Neuro-Ophthalmology Notions: Retinal Artery Occlusion—Diagnosis and Treatment Considerations

In this article, Practical Neurology’s Neuro-Ophthalmology Notions column editor, Peter Sguigna, MD, asked ophthalmology specialists to respond to 4 questions about the diagnosis and treatment of retinal artery occlusion (RAO). In addition to discussing such topics as diagnostic protocols and the use of thrombolytics, the authors address recent clinical trial results as well as the the need for collaboration between ophthalmologists and stroke neurologists. 

Stroke neurologists are very busy, traditionally with a lot of inpatient involvement. I imagine you address cases of hyperacute/acute vision loss. From the neurology perspective, does this chief complaint change your approach, departing from the typical “stroke protocol?”
Vision loss is a common reason for emergent stroke consultation. These cases are handled similarly to other stroke activations with an additional emphasis on detailed ophthalmologic history and exam. Acuity of onset, unilateral vs bilateral findings, complete blindness vs other more vague descriptions, and particular patterns of loss can suggest a vascular etiology of symptoms. For example, a visual field cut (loss of vision in a quarter or half of the patient’s field of vision) easily localizes to the brain and can return the assessment to a typical stroke protocol. Similarly, unilateral blindness (complete vision loss on one side), especially with exam findings related to the hemisphere of the affected eye, can suggest ipsilateral vessel involvement. Central vision loss and in some cases patchy vision loss with acute onset are still equally acute concerns, especially in the setting of other vascular risk factors. However, a more extensive evaluation is often necessary to determine the level of suspicion for an ischemic cause. Our institution has a specific protocol for RAO cases that are within the acute treatment window for stroke. In these cases the typical stroke activation protocol is followed, and the ophthalmologist on call is immediately consulted to perform an exam to determine the level of suspicion for a smaller occlusion and to rule out ocular hemorrhages. If following both exams the consensus between the neurologist and ophthalmologist is an acute RAO, whether central or branch, then acute interventions are quickly discussed and possibly given at that time. In situations during which the patient is diagnosed with an acute RAO at the ophthalmology clinic, the same protocol is initiated; however, instead of an emergent consult, the diagnosing ophthalmologist relays the results of the clinic examination and diagnosis with the stroke neurologist on call. Individuals with RAO should undergo a stroke workup as it is considered an acute stroke equivalent (a “stroke of the eye”) by the American Heart Association.¹ This also applies to patients outside of the acute time window. 

There have been many exciting developments in the field of stroke, including the Food and Drug Administration (FDA) approval of tenecteplase (TNKase; Genentech, South San Francisco, CA) for the treatment of acute ischemic stroke. Is there consensus among stroke neurologists as to whether or not individuals with central retinal artery occlusion (CRAO) who present within the treatment time window should receive treatment with alteplase (Activase; Genentech, South San Francisco, CA) and/or tenecteplase?
Although this issue has been debated for many years, the general consensus is to consider treatment within the 4.5 hour treatment window if a diagnosis of CRAO is strongly suspected.^2,3 The debate has been less around whether or not to attempt treatment and more specifically focused on if individuals with CRAO benefit from treatment, but the literature does indicate that alteplase may be effective.³ Data on the efficacy of thrombolytic treatment for individuals with CRAO remain limited because CRAO is relatively rare and patients often present outside of the thrombolytic treatment window. Tenecteplase is also a newer treatment option, and data regarding the specific efficacy of tenecteplase treatment in individuals with CRAO are even more limited than with alteplase. Many hospitals have transitioned from treatment with alteplase to tenecteplase, which may generate more data on the efficacy of tenecteplase treatment in individuals with CRAO in the near future. 

There is a wide body of literature and history on the management of CRAO in the field of ophthalmology, including acute surgical intervention and techniques such as ocular massage. The interface between an ophthalmologic emergency and stroke codes in which “time is brain” can be a challenge for ophthalmologists, who often have a very busy surgical/outpatient practice. Many centers are beginning to deploy ocular imaging technologies (eg, ultrasound, fundus photography, optical coherence tomography) to help triage possible ophthalmologic emergencies. Do you think these technologies have a role in evaluating potential CRAO patients?
It is now a matter of when, not if, we establish imaging protocols that provide a reliable triage mechanism and can be performed by non-ophthalmologists. Several imaging modalities show promise in emergency settings. For example, fundus photography offers objective documentation of the retina and can reveal classic findings in CRAO, such as arterial attenuation, a cherry-red spot, and retinal pallor. Similarly, optical coherence tomography provides high-resolution cross-sectional images of the retina, which are valuable in identifying acute retinal changes.

Looking even further ahead, artificial intelligence tools may offer more standardized image interpretation and diagnosis, making the triage process even more efficient and accessible.⁴

From an ophthalmic perspective, “time is vision.” Imaging technologies already play a critical role in both the acute and chronic management of CRAO. They are already used daily in the outpatient setting and are simple enough to be incorporated broadly into standardized protocols within emergency departments and the inpatient setting. 

The multicenter phase 3 THEIA clinical trial (NCT03197194) assessing the use of alteplase in patients with acute CRAO was recently completed in France, and an update on this trial was presented at the 2025 International Stroke Conference. As more data comes out, I think there will be much discussion about the results and implications of this study. What are the key considerations for neurologists and ophthalmologists as they continue to collaborate and consider the use alteplase or tenecteplase to treat patients with CRAO?
Now is the time to address key considerations for individuals with CRAO, such as how extensive the stroke workup should be in these patients, how to determine eligibility for thrombolysis, the risks of intracranial hemorrhage, and the possibility of an optimal therapeutic window. These issues highlight the urgent need for a standardized management protocol, especially as new, up-to-date evidence continues to emerge.

The recently completed THEIA clinical trial marks a significant step in our understanding of treatment options for CRAO and creates an interesting debate. Although results of this trial did not demonstrate a statistically significant benefit in visual outcomes for individuals with CRAO who received thrombolysis treatment vs those treated with aspirin, alteplase treatment was safe and vision improvement was observed when treatment was given within the first 4.5 hours of symptom onset.⁵ There are 2 ongoing clinical trials which are also assessing the efficacy and safety of tenecteplase (TenCRAOS, NCT04526951)⁶ and alteplase (REVISION, NCT04965038),⁷ and pooled analysis of all 3 trials is planned.⁵ Collaboration between neurology and ophthalmology is expanding, not only in diagnosing CRAO but, more importantly, in managing it. CRAO is a medical emergency, and ophthalmologists must be integrated into the development of acute stroke response systems for these patients.