Pub Date: Monday, Mar 08, 2021
Author: Anthony C. Arnold, MD
Affiliation: Mary Oakley Foundation Chair in Neurodegenerative Diseases, Chief, Neuro-Ophthalmology Division, Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles
Central retinal artery occlusion (CRAO) is an entity with high-risk implications for both vision and vascular health, yet details of diagnosis, etiology, prognosis, and treatment are incompletely understood, with little evidence-based data available. The diagnosis of a classic presentation of CRAO, with acute, severe, painless monocular visual loss and funduscopic findings of retinal opacification and visibly slowed or absent retinal arterial flow, is straightforward. In other scenarios, such as the hyperacute stage prior to visible retinal changes, in the realm of hours after symptom onset, when intervention has the best chance at improving visual outcome, consideration of other causes, such as retrobulbar optic neuropathy, may confuse diagnosis and delay appropriate management. While the etiology of CRAO is thought most commonly to be embolic, the composition and origin of the embolus is often unclear, presumed to be invisible within the retinal circulation behind the lamina cribrosa of the optic disc. Evaluation for etiology is therefore often unfocused, looking for evidence of carotid or cardiac source, vasculitis (including giant cell arteritis), and hypercoagulable state, and is not infrequently negative. Data on visual recovery if untreated are limited and consistently limited by small sample size and variable assessment parameters. Similarly, effectiveness of the many proposed therapies is difficult to assess in the face of small sample size and variations in severity of visual loss, time to treatment, and parameters for followup; there is no proven effective therapy to date. Finally, the critical implications of CRAO for subsequent stroke are not as yet widely recognized or acted upon.
In this AHA Scientific Statement, Mac Grory and associates1 provide valuable clarity on several of these important issues in management of CRAO. Three essential points arise from their discussion. First, that the relatively infrequent occurrence of CRAO and the anecdotal nature of previous reports on the common therapeutic attempts, including ocular massage, anterior chamber paracentesis, topical intraocular pressure lowering agents, carbogen inhalation, systemic vasodilators, and erythrocyte viscosity reduction, make it difficult to support their use as attaining visual outcomes better than the natural history of the disorder. Second, that CRAO may be classified as an ischemic stroke2, and that education of the medical community and the public regarding this fact is essential in improving the time to therapy in these cases, as it is critical to the effectiveness of therapy. In this regard, the authors emphasize that there are currently several ongoing clinical trials of stroke-like protocols for intravenous thrombolytic therapy for CRAO and that in selected cases, this may be the treatment of choice. Third, that urgent evaluation for secondary prevention is essential; there is ample evidence that patients with CRAO are at high risk for carotid and cardiac disease, with subsequent stroke or myocardial infarction, along with systemic risk factors such as hypertension, hyperlipidemia, and diabetes3.
The newer options for therapy of CRAO bear further comment. The prognosis for spontaneous visual recovery in CRAO is poor, and the most commonly attempted previous therapies have demonstrated very little benefit. As with cerebral stroke, a major obstacle to effective therapy is the need for extremely early intervention, and in contrast to cerebral stroke, painless visual loss in only one eye in CRAO may go unnoticed for hours or even days. While a major educational effort has resulted in increased public awareness of the need for early intervention for cerebral stroke, the same is not true for CRAO. This has hindered recruitment for clinical trials of stroke-like therapy for CRAO. With the well-documented positive effect of thrombolytics in non-hemorrhagic cerebral ischemic events, this approach is now being studied intensely for CRAO. The large-scale prospective multicenter trial of intra-arterial tPA (the European Assessment Group for Lysis in the Eye, EAGLE) was limited by recruitment difficulties and delay to treatment, with no subjects treated within the standard 4.5-hour window used for cerebral stroke; it did not confirm a therapeutic benefit4. Intravenous tPA therapy, without the need for an on-call neurointerventional team, has shown benefit in several small studies for patients treated within the 4.5-hour window. It is currently under investigation in the three clinical trials described in the Statement. Although not yet proven effective, there is enough evidence in smaller studies to justify consideration of this therapy in selected cases, and practitioners should be aware of the option and how to pursue it. While the Statement stops short of recommending hyperbaric oxygen therapy (HBOT) as an adjuvant treatment, there are a number of uncontrolled series suggesting some benefit for visual outcome5-7. It is not widely available, but in centers where it can be accessed rapidly, consideration may be given to its use as a temporizing measure until more definitive therapy such as tPA may be instituted.
Finally, there is a fourth point that is not explicitly raised in this Statement but is related and equally critical for risk management: that transient monocular visual loss (TMVL), more commonly known as “amaurosis fugax,” is classified as a transient ischemic attack (TIA), and requires the same urgent evaluation for secondary prevention as does CRAO. TMVL is more common than CRAO, and although it has been formally classified as a TIA for 10 years8, the ophthalmologic and neurologic communities that are most likely to be the first line providers for these patients have been slow to recognize the significance of that point. TMVL has the same risk factors and origins in the cardiovascular system as CRAO, and the risk of subsequent cerebral infarctions, although lower, is significant. Biousse and associates9 have summarized the guidelines for management of TMVL in this regard, and the emphasis is this: TMVL is an emergency and requires urgent referral to a facility capable of providing immediate diffusion-weighted imaging (DWI) brain MRI to assess for evidence of additional ischemic lesions, even if subclinical, which would substantially increase the risk of subsequent stroke with 24-72 hours. If they are present, such patients require immediate management via stroke protocol.
In conclusion, Mac Grory and associates summarize the current recommendations for management of CRAO and focus the discussion for areas of uncertainty. They provide invaluable guidance for all practitioners who care for these patients.
Mac Grory B, Schrag M, Biousse V, Furie KL, Gerhard-Herman M, Lavin PJ, Sobrin L, Tjoumakaris SI, Weyand CM, Yaghi S; on behalf of the American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Council on Peripheral Vascular Disease. Management of central retinal artery occlusion: a scientific statement from the American Heart Association [published online ahead of print March 8, 2021]. Stroke. doi: 10.1161/STR.0000000000000366
- Mac Grory B, Schrag M, Biousse V, Furie KL, Gerhard-Herman M, Lavin PJ, Sobrin L, Tjoumakaris SI, Weyand CM, Yaghi S; on behalf of the American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Council on Peripheral Vascular Disease. Management of central retinal artery occlusion: a scientific statement from the American Heart Association [published online ahead of print March 8, 2021]. Stroke. doi: 10.1161/STR.0000000000000366
- Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, Elkind MSV, George MG, Hamdan AD, Higashida RT, Hoh BL, Janis LS, Kase CS, Kleindorfer DO, Lee J-M, Mosely ME, Peterson ED, Turan TN, Valderrama AL, Vinters HV. 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.
- Lavin P, Patrylo M, Hollar M, Espaillat KB, Kirshner H, Schrag M. Stroke risk and risk factors in patients with central retinal artery occlusion. Am J Ophthalmol. 2018;196:96-100.
- Schumacher M, Schmidt D, Jurklies B, Gail C, Wanke I, Schmoor C, Maier-Lenz H, Solymosi L, Brueckmann H, Neubauer AS, Wolf A, Feltge N, EAGLE-Study group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology. 2010;117:1367-1375.
- Menzel-Severing J, Siekmann U, Weinberger A, Roessler G, Walter P, Mazinani B. Early hyperbaric oxygen treatment for nonarteritic central retinal artery obstruction. Am J Ophthalmol. 2012;153:454-459.
- Hadanny A, Maliar A, Fishlev G, Bechor Y, Bergan J, Friedman M, Avni, I, Efrati S. Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen. Clin Ophthalmol. 2016;11:115-125.
- Lopes AS, Basto R, Henriques S, Colaco L, Costa E Silva F, Prieto I, Guerreiro F. Hyperbaric oxygen therapy in retinal arterial aooclusion: epidemiology, clinical approach, and visual outcome. Case Rep Ophthalmol Med. DOI: 10.1155/2019/9765938.
- Furie KL, Kasner SE, Adams RJ, et al, American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:227-276.
- Biousse V, Nahab F, Newman NJ. Management of acute retinal ischemia. Follow the guidelines! Ophthalmology. 2018;125:1597-1607.
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