogMAR \> 0.5 and ≤ 1.0), severe vision impairment (LogMAR \> 1.0 and ≤ 1.3), counting fingers (LogMAR \> 1.3 and ≤ counting fingers), hand motion or light perception, and no light perception.
Time frame: 90 days
Dichotomized analysis of visual outcome at visits 2, 3, and 4
Dichotomized analysis of visual outcome: 'normal vision to moderate vision impairment' vs. 'severe vision impairment or functional blindness' and 'normal vision to severe vision impairment' vs. 'functional blindness'.
Time frame: 90 days
Visual field at visits 3 and 4
Kinetic visual field using III4e mark
Time frame: 90 days
Central retinal artery recanalization at visits 2, 3, and 4
Central retinal artery recanalization assessed using optical coherence tomography angiography (OCTA) of the optic nerve head and the macula.
Time frame: 90 days
Retinal arterial perfusion at visits 3 and 4
Retinal arterial perfusion assessed using fluorescein angiography.
Time frame: 90 days
National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) at visits 3 and 4
NEI-VFQ-25 for assessment of relevant visual impairment
Time frame: 90 days
National Institutes of Health Stroke Scale (NIHSS) score at visit 2
NIHSS for assessment of neurological deficits due to ischemic stroke or intracranial hemorrhage
Time frame: 72 hours
Modified Rankin Scale (mRS) score at visits 3 and 4
Dichotomized analysis and shift analyses of mRS (categories 0 - 1 (excellent outcome) vs. 2 - 6, 0 - 2 (functional independence) vs. 3 - 6, 0 - 3 (walking) vs. 4 - 6, and 0 - 4 vs. 5 - 6 (bedridden or death), and shift analysis)
Time frame: 90 days
Fresh ischemic lesions on cranial magnetic resonance imaging (MRI) at visit 2
Fraction of patients with and number of acute ischemic lesions on follow-up diffusion-weighted cranial MRI
Time frame: 72 hours
Death at visits 3 and 4
All-cause and stroke-related death
Time frame: 90 days
Any intracranial hemorrhage (ICH) at visit 2
Any ICH (except microhemorrhages) on follow-up magnetic resonance imaging; in case of missing follow-up brain imaging due to premature death, ICH will be replaced by "ICH or death without repeat scan")
Time frame: 72 hours
Symptomatic intracranial hemorrhage (ICH) until visit 2
Symptomatic ICH (as per ECASS III and Heidelberg bleeding classification) until follow-up magnetic resonance imaging; in case of missing follow-up brain imaging due to premature death, symptomatic ICH will be replaced by "symptomatic ICH or death without repeat scan")
Time frame: 72 hours
Intraocular hemorrhage in the affected eye at visit 2
Intraocular hemorrhage in the affected eye
Time frame: 72 hours
Major bleeding until visit 2
Major bleeding, defined as clinically overt bleeding associated with at least one of the following features: decrease in hemoglobin levels of ≥ 2 g/dL over 24 hours, bleeding requiring transfusion of ≥ 2 units of packed red cells, bleeding at a critical site (i.e., intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal), or bleeding resulting in the death of the patient
Time frame: 72 hours
Retinal neovascularization requiring therapy at visit 3 and 4
Retinal neovascularization requiring therapy
Time frame: 90 days
(Serious) adverse events ((S)AE)
AE until visit 2, serious AE and AE of special interest until visit 3 and 4
Time frame: 90 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.