Central retinal artery occlusion following COVID-19 vaccine administration

Introduction Increased risk of thromboembolic events has been associated with SARS-CoV-2 infections and more recently, with COVID-19 vaccination. To date, however, there are no reports of an association between the COVID-19 vaccination and retinal artery occlusions. We report a case of a patient who developed central retinal artery occlusion (CRAO) 2 days following the administration of the AstraZeneca COVID-19 vaccine. Case description A 76-year-old woman presented to our Department of Ophthalmology complaining of painless vision loss in her left eye 48 hours after she had received her first dose of the AstraZeneca COVID-19 vaccine. Her best-corrected visual acuity was only hand movement in the left eye. Left eye ophthalmologic examination showed the presence of arterial narrowing and a cherry red spot. Optical coherence tomography showed severe macular swelling of the inner retinal layers in the left eye Fluorescein angiography performed the following day confirmed the diagnosis. The cardiovascular examination including Holter ECG was unremarkable. Complete blood count was within normal limits, without thrombocytopenia. A subsequent cerebral CT and CT-angiography scans did not show any other acute vascular event. Doppler angiography of the carotid artery was performed and showed normal flow without clinically significant plaques, stenoses, occlusions or dissections. Conclusions To our knowledge, this is the first case of an isolated CRAO following the administration of the AstraZeneca COVID-19 vaccine. Further studies are needed to evaluate this potential association and identify pathophysiologic relationships between COVID-19 vaccinations and CRAO.


Introduction
Increased risk of thromboembolic events has been associated with SARS-CoV-2 infections 1 and more recently, with COVID-19 vaccination. 2 In particular, several reports have studied the association between cerebral venous thrombosis and the vector-based AstraZeneca COVID-19 vaccine (Vaxzevria) administration. 2 To date, however, there are no reports of an association between the COVID-19 vaccination and retinal artery occlusions (RAO), which have unique characteristics and pathogenesis. 3 We report a case of a patient who developed central retinal artery occlusion (CRAO) 2 days following the administration of the AstraZeneca COVID-19 vaccine.

Case Description
A 76-year-old woman presented to our Department of Ophthalmology complaining of painless vision loss in her left eye 48 hours after she had received her first dose of the AstraZeneca COVID-19 vaccine. The patient was known to have hypothyroidism, but no previous history of cardiovascular disease, hypercoagulable state, malignancy or diabetes.
A nasopharyngeal swab (PCR test) on admission ruled out an ongoing COVID-19 infection. Her best-corrected visual acuity was 20/20 in the right eye, but only hand movement in the left eye. Left eye ophthalmologic examination showed a nonreactive mydriasis, and dilated fundus ophthalmoscopy revealed the presence of arterial narrowing and a cherry red spot with central retinal whitening. Optical coherence tomography showed severe macular swelling of the inner retinal layers in the left eye ( Fig. 1 A, B). Fluorescein angiography performed the following day confirmed the diagnosis of CRAO evident by a severe delay in the filling of the retinal arteries in the early arterial phase and an obscuring of the background choroidal fluorescence by retinal swelling in the late phase ( Fig. 2 A, B).
The patient was, therefore, admitted for inpatient management and was treated with:  (Table 1). A subsequent cerebral CT and CT-angiography scans did not show any other acute vascular event. Doppler angiography of the carotid artery was performed and showed normal flow without clinically significant plaques, stenoses, occlusions or dissections. Giant cell arteritis could be excluded by normal values of erythrocyte sedimentation rate (ESR 20, 70 mm/hr) and C-reactive protein (4.9 mg/ L.). In addition, patient had no headache, no temporal artery tenderness, and no decreased temporal artery pulse.

Discussion
RAOs are divided into arteritic, due to giant cell arteritis, and nonarteritic, in which thromboembolic events have been reported as potential mechanisms. 3 There is an overall higher incidence of cardiovascular risk factors in CRAO patients than in the age-matched control population. In some studies, cardiovascular risk factors were found in 78% of RVO patients. 4 More recently and over the past 12 months, COVID-19 infection has also emerged as a potential risk factor for CRAO due to the hypothesized activation of a prothrombotic vascular endothelial microenvironment and increased hypercoagulability. 5,6 In March 2021, 13 cases of sinus or cerebral venous thrombosis in association with the AstraZeneca vaccine were reported in Germany. Some of these cases showed features of heparin-induced thrombocytopenia (HIT)-like syndrome. 7 Furthermore, increased rates for venous thromboembolism were observed within 28 days of vaccination with   AstraZeneca in Denmark and Norway. 2 Smadja et al. assessed the phenotypes and the time frames of the thromboembolic events following the administration of three different COVID-19 vaccines, and reported that both venous and arterial thrombotic events were observed following various COVID-19 vaccines. In addition, they reported that whilst the time period between vaccination and arterial thrombotic events was comparable in all three vaccines (median 2 days), there was a significant difference in incidence time of the venous thrombotic events between AstraZeneca (median 6 days) and the two mRNA vaccines (median 4 days). 7 This may correlate with our patient having an arterial thrombotic event two days after vaccination.

Conclusions
To our knowledge, this is the first case of an isolated CRAO following the administration of the AstraZeneca COVID-19 vaccine. Further studies are needed to evaluate this potential association and identify pathophysiologic relationships between COVID-19 vaccinations and CRAO.

Patient consent
Consent to publish the case report was not obtained. This report does not contain any personal information that could lead to the identification of the patient.

Intellectual property
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Research ethics
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Funding
No funding was received for this work.

Authorship
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