Article In Brief
Central retinal arterial occlusion (CRAO) warrants quick triage and early identification similar to those that have evolved for ischemic stroke, according to a scientific statement from the American Heart Association. The document, developed by multiple associations, describes the epidemiology and risk factors associated with CRAO, pathophysiology, diagnosis, natural history of the condition, and acute and conservative treatments.
Central retinal arterial occlusion (CRAO) is a medical emergency requiring systems of rapid triage and early identification similar to those that have evolved for ischemic stroke, according to a statement released online on March 8 by the American Heart Association in Stroke.
Currently, however, there is considerable variability in how CRAO is treated. Although evidence suggests that intravenous tissue plasminogen activator (IV-tPA) is effective in the early window for treatment, there is a pressing need for high-quality, randomized clinical trials to develop a consensus around best practices.
“The care of patients with CRAO in 2021 is at the same level as the care of people with brain strokes was in 1991,” Brian Mac Grory, MBChB, MRCP, assistant professor of neurology at Duke University and chair of the 10-member AHA writing group that developed the statement, said in comments to Neurology Today.
“As with brain strokes 30 years ago, people with eye strokes present to the hospital late, if at all, and systems of care have not yet evolved for treatment because the medical community still has a fatalistic approach to this condition.”
Dr. Mac Grory added: “Because people [with CRAO] aren't referred to the emergency department [ED] quickly, we don't have proven effective treatments. Because we don't have effective treatment there remains no reason to send to the ED—and so the cycle perpetuates itself.”
The AHA statement was developed on behalf of the American Heart Association Stroke Council; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and the Council on Peripheral Vascular Disease. The statement is endorsed by the North American Neuro-Ophthalmology Society, the American Academy of Ophthalmology Quality of Care Secretariat, and the American Academy of Optometry. Additionally, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section affirms the educational benefit of the statement.
The ten-member writing group comprised experts in vascular neurology, neuro-ophthalmology, vitreo-retinal surgery, immunology, endovascular neurosurgery, and cardiology. Each member received an assignment to perform a literature review, synthesize the data, and offer considerations for practice. Multiple drafts were circulated among the group until consensus was achieved.
The AHA statement describes epidemiology and risk factors associated with CRAO, pathophysiology, diagnosis, natural history of the condition, and acute and conservative treatments.
Broadly, the statement calls for an outreach campaign aimed at educating the public about sudden, painless monocular visual loss as a symptom of potential stroke, emphasizing that patients with suspected CRAO should be triaged to the nearest ED. And it calls for stroke centers to develop relationships with community ophthalmologists and optometrists to promote efficient pathways for transfer of patients with CRAO.
The statement also outlines a treatment algorithm following triage to the ED involving CT scans and blood work to exclude giant cell arteritis and other possible causes for monocular visual loss. When CRAO appears to be the likely cause, IV-tPA should be considered within 4.5 hours of symptom onset, the statement said.
In cases in which IV-thrombolysis is contraindicated, intra-arterial tPA (IA-tPA) should be considered within six hours of symptom onset. But Dr. Mac Grory and colleagues caution that IA-tPA is “an unproven therapy and should be considered only in light of the devastating visual outcome associated with CRAO.”
Underscoring the acute nature of CRAO, they also noted that there is no compelling evidence for the effectiveness of conservative treatments—ocular massage, anterior chamber paracentesis, hemodilution—adding that they may even be harmful.
“This statement was undertaken because CRAO or eye stroke is an under-recognized and under-treated form of stroke,” Dr. Mac Grory said. “The difficulty with CRAO is that it causes only painless visual loss. So, from a diagnostic point of view it has more in common with an eye problem than a stroke. In many peoples' minds, including many physicians, CRAO is still not considered a stroke equivalent because of the strange way in which it presents.”
Experts who reviewed the statement for Neurology Today agreed that the statement successfully summarizes the current state of the art for CRAO, the differential diagnosis at presentation, the limitations of the current medical literature, and the challenges associated with acute management of the condition in the absence of research-driven consensus.
“CRAO should be considered an emergency, a ‘stroke to the eye,’ parallel to acute ischemic stroke,” said Warren L. Felton, MD, chair of the division of neuro-ophthalmology at Virginia Commonwealth University, in comments to Neurology Today. “Steps should be taken to rapidly evaluate such patients for underlying etiology to determine appropriate management.”
He said acute treatment of CRAO, like the treatment of stroke, is time dependent, noting that for ischemic stroke the Food and Drug Administration has approved a three-hour window from symptom onset for treatment with IVTPA/alteplase; the American Stroke Association has endorsed a 4.5 hour window.
Because of the lack of controlled studies, risk associated with use of alteplase in the CRAO population is not known. “The risk of hemorrhage in patients with acute CRAO is probably lower than for those patients with acute ischemic stroke, given the differences in retinal and brain tissue,” Dr. Felton said. “However, patients with acute CRAO may present concurrently with acute ischemic brain stroke (for which the patient may or may not be symptomatic), and therefore the risk of brain hemorrhage should be considered when considering IV-tPA/alteplase for such patients.”
He added that tenecteplase is a possible alternative, which is currently being tested in trials, but it has not yet clearly shown to be equivalent or superior to alteplase.
“I think the most significant implication of the paper is alerting clinicians to the importance of CRAO as a potentially treatable condition with the goal of adding CRAO to current ‘stroke code’ protocols and procedures,” Dr. Felton said.
Victor C. Urrutia, MD, associate professor of neurology at Johns Hopkins University and director of the Comprehensive Stroke Center at Johns Hopkins Hospital, said IV-tPA is considered for patients who present at Hopkins within 4.5 hours of symptom onset with CRAO.
“This is very rare, however, because patients tend to arrive too late,” he said.
“The Stroke paper is really a call to action to build the infrastructure for early arrival and evaluation of patients with CRAO in the emergency department,” Dr. Urrutia told Neurology Today. That will require developing evidenced-based best practices, he added.
Dr. Urrutia said the paper admirably balances the apparent effectiveness of IV-tPA derived from small studies, with an emphasis on the need for a stronger research base. “The ideal situation is that every patient with CRAO is enrolled in a randomized clinical trial,” he said.
In the meantime, Dr. Urrutia said clinicians should be aware that there may be benefit for IV-tPA in the early window and that risks of hemorrhage are relatively low. The evidence for intra-arterial thrombolysis is weaker, the risk for complications is higher, and IA-tPA requires a team of specialists in addition to the interventionist. “For these reasons we don't currently offer it as a treatment,” he said.
For patients and clinicians alike, the take-home message is that CRAO is a form of stroke requiring the same rapid evaluation, diagnosis, and treatment.
Dr. Mac Grory said: “People who develop sudden, painless visual loss in one eye should be treated with the same level of urgency as people who present with weakness, facial droop or difficulty speaking. It is important that there be close collaboration between neurologists, ophthalmologists, emergency physicians and other specialists to effectively recognize and treat this condition.”
Dr. Mac Grory had no disclosures. Dr. Urrutia has received funding from Genentech, Inc., for an investigator-sponsored trial, OPTIMISTmain, and is the site principal investigator of TIMELESS, also funded by Genentech. Dr. Felton had no relevant disclosures.