Current Topics in Acute Stroke Care - Stroke EXTRA Supplement (Stroke CME)

Table of Contents

 

Clinicians are highly likely to encounter patients with stroke in the emergency department and must be able to diagnose and manage stroke in a timely and effective manner to opti-mize patient outcomes. Emergency department management of stroke includes utilizing imaging appropriately based on the type of stroke, assessing patient risk for additional cardiovascular or stroke events, and recognizing subtle or different forms of stroke, such as patients who have normal initial imaging or patients who present with a central retinal artery occlusion. This supplement reviews these aspects of stroke management and provides useful management strategies that can be applied to practice.

What are the most useful imaging tools to diagnose acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage quickly and effectively?

What assessment tools and scores can best be used in conjunction with imaging to assess a patient’s risk and guide management?

How do findings in the history and physical examination, such as the timing of vision loss or the absence of a visible embolus, affect diagnosis and management of CRAO?

Which patients diagnosed with CRAO would be candidates for thrombolysis versus other pharmacological or nonpharmacological management?

1. Part 1: Imaging Modalities in the Assessment of Acute Stroke
   1. Introduction
   2. Acute Ischemic Stroke
      1. Computed Tomography of the Brain in Acute Ischemic Stroke
         • Windowing of the Computed Tomography Image
         • Alberta Stroke Program Early Computed Tomography Score
         • Major Artery Hyperdensity Sign
      2. Computed Tomographic Angiography of the Brain in Acute Ischemic Stroke
      3. Magnetic Resonance Imaging of the Brain in Acute Ischemic Stroke
      4. Computed Tomographic Perfusion Imaging of the Brain in Acute Ischemic Stroke
   3. Intracerebral Hemorrhage
      1. Computed Tomography of the Brain in Intracerebral Hemorrhage
         • Intracerebral Hemorrhage Score
         • External Ventricular Drains
         • Computed Tomographic Angiography of the Brain in Intracerebral Hemorrhage
   4. Subarachnoid Hemorrhage
      1. Computed Tomography of the Brain in Subarachnoid Hemorrhage
      2. Computed Tomographic Angiography of the Brain in Subarachnoid Hemorrhage
   5. Conclusion
   6. Tables and Figures
      1. Table 1. "Blood Can Be Very Bad" Mnemonic
      2. Figure 1. Left Basal Ganglia ICH on Noncontrast Head CT
      3. Figure 2. Noncontrast Head CT 2 Hours After AIS Symptom Onset
      4. Figure 3. Normal-Appearing Noncontrast Head CT 3 Hours After Onset of AIS Symptoms
      5. Figure 4. Evidence of Stroke on Noncontrast Head CT 9 hours After Onset of AIS Symptoms
      6. Figure 5. Noncontrast Head CT Seen in Figure 4, Windowed to 40:40 HU
      7. Figure 6. Right MCA Hyperdensity Sign Seen on Noncontrast Head CT
      8. Figure 7. Right MCA Occlusion on CTA
      9. Figure 8. Basilar Occlusion Seen on CTA
      10. Figure 9. Acute Left MCA Distribution Stroke Seen on ADC Sequence
      11. Figure 10. Acute Left MCA Distribution Stroke Seen on DWI Sequence
      12. Figure 11. Acute Left MCA Distribution Stroke Seen on Fluid-Attenuated Inversion Recovery Sequence
      13. Figure 12. Left Posterior Inferior Cerebellar Artery Stroke on MRI DWI
      14. Figure 13. Right Parietal Infarct Seen on Computed Tomographic Perfusion
      15. Figure 14. Penumbra Seen on Computed Tomographic Perfusion
      16. Figure 15. Left Putamen ICH With IVH On Noncontrast Head CT
      17. Figure 16. Dilation of Temporal Horns Indicative of Early Hydrocephalus
   7. References
2. Part 2: Central Retinal Artery Occlusion: A Stroke of the Eye
   1. Introduction
   2. Anatomy and Pathophysiology of Central Retinal Artery Occlusion
      1. Nonarteritic Central Retinal Artery Occlusion
      2. Arteritic Central Retinal Artery Occlusion
   3. Differential Diagnosis
   4. Emergency Department Evaluation
      1. Symptoms and Physical Examination Findings of Central Retinal Artery Occlusion
      2. Diagnostic Studies for Central Retinal Artery Occlusion
      3. Stroke and Cardiovascular Risk Evaluation
   5. Treatment
      1. Acute Management in the Emergency Department
      2. Thrombolysis
      3. Nonpharmacologic Interventions
         • Ocular Massage
         • Rebreathing
      4. Pharmacologic Interventions
         • Intraocular-Pressure–Lowering Agents
         • Carbogen
         • Hyperbaric Oxygen
         • Pentoxifylline and Sublingual Isosorbide Dinitrate
      5. Surgical Interventions
         • Anterior-Chamber Paracentesis
         • Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) Laser Embolectomy
         • Pars Plana Vitrectomy
      6. Follow-Up Care
   6. Conclusion
   7. Clinical Pathway for Acute Management of Central Retinal Artery Occlusion
   8. Figures
      1. Figure 1. Arterial Circulation of the Eye and Orbit
      2. Figure 2. Swinging Flashlight Test
      3. Figure 3. “Cherry-Red” Spot Seen in Central Retinal Artery Occlusion
   9. References

Part 1: Imaging Modalities in the Assessment of Acute Stroke

Introduction

Acute focal neurological deficits secondary to a vascular condition include acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Imaging tools, such as computed tomography (CT), magnetic resonance imaging (MRI), and angiography, can assess and diagnose each subtype quickly so that emergent treatment can be provided. In all stroke subtypes, rapid diagnosis and management can lead to improved functional outcomes.

Clinical suspicion of stroke—based on symptoms of new-onset hemiparesis, vision loss, sensory loss, double vision, vertigo, or ataxia—should be managed with rapid evaluation and noncontrast head CT in nearly all cases. While other imaging modalities can provide more precise information, the noncontrast head CT can distinguish between hemorrhage and ischemic stroke. Head CT can be obtained quickly and is usually adequate to make emergent treatment decisions. The American Heart Association/American Stroke Association guidelines recommend emergent noncontrast head CT within 10 minutes of patient arrival, with Class I, Level A evidence.¹

The mnemonic “Blood Can Be Very Bad” (Blood, Cisterns, Brain, Ventricles, Bone) provides a quick guide for the emergency clinician to review a CT scan quickly. See Table 1 for an explanation of this guide.

Note that in the initial period after an acute ischemic stroke (up to 6 hours after onset), noncontrast head CT can be completely normal.³ (See Figure 2.) Of note, the patients in Figures 1 and 2 presented with the same symptoms (aphasia with right hemiparesis) and the same National Institutes of Health Stroke Scale (NIHSS) score, highlighting the challenges in distinguishing between ICH and AIS without imaging.

References

Evidence-based medicine requires a critical appraisal of the literature based upon study meth-odology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available.

1. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947. (Guidelines)
2. Perron AD. How to read a head CT scan. In: Adams JG, ed. Emergency Medicine. Philadelphia, PA: Saunders Elsevier; 2008:753-763. (Textbook chapter)
3. Birenbaum D, Bancroft LW, Felsberg GJ. Imaging in acute stroke. West J Emerg Med. 2011;12(1):67-76. (Systematic review)
4. von Kummer R, Allen KL, Holle R, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology. 1997;205(2):327-333. (Retrospective review; 620 patients)
5. Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol. 2001;22(8):1534-1542. (Comparison study)
6. Lin K, Zink WE, Tsiouris AJ, et al. Risk assessment of hemorrhagic transformation of acute middle cerebral artery stroke using multimodal CT. J Neuroimaging. 2012;22(2):160-166. (Retrospective review; 84 patients)
7. Moulin T, Cattin F, Crepin-Leblond T, et al. Early CT signs in acute middle cerebral artery infarction: predictive value for subsequent infarct locations and outcome. Neurology. 1996;47(2):366-375. (Prospective review; 100 patients)
8. Manno EM, Nichols DA, Fulgham JR, et al. Computed tomographic determinants of neurologic deterioration in patients with large middle cerebral artery infarctions. Mayo Clin Proc. 2003;78(2):156-160. (Retrospective review; 36 patients)
9. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018. (Prospective randomized controlled trial; 70 patients)
10. Douglas V, Shamy M, Bhattacharya P. Should CT angiography be a routine component of acute stroke imaging? Neurohospitalist. 2015;5(3):97-98. (Editorial)
11. Bash S, Villablanca JP, Jahan R, et al. Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol. 2005;26(5):1012-1021. (Prospective study; 28 patients)
12. Sun K, Li K, Han R, et al. Evaluation of high-pitch dual-source CT angiography for evaluation of coronary and carotid-cerebrovascular arteries. Eur J Radiol. 2015;84(3):398-406. (Prospective study; 85 patients)
13. Gasecki AP, Eliasziw M, Ferguson GG, et al. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg. 1995;83(5):778-782. (Prospective randomized controlled trial; 659 patients)
14. Barber PA, Darby DG, Desmond PM, et al. Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography. Stroke. 1999;30(10):2059-2065. (Prospective study; 17 patients)
15. Kattah JC, Talkad AV, Wang DZ, et al. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009;40(11):3504-3510. (Prospective study; 101 patients)
16. Lansberg MG, Thijs VN, O’Brien MW, et al. Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke. AJNR Am J Neuroradiol. 2001;22(4):637-644. (Prospective study; 27 patients)
17. Mayer TE, Hamann GF, Baranczyk J, et al. Dynamic CT perfusion imaging of acute stroke. AJNR Am J Neuroradiol. 2000;21(8):1441-1449. (Prospective study; 70 patients)
18. Kamalian S, Kamalian S, Konstas AA, et al. CT perfusion mean transit time maps optimally distinguish benign oligemia from true “at-risk” ischemic penumbra, but thresholds vary by postprocessing technique. AJNR Am J Neuroradiol. 2012;33(3):545-549. (Prospective study; 23 patients)
19. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21. (Prospective randomized controlled trial; 206 patients)
20. Albers GW, Lansberg MG, Kemp S, et al. A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3). Int J Stroke. 2017;12(8):896-905. (Prospective randomized controlled trial; 476 patients)
21. Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450-1460. (Systematic review)
22. Hemphill JC 3rd, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891-897. (Retrospective review; 152 patients)
23. Jamora RD, Kishi-Generao EM Jr, Bitanga ES, et al. The ICH score: predicting mortality and functional outcome in an Asian population. Stroke. 2003;34(1):6-7. (Prospective study; 302 patients)
24. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27(8):1304-1305. (Retrospective review; 118 patients)
25. Delgado Almandoz JE, Schaefer PW, Goldstein JN, et al. Practical scoring system for the identification of patients with intracerebral hemorrhage at highest risk of harboring an underlying vascular etiology: the Secondary Intracerebral Hemorrhage Score. AJNR Am J Neuroradiol. 2010;31(9):1653-1660. (Retrospective review; 623 patients)
26. Wada R, Aviv RI, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38(4):1257-1262. (Prospective study; 39 patients)
27. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354(4):387-396. (Systematic review)
28. Adams HP Jr, Kassell NF, Torner JC, et al. CT and clinical correlations in recent aneurysmal subarachnoid hemorrhage: a preliminary report of the Cooperative Aneurysm Study. Neurology. 1983;33(8):981-988. (Retrospective review; 1378 patients)
29. Byyny RL, Mower WR, Shum N, et al. Sensitivity of noncontrast cranial computed tomography for the emergency department diagnosis of subarachnoid hemorrhage. Ann Emerg Med. 2008;51(6):697-703. (Retrospective review; 149 patients)
30. Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ. 2011;343:d4277. (Prospective cohort study; 3132 patients)
31. Agid R, Lee SK, Willinsky RA, et al. Acute subarachnoid hemorrhage: using 64-slice multidetector CT angiography to “triage” patients’ treatment. Neuroradiology. 2006;48(11):787-794. (Prospective study; 73 patients)
32. Al-Mufti F, Roh D, Lahiri S, et al. Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2017;126(5):1545-1551. (Retrospective review; 1286 patients)
33. McCormack RF, Hutson A. Can computed tomography angiography of the brain replace lumbar puncture in the evaluation of acute-onset headache after a negative noncontrast cranial computed tomography scan? Acad Emerg Med. 2010;17(4):444-451. (Systematic review)

Part 2: Central Retinal Artery Occlusion: A Stroke of the Eye

Introduction

A central retinal artery occlusion (CRAO) is an ophthalmologic emergency that causes severe visual and functional disability. More than 80% of patients with a CRAO are unable to read a standard eye chart and will only be able to count fingers or worse, with the potential for permanent blindness.¹ Occlusion of the central retinal artery is often secondary to serious underlying systemic medical conditions, such as carotid artery stenosis, cardiac valvular disease, atrial fibrillation, and hypercoagulable states.

CRAO presents as painless unilateral vision loss, and occurs in approximately 1 in 10,000 to 100,000 individuals, with a male predominance and a mean age of 60 to 65 years.¹ In 1% to 2% of cases, CRAO presents bilaterally.² In general, the incidence of retinal artery occlusions has been observed to increase with age.² Incidence patterns of CRAO and stroke are similar, with peak incidence around age 80 years.³ CRAO is divided into arteritic or nonarteritic occlusion based on its etiology. It is critical to distinguish a nonarteritic CRAO, which is embolic, from an arteritic CRAO. Autoimmune diseases have been implicated in arteritic CRAOs, caused by an inflammatory narrowing of the vessel lumen.^3,4

Recent evidence recognizes CRAO as a type of stroke, and presenting patients require immediate stroke evaluation to minimize risk of secondary ischemic events, such as myocardial or cerebral infarction. Studies have shown that acute cerebral infarcts often accompany a CRAO. Furthermore, peak incidence of concomitant cerebral stroke and acute myocardial infarction occur within 1 month after the CRAO.³ In the acute setting, therapy is directed at resolving the occlusion to maximize visual outcomes and identify risk factors for stroke. As with cerebrovascular stroke, the interval between symptom onset and intervention is critical in CRAO, because management options can be limited by delays in presentation and diagnosis. Clinicians should note that, while thrombolytic- and catheter-based therapies have been used to manage this disease process, the optimal management strategy is still unclear.

References

Evidence-based medicine requires a critical appraisal of the literature based upon study meth-odology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

1. Leavitt JA, Larson TA, Hodge DO, et al. The incidence of central retinal artery occlusion in Olmsted County, Minnesota. Am J Ophthalmol. 2011;152(5):820-823. (Retrospective chart review; 43 cases)
2. Brown GC, Magargal LE. Central retinal artery obstruction and visual acuity. Ophthalmology. 1982;89(1):14-19. (Retrospective review; 72 patients)
3. Park SJ, Choi NK, Yang BR, et al. Risk and risk periods for stroke and acute myocardial infarction in patients with central retinal artery occlusion. Ophthalmology. 2015;122(11):2336-2343. (Retrospective review; 1655 patients) 
4. Merchut MP, Gupta SR, Naheedy MH. The relation of retinal artery occlusion and carotid artery stenosis. Stroke. 1988;19(10):1239-1242. (Retrospective review; 48 patients)
5. Hayreh SS, Kolder HE, Weingeist TA. Central retinal artery occlusion and retinal tolerance time. Ophthalmology. 1980;87(1):75-78. (Animal research study)
6. Ahuja RM, Chaturvedi S, Eliott D, et al. Mechanisms of retinal arterial occlusive disease in African American and Caucasian patients. Stroke. 1999;30(8):1506-1509. (Retrospective review; 46 patients)
7. Babikian V, Wijman CA, Koleini B, et al. Retinal ischemia and embolism. Etiologies and outcomes based on a prospective study. Cerebrovasc Dis. 2001;12(2):108-113. (Prospective study; 77 patients)
8. Cho SC, Jung C, Lee JY, et al. Retinal artery occlusion after intravascular procedures: case series and literature review. Retina. 2019;39(4):766-778. (Retrospective case series; 27 patients)
9. Rudkin AK, Lee AW, Aldrich E, et al. Clinical characteristics and outcome of current standard management of central retinal artery occlusion. Clin Exp Ophthalmol. 2010;38(5):496-501. (Retrospective review; 40 patients)
10. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236. (Guideline)
11. Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology. 2009;116(10):1928-1936. (Cohort study; 439 patients)
12. Callizo J, Feltgen N, Pantenburg S, et al. Cardiovascular risk factors in central retinal artery occlusion: results of a prospective and standardized medical examination. Ophthalmology. 2015;122(9):1881-1888. (Prospective study; 84 patients)
13. Patel M, Shah G, Davies JB, et al. Re-evaluating our perspective on retinal artery occlusion from carotid dissection: a report of three cases and review of the literature. Ophthalmic Surg Lasers Imaging Retina. 2013;44(6):555-560. (Case series; 3 patients)
14. Hayreh SS, Podhajsky PA, Raman R, et al. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997;123(3):285-296. (Retrospective review; 363 patients)
15. Mazlumzadeh M, Hunder GG, Easley KA, et al. Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial. Arthritis Rheum. 2006;54(10):3310-3318. (Double-blind placebo-controlled randomized prospective clinical trial; 72 patients)
16. Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol. 2005;140(3):376-391. (Cohort study; 244 patients)
17. Sharma S, Brown GC, Pater JL, et al. Does a visible retinal embolus increase the likelihood of hemodynamically significant carotid artery stenosis in patients with acute retinal arterial occlusion? Arch Ophthalmol. 1998;116(12):1602-1606. (Cross-sectional study; 256 patients)
18. Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol. 2014;157(6):1119-1121. (Editorial)
19. Helenius J, Arsava EM, Goldstein JN, et al. Concurrent acute brain infarcts in patients with monocular visual loss. Ann Neurol. 2012;72(2):286-293. (Retrospective; 129 patients)
20. Tanaka K, Uehara T, Kimura K, et al. Features of patients with transient monocular blindness: a multicenter retrospective study in Japan. J Stroke Cerebrovasc Dis. 2014;23(3):e151-e155. (Multicenter retrospective study; 444 patients)
21. Golsari A, Bittersohl D, Cheng B, et al. Silent brain infarctions and leukoaraiosis in patients with retinal ischemia: a prospective single-center observational study. Stroke. 2017;48(5):1392-1396. (Prospective single-center observational study; 112 patients)
22. Cho KH, Kim CK, Woo SJ, et al. Cerebral small vessel disease in branch retinal artery occlusion. Invest Ophthalmol Vis Sci. 2016;57(13):5818-5824. (Retrospective registry review; 46 patients)
23. Kilani R, Marshall L, Koch S, et al. DWI findings of optic nerve ischemia in the setting of central retinal artery occlusion. J Neuroimaging. 2013;23(1):108-110. (Case report)
24. Plant GT, Landau K. Thrombolysis for central retinal artery occlusion. J Neurol Neurosurg Psychiatry. 2005;76(2):160-161. (Review)
25. Atkins EJ, Bruce BB, Newman NJ, et al. Translation of clinical studies to clinical practice: survey on the treatment of central retinal artery occlusion. Am J Ophthalmol. 2009;148(1):172-173. (Survey study; 1595 physicians)
26. Biousse V, Nahab F, Newman NJ. Management of acute retinal ischemia: follow the guidelines! Ophthalmology. 2018;125(10):1597-1607. (Review)
27. Aldrich EM, Lee AW, Chen CS, et al. Local intraarterial fibrinolysis administered in aliquots for the treatment of central retinal artery occlusion: the Johns Hopkins Hospital experience. Stroke. 2008;39(6):1746-1750. (Single-center nonrandomized interventional study; 21 patients)
28. Schumacher M, Schmidt D, Jurklies B, et al. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology. 2010;117(7):1367-1375. (Multicenter randomized trial; 84 patients)
29. Hayreh SS. Comment re: multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. Graefes Arch Clin Exp Ophthalmol. 2007;245(3):464-466. (Letter to the editor)
30. Varma DD, Cugati S, Lee AW, et al. A review of central retinal artery occlusion: clinical presentation and management. Eye (Lond). 2013;27(6):688-697. (Review)
31. Rudkin AK, Lee AW, Chen CS. Vascular risk factors for central retinal artery occlusion. Eye (Lond). 2010;24(4):678-681. (Retrospective review; 33 patients)
32. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641. (Review)
33. Hattenbach LO, Kuhli-Hattenbach C, Scharrer I, et al. Intravenous thrombolysis with low-dose recombinant tissue plasminogen activator in central retinal artery occlusion. Am J Ophthalmol. 2008;146(5):700-706. (Interventional case series; 28 patients)
34. Egan RA, Van Stavern R. Should patients with acute central retinal artery occlusion be treated with intra-arterial t-PA? J Neuroophthalmol. 2015;35(2):205-209. (Editorial)
35. Schrag M, Youn T, Schindler J, et al. Intravenous fibrinolytic therapy in central retinal artery occlusion: a patient-level meta-analysis. JAMA Neurol. 2015;72(10):1148-1154. (Meta-analysis; 147 patients) 
36. Pielen A, Pantenburg S, Schmoor C, et al. Predictors of prognosis and treatment outcome in central retinal artery occlusion: local intra-arterial fibrinolysis vs. conservative treatment. Neuroradiology. 2015;57(10):1055-1062. (Post hoc analysis)
37. Rumelt S, Dorenboim Y, Rehany U. Aggressive systematic treatment for central retinal artery occlusion. Am J Ophthalmol. 1999;128(6):733-738. (Prospective study; 11 patients)
38. Atebara NH, Brown GC, Cater J. Efficacy of anterior chamber paracentesis and carbogen in treating acute nonarteritic central retinal artery occlusion. Ophthalmology. 1995;102(12):2029-2034. (Retrospective review; 89 patients)
39. Cugati S, Varma DD, Chen CS, et al. Treatment options for central retinal artery occlusion. Curr Treat Options Neurol. 2013;15(1):63-77. (Review)
40. Menzel-Severing J, Siekmann U, Weinberger A, et al. Early hyperbaric oxygen treatment for nonarteritic central retinal artery obstruction. Am J Ophthalmol. 2012;153(3):454-459. (Retrospective nonrandomized case series; 51 patients)
41. Hadanny A, Maliar A, Fishlev G, et al. Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen. Clin Ophthalmol. 2017;11:115-125. (Retrospective analysis; 128 patients)
42. Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev. 2009(1):CD001989. (Systematic review)
43. Garcia-Arumi J, Martinez-Castillo V, Boixadera A, et al. Surgical embolus removal in retinal artery occlusion. Br J Ophthalmol. 2006;90(10):1252-1255. (Prospective study; 7 patients)