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Abstract
The aim of this paper is to inform on the surge of cases of acute macular neuroretinopathy
(AMN) – a rare disease characterized by the sudden onset of acute scotomas caused
by ischemia of the retinal capillary plexus – during the COVID-19 pandemic. In 2021,
during the COVID-19 pandemic, a sudden rise in patients with AMN was observed in our
clinic. In this paper, 4 cases from a hospital in the south of the Netherlands are
reported, all of which could directly be linked to a COVID-19 infection or vaccination
against the corona virus. A search for similar cases in the PubMed database produced
thirteen relevant reports, which revealed that a similar increase in cases of AMN,
all linked to COVID-19, has been observed worldwide. Analysis of the literature revealed
that AMN is seen more often during the pandemic and that AMN after COVID-19 happens
at a significantly older age than typically reported. This is the largest case series
of patients with AMN after COVID-19 infection or vaccination. With the ongoing pandemic
and extensive vaccination programs, it is expected that cases of AMN will surge. It
is important for ophthalmologists to be aware of this disease, especially since typical
patient characteristics may differ.
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.
Purpose We report a case of acute macular neuroretinopathy (AMN) following routine annual inactivated influenza vaccination. Projection-resolved optical coherence tomography angiography (PR-OCTA) was used to analyze the retinal capillary flow within the AMN lesion. Observations Our patient reported visual symptoms of her right eye nine days after routine annual influenza vaccination. Multimodal imaging revealed small vessel peripheral vasculitis and AMN in the affected eye. Infectious, immunologic, and hypercoagulable etiologies were investigated and excluded. PR-OCTA B-scans within the AMN lesion demonstrated reduced flow in the deep capillary plexus (DCP) at baseline with relatively improved flow signal in the DCP on follow up, 3 weeks later. Conclusions and importance We report a new association of AMN following routine inactivated influenza immunization. Recent influenza vaccination should be included in the differential diagnosis for patients presenting with AMN. PR-OCTA demonstrated compromised DCP flow in the AMN lesion which has not been previously described.
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