Non-arteritic Central Retinal Artery Occlusion Research Articles

Early REperfusion Therapy with Intravenous Alteplase for Recovery of VISION in Acute Central Retinal Artery Occlusion (REVISION): Study Protocol of a Phase III Trial.

Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question. REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO. Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted. Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology. ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

A Review of Current Literature on Central Retinal Artery Occlusion: Its Pathogenesis, Clinical Management, and Treatment.

The ocular analogue of a cerebral stroke is central retinal artery occlusion (CRAO), a medical emergency concerning the eyes. Most patients experience substantial acute vision loss with a visual acuity of 20/400 or worse, resulting in decreased quality of life (QoL) and decreased functional ability. An impending cerebral stroke and ischemic heart disease are also more likely. The four distinct clinical entities that make up CRAO are non-arteritic CRAO, transitory non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, and arteritic CRAO. Depending on the CRAO type, clinical traits, visual results, and treatment all vary greatly. Contrary to current belief, there is a spontaneous improvement in the optical field and vision, mainly in the first week. The likelihood of instinctive development in optical acuity in the first seven days varies greatly. The pathogenesis, epidemiology, and medical features of CRAO will be described in this review, along with present and potential management future options.

OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity.

To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion (NA-CRAO) via optical coherence tomography angiography (OCTA) and analyze their correlation with visual acuity. Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into: A type (mild n=29), B type (moderate n=27) and C type (severe n=6) based on the degree of visual loss, retinal edema, and arterial blood flow delay in fundus fluorescence angiography (FFA). Contralateral healthy eyes were used as the control group. Best-corrected visual acuity (BCVA), slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, OCTA, and FFA were performed. Spearman's correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity. There were no statistically significant differences in age, gender, and intraocular pressure among the three types and the control group (P>0.05). Vessel density in deep capillary plexus (VD-DCP) significantly decreased (P<0.05) in all three types of NA-CRAO patients compared to the control group. Vessel density in superficial vascular plexus (VD-SVP) significantly decreased (P<0.05) in type A patients and choriocapillaris flow area significantly decreased (P<0.05) in type B and type C patients compared to the control group; while outer retinal flow areas significantly increased in the type A (P<0.05) and decreased in type C patients (P<0.05). The retinal thickness significantly increased in type C group (P<0.05). The VD-SVP at fovea in the type A was significantly lower than both of type B and C. The VD-SVP at nasal parafovea in type A and B was significantly lower than type C (P<0.05). The logMAR BCVA of type A was significantly better than that of type B and C groups (P<0.05). Spearman's correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea (r=0.679, P=0.031) and nasal parafovea (r=0.826, P=0.013). OCTA is valuable for assessing retinal ischemia, and evaluating visual impairment. Deep retinal vasculature is commonly affected in all NA-CRAO types. VD-SVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.

Abstract TP125: Retina and Optic Nerve Diffusion Restriction in Acute Central Retinal Artery Occlusion: A Case-Control Study

Objective: To assess whether diffusion restriction (DR) of the retina and optic nerve (ON) can be accurately and reliably identified on standard stroke protocol brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Background: Retinal DR (RDR) and ONDR in patients with acute non-arteritic CRAO have been described with various diagnostic accuracies and often identified by experienced neuroradiologists with fair inter-rater agreement. Methods: This retrospective case-control study included patients that presented to our academic center from 2013-2021 with acute non-arteritic CRAO or acute cerebral ischemia (controls, age and gender-matched) and had brain MRI performed within 14 days from symptom onset. Two neuroradiologists, blinded to the site of CRAO and diagnosis, independently reviewed MRI of CRAO cases and controls to assess for the presence of RDR and ONDR. Their inter-rater agreement was calculated (prevalence and bias- adjusted kappa coefficient) and their final consensus was used to perform sensitivity and specificity analyses. Results: We included 128 patients with CRAO (mean age 69 years; 50% males; median time from CRAO to MRI 2 days (IQR 1-5)) and 128 matched controls with acute cerebral ischemia (mean age 68 years; 51% males). After neuroradiologists’ consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%), retina alone 35/128 (27.3%), ON alone 31/128 (24.2%), both retina and ON 15/128 (11.7%), with excellent inter-rater agreement for retina (K=0.91) and ON (K=0.83). There were no cases of RDR or ONDR in the control group. After neuroradiologists’ consensus, sensitivity, specificity, PPV and NPV were 28.1%, 100%, 100%, and 58.2% for RDR and 27.3%, 100%, 100%, and 57.9% for ONDR. Conclusion: Though RDR and ONDR can be identified with excellent interrater reliability, they are infrequent findings and their role in diagnosing acute CRAO is unclear. Observational prospective studies with large cohort of patients, optimization of dedicated and standardized orbit DWI-MRI protocols, and education of neurology and neuroradiology providers are needed to facilitate more accurate identification of RDR and ONDR in hyperacute CRAO.

Central Retinal Artery Occlusion: Visual Outcomes from a Large Northern California Cohort

To assess visual acuity (VA) outcomes in a large cohort of patients diagnosed with non-arteritic central retinal artery occlusion (CRAO), and to ascertain whether time from symptom onset to presentation, presenting visual acuity, or conservative treatment delivery (anterior chamber paracentesis, ocular massage, intraocular pressure lowering drugs, hyperventilation, or some combination of those) impacted ultimate VA outcomes. Retrospective cohort study. Participants, and/or Controls: The study included 794 patients who presented with CRAO between 2011 and 2020. Within this cohort, 484 individuals presented within 30 days of symptom onset and had comprehensive documentation regarding the details of their presentation, management, and follow-up at least 90 days post-diagnosis. Intervention, or Testing: Retrospective chart review was conducted for all patients with a diagnosis of CRAO initially identified via ICD coding, followed by confirmation of diagnosis by two retina specialists. Cases of arteritic CRAO were excluded. VA recovery, defined as improvement from < 20/200 or worse at presentation to > 20/100 at least 90 days after diagnosis. Of the 794 identified patients, 712 (89.7%) presented with VA of < 20/200. Similarly, 447 (92.4%) of the 484-patient subset that presented within 30 days and had comprehensive documentation, presented with VA < 20/200. Of the 441 of those patients with documented follow up, 380 (86.2%) remained at that level. Of the 244 patients who presented within 4.5 hours of symptom onset, 227 (93%) presented < 20/200 and 201 (92.6%) of the 217 of those with follow-up data did not improve beyond that threshold. There was no significant difference (p < 0.05) in final VA between patients presenting before versus after 4.5 hours from time of vision loss. There was also no significant difference (p < 0.05) in VA outcomes between patients who did or did not receive conservative treatment. This large retrospective study further highlights the poor visual prognosis for patients with CRAO. Earlier time to presentation did not seem to impact final VA outcome, nor did conservative treatment efforts. Efficacious evidence-based treatment options are needed for this patient population.

Treatments for Acute Nonarteritic Central Retinal Artery Occlusion: Findings From a Cochrane Systematic Review.

Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on the findings of a Cochrane systematic review that searched seven databases for peer-reviewed articles reporting on treatments for acute nonarteritic CRAO. We assessed six randomized controlled trials, including interventions such as tissue plasminogen activator (t-PA), isovolumic hemodilution, eyeball massage, intraocular pressure reduction, anticoagulation, vasodilation, oxygen inhalation, laser embolysis, transcorneal electrical stimulation, thrombolysis, pentoxifylline, and enhanced external counterpulsation. However, none of the randomized controlled trials demonstrated significant improvement in visual acuity at 1 month compared to observation, and some patients treated with t-PA experienced serious adverse effects including intracranial hemorrhage. Proposed interventions for acute nonarteritic CRAO may not be better than observation, but the evidence is uncertain. Larger, well-designed studies are necessary to determine the most effective management option for acute nonarteritic CRAO. [Ophthalmic Surg Lasers Imaging Retina 2023;54:xx-xx.].

Neuroprotection for Nonarteritic Central Retinal Artery Occlusion: Lessons from Acute Ischemic Stroke.

Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe loss of vision. There are guidelines by the American Heart Association and the American Stroke Association for the care of CRAO patients. This review explores the basis of retinal neuroprotection for CRAO and its potential for improving the outcome of NA-CRAO. Recently, there have been significant advances in research into the use of neuroprotection to treat retinal diseases, including retinal detachment, age-related macular degeneration, and inherited retinal diseases. Also, neuroprotective research in AIS has been extensive, and newer drugs tested, including Uric acid, Nerinetide, and Otaplimastat, with promising results. Progress in cerebral neuroprotection after AIS offers hope for retinal neuroprotection after CRAO; and a possibility of extrapolating research findings from AIS into CRAO. Combining neuroprotection and thrombolysis can extend the therapeutic window for NA-CRAO treatment and potentially improve outcomes. Experimented neuroprotection for CRAO includes Angiopoietin (Comp Ang1), KUS 121, Gene therapy (XIAP), and hypothermia. Efforts in the field of neuroprotection for NA-CRAO should focus on better imaging to delineate the penumbra after an acute episode of NA-CRAO (using a combination of high-definition optical coherence angiography and electrophysiology). Also, research should explore details of pathophysiologic mechanisms involved in NA-CRAO, allowing for further neuroprotective intervention, and closing the gap between preclinical and clinical neuroprotection.

Thrombolytic Therapy for Non-arteritic Central Retinal Artery Occlusion in an Academic Multi-site Stroke Center (S45.010)

<h3>Objective:</h3> To review our academic multi-site stroke center experience with intravenous (IVT) and intra-arterial thrombolysis (IAT) for central retinal artery occlusion (CRAO). <h3>Background:</h3> CRAO is a subtype of acute ischemic stroke leading to severe visual loss. Conventional management is not effective and potentially harmful. 2021 American Heart Association scientific statement proposes similar time-windows for thrombolysis in CRAO and cerebral strokes (4.5hours for IVT, 6hours for IAT). <h3>Design/Methods:</h3> We retrospectively identified consecutive CRAO patients that received IVT or IAT in our academic enterprise stroke centers (1997–2022). Demographic, clinical characteristics, thrombolysis timeline, concurrent CRAO therapies, hospital complications, and follow-up visual outcomes were collected and analyzed using descriptive statistics. <h3>Results:</h3> Of 563 CRAO admissions, 20 (3.55%) received thrombolytic therapy: 13 IVT (mean age 68, range 55–82, 61.5% male, 12 alteplase and 1 tenecteplase, all embolic etiology) and 7 IAT (mean age 55, range 17–83, 85.7% male, 4 post-operative and 3 embolic). 11/20 (55%) received additional therapies (ocular massage, intraocular pressure lowering drops, diuretics, intra-arterial verapamil). 1 CRAO mimic received IVT. Median visual loss to IVT was 158 minutes (range 67–260 min). Baseline mean logMAR visual acuity (VA) was −3.11 (±1.16). 8/13 IVT had 3-month follow-up VA recorded (mean VA −2.53). 50% improved at least one Snellen line, 12.5% had VA &gt; 20/100. 1/13 (7.6%) had intracranial hemorrhage after IVT. Median visual loss to IAT was 335 minutes (131 minutes to 20 hours). Dose range was 5–30 mg. Baseline IAT mean logMAR VA was −3.5 (±1.19). 5/7 showed VA improvement. 1/7 had profuse epistaxis after IAT. <h3>Conclusions:</h3> The management of acute CRAO in a multi-site academic stroke center remains heterogeneous, consultant specific. Most received a combination of thrombolytic and other conventional therapies, hence thrombolysis-specific outcomes could not be described. Prospective studies comparing thrombolysis and placebo are warranted to guide hyperacute CRAO practice. <b>Disclosure:</b> Dr. Alhayek has nothing to disclose. Mr. Sobczak has nothing to disclose. Miss Weinberg has nothing to disclose. Dr. Demaerschalk has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Neurologist . Dr. Dumitrascu has nothing to disclose.

Central Retinal Artery Occlusion with Sparing of a Double Cilioretinal Artery: A Case Report

Central Retinal Artery Occlusion (CRAO) is a rare condition that is functionally life-threatening. It is the equivalent of an ischemic stroke. The cilio retinal artery is an anatomical variant that allows supplementing the vascularization of the macula in case of occlusion of the central retinal artery. CRAO consists of the following four distinct clinical entities: non-arteritic CRAO (NA-CRAO), transient NA-CRAO, NA-CRAO with cilioretinal artery sparing, and arteritic CRAO. Clinical characteristics, visual outcome, and management very much depend upon the type of CRAO. We report the case of a 29-year-old patient, with a history of recurrent angina, who presented with a sudden decrease in visual acuity in his left eye two days before his consultation. The diagnosis of central retinal artery occlusion sparing a double cilioretinal artery was evoked and treated early, allowing a significant visual recovery.

VIsion Salvage Using Intra-Ophthalmic Arterial Alteplase Combine with Nimodipine in Central Retinal Artery Occlusion (VISION).

To investigate the efficacy and safety of selective intra-ophthalmic arterial combined nimodipine and alteplase infusion in patients with central retinal artery occlusion (CRAO). Non-randomized, prospective interventional study. All patients with CRAO who presented at our institute within 24 hours from CRAO onset from August 2020 to July 2022 were included. Intra-arterial nimodipine and alteplase were given selectively into the ophthalmic artery. Visual acuity was recorded during and after the procedure. Change in best corrected visual acuity (BCVA) 1 month post-treatment, relative to baseline, was set as the primary outcome measure. Significant improvement in vision and adverse events are reported as secondary outcomes. Nine patients with non-arteritic CRAO were enrolled. A total of nine patients with CRAO underwent selective intra-ophthalmic arterial nimodipine and alteplase injection. Overall, BCVA had statistically significantly improved by 0.78 logarithm of the minimum angle of resolution (logMAR) at 1 month compared with baseline (95% confidence interval: (-1.24, -0.31), p-value = 0.001). Seven (77.8%) patients had significant visual improvement (≥0.3 logMAR) at 1-month post-treatment. There were minor adverse events during administration of the nimodipine, including chemosis and headache, which resolved after the discontinuation of nimodipine. There were also asymptomatic thromboembolic events in 2 patients (22.2%) after the intervention procedure, without any morbidity or mortality. The use of selective intra-ophthalmic arterial combined nimodipine and alteplase was efficacious in improving BCVA at 1 month for patients with non-arteritic CRAO presenting between 24 hours from onset, with minor adverse events but no serious adverse events.

Interventions for acute non-arteritic central retinal artery occlusion.

Acute non-arteritic central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and typically results in severe loss of vision in the affected eye. Although many therapeutic interventions have been proposed, there is no generally agreed upon treatment regimen. To assess the effects of treatments for acute non-arteritic CRAO. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 February 2022. We included randomized controlled trials (RCTs) comparing any interventions with another treatment in participants with acute non-arteritic CRAO in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for primary (mean change in best-corrected visual acuity [BCVA]) and secondary (quality of life and adverse events) outcomes using the GRADE classification. We included six RCTs with 223 total participants with acute non-arteritic CRAO; the studies ranged in size from 10 to 84 participants. The included studies varied geographically: one in Australia, one in Austria and Germany, two in China, one in Germany, and one in Italy. We were unable to conduct any meta-analyses due to study heterogeneity. None of the included studies compared the same pair of interventions: 1) tissue plasminogen activator (t-PA) versus intravenous saline; 2) t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation; 3) nitroglycerin, methazolamide, mecobalamin tablets, vitamin B1 and B12 injections, puerarin and compound anisodine (also known as 654-2) along with oxygen inhalation, eyeball massage, tube expansion, and anticoagulation compared with and without intravenous recombinant tissue plasminogen activator (rt-PA); 4) transcorneal electrical stimulation (TES) with 0 mA versus with 66% of the participant's individual electrical phosphene threshold (EPT) at 20 Hz (66%) versus with 150% of the participant's individual EPT (150%) at 20 Hz; 5) ophthalmic artery branch retrograde thrombolysis versus superselective ophthalmic artery thrombolysis; and 6) pentoxifylline versus placebo. There was no evidence of an important difference in visual acuity between participants treated with t-PA versus intravenous saline (mean difference [MD] at 1 month -0.15 logMAR, 95% confidence interval [CI] -0.48 to 0.18; 1 study, 16 participants; low certainty evidence); t-PA versus isovolemic hemodilution, eyeball massage, intraocular pressure reduction, and anticoagulation (MD at 1 month -0.00 logMAR, 95% CI -0.24 to 0.23; 1 study, 82 participants; low certainty evidence); and TES with 0 mA versus TES with 66% of EPT at 20 Hz versus TES with 150% of EPT at 20 Hz. Participants treated with t-PA experienced higher rates of serious adverse effects. The other three comparisons did not report statistically significant differences. Other studies reported no data on secondary outcomes (quality of life or adverse events). AUTHORS' CONCLUSIONS: The current research suggests that proposed interventions for acute non-arteritic CRAO may not be better than observation or treatments of any kind such as eyeball massage, oxygen inhalation, tube expansion, and anticoagulation, but the evidence is uncertain. Large, well-designed RCTs are necessary to determine the most effective treatment for acute non-arteritic CRAO.

Hyperbaric oxygen therapy for central retinal artery occlusion: Presenting visual acuity and time to treatment as factors associated with visual recovery

Purpose: To evaluate the effectiveness of hyperbaric oxygen (HBO2) therapy as a treatment for central retinal artery occlusion (CRAO). Methods: A total of 38 patients who underwent HBO2 for non-arteritic CRAO were identified. Patients with arteritic CRAO, branch retinal artery occlusion, ophthalmic artery occlusion, and other diagnoses were excluded from the analysis. The main outcome measured was the change in visual acuity at the most recent follow-up exam compared to the visual acuity at presentation before the initiation of HBO2 therapy. Results: The overall visual acuity after HBO2 compared with the visual acuity at presentation showed a mean improvement of 0.5 logMAR from 2.2 to 1.7 logMAR (p=0.0003). Patients who presented with hand motion and light perception vision had a mean improvement of 0.4 logMAR (p=0.058) and 0.8 logMAR (p=0.004) after HBO2, respectively. An average visual acuity improvement of 0.5 logMAR (p=0.012) was observed when patients underwent HBO2 earlier than 24 hours of symptom onset. This mean improvement increased to 0.9 logMAR (p=0.009) if HBO2 was initiated within eight hours. Conclusions: HBO2 may be an effective treatment for non-arteritic CRAO, especially if patients are treated early and present with salvageable vision. The time to treatment and the presenting visual acuity may be predictive factors on the visual prognosis following HBO2. Further studies with a prospective design and more patients are necessary to determine the long-term outcomes and the optimal protocol for HBO2 in CRAO patients.

Color Doppler Eye Ultrasonography in giant cell arteritis: differential diagnosis between arteritic and non-arteritic sudden blindness.

Temporal (TA) and axillary (AXA) arteries Color Doppler Ultrasonography (CDUS) is the most reliable diagnostic technique for the diagnosis of giant cell arteritis (GCA), displaying high sensitivity and specificity. Nevertheless, CDUS is still poorly performed in the common clinical practice, being employed only by rheumatologists with a relevant expertise in this field. Color Doppler Eye Ultrasound (CDEUS) is a procedure variously employed in ophthalmology and preliminary findings have displayed a possible role also in the diagnostic work-up of GCA. Aim of this study was to assess whether CDEUS may play a role in the differential diagnosis between arteritic and non-arteritic blindness. We prospectively included all patients evaluated since September 2021 to May 2022 by our Ophthalmology Unit for sudden blindness and referred to our Vasculitis Clinic in the suspicion of GCA. All patients underwent complete ophthalmological evaluation, routine blood tests, AxA and TA CDUS and CDEUS. According to the definite diagnosis, patients were divided in the following subgroups: (A) patients suffering from arteritic central retinal artery occlusion (CRAO), (B) patients suffering from non-arteritic CRAO, (C) patients suffering from arteritic anterior ischemic optic neuropathy (AION), (D) patients suffering from non-arteritic AION. During the observational period, we included a total of 25 patients suffering from sudden blindness and referred to Vasculitis Clinic for ruling out GCA. Patients belonging to group A showed no flow or reduced flow within the territory of central retinal artery (CRA), no "spot sign" and positive TA CDUS; on the other hand, patients from group B presented normal TA CDUS, no flow or reduced flow within the territory of CRA and the presence of "spot sign". Conversely, no relevant difference was evidenced at CDEUS in patients with and without arteritic AION. Our preliminary data displayed a good reliability of CDEUS in distinguishing between arteritic and non-arteritic CRAO, while no difference was assessed between arteritic and non-arteritic AION. Since AION represents the most common presentation of cranial GCA, CDEUS does not seem a reliable procedure in the diagnostic work-up of GCA and should be restricted only to the exclusion of thrombo-embolic occlusions within the territory of central retinal artery.

Thrombolysis in central retinal artery occlusion: a retrospective observational study

BackgroundThere is no evidence-based therapy for non-arteritic central retinal artery occlusion (NA-CRAO). Intravenous thrombolysis (IVT) with alteplase in a time window < 4.5 h may lead to a favorable outcome. Purpose of this study was to investigate the feasibility, efficacy and safety of IVT in patients classified as functionally blind.MethodsWe conducted a retrospective observational study of NA-CRAO-patients. All patients underwent an ophthalmological and neurological examination including cerebral magnetic resonance imaging (MRI) for assessment of additional stroke lesions. Patients were treated either conservatively or with IVT within 4.5 h. Visual acuity (VA) was evaluated in logMAR and a categorical analysis was performed.ResultsThirty-seven patients were included in the study, 21 patients in the conservative treatment group (CTG) and 16 patients in the IVT group. The median logMAR visual acuity at admission and discharge was similar in both groups. The medium symptom to treatment time in the IVT group was 158.0 min. 3 patients (19%) of the IVT group showed a favorable outcome, all CTG patients remained at the level of functional blindness. No serious adverse events were observed after IVT. MRI showed additional acute stroke in over one-third of the patients (n = 14).ConclusionsEarly intravenous thrombolysis therapy according to the current stroke protocol n a time window up to 4.5 h after the onset of symptoms was feasible and might be a potential treatment option for NA-CRAO. Patients with NA-CRAO are at very high risk of ischemic stroke and MRI should be done in all patients for optimized treatment and secondary stroke prevention. A prospective randomized study is required.

Retinal Infarction: A Pilot Study on the Efficacy and Safety of Intravenous Thrombolysis and Underlying Aetiologies.

Background: Treatment of non-arteritic central retinal artery occlusion is still inconsistent. Therefore, the current study aimed to evaluate the efficacy of intravenous thrombolysis (IVT) and describe the prevalence of co-occurring ischemic brain lesions in patients with acute visual loss due to ischemia. Methods: We analysed 38 consecutive patients with acute visual loss between January 2015 and June 2020. Patients presenting within 4.5 h of symptom onset without any contraindication were treated with IVT. Patients underwent neurologic and ophthalmologic examination and diagnostic workup for the underlying aetiology. Follow-up was performed after 3 and 12 months. Results: Patients treated with IVT had a significantly better functional outcome at discharge compared to patients treated conservatively. No additional ischemic brain lesions were detected (0 of 38). Three patients had extracranial carotid artery stenosis ≥50%. Atrial fibrillation was present in four patients, three of whom already received oral anticoagulation. In the remaining 31 patients no embolic source was detected. However, the number of plaques were rated mild to moderate. Within three months, one patient developed transient visual loss while another suffered a contralateral transient ischemic attack. Conclusions: IVT may represent a safe and effective treatment option in patients with isolated visual loss due to ischemia. The aetiology was atherosclerotic burden rather than embolism caused by carotid stenosis or atrial fibrillation, bringing the current diagnostic procedure and therapy into question. Randomized trials are necessary to evaluate the efficacy and safety of IV thrombolysis and clarify the aetiology of isolated visual loss due to ischemia.

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion

ObjectivesDiffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. Materials and methodsRetrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. ResultsWe included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). ConclusionsIn this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.

INTRAVENOUS THROMBOLYTIC THERAPY FOR ACUTE NONARTERITIC CENTRAL RETINAL ARTERY OCCLUSION. A REVIEW.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke. It is a critical condition that often leads to severe visual loss or blindness and can be a harbinger of further cerebrovascular events. Due to the lack of scientific data, there are no effective evidence-based forms of therapy for this condition. None of the conservative therapies have proven effective. The results of some previously published studies suggest a benefit of intravenous thrombolytic therapy in the same regimen as in the treatment of ischemic stroke. This work aims to present an overview of published clinical studies focused on the use of intravenous thrombolysis for CRAO, evaluate its efficacy and safety, and propose an optimal diagnostic and therapeutic algorithm for acute management of CRAO. Summary statistics of patient data from relevant studies indicate that a significant visual acuity improvement was achieved by a total of 45 % of patients receiving alteplase within 4.5 hours of symptoms onset. The occurrence of adverse events in this time window was not significant. Intravenous thrombolytic therapy in CRAO thus appears to be effective and safe. However, we still lack data from adequate prospective randomized controlled trials to confirm this conclusion. To date, two randomized trials are being conducted. The intravenous thrombolysis administration, patient monitoring, etiologic workup, and setting of effective secondary prevention should be ensured at the centre of highly specialized cerebrovascular care. Urgent transport of the CRAO patient to the nearest centre is essential.

Abstract WP58: Telestroke Assessment Of Acute Monocular Visual Loss Fails To Routinely Diagnose Retinal Artery Occlusion And Recommend Thrombolytic Therapy

Introduction: Central retinal artery occlusion (CRAO) is a neurovascular emergency and acute monocular visual loss should trigger a stroke code activation. As thrombolytic therapy is considered for non-arteritic CRAO in the stroke therapeutic window, we aimed to review all telestroke encounters for acute visual loss in Mayo Clinic national telestroke network, focusing on the ocular diagnosis and the management recommendations. Hypothesis: patients evaluated via telestroke for acute visual loss are less likely to receive thrombolysis Methods: We conducted a retrospective review of the Mayo Clinic Arizona Telestroke/Teleneurology (2010-2017, 6364 encounters) and Mayo Clinic Enterprise Telestroke databases (2018-2020, 3147 encounters), searching for visits requested for acute visual loss. We recorded the subjects’ demographics, time from last seen normal to telestroke evaluation, preliminary diagnosis, and therapeutic/diagnostic recommendation. Results: From a total of 9511 audio-video telestroke encounters, 49 (0.51%) had an ocular diagnosis. Out of those, 6 patients (12.2%) had a provisional diagnosis of CRAO. 4/6 (66.6%) CRAO patients presented within 4.5h from symptom onset (median 2 hours) and none received thrombolytic therapy. All telestroke physicians recommended antiplatelet, ophthalmology consultation for diagnostic evaluation and comprehensive stroke work-up. Conclusions: Telestroke evaluations for CRAO, in routine practice, are less common than the disease prevalence would predict, suggesting that education is urgently mandated to increase the index of awareness. Even when CRAO subjects are evaluated via telestroke within 4.5 hours from symptom onset, they do not receive thrombolytic therapy nor timely ophthalmologic evaluation. Telestroke visits may benefit from the inclusion of tele-ophthalmologic consults to help with establishing the diagnosis in the narrow time-window of intravenous thrombolysis.

Efficacy of Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Meta-Analysis

Introduction: The best management strategy still remains strong controversy for acute nonarteritic central retinal artery occlusion (CRAO). We thus performed a meta-analysis to determine the efficacy of intra-arterial thrombolysis (IAT) for visual improvement according to different times from symptom onset. Methods: We searched EMBASE, PubMed, and Web of Science for relevant studies assessing efficiency of IAT in patients with CRAO compared with standard therapy. Fixed-effects and random-effects models were performed. Results: Five eligible studies including 459 patients with acute CRAO were pooled in the meta-analysis. In all, 219 (47.7%) received IAT, and the mean time from symptom onset to IAT was 13 h. The pooled analysis demonstrates odds ratio (OR) for the procedure of IAT and any visual improvement to be 1.520 (95% confidence intervals [CIs] 1.258–1.837; p < 0.001). Subgroup analyses further indicated that the CRAO patients who received IAT achieved any visual improvement more easily within 6 h from symptom onset (OR = 1.703, 95% CI 1.219–2.381; p = 0.002), but not those beyond 6 h (OR = 1.260, 95% CI 0.973–1.632; p = 0.080). Conclusion: Our meta-analysis of available published data supports IAT to be an alternative treatment option for CRAO patients within 6 h from symptom onset.

Update on intravenous lysis treatment : The REVISION trial

To date, no evidence-based treatment for acute non-arteritic central retinal artery occlusion (CRAO) exists. Considering the limited ischemia tolerance of the retina and the results of multiple case series, increasing expectations are directed towards an early intravenous thrombolysis within 4.5 h after CRAO onset. The current literature regards timely retinal reperfusion as the only potentially beneficial therapeutic option to treat non-arteritic CRAO. Available data on the efficacy and safety of thrombolysis in CRAO are presented and discussed. On the basis of these data, the prospective, randomized, double-blind, placebo-controlled REVISION trial (early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion) will shortly be initiated in 25centers across Germany in order to investigate early intravenous thrombolysis in acute CRAO. The main inclusion criteria of the REVISION trial are outlined, which may help ophthalmologists to identify study candidates and facilitate rapid referral to astudy center. The efficacy of intravenous thrombolysis in acute ischemic stroke is critically time dependent. This may also be assumed in acute CRAO; however, definite evidence still needs to be provided. Until then, the motto "time is retina" should be applied and intravenous thrombolysis should be offered to CRAO patients as part of randomized trials (such as REVISION). According to the current literature, other acute treatment approaches (such as paracentesis) are not indicated.