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      Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection

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      Eye
      Nature Publishing Group UK
      Tomography, Infection

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          Abstract

          To the Editor: Ophthalmic complications of COVID-19 are predicted based on prior knowledge of other coronaviruses [1]. Conjunctivitis can be the presenting sign/symptom and its presence correlates with severity [2–4]. Cotton wool spots and retinal microhaemorrhages have also been reported [5]. We report two patients who presented with a new paracentral scotoma following SARS-CoV-2 infection. Patient 1: A 37-year-old Caucasian female in week 14 of an uncomplicated pregnancy presented with a 1-day history of abrupt onset, faintly colourful, left eye paracentral scotoma. This was 35 days following the onset of a febrile illness with cough and anosmia. SARS-CoV-2 nasopharyngeal swab was not performed during the infection, but subsequently positive serology (IgG) has been confirmed. Past medical history included acephalgic visual migraine aura and right toxoplasma chorioretinitis. Examination showed normal visual acuity, no uveitis and fundoscopy was normal in the left eye. OCT changes correlated with the location of the scotoma (Fig. 1). A focal area of hyper-reflective change in the inner and outer plexiform layers with inner nuclear layer volume loss was seen consistent with paracentral acute middle maculopathy (PAMM). Bloods were normal, including ESR, CRP, lipids, glucose, ANA and anti-phospholipid antibodies. An electrocardiogram and carotid Doppler ultrasound were normal. Fig. 1 Optical coherence tomography image from patient 1. Focal area of hyper-reflective change in the inner and outer plexiform layers with inner nuclear layer volume loss consistent with paracentral acute middle maculopathy. Patient 2: A 32-year-old Caucasian male presented with a 4-day history of abrupt onset, faintly colourful, right eye paracentral scotoma. This was 16 days following the onset of nasopharyngeal swab confirmed COVID-19. Past medical history included acephalgic visual migraine aura. Examination showed normal visual acuity, no uveitis and fundoscopy was normal. Changes on infrared reflectance (white arrow) and OCT correlated with the location of the scotoma (Fig. 2). A focal area of faint outer plexiform layer hyper-reflective change (black arrow) and disruption of the interdigitation zone (white box) were seen consistent with acute macular neuroretinopathy (AMN). Fig. 2 Infrared reflectance and optical coherence tomography images from patient 2. Focal area of IR change (white arrow) due to faint outer plexiform layer hyper-reflective change (black arrow) and disruption of the interdigitation zone (white box) on OCT consistent with acute macular neuroretinopathy. These patients developed PAMM and AMN soon after confirmed SARS-CoV-2 infection and possibly represent postinfectious complications. COVID-19 has been reported in association with acute limb ischaemia, stroke and the so called “paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection” [6–8]. PAMM and AMN have similar underlying pathophysiology. PAMM was first described as a variant of AMN [9], but they are now regarded as distinct conditions with overlapping features. PAMM OCT changes are seen in various retinal vascular diseases, such as retinal vein and artery occlusion. OCT angiography (OCT-A) has provided further support for a retinal vascular aetiology in PAMM and AMN [10–15]. Projection resolved OCT-A distinguishes the intermediate from the deep capillary plexus, which run either side of the inner nuclear layer. Using this technique, it has been shown that PAMM occurs in association with reduced flow in the intermediate, deep and occasionally the superficial capillary plexuses, whereas AMN occurs in association with reduced flow in the deep capillary plexus [15]. Finally, in a series of 101 AMN cases, an associated infection or febrile illness was reported in 47.5% [16]. This is the first report of PAMM/AMN following COVID-19. A larger case series is needed to determine if there is a true association.

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          Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

          To rapidly communicate information on the global clinical effort against Covid-19, the Journal has initiated a series of case reports that offer important teaching points or novel findings. The case reports should be viewed as observations rather than as recommendations for evaluation or treatment. In the interest of timeliness, these reports are evaluated by in-house editors, with peer review reserved for key points as needed. We report five cases of large-vessel stroke in patients younger than 50 years of age who presented to our health system in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all five patients. Cough, headache, and chills lasting 1 week developed in a previously healthy 33-year-old woman (Patient 1) (Table 1). She then had progressive dysarthria with both numbness and weakness in the left arm and left leg over a period of 28 hours. She delayed seeking emergency care because of fear of Covid-19. When she presented to the hospital, the score on the National Institutes of Health Stroke Scale (NIHSS) was 19 (scores range from 0 to 42, with higher numbers indicating greater stroke severity), and computed tomography (CT) and CT angiography showed a partial infarction of the right middle cerebral artery with a partially occlusive thrombus in the right carotid artery at the cervical bifurcation. Patchy ground-glass opacities in bilateral lung apices were seen on CT angiography, and testing to detect SARS-CoV-2 was positive. Antiplatelet therapy was initiated; it was subsequently switched to anticoagulation therapy. Stroke workup with echocardiography and magnetic resonance imaging of the head and neck did not reveal the source of the thrombus. Repeat CT angiography on hospital day 10 showed complete resolution of the thrombus, and the patient was discharged to a rehabilitation facility. Over a 2-week period from March 23 to April 7, 2020, a total of five patients (including the aforementioned patient) who were younger than 50 years of age presented with new-onset symptoms of large-vessel ischemic stroke. All five patients tested positive for Covid-19. By comparison, every 2 weeks over the previous 12 months, our service has treated, on average, 0.73 patients younger than 50 years of age with large-vessel stroke. On admission of the five patients, the mean NIHSS score was 17, consistent with severe large-vessel stroke. One patient had a history of stroke. Other pertinent clinical characteristics are summarized in Table 1. A retrospective study of data from the Covid-19 outbreak in Wuhan, China, showed that the incidence of stroke among hospitalized patients with Covid-19 was approximately 5%; the youngest patient in that series was 55 years of age. 1 Moreover, large-vessel stroke was reported in association with the 2004 SARS-CoV-1 outbreak in Singapore. 2 Coagulopathy and vascular endothelial dysfunction have been proposed as complications of Covid-19. 3 The association between large-vessel stroke and Covid-19 in young patients requires further investigation. Social distancing, isolation, and reluctance to present to the hospital may contribute to poor outcomes. Two patients in our series delayed calling an ambulance because they were concerned about going to a hospital during the pandemic.
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            Is Open Access

            Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China

            Key Points Question What are the ocular manifestations and conjunctival viral prevalence in patients from Hubei province, China, with coronavirus disease 2019 (COVID-19)? Findings In this case series including 38 patients with COVID-19, 12 patients had ocular manifestations, such as epiphora, conjunctival congestion, or chemosis, and these commonly occurred in patients with more severe systemic manifestations. Reverse transcriptase–polymerase chain reaction results were positive for severe acute respiratory syndrome coronavirus 2 in 28 nasopharyngeal swabs and 2 conjunctival swabs, and more significant changes in blood test values appeared in patients with ocular abnormalities. Meaning These data may assist ophthalmologists and others to understand the ocular manifestations of COVID-19, thus enhancing the diagnosis and prevention of the transmission of the disease.
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              Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals

              ABSTRACT In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there have been anecdotal reports of ocular infection. The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.
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                Author and article information

                Contributors
                jdvirgo@nhs.net
                Journal
                Eye (Lond)
                Eye (Lond)
                Eye
                Nature Publishing Group UK (London )
                0950-222X
                1476-5454
                3 July 2020
                : 1-2
                Affiliations
                [1 ]GRID grid.425213.3, Medical Eye Unit, St Thomas’ Hospital, ; London, SE1 7EH UK
                [2 ]GRID grid.425213.3, Medical Retina Department, , St Thomas’ Hospital, ; London, SE1 7EH UK
                Author information
                http://orcid.org/0000-0002-9335-2261
                Article
                1069
                10.1038/s41433-020-1069-8
                7333786
                32620843
                91aa9b36-9d43-4303-bed7-a88aadf65b7b
                © The Royal College of Ophthalmologists 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 12 June 2020
                : 18 June 2020
                : 23 June 2020
                Categories
                Correspondence

                Vision sciences
                tomography,infection
                Vision sciences
                tomography, infection

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