[Thrombolysis treatment and multi- disciplinary management of central retinal artery occlusion in comparison with traditional ophthalmological treatment options]. / Arteria centralis retinae elzáródás thrombolysiskezelése és multidiszciplináris ellátása a hagyományos szemészeti kezelési formákkal összehasonlítva.

Background and purpose:

The management of central retinal artery occlusion (CRAO) has long been conservative therapy with limited efficacy carried out in ophthalmology departments together with etiolo­gi­cal investigations lacking a standardised protocol. However, CRAO is analogous to ischemic central nervous system stroke and is associated with increased stroke risk, thus, systemic thrombolysis treatment and multidisciplinary management can be beneficial. Since May 2022, at Semmelweis University CRAO patients diagnosed within 4.5 hours are given intravenous thrombolysis therapy and undergo etiologic workup based on current stroke protocols. Here we report our experience with the multidisciplinary, protocol-based management of CRAO in comparison with former non-protocol based ophthalmological conservative treatment.

We reviewed CRAO patients’ data treated conservatively and with paracentesis within 6 hours at the Department of Ophthalmology between 2013 and 2022 including changes in visual acuity, neurolo­gical and cardiovascular findings compared to those in the thrombolysis project. 

Of the 78 patients receiving non-protocol care, visual improvement was seen in 37% with natural course, 47% with conservative treatment and 47% with paracentesis. Four patients had significant carotid stenosis (2 underwent endarterectomy), 1 carotid dissection, 6 cardioembolism and 1 giant cell arteritis. Of the 4 patients within 4,5 hours, 3 gave their consent to the clinical trial and were treated with thrombolysis and underwent a full etiological assessment. 
2 pa­tients had improved visual acuity, 2 pa­tients had significant carotid stenosis and underwent endarterectomy, 1 patient was started on anticoagulation for newly diagnosed atrial fibrillation.

CRAO patients presenting within 4,5 hours are rare and more patients are needed in our study to establish the efficacy of thrombolysis. However uniform protocollized evaluation helps identifying embolic sources thus, avoiding further and potentially more serious thromboembolic events.

Incidence rates of retinal vascular occlusive diseases from 2011 to 2020 in South Korea: a nationwide cohort study.

BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years. CONCLUSION: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.

Peripheral blood transcriptomic analysis identifies potential inflammation and immune signatures for central retinal artery occlusion.

Central retinal artery occlusion (CRAO) is an acute retinal ischaemic disease, but early diagnosis is challenging due to a lack of biomarkers. Blood samples were collected from CRAO patients and cataract patients. Gene expression profiles were distinct between arterial/venous CRAO blood (A-V group) and venous CRAO/control blood (V-C group) samples. Differentially expressed genes (DEGs) were subjected to GO and KEGG enrichment analyses. Hub genes were identified by Cytoscape and used to predict gene interactions via GeneMANIA. Immune cell infiltration was analysed by CIBERSORT. More than 1400 DEGs were identified in the A-V group and 112 DEGs in the V-C group compared to controls. The DEGs in both groups were enriched in the ribosome pathway, and those in the V-C group were also enriched in antigen processing/MHC pathways. Network analysis identified ribosomal proteins (RPS2 and RPS5) as the core genes of the A-V group and MHC genes (HLA-F) as the core genes of the V-C group. Coexpression networks showed ribosomal involvement in both groups, with additional immune responses in the V-C group. Immune cell analysis indicated increased numbers of neutrophils and T cells. Ribosomal and MHC-related genes were identified as potential CRAO biomarkers, providing research directions for prevention, diagnosis, treatment and prognosis.

Central Retinal Artery Occlusion With Cilioretinal Artery Sparing.

This case report describes a diagnosis of central retinal artery occlusion in a patient in their early 30s who presented with decreased vision in the left eye for 1 week.

IV Thrombolysis for central retinal artery occlusion - Real-world experience from a comprehensive stroke center.

OBJECTIVES: Central retinal artery occlusion (CRAO) is a stroke of the retina potentially amenable to intravenous thrombolysis (IVT). We aimed to determine feasibility of an emergency treatment protocol and risk profile of IVT for CRAO in a comprehensive stroke center (CSC). METHODS: We performed a retrospective, observational cohort study including patients with acute CRAO admitted to a CSC over 4 years. Patients are offered IVT if they present with acute vision loss of ≤ 20/200 in the affected eye, have no other cause of vision loss (incorporating a dilated ophthalmologic exam), and meet criteria akin to acute ischemic stroke. We collected socio-demographic data, triage data, time from onset to presentation, IVT candidacy, and rates of symptomatic intracranial hemorrhage (sICH)- or extracranial hemorrhage. RESULTS: 36 patients presented within the study period, mean (standard deviation (SD)) age of 70.7 (10), 52 % female, and median time (Q1, Q3) to ED presentation of 13.5 (4.3, 18.8) h. Patients within 4.5 h from onset presented more commonly directly to our ED (66.6 % vs 37.1 %, p = 0.1). Nine patients (25 %) presented within the 4.5 h window. Of those eligible, 7 (77 %) received IVT. There were no events of intracranial or extracranial hemorrhage. CONCLUSIONS: Our study confirmed that IVT for acute CRAO is feasible. We found a high rate of treatment with IVT of those eligible. However, because 75 % of patients presented outside the treatment window, continued educational efforts are needed to improve rapid triage to emergency departments to facilitate evaluation for possible candidacy with IVT.

Retinal arterial and vein occlusion: is surgery ever indicated?

PURPOSE OF REVIEW: To highlight the recent progression in surgical treatments for central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO). RECENT FINDINGS: Anti-VEGF treatment, accepted as a primary treatment for CRVO, is unable to effectively treat all types of the diseases. Regarding CRAO, there are not any accepted therapies available. There have however been recent innovations in surgery, such as utilizing robotics-assisted tools in cannulation procedures for central retinal artery occlusion, or micro-cystotomy for refractory macular edema resulting from ischemic CRVO. SUMMARY: Refractory macular edema due to CRVO can be treated with aspiration of the fluid found inside the large cysts often seen in edema. The success rate of micro-cystotomy has been reported at 78% in eyes with refractory macular edema. Recent studies have shown that cannulation with tissue plasminogen activator (tPA) is effective for eyes with CRAO due to thrombus.Recent cannulation or micro-cystotomy procedures can be enhanced with the use of robotic tools which allow us to perform this difficult procedure more easily. Newly developed technology, and consequent developments in surgical procedures, will allow us to deal with unmet needs for retinal vessel occlusive diseases.

Exploring Superselective Intraarterial Thrombolysis for Autologous Fat Injection-Induced Vision Loss.

BACKGROUND: Intravascular injection represents the most severe complication in fat transplantation procedures. Currently, the prognosis for patients who suffer from blindness due to fat transplantation-induced ocular vascular occlusion is far from optimistic. OBJECTIVES: The aim of this study was to explore and evaluate the efficacy and safety of arterial thrombolysis in the treatment of ocular vascular occlusion caused by fat transplantation. METHODS: We analyzed the data of 12 patients who underwent intraarterial thrombolysis and conservative treatments for facial autologous fat grafting-associated ocular vascular occlusion. Among the cases, there were 6 instances of ophthalmic artery embolism and 6 cases of central retinal artery occlusion. All patients suffered with sudden blindness, sometimes accompanied by eye pain, ptosis, strabismus, skin necrosis at the injection site, or cerebral microinfarction. They received symptomatic conservative treatments and intraarterial thrombolysis, encompassing mechanical vessel recanalization, vessel dilation, and dissolution of thrombus constituents. RESULTS: Following intraarterial thrombolysis, a noteworthy improvement in the blood flow of both the main trunk and peripheral branches of the ophthalmic artery was observed in the majority of patients when contrasted with their pretreatment status. One patient experienced a headache intraoperatively, while no significant discomfort was reported by the remaining patients. After conservative treatments and intraarterial thrombolysis, all patients experienced improvement in ocular symptoms, skin necrosis, and cerebral infarction. Three patients demonstrated improvement in visual acuity. These patients had surpassed the recommended time window for treatment, yet the occlusion of the ophthalmic artery was not complete. CONCLUSIONS: Intraarterial thrombolysis combined with conservative treatments achieves early perfusion and is expected to promote visual recovery. Hospitals that possess the necessary treatment capabilities are encouraged to establish this therapeutic pathway.

The Role of microRNAs Related to Apoptosis for N-Methyl-d-Aspartic Acid-Induced Neuronal Cell Death in the Murine Retina.

Glaucoma is one of the leading causes of acquired blindness and characterized by retinal ganglion cell (RGC) death. MicroRNAs are small noncoding RNAs that degrade their target mRNAs. Apoptosis is one of the common mechanisms leading to neuronal death in many neurodegenerative diseases, including glaucoma. In the present study, we identified microRNAs that modulate RGC death caused by the intravitreal injection of N-methyl-d-aspartic acid (NMDA). We found an upregulation of miR-29b and downregulation of miR-124 in the retina of the NMDA-injected eyes. The intravitreal injection of an miR-29b inhibitor 18 h before NMDA injection reduced RGC death and the downregulation of myeloid cell leukemia 1 (MCL-1), an anti-apoptotic factor, induced by intravitreal NMDA. The intravitreal injection of an miR-124 mimic 18 h before NMDA injection also reduced RGC death and the upregulation of B-cell/chronic lymphocytic leukemia lymphoma 2 (bcl-2)-associated X protein (Bax) and bcl-2 interacting protein (Bim), pro-apoptotic factors, induced by intravitreal NMDA. These data suggest that expressional changes in microRNA are involved in the excitotoxicity of RGCs, and that complement and/or inhibition of microRNA may be a potential therapeutic approach for the diseases related to the excitotoxicity of RGCs, such as glaucoma and retinal central artery occlusion.

Serum vitamin D level alterations in retinal vascular occlusions.

AIM: To evaluate serum vitamin D levels in sub-types of retinal vascular occlusions and compare the levels in ischemic and non-ischemic presentations. METHODS: This study included 50 patients of retinal vascular occlusions comprising central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, branch retinal artery occlusion (study group) diagnosed on basis of clinical characteristics as well as investigations and an age and gender-matched healthy control group (control group). The study group was further classified into ischemic and non-ischemic subtypes and serum vitamin D levels were analysed and compared. RESULTS: There were 50 patients of various sub-types of retinal vascular occlusions comprising 13 cases of CRVO, 30 cases of BRVO, 05 cases of CRAO, 02 cases of BRAO and 50 age and sex-matched controls. Mean BCVA and CMT in RVO patients was +1.12 log MAR, 346.72 ± 27.93 µm while in control group was +0.37 log MAR, 236.22 ± 3.71 µm which were statistically significant (p = 0.004; p = 0.002). The mean serum vitamin D value in study group was 18.39 ng/dl as compared to 32.31 ng/dl in control group which was statistically significant (p = 0.001). The difference in the baseline vitamin D value between the ischemic and non -ischemic sub groups among total vascular occlusion was found to be statistically significant (p = 0.010). However, baseline vitamin D levels difference among ischemic and non-ischemic cases in individual sub-types of vascular occlusion was statistically insignificant. CONCLUSION: High prevalence of low serum vitamin D levels is seen in patients of retinal vascular occlusion spectrum diseases. Moreover, ischemic types of retinal vascular occlusion have significantly lower serum vitamin D levels as compared to non - ischemic despite having fewer no of patients in arterial occlusion sub-types. Therefore, vitamin D supplements may be considered as possible future targeted therapy in optimizing the severity of disease.

Central retinal artery occlusion after spinal surgery: Case report and literature review.

AIM: To report a rare case of unilateral central retinal artery occlusion (CRAO) following spinal surgery. METHODS: Observational case report. RESULTS: A 15-year-old female patient underwent scoliosis surgery under general anesthesia in a prone position, her head being supported by a horseshoe headrest for approximately four hours, with stable vitals and without significant blood loss during surgery. Upon waking up from general anesthesia, the patient immediately reported severe visual loss in her right eye (RE), associated to marked periocular ecchymosis and chemosis. Visual acuity was limited to light perception. Fundus examination showed normal optic disc appearance with diffuse retinal pallor and a macular cherry red spot. Optical coherence tomography (OCT) showed increased reflectivity in the inner retina, consistent with ischemic maculopathy in the RE. Brain and neck magnetic resonance imaging angiograms were unremarkable. Further investigations ruled out collagen vascular disease, Behcet disease, syphilis, sickle cell disease and hypercoagulable states. CONCLUSION: Central retinal artery occlusion is rarely observed following spinal surgery. The cause was presumed to be compression of the orbit by a horseshoe headrest in a prone position due to an accidental shift in position during surgery. This catastrophic complication, albeit rare, is usually irreversible and thus must be prevented. Proper positioning and vigilance by both the surgeon and the anesthesiologist during surgery are fundamental to ensure that the orbits are not under pressure.

Retinal artery occlusion after ophthalmic surgery under regional anaesthesia: A narrative review.

Two recent cases of central retinal artery occlusion under otherwise uncomplicated sub-Tenon's block that resulted in significant visual loss after cataract surgery prompted us to undertake a literature review of such cases. We identified 97 cases of retinal artery occlusion after ophthalmic surgery under regional anaesthesia that had no immediate signs of block-related complications. These occurred after various intraocular (87%) and extraocular (13%) operations, across a wide range of ages (19-89 years) on patients with (59%) or without (39%) known risk factors. The anaesthetic techniques included 40 retrobulbar blocks, 36 peribulbar blocks, 19 sub-Tenon's blocks, one topical anaesthetic and one unspecified local anaesthetic. Different strengths of lidocaine, bupivacaine, mepivacaine and ropivacaine, either alone or in various combinations, were used. The details of the anaesthetic techniques were often incomplete in the reports, which made comparison and analysis difficult. Only nine cases had their cause (optic nerve sheath injury) identified, while the mechanism of injury was unclear in the remaining patients. Various mechanisms were postulated; however, the cause was likely to be multifactorial due to patient, surgical and anaesthetic risk factors, especially in those with compromised retinal circulation. As there were no definite risk factors identified, no specific recommendations could be made to avoid this devastating outcome. We have provided rationales for some general considerations, which may reduce this risk, and propose anaesthetic options for ophthalmic surgery on the fellow eye if required, based both on our literature review and our personal experience.

Retinal arterial occlusion and patent foramen ovale: A case study-based review.

PURPOSE: To identify all reported cases of retinal artery occlusion (RAO) associated with patent foramen ovale (PFO) in the literature and present a similar case of CRAO from our clinic. METHODS: PubMed database was searched for studies reporting RAO in individuals with PFO. Relevant data were tabulated and reviewed. We estimated each case's Risk of Paradoxical Embolism (RoPE) score. RESULTS: 23 cases of CRAO (n=10; including ours), BRAO (n=10), and CILRAO (n=3) were reviewed. Most cases were under 50 years of age (78.3%). The reported predisposing factors were: hypertension (26.1%), migraine (17.3%), smoking (13.0%), recent immobilization (13.0%), strenuous exertion (8.7%), pregnancy (8.7%), and diabetes (4.3%). A high RoPE score (≥7; suggestive of paradoxical embolism via PFO) was estimated for 71.4% of patients. In most cases, the neurological and cardiovascular examinations, laboratory studies, and imaging were unremarkable, except for the PFO±atrial septal aneurysm (present in 21.7%). In only 28.6% of cases, transthoracic echocardiography (TTE) (± saline contrast) could visualize the PFO; transesophageal echocardiography (TEE) was necessary to detect the PFO in 71.4%. Approximately one-half of the patients underwent percutaneous closure of the PFO; no complications or subsequent acute ischemic events ensued. The visual prognosis was poorer for CRAO than for BRAO or CILRAO. CONCLUSION: Timely diagnosis, acute management, and ensuring urgent initiation of stroke workup in cases with RAO or transient monocular vision loss are crucial. Clues to a possible paradoxical embolism as the cause include the absence of known cardiovascular risk factors, young age, migraine, recent immobility, vigorous exercise, and pregnancy.