Abstract
Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke which affects
the retina. Intravenous thrombolysis is emerging as a compelling therapeutic approach.
However, it is not known which patients may benefit from this therapy because there
are no imaging modalities that adequately distinguish viable retina from irreversibly
infarcted retina. The inner retina receives arterial supply from the central retinal
artery and there is robust collateralization between this circulation and the outer
retinal circulation, provided by the posterior ciliary circulation. Fundus photography
can show canonical changes associated with CRAO including a cherry-red spot, arteriolar
boxcarring and retinal pallor. Fluorescein angiography provides 2-dimensional imaging
of the retinal circulation and can distinguish a complete from a partial CRAO as well
as central versus peripheral retinal non-perfusion. Transorbital ultrasonography may
assay flow through the central retinal artery and is useful in the exclusion of other
orbital pathology that can mimic CRAO. Optical coherence tomography provides structural
information on the different layers of the retina and exploratory work has described
its utility in determining the time since onset of ischemia. Two experimental techniques
are discussed. 1) Retinal functional imaging permits generation of capillary perfusion
maps and can assay retinal oxygenation and blood flow velocity. 2) Photoacoustic imaging
combines the principles of optical excitation and ultrasonic detection and - in animal
studies - has been used to determine the retinal oxygen metabolic rate. Future techniques
to determine retinal viability in clinical practice will require rapid, easily used,
and reproducible methods that can be deployed in the emergency setting.
Key Words
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Referenecs
- An updated definition of stroke for the 21st century: a statement for healthcare professionals from the american heart association/american stroke association.Stroke. 2013; 44: 2064-2089
- Retinal vascular occlusions.Lancet. 2020; 396: 1927-1940
- Intravenous fibrinolytic therapy in central retinal artery occlusion: a patient-level meta-analysis.JAMA Neurol. 2015; 72: 1148-1154
- Mri-guided thrombolysis for stroke with unknown time of onset.N Engl J Med. 2018; 379: 611-622
- Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct.N Engl J Med. 2018; 378: 11-21
- Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging.N Engl J Med. 2018; 378: 708-718
- Retinal and ophthalmic artery occlusions preferred practice pattern®.Ophthalmology. 2020; 127: P259-P287
- Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association.Stroke. 2019; 50 (e344-e418)
- Intravenous fibrinolysis for central retinal artery occlusion: a cohort study and updated patient-level meta-analysis.Stroke. 2020; 51: 2018-2025
- Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: The prisms randomized clinical trial.JAMA. 2018; 320: 156-166
- Risk of acute stroke in patients with retinal artery occlusion: A systematic review and meta-analysis.Eye (Lond), 2019
- Risk of acute ischemic stroke in patients with monocular vision loss of vascular etiology.J Neuroophthalmol. 2018; 38: 328-333
- Stroke risk and risk factors in patients with central retinal artery occlusion.Am J Ophthalmol. 2018; 196: 96-100
- Acute silent brain infarction in monocular visual loss of ischemic origin.Cerebrovasc Dis. 2015; 40: 151-156
- Therapeutic decisions involving disparate clinical outcomes: Patient preference survey for treatment of central retinal artery occlusion.Ophthalmology. 1996; 103: 691-696
- Thrombolytic therapy for acute central retinal artery occlusion.Stroke. 2020; 51: 687-695
- Thrombolysis for central retinal artery occlusion in 2020: Time is vision!.J Neuroophthalmol. 2020;
- Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy.Prog Retin Eye Res. 2015; 49: 82-119
- Experimental occlusion of the central artery of the retina. Iv: Retinal tolerance time to acute ischaemia.Br J Ophthalmol. 1980; 64: 818-825
- Experimental occlusion of the central artery of the retina. I. Ophthalmoscopic and fluorescein fundus angiographic studies.Br J Ophthalmol. 1980; 64: 896-912
- Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: An experimental study in rhesus monkeys.Am J Ophthalmol. 2000; 129: 786-795
- Central retinal artery occlusion. Retinal survival time.Exp Eye Res. 2004; 78: 723-736
- Tissue plasminogen activator for acute ischemic stroke. The national institute of neurological disorders and stroke rt-pa stroke study group.N Engl J Med. 1995; 333: 1581-1587
- Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.N Engl J Med. 2008; 359: 1317-1329
- Time to Treatment with Intravenous Alteplase and Outcome in Stroke: An Updated Pooled Analysis of Ecass, Atlantis, Ninds, and Epithet Trials. 375. Lancet (London, England, 2010: 1695-1703
- Dwi-flair mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (pre-flair): a multicentre observational study.The Lancet Neurol. 2011; 10: 978-986
- Intravenous thrombolysis in unwitnessed stroke onset: Mr witness trial results.Ann Neurol. 2018; 83: 980-993
- MRI-guided thrombolysis for stroke with unknown time of onset.N Engl J Med. 2018; 379: 611-622
- Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke.N Engl J Med. 2019; 380: 1795-1803
- A randomized trial of intraarterial treatment for acute ischemic stroke.N Engl J Med. 2015; 372: 11-20
- Randomized assessment of rapid endovascular treatment of ischemic stroke.N Engl J Med. 2015; 372: 1019-1030
- Endovascular therapy for ischemic stroke with perfusion-imaging selection.N Engl J Med. 2015; 372: 1009-1018
- Stent-retriever thrombectomy after intravenous t-pa vs. T-pa alone in stroke.N Engl J Med. 2015; 372: 2285-2295
- Thrombectomy within 8 hours after symptom onset in ischemic stroke.N Engl J Med. 2015; 372: 2296-2306
- Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.Lancet. 2016; 387: 1723-1731
- The growth rate of early dwi lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion.Int J Stroke. 2015; 10: 723-729
- Late window paradox.Stroke. 2018; 49: 768-771
- Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke.N Engl J Med. 2019; 380: 1795-1803
- Cilioretinal arteries and retinal arterial occlusion.Arch Ophthalmol. 1979; 97: 84-92
- Ischemic optic neuropathies.N Engl J Med. 2015; 372: 2428-2436
- Central retinal artery occlusion - rethinking retinal survival time.BMC Ophthalmol. 2018; 18: 101
- Retinal oxygenation via the choroidal circulation.Trans Am Ophthalmol Soc. 1978; 76: 528-556
- Retinal oxygen: fundamental and clinical aspects.Arch Ophthalmol. 2003; 121: 547-557
- Oxygen supply to the retina from the retinal and choroidal circulations at normal and increased arterial oxygen tensions.Invest Ophthalmol. 1969; 8: 588-594
- Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc.Br J Ophthalmol. 1969; 53: 721-748
- The effect of adjunctive hyperbaric oxygen therapy in patients with central retinal artery occlusion.Undersea Hyperb Med. 2020; 47: 57-64
- Acute phase treatment in central retinal artery occlusion: thrombolysis, hyperbaric oxygen therapy or both?.J Thromb Thromb. 2020;
- Case series of hyperbaric oxygen therapy for central retinal artery occlusion.Retin Cases Brief Rep. 2019;
- Oxygen therapy in patients with retinal artery occlusion: A meta-analysis.PLoS One. 2018; 13 (e0202154)
- Management of central retinal artery occlusion: a scientific statement from the american heart association.Stroke. 2021; (STR0000000000000366)
- Animal models used to simulate retinal artery occlusion: a comprehensive review.Transl Vis Sci Technol. 2019; 8: 23
- Fundus changes in central retinal artery occlusion.Retina. 2007; 27: 276-289
- Fluorescein and indocyanine green angiography in vascular chorioretinal diseases.Semin Ophthalmol. 1998; 13: 189-198
- Fluorescein angiography complication survey.Ophthalmology. 1986; 93: 611-617
- Adverse reactions due to indocyanine green.Ophthalmology. 1994; 101: 529-533
- Frequency of adverse systemic reactions after fluorescein angiography. results of a prospective study.Ophthalmology. 1991; : 1139-1142
- Prevalent misconceptions about acute retinal vascular occlusive disorders.Prog Retin Eye Res. 2005; 24: 493-519
- Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail.Invest Ophthalmol Vis Sci. 2010; 51: 5864-5869
- Ocular neovascularization following central retinal artery occlusion: prevalence and timing of onset.Eur J Ophthalmol. 2010; 20: 1042-1046
- Explaining the current role of high frequency ultrasound in ophthalmic diagnosis (ophthalmic ultrasound).Expert Rev Ophthalmol. 2006; 1: 63-76
Fda guidance for industry and fda staff. Information for manufacturers seeking marketing clearance of diagnostic ultrasound systems and transducers, september 9, 2008. https://www.Fda.Gov/downloads/ucm070911.Pdf. accessed february 25, 2019.
- The assessment of ocular injury by ultrasound.Clin Radiol. 2004; 59: 301-312
- 20 mhz/40 mhz dual element transducers for high frequency harmonic imaging.IEEE Trans Ultrason Ferroelectr Freq Control. 2008; 55: 2683-2691
- Variability in measurement of central retinal artery velocity using color doppler imaging.J Ultrasound Med. 1995; 14: 463-466
- Color doppler imaging of retinal diseases.Surv Ophthalmol. 2010; 55: 193-214
- Coherent plane-wave compounding for very high frame rate ultrasonography and transient elastography.IEEE Trans Ultrason Ferroelectr Freq Control. 2009; 56: 489-506
- Functional ultrasound imaging of the brain.Nat Methods. 2011; 8: 662-664
- Ultrafast compound doppler imaging: providing full blood flow characterization.IEEE Trans Ultrason Ferroelectr Freq Control. 2011; 58: 134-147
- Ultrafast ultrasound imaging of ocular anatomy and blood flow.Invest Ophthalmol Vis Sci. 2016; 57: 3810-3816
- Ultrasound imaging and measurement of choroidal blood flow.Transl Vis Sci Technol. 2018; 7: 5
- In vivo acoustic super-resolution and super-resolved velocity mapping using microbubbles.IEEE Trans Med Imaging. 2015; 34: 433-440
- Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging.Nature. 2015; 527: 499-502
- In vivo visualization of eye vasculature using super-resolution ultrasound microvessel imaging.IEEE Trans Biomed Eng. 2020;
- Contrast-enhanced plane-wave ultrasound imaging of the rat eye.Exp Eye Res. 2020; 193107986
- Blood-flow velocities in the extraocular vessels in normal volunteers.Am J Ophthalmol. 1996; 122: 364-370
- The retrobulbar "Spot sign" As a discriminator between vasculitic and thrombo-embolic affections of the retinal blood supply.Ultraschall Med. 2012; 33 (E263-e267)
- Embolic central retinal artery occlusion detected by orbital color doppler imaging.Ophthalmology. 2002; 109 (discussion 747-748): 744-747
- Retrobulbar spot sign predicts thrombolytic treatment effects and etiology in central retinal artery occlusion.Stroke. 2015; 46: 2322-2324
- Low endogenous recanalization in embolic central retinal artery occlusion-the retrobulbar "Spot sign".J Neuroimaging. 2015; 25: 251-256
- Spot sign" In recurrent amaurosis fugax and central retinal artery occlusion.J Stroke Cerebrovasc Dis. 2014; 23: e421-e422
- Reliability of ocular and orbital diagnosis with b-scan ultrasound. 1. ocular diagnosis.Am J Ophthalmol. 1972; 73: 501-516
- Use of ultrasound in the diagnosis and management of the vasculitides.Curr Rheumatol Rep. 2020; 22: 31
- The predictive value of the halo sign in color doppler ultrasonography of the temporal arteries for diagnosing giant cell arteritis.J Rheumatol. 2002; 29: 1224-1226
- Optical coherence tomography.Science. 1991; 254: 1178-1181
- En face enhanced-depth swept-source optical coherence tomography features of chronic central serous chorioretinopathy.Ophthalmology. 2014; 121: 719-726
- In vivo detection of acute ischemic damages in retinal arterial occlusion with optical coherence tomography: A "Prominent middle limiting membrane sign".Retina. 2013; 33: 2110-2117
- Retinal and choroidal changes and visual outcome in central retinal artery occlusion: An optical coherence tomography study.Am J Ophthalmol. 2015; 159: 667-676
- Acute retinal ischemia in central versus branch retinal artery occlusion: Changes in retinal layers' thickness on spectral-domain optical coherence tomography in different grades of retinal ischemia.Retina. 2020; 40: 1118-1123
- Correlation of optical intensity on optical coherence tomography and visual outcome in central retinal artery occlusion.Retina. 2016; 36: 1964-1970
- Retinal oedema in central retinal artery occlusion develops as a function of time.Acta Ophthalmol. 2020;
- Optical coherence tomography-based determination of ischaemia onset - the temporal dynamics of retinal thickness increase in acute central retinal artery occlusion.Acta Ophthalmol. 2020;
- Intravenous thrombolysis in acute central retinal artery occlusion - a prospective interventional case series.PLoS One. 2018; 13 (e0198114)
- Retinal changes in different grades of retinal artery occlusion: an optical coherence tomography study.Invest Ophthalmol Vis Sci. 2017; 58: 5209-5216
- Three dimensional optical angiography.Opt Express. 2007; 15: 4083-4097
- Optical coherence tomography angiography in retinal artery occlusion.Retina. 2015; 35: 2339-2346
- Optical coherence tomography angiography of retinal artery occlusion.Dev Ophthalmol. 2016; 56: 122-131
- Optical coherence tomography angiography characteristics of acute retinal arterial occlusion.BMC Ophthalmol. 2019; 19: 147
- Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using oct angiography.Am J Ophthalmol Case Rep. 2020; 19100740
- Evaluation of macular ischemia in eyes with central retinal vein occlusion: an optical coherence tomography angiography study.Retina. 2018; 38: 1571-1580
- Optical coherence tomography angiography.Invest Ophthalmol Vis Sci. 2016; 57 (OCT27-36)
- Optical coherence tomography angiography in chorioretinal disorders.Can J Ophthalmol. 2017; 52: 125-136
- Special report: Noninvasive multi-parameter functional optical imaging of the eye.Ophthalmic Surg Lasers Imaging. 2005; 36: 57-66
- Noninvasive technique for oximetry of blood in retinal vessels.Appl Opt. 1988; 27: 1113-1125
- Segmental reproducibility of retinal blood flow velocity measurements using retinal function imager.Graefes Arch Clin Exp Ophthalmol. 2013; 251: 2665-2670
- Reduced retinal blood flow velocity in diabetic retinopathy.Retina. 2010; 30: 765-773
- Impaired retinal microcirculation in multiple sclerosis.Mult Scler. 2016; 22: 1812-1820
- Retinal blood flow velocity measured by retinal function imaging in retinitis pigmentosa.Graefes Arch Clin Exp Ophthalmol. 2011; 249: 1855-1858
- Retinal blood-flow velocity and oximetry status monitoring in a central retinal vein occlusion patient.. 2009; 6: 52-54
- Photoacoustic imaging platforms for multimodal imaging.Ultrasonography. 2015; 34: 88-97
- A review of methods for human retinal oximetry.Ophthalmic Surg Lasers Imaging. 2003; 34: 152-164
- A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography.Sci Rep. 2014; 4: 6525
- Optical coherence photoacoustic microscopy for in vivo multimodal retinal imaging.Opt Lett. 2015; 40: 1370-1373
- Noninvasive chorioretinal imaging in living rabbits using integrated photoacoustic microscopy and optical coherence tomography.Opt Express. 2017; 25: 15947-15955
- In vivo photoacoustic imaging of chorioretinal oxygen gradients.J Biomed Opt. 2018; 23: 1-8
- Laser speckle contrast imaging: Theoretical and practical limitations.J Biomed Opt. 2013; 18066018
- Transcranial chronic optical access to longitudinally measure cerebral blood flow.J Neurosci Methods. 2020; 350109044
- Laser speckle contrast imaging of cerebral blood flow.Ann Biomed Eng. 2012; 40: 367-377
- Retinal blood-flow visualization by means of laser speckle photography.Invest Ophthalmol Vis Sci. 1982; 22: 255-259
- Laser speckle analysis of retinal vascular dynamics.Biomed Opt Express. 2016; 7: 1375-1384
- Retinal endovascular surgery with tissue plasminogen activator injection for central retinal artery occlusion.Case Rep Ophthalmol. 2018; 9: 327-332
- Validating a low-cost laser speckle contrast imaging system as a quantitative tool for assessing retinal vascular function.Sci Rep. 2020; 10: 7177
- Photoacoustic ophthalmoscopy for in vivo retinal imaging.Opt Express. 2010; 18: 3967-3972
Article info
Publication history
Published online: May 17, 2021
Accepted:
April 8,
2021
Received in revised form:
April 6,
2021
Received:
March 1,
2021
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105828
Copyright
© 2021 Elsevier Inc. All rights reserved.
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- Response by Mac Grory et al. to Letter regarding “Structural and Functional Imaging of the Retina in Central Retinal Artery Occlusion – Current Approaches and Future Directions”Journal of Stroke and Cerebrovascular DiseasesVol. 30Issue 10
- PreviewWe wish to thank Drs. Tuuminen, Achiron and Kanclerz for the interest in our paper and for the opportunity to address several entrenched misconceptions about the treatment of central retinal artery occlusion (CRAO). In 2015, Schrag et al.1 published a subject level meta-analysis concerning visual outcomes in patients with CRAO who were untreated, treated with thrombolysis or treated with a variety of conservative therapies (anterior chamber paracentesis, ocular massage and/or hemodilution). An important innovation in this work was the use of a simple, reproducible definition of visual recovery as the attainment of a final visual acuity of ≥20/100 in the affected eye.
- Full-Text
- Preview
- Controversies on the Recommended Treatment for Central Retinal Artery OcclusionJournal of Stroke and Cerebrovascular DiseasesVol. 30Issue 10
- PreviewIn a recent article, Mac Grory et al.1 described the structural and functional retinal imaging modalities in central retinal artery occlusion (CRAO). They have also suggested that thrombolysis is emerging as a compelling therapeutic approach for CRAO treatment, and should be administered shortly after the onset of visual loss to induce recanalisation of the occluded retinal arteries and reperfusion of the ischemic retina before retinal cell death. Importantly, there is considerable variability in CRAO management patterns among practitioners, institutions, and subspecialty groups.
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- Preview