Acute 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 are lacking to address this question. The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. This study is the 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 Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes 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 tomography/angiography, ultrasound and magnetic resonance imaging (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 h 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 translate to CRAO with its similar pathophysiology. ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Clinical application of multicolor scanning laser ophthalmology in diagnosis and grading of central retinal artery occlusion.

To characterize features of central retinal artery occlusion (CRAO) using multicolor (MC) imaging and to assess the differences in CRAO grading between color fundus photography (CFP) and MC image qualitatively and quantitatively. We conducted a prospective, cross-sectional study in the Department of Ophthalmology of Renmin Hospital of Wuhan University. In total, 86 acute CRAO patients were included. Spectral-domain optical coherence tomography (SD-OCT), CFP, and MC examinations were taken at baseline. Based on the findings of these three examinations, CRAO was divided into three grades (incomplete, subtotal, and total). Based on OCT grading criteria, we qualitatively compared the ability of grading CRAO by CFP and MC. CRAO patient's visual acuity (VA) was obtained from the initial visit. The retinal thickness was measured by SD-OCT. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained from optical coherence tomography angiography (OCTA) examinations. Quantitative data were compared across the three acute CRAO subgroups and against three examination findings. MC image had significantly higher power of acute CRAO detection than CFP (P = 0.03). In the same group of CRAO patients, there was no significant difference in VA when comparing OCT with the MC grading system or with the CFP grading system (all P > 0.05). Significant differences in VA were found between the three CRAO subgroups only under MC grading (P = 0.016). In incomplete CRAO patients, significant differences were found in central fovea thickness (CFT) when comparing OCT with the CFP grading system (P = 0.019). In the same group of CRAO patients, there was no significant difference in retinal thickness when comparing OCT with the MC grading system (All P > 0.05). Significance differences in CFT (P < 0.001), innermost retinal layer (IMRL; P < 0.01), middle retinal layer (MRL; P < 0.001), and outer retinal layer (ORL; P = 0.021) were found between the three CRAO subgroups by MC grading. Vessel density of SCP showed a statistically increased as the severity of three CRAO subgroups (P = 0.03), whereas DCP did not have significant differences (P = 0.745). Comparisons were made between the OCT grading method and the MC and CFP grading methods; there is no significant difference in vessel density of SCP and DCP (All P > 0.05). The images obtained by MC are superior to those obtained by CFP in CRAO grading, retinal thickness, and vessel density measurement. MC imaging may be more capable of CRAO grading than OCT. We recommend MC imaging to determine CRAO severity to guide disease treatment and predict visual prognosis.

Prevalence and Distribution of Macular Fluid with Central Retinal Artery Occlusion and Anterior Ischemic Optic Neuropathy.

To examine the prevalence and distribution of fluid within a cohort of eyes with acute central retinal artery occlusion (CRAO) and non-arteritic anterior ischemic optic neuropathy (AION) using optical coherence tomography (OCT). A retrospective analysis of patient records and OCT imaging. Patients presenting with acute CRAO or AION who had available macular OCT imaging and no co-morbidities known to cause macular fluid were included in the analysis. Baseline characteristics, visual acuity (VA), and fluid presence and distribution among the retinal layers were recorded. In the 16 eyes with acute CRAO, fluid was noted in 5 eyes (31%), which was mainly subretinal (3 eyes) or intraretinal located within the outer retinal layers (3 eyes). Only one eye had inner retinal cysts. Of the 11 eyes with acute AION, fluid was present in 8 eyes (73%). Subretinal fluid was noted in 4 eyes and extended to the foveal area in 3 of them, and outer retinal versus inner retinal cysts were noted in 6 versus 3 eyes, respectively. None of the eyes showed hard exudate deposition. In the small subset of eyes with CRAO and macular fluid that were followed-up, VA improved, while in eyes with AION, VA remained stable. Macular fluid on OCT is not an uncommon feature of acute CRAO and AION and is mainly distributed within the outer retinal layers or subretinal space. Fluid is an understudied feature of retinal and optic nerve head infarction and may have a role in predicting neuronal damage extent and visual outcome.

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.

Abstract WMP56: Diagnosis of Acute Central Retinal Artery Occlusion With a Nonmydriatic Ocular Fundus Camera Combined With Optical Coherence Tomography in the Emergency Department: A New Paradigm

Background: Central retinal artery occlusion (CRAO) is a retinal infarction with causes/management similar to cerebral infarction. However, CRAO diagnosis is often delayed, resulting in missed opportunities for rapid treatment. Diagnosis by ophthalmologists is essential prior to management by stroke neurologists and may be challenging within a few hours of vision loss. Our goal is to provide a new paradigm in the emergency department (ED) with the implementation of a nonmydriatic ocular fundus camera (NMFP) combined with optical coherence tomography (OCT) to allow for ultrarapid remote diagnosis and stroke alert as soon as patients present to the ED. Methods: Prospective collection of data from consecutive patients who had NMFP-OCT for acute monocular vision loss in our general ED affiliated with a comprehensive stroke center. We collected timing of photographs; final diagnosis (CRAO/other causes of vision loss); time between vision loss onset and CRAO diagnosis; NMFP-OCT findings. Results: Over 9 weeks, 27 patients had NMFP-OCT obtained for acute monocular visual loss, including 9 CRAO [others included 7 retinal detachments; 8 vitreous hemorrhages; 3 temporal arteritis]. Diagnosis of acute CRAO was made remotely on NMFP-OCT obtained 30, 33, 36 min after arriving in ED in 3 patients presenting to ED within 3.5 hrs of vision loss. In all 3 patients, the ocular color photographs were almost normal and acute CRAO diagnosis was made primarily from the OCT showing inner retinal edema/hyperreflectivity. Conclusion: Incorporating NMFP-OCT into the ED workflow can be used as a substitute for funduscopic examination/pupillary dilation, allowing for remote diagnosis of CRAO by ophthalmologists who can provide real time recommendations before in person visit. These positive preliminary results suggest that this strategy accelerates the diagnosis of urgent vision loss, resulting in improved patient outcomes. Results of the first 6 months will be presented at the conference.

Laporan Kasus : Oklusi Arteri Retina Sentra

AbstractCentral retinal artery occlusion is an occlusion that occurs suddenly in the central retinal artery, which causes hypoperfusion of the retina, progressive cellular damage, and loss of visual acuity. Risk factors are similar to other thromboembolic diseases and include hypertension, smoking, hyperlipidemia, diabetes, hypercoagulability, and male gender. All therapy for central retinal artery occlusion aims to restore perfusion or oxygenation of the retina. Management for acute central retinal artery occlusion can only be effective if performed less than 6 hours after symptoms.41-year-old woman, came to the Retina Eye Polyclinic, Surabaya Community Eye Hospital with complaints of sudden blurring of the right eye since 3 days ago. On examination of the anterior segment of the right eye, relative afferent pupillary defect was found and on the posterior segment of the right eye, pale retina and cherry red spot was found. Timolol, artificial tears, and eye supplement was given but did not give good results

Thrombolytic Therapy for Central Retinal Artery Occlusion in an Academic Multi-Site Stroke Centre

ABSTRACT Central retinal artery occlusion (CRAO) is a subtype of acute ischaemic stroke leading to severe visual loss. A recent American Heart Association scientific statement proposed time-windows for thrombolysis in CRAO similar to acute ischaemic cerebral strokes. We aimed to review our academic multi-site stroke centre experience with intravenous (IVT) and intra-arterial thrombolysis (IAT) in CRAO between 1997 and 2022. Demographic, clinical characteristics, thrombolysis timeline, concurrent therapies, complications, and 3-month follow-up visual acuity (VA) were collected. The thrombolysed cohort follow-up VA was compared with an age, gender and baseline VA matched cohort of CRAO patients that received conservative therapies. Thrombolytic therapy was administered to 3.55% (n = 20) of CRAO admissions; 13 IVT (mean age 68, 61.5% male, 12 alteplase and 1 tenecteplase, all embolic aetiology, 1 CRAO mimic) and 7 IAT (mean age 55, 85.7% male, 3 post-operative and 3 embolic). Additional conservative CRAO-targeting therapies was received by 60%. The median time from onset of visual loss to IVT was 158 minutes (range 67–260). Improvement by at least two Snellen lines was achieved by 25% with 12.5% improving to 20/100 or better. Intracranial haemorrhage post IVT occurred in 1/13 (7.6%). The median time from onset of visual loss to IAT was 335 minutes. Improvement by at least two Snellen lines was achieved by 42%. No difference in 3-month VA was noted between patients that received thrombolysis, either alone (n = 8) or combined with other therapies, and those that received conservative therapies. Our results suggest that the management of acute CRAO remains heterogeneous. The lack of obvious benefit of thrombolysis in our small series supports the need for randomizsd clinical trials comparing thrombolysis to placebo to guide hyperacute CRAO management.

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.].

Optometric Practice Patterns for Acute Central and Branch Retinal Artery Occlusion.

Optometrists are often the first providers to evaluate patients with acute vision loss and are often the first to diagnose a central retinal artery occlusion (CRAO). How quickly these patients present to the optometrist, are diagnosed, and referred for evaluation are major factors influencing the possibility of acute therapeutic intervention. Our aim was to survey the U.S. optometric community to determine current optometric practice patterns for management of CRAO. An anonymous seven-question survey was emailed in 2020 to the 5,101 members of the American Academy of Optometry and the 26,502 members of the American Optometric Association. Of 31,603 optometrists who were sent the survey, 1,926 responded (6.1%). Most respondents (1,392/1,919, 72.5%) worked in an optometry-predominant outpatient clinic and were less than 30 minutes from a certified stroke center (1,481/1,923, 77.0%). Ninety-eight percent (1,884/1,922) of respondents had diagnosed less than 5 CRAOs in the previous year, and 1,000/1,922 (52.0%) had not diagnosed a CRAO in the prior year. Of the optometrists who diagnosed at least one CRAO in the previous year, 661/922 (71.7%) evaluated these patients more than 4 hours after the onset of vision loss. Optometrists who diagnosed a CRAO or branch retinal artery occlusion referred patients to an emergency department (ED) affiliated with a certified stroke center (844/1,917, 44.0%), an outpatient ophthalmology clinic (764/1,917, 39.9%), an ED without a stroke center (250/1,917, 13.0%), an outpatient neurology clinic (20/1,917, 1.0%), or other (39/1,917, 2.0%); most (22/39, 56.4%) who responded "other" would refer to a primary care physician. Optometrists are likely the first providers to evaluate patients with acute vision loss, including from a retinal artery occlusion. However, only 6.1% of optometrists responded to our survey despite 2 reminder emails, likely reflecting the lack of exposure to acute retinal artery occlusions, and a potential lack of interest of optometrists in participating in research. Of the optometrists who reported evaluating a CRAO in the previous year, less than 29% saw the patient within 4 hours of vision loss. In addition, a large portion of optometrists are referring acute CRAO patients to outpatient ophthalmology clinics, delaying appropriate acute management. Therefore, it is imperative that optometrists and ophthalmologists are educated to view acute retinal arterial ischemia as an acute stroke and urgently refer these patients to an ED affiliated with a stroke center. The delay in patient presentation and these referral patterns make future clinical trials for acute CRAO challenging.

Mid-phase pinpoint hyperfluorescent spots on fundus fluorescein angiography in acute central retinal artery occlusion – a novel imaging finding

PurposeTo describe the development and outcome of mid-phase pinpoint hyperfluorescent spots (MPHS) on fundus fluorescein angiography (FFA) in acute (< 7-day symptom onset) central retinal artery occlusion (CRAO) patients.MethodsThis retrospective study included acute CRAO patients who underwent multimodal imaging utilizing optical coherence tomography (OCT) and FFA between June 2017 and January 2023. The correlation of FFA images with the OCT images in various stages and severity of CRAO were studied.ResultsTwenty-three FFA studies on 23 patients with acute CRAO were included. In 11 (48%) cases, an important finding noted on FFA was the presence of single or multiple MPHS with adjacent minimal late vascular leakage. Of these 11 cases, eight (73%) were males and median age was 41 years (inter quartile range: 33–55 years). Visual acuity ranged from ‘light perception’ to 6/18, and these patients presented anytime on the same day to seven days after symptom onset. On OCT, three eyes had severe CRAO, seven eyes had moderate CRAO, and one eye had mild CRAO. MPHS were primarily observed at the posterior pole and more frequently observed in moderate CRAO severity. During follow-up, the MPHS and retinal vessel staining on FFA disappeared as the CRAO showed signs of resolution.ConclusionMPHS at the posterior pole on FFA in acute CRAO patients could indicate a more severe occlusion and poor visual outcomes, even after treatment. This finding is most likely caused by red blood cell aggregation or rouleaux formation.Trial registration numberNot applicable.

Acute central retinal artery occlusion with emboli

Key Clinical MessageCRAO is an ophthalmic and medical emergency. This case is a reminder that diagnosis and management of CRAO begins with ophthalmologists but immediately thereafter care involves emergency cardiovascular and neurological similar to cerebral stroke.

Retinal OCT findings in acute central retinal artery occlusion of varying severity at different disease stages – a retrospective, observational study

PurposeTo study the optical coherence tomography (OCT) changes in eyes with acute central retinal artery occlusion (CRAO) of different severity and at different disease stages.MethodsThe study included acute CRAO cases of < 7 days duration, imaged on OCT at various time points. Based on the OCT findings at presentation, cases were classified into three severity groups: mild, moderate, and severe. OCT scans were evaluated and classified into four-time intervals based on symptom duration.ResultsThere were 39 eyes from 38 patients with acute CRAO who underwent 96 OCT scans. At presentation, the study had 11, 16, and 12 cases of mild, moderate, and severe CRAO, respectively. Middle retinal layer opacification was more common in mild CRAO cases, which caused inner retinal layer thinning over time. Moderate CRAO cases had total inner retinal layer opacification, which resulted in retinal thinning over time. Prominent middle limiting membrane (p-MLM) sign was seen in mild and moderate CRAO eyes while were not visualised in severe CRAO. This sign gradually faded out over time. Other OCT findings in higher grades of CRAO included inner retinal fluid, neurosensory detachment, internal limiting membrane detachment, hyperreflective foci, and posterior vitreous opacities. Regardless of the CRAO grade, the final end-point seen was inner retinal layer thinning over time.ConclusionOCT in CRAO is a useful for determining the severity of retinal ischemia, disease stage, tissue damage mechanism, and final visual outcome. More prospective studies analysing a larger number of cases at fixed time points will be required in the future.Trial RegistrationTrial Registration Number: Not applicable.

Retina and optic nerve diffusion restriction in acute central retinal artery occlusion (P2-9.007)

<h3>Objective:</h3> To determine whether diffusion restriction (DR) of the retina and/or optic nerve (ON) in acute central retinal artery occlusion (CRAO) can be accurately identified on brain diffusion-weighted magnetic resonance imaging (DW-MRI) by junior versus senior neurology residents and vascular neurologists. <h3>Background:</h3> Retina and/or ON DR in CRAO was described with various accuracies and fair inter-rater reliability even between experienced neuroradiologists. The identification of these subtle DW-MRI findings by the forefront neurology residents or vascular neurologists was not previously investigated. <h3>Design/Methods:</h3> Retrospective cohort study of consecutive acute CRAO patients that had stroke-protocol DW-MRI at our tertiary academic center (2013–2020). Two neurology residents (junior and senior), vascular neurologist, and two neuroradiologists blinded to the CRAO site independently reviewed the DW-MRI for retina and/or ON DR. Their inter-rater reliability was calculated using kappa statistics. The neuroradiologists’ consensus agreement was the reference for the non-radiologists. <h3>Results:</h3> We included 128 patients (mean age 68 years; 55% right eye, median time from CRAO to DW-MRI 2 days (IQR 1–4). 28/128 (21.8%) had a discrepancy between the neuroradiologists. After neuroradiologist 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%). Upon comparing the neurology trainees and vascular neurologist, the positive agreement was low (22.2% to 43.9%) but the negative agreement was high (88.0% to 92.9%). The senior resident had the highest observer agreement. Overall substantial agreement (P-B adjusted Kappa &gt; 0.6) between the readings, excepting for moderate (P-B adjusted kappa= 0.59) for ON DR for the junior resident. <h3>Conclusions:</h3> Incongruities in identifying retina and/or ON DR in CRAO are encountered by various specialists. When compared to experienced neuroradiologists, neurology trainees and attending have substantial agreement on the negative findings but low agreement for the positive findings. <b>Disclosure:</b> Dr. Gomez Ramos has nothing to disclose. Dr. Harahsheh has nothing to disclose. Nan Zhang has nothing to disclose. Mr. Parikh has nothing to disclose. Mr. Elshaigi has nothing to disclose. Tanya Rath has nothing to disclose. Dr. Hoxworth has nothing to disclose. Dr. Dumitrascu has nothing to disclose.

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.

Abstract WP190: Central Retinal Artery Occlusion: Do Patient Presentation Patterns Complicate Use Of Potential Treatments?

Introduction: For patients diagnosed with central retinal artery occlusion (CRAO), timely screening for underlying risk factors to prevent secondary stroke and other cardiovascular events is required. Given the profound impact on vision, there is also great interest in the potential to treat CRAO. Thrombolytic therapy is the current standard of care in acute ischemic cerebral stroke, but the window for administration is short. As part of a larger pilot to investigate the prospect of intravenous thrombolysis for patients presenting with acute CRAO in our institution, we set out to evaluate the specific presentation patterns of this population within our system. Methods: Retrospective study performed on 804 patients correctly diagnosed with CRAO from 2011-2020. From this cohort of patients, we identified 484 for whom we could accurately determine the time of first symptoms, the time of first contact with the healthcare system, and the time of evaluation by an ophthalmologist. Results: While 18.0% (87/484) of patients waited over 24 hours from time of vision loss to contact the health care system, 50.2% of patients did connect in under 4.5 hours (243/484). However, only 16.7% (81/484) of patients saw an ophthalmologist within that window, and 35.5% (172/484) did not have any ophthalmologic evaluation within 24 hours of vision loss. Conclusion: Half of CRAO patients within our institution connect with the health care system within a potential window for intravenous thrombolytic treatment, but the majority do not receive ophthalmic diagnosis within that time frame. In conclusion, public health education efforts to speed up presentation times and system-based strategies to decrease the time to ophthalmic diagnosis are needed if thrombolytic treatment either via compassionate use or within a clinical trial setting is to be more widely offered.

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.

Internal limiting membrane detachment in acute Central Retinal Artery Occlusion: clinical features, multimodal imaging, outcomes & prognostic biomarker

PurposeTo report the clinical features, multi-modal imaging characteristics and their corroboration, and prognostic value of internal limiting membrane detachment (ILMD), a novel OCT biomarker in acute CRAO.DesignRetrospective observational case-control study at institutional tertiary eye care centers.Methods60 eyes of 60 patients of acute CRAO with optical coherence tomography (OCT) at baseline were included. Eyes were grouped in (a) With ILMD; (b) With no-ILMD. Multimodal imaging correlation, BCVA change and binary logistic regression were studied.ResultsEighteen eyes (30%) were noted to have ILMD. At presentation, ILMD on OCT corroborated with macular non-perfusion with enlarged foveal avascular zone both on OCT-angiography (OCTA) and fundus fluorescein angiography (FFA). On follow-up, ILMD had resolved in all cases with fragmentation, disruption and atrophy of the retinal layers. Logistic regression showed poor baseline visual acuity was significantly associated with the odds of ILMD [Odds Ratio (OR) 31.02, p = 0.0018, 95% confidence interval: 1.81–529] while controlling for potential confounders including age (p = 0.60), gender (p = 0.316) duration of symptoms (p = 0.114), follow-up duration (p = 0.450) and final BCVA (p = 0.357). Eyes with ILMD and no-ILMD had a baseline BCVA of 2.62 LogMAR (light perception) and 2.05 LogMAR (Snellen equivalent 20/2000), respectively. On follow up, none of the eyes with ILMD showed any improvement. In contrast, nine (21.4%) eyes in no-ILMD had a vision of 20/400 and above with a mean final visual acuity of 1.87 + 0.78 LogMAR (p = 0.000).ConclusionILMD correlated with macular non-perfusion and poor baseline visual acuity which showed no improvement on follow-up, suggesting it to be poor prognostic biomarker.

Changes in macrophage-like cells characterized by en face optical coherence tomography after retinal stroke.

PurposeThe retina could serve as a window of neuroinflammation, but the in vivo changes in macrophage-like cell (MLC), such as microglia, in acute ischemic retinal stroke remain unclear. Thus, the current study aimed to investigate the in vivo changes in MLC characterized by en face optical coherence tomography (OCT) after acute ischemic retinal stroke.MethodsTwenty patients with unilateral acute nonarteritic reperfused central retinal artery occlusion (CRAO) were participated in this study, and their contralateral eyes served as control group. A 3 μm en face OCT slab on the inner limiting membrane of the optic nerve head (ONH) region or macular region was used to visualize and binarize the MLCs. The MLCs were binarized and quantified using a semiautomated method. OCT angiography was used to evaluate the reperfusion status and obtain the structural data of the inner retina in the ONH and macula. The thickness of the ganglion cell complex in the macular region was measured. The optical intensity and optical intensity ratio of the inner retina were calculated to evaluate the ischemia severity.ResultsIn the ONH region, decreased vessel densities of radial peripapillary capillaries accompanied by increased thickness of the retinal nerve fiber layer were found in the CRAO eyes in comparison to the unaffected eyes (p=0.001, p=0.009, respectively). In the macular region, significantly lower vessel densities in both the superficial and deep capillary plexus and increased thickness of the ganglion cell complex were also found in the CRAO eyes (all p ≤ 0.001). The ONH and macular MLC quantities and densities in CRAO eyes were significantly higher than those in the unaffected eyes (both p<0.001). Larger and plumper MLCs were observed in the CRAO eyes compared with their unaffected eyes. ONH and macular MLC densities were positively associated with the disease duration in the acute phase and the optical intensity ratio of inner retina.ConclusionsThe increased density and morphological changes of MLCs may indicate the aggregation and activation of MLCs following acute reperfused CRAO. The aggregation of MLCs may be more pronounced in CRAO eyes with longer disease duration and more severe ischemia. MLCs characterized by en face OCT may serve as an in vivo visual tool to investigate neuroinflammation in the ischemic-reperfusion process of stroke.

Central Retinal Artery Occlusion: Can We Effectively Manage This Ocular Emergency in a Hospital Setting?

Central retinal artery occlusion (CRAO) is an ophthalmological emergency characterized by partial or complete occlusion of the central retinal artery. It is the ocular equivalent of an ischemic cerebral stroke. Patients frequently present with a significant, abrupt, painless loss of vision in one eye, with only around 20% of those affected getting functional visual acuity restored in the affected eye. Despite more than 150 years of clinical research, no consensus has been achieved regarding the most effective method of treating CRAO. The efficacy of all proposed treatments is debatable, and many of them have ambiguous risk profiles that present particular diagnostic and management difficulties and cause variations in clinical practice. In certain circumstances, thrombolysis may be attempted as a treatment option. However, the evidence to support the general use of thrombolytics in treating acute CRAO remains elusive. It is known that the risk factors predisposing to other cardiovascular and cerebrovascular events are often present in CRAO. Accordingly, identifying patients at the highest risk of stroke and secondary prevention of ischemic events remains the primary focus of management. This review offers a summary of all the current treatment options available for managing CRAO, with particular reference to their limitations and inconsistent results found in relevant studies until 2022.

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.