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      Branch Retinal Vein Occlusion after Messenger RNA-Based COVID-19 Vaccine

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          Abstract

          Two days after the second dose of the messenger RNA-based COVID-19 vaccine (BNT162b2), a healthy 38-year-old man developed branch retinal vein occlusion (BRVO) in his left eye (OS). His previous medical history was unremarkable and he was a nonsmoker. His blood pressure was 117/78 mm Hg. Blood examination did not suggest thrombophilia. His best-corrected visual acuity (BCVA) was 0.9 OS with myopic correction. A fundus examination showed a retinal hemorrhage and cotton wool spots in the superotemporal region of the posterior pole OS. Optical coherence tomography macular scans showed subfoveal fluid accumulation and retinal thickening in the superior macular region OS. Two intravitreal injections of aflibercept were administered 2 months apart. By 7 months after the initial visit, the BCVA was 1.2 OS and the retinal hemorrhage and macular edema have resolved. BRVO can be seen after BNT162b2 vaccinations. Because the third doses of the vaccine are beginning to be administered more widely, ocular complications including RVO can develop and require attention.

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          First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland

          Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events. New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.
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            Bilateral superior ophthalmic vein thrombosis, ischaemic stroke, and immune thrombocytopenia after ChAdOx1 nCoV-19 vaccination

            A 55-year-old woman presented with conjunctival congestion, retro-orbital pain, and diplopia. She had received her first vaccine against SARS-CoV-2—ChAdOx1 nCoV-19—10 days before admission. Both on the night after the vaccination and 7 days later, the patient reported marked flu-like symptoms and a fever. She had no medical history of visual problems, autoimmune disorders, stroke, thrombosis, thrombocytopenia, neurological disorders, or arterial disease risk factors—including hypertension, diabetes, or smoking. On examination, she had binocular diplopia at vertical and right lateral gaze, and her visual acuity was 0·85 in both eyes. MRI showed superior ophthalmic vein thrombosis (SOVT) with no contrast filling (figure ) and bilateral high T2 signal intensity of the superior ophthalmic vein (figure). Figure SOVT and ischaemic stroke after ChAdOx1 nCoV-19 vaccination MRI shows SOVT with no contrast filling (arrows; A) and bilateral high T2 signal intensity of the superior ophthalmic vein (arrows; B). MRI shows an ischaemic stroke in the left parietal lobe, MCA territory, with restricted diffusion (C). Diagram shows the timeline of symptoms, MRI findings, dexamethasone treatment, and platelet count (D). FLS=flu-like symptoms. HP=hemiparesis. SOVT=superior ophthalmic vein thrombosis. MCA=middle cerebral artery. Laboratory investigations on admission showed a marked isolated thrombocytopenia of 30 × 109 per L (figure). IgG antiplatelet antibodies were positive, and IgM antiplatelet antibodies were borderline; a platelet suspension immunofluorescence test and a monoclonal antibody-specific immobilisation of platelet antigens assay were positive—supporting a diagnosis of secondary immune thrombocytopenia (ITP). IgG antibodies against platelet factor 4/polyanion complexes—tested using a lateral flow immunoassay, 4 days after starting heparinisation—were negative. Other possible causes of thrombocytopenia—including antiphospholipid syndrome, thrombotic microangiopathy, and hepatitis B virus and hepatitis C virus, HIV, cytomegalovirus, hantaviruses, and Helicobacter pylori infections—were excluded. Because we suspected ITP, intravenous dexamethasone 40 mg daily was given for 4 days which resulted in an increasing platelet count (figure). Despite the therapeutic heparinisation, 8 days after admission, the patient developed a transient, mild, right-sided hemiparesis, and aphasia. An MRI showed an ischaemic stroke in the left parietal lobe, middle cerebral artery territory, with restricted diffusion (figure), which had not been detected in the earlier scan. The patient then developed right-sided focal seizures which were controlled with levetiracetam and lacosamide; anticoagulation was switched to phenprocoumon, and 26 days after admission, she was allowed home. That 8, 10, and 18 days after the ChAdOx1 nCoV-19 vaccination, our previously healthy patient developed marked flu-like symptoms, two rare disorders—namely, bilateral SOVT and ITP, and an ischaemic stroke, may indicate a causal relationship. According to the European Medicines Agency review, March 18, health-care professionals should be on the alert for possible cases of thromboembolism—like cerebral venous sinus thrombosis, pulmonary embolus, and deep vein thrombosis—occurring in people who have recently received the ChAdOx1 nCoV-19 vaccine. The thrombotic events—including bilateral SOVT as seen in our patient—may occur in the context of thrombocytopenia (video). Declaration of interests We declare no competing interests.
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              Blood clots and bleeding events following BNT162b2 and ChAdOx1 nCoV-19 vaccine: An analysis of European data

              The involvement of viruses and SARS-CoV-2 in autoimmune diseases is well known. The recent demonstration that ChAdOx1 nCoV-19 Covid-19 (AstraZeneca) vaccine (ChA) favors the production of anti-platelet factor 4 (anti-PF4) antibodies, blood clots, and thrombocytopenia raises the question of whether other anti-CoViD-19 vaccines favor the same patterns of events. We assessed the frequency of severe adverse events (SAEs) documented in the EudraVigilance European database up to April 16, 2021 related to thrombocytopenia, bleeding, and blood clots in recipients of ChA compared to that of recipients of the BNT162b2 Covid-19 (Pfizer/BioNTech) vaccine (BNT). ChA administration was associated with a much higher frequency of SAEs in each AE Reaction Group as compared with that elicited by BNT. When considering AEs caused by thrombocytopenia, bleeding and blood clots, we observed 33 and 151 SAEs/1 million doses in BNT and ChA recipients, respectively. When considering patients with AEs related to cerebral/splanchnic venous thrombosis, and/or thrombocytopenia, we documented 4 and 30 SAEs and 0.4 and 4.8 deaths/1 million doses for BNT and ChA recipients, respectively. The highest risk following ChA vaccination is in young people and, likely, women of reproductive age, as suggested by hypothesized scenarios. In conclusion, the immune reaction promoted by ChA vaccine may lead to not only thrombocytopenia and cerebral/splanchnic venous thrombosis but also other thrombotic and thromboembolic SAEs. These events are not favored by BNT vaccine. Our study may help in the evaluation of the benefit/risk profile of the ChA vaccine considering the epidemic curve present in a country.
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                Author and article information

                Journal
                COP
                COP
                10.1159/issn.1663-2699
                Case Reports in Ophthalmology
                S. Karger AG
                1663-2699
                2022
                January – April 2022
                31 January 2022
                : 13
                : 1
                : 28-32
                Affiliations
                Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Japan
                Author information
                https://orcid.org/0000-0001-6512-7203
                Article
                521838 PMC8832183 Case Rep Ophthalmol 2022;13:28–32
                10.1159/000521838
                PMC8832183
                35221977
                62393b43-e297-4fee-b798-352d25beeb01
                © 2022 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 December 2021
                : 30 December 2021
                Page count
                Figures: 3, Pages: 5
                Categories
                Case Report

                Vision sciences,Ophthalmology & Optometry,Pathology
                Messenger RNA,Thrombosis,BNT162b2,Eye,Branch retinal vein occlusion,Coronavirus disease 2019

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