KeywordsAbbreviations: AZV (Astra Zeneca vaccine), BPV (Biontech Pfizere vaccine), JJV (Johnson and Johnson vaccine)

Letter to the Editor

We read with interest the review article by Su et al. about central retinal artery/vein occlusion following a SARS-CoV-2 vaccination.1Isolated and combined unilateral central retinal artery and vein occlusions after vaccination. A review of the literature. Altogether, six patients from 5 articles were retrieved as per the 10th January 2022 upon an appropriate search in the database PubMed.1Isolated and combined unilateral central retinal artery and vein occlusions after vaccination. A review of the literature. It was concluded that vaccine-related central retinal artery/vein occlusion is a rare complication of SARS-CoV-2 vaccination and that a temporal sequence does not establish a causal link.1Isolated and combined unilateral central retinal artery and vein occlusions after vaccination. A review of the literature. The study is attractive but raises concerns that should be discussed.

The design of the study does not allow drawing conclusions as presented. At maximum it can be concluded that SARS-CoV-2 vaccination related central retinal artery/vein occlusion is not frequently reported. However, it cannot be concluded that central retinal artery/vein occlusion is a rare complication of vaccinations. Studies with another design (prospective multi-center studies) are required to assess the actual frequency of central retinal artery/vein occlusion after vaccinations. Most likely, the actual frequency is higher as not each case is published.

Matching with this consideration, several other cases of vaccine-related occlusion of the central retinal artery/vein have been reported after the 10th January 2022. Chen et al. reported a 48yo female who developed sudden onset of inferior visual field defects in the left eye four weeks following the first dose of the ChAdOx1 (Astra Zeneca) vaccine (AZV).2Chen PJ Chang YS Lim CC Lee YK. Susac syndrome following COVID-19 vaccination: a case report. Romano et al. reported a 54yo female who developed central retinal vein occlusion 2 days after the second dose of the AZV.3Romano D Morescalchi F Romano V Semeraro F. COVID-19 adenoviral vector vaccine and central retinal vein occlusion. Retinal vein occlusion was also diagnosed in a 28yo male after the third AZV dose.4Dutta Majumder P Prakash VJ Retinal venous occlusion following COVID-19 vaccination: Report of a case after third dose and review of the literature. In a retrospective study evaluating data between May 1st and October 31st 2021, 14 patients with retinal vascular occlusions after COVID vaccinations were collected.5Vujosevic S Limoli C Romano S Vitale L Villani E Nucci P. Retinal vascular occlusion and SARS-CoV-2 vaccination. Two patients with retinal ischemic events after application of the Moderna vaccine (MOV) respectively the Johnson & Johnson vaccine (JJV) have been recently reported.6Priluck AZ Arevalo JF Pandit RR. Ischemic retinal events after COVID-19 vaccination. Kang et al. reported a 64yo male who experienced a branch retinal artery occlusion three days after the first dose of the Biontech Pfizer vaccine (BPV).7Case report: recanalization of branch retinal artery occlusion due to microthrombi following the first dose of SARS-CoV-2 mRNA vaccination. A 76yo female developed unilateral, painless visual loss 2 days after the first dose of the AZV.8Abdin AD Gärtner BC Seitz B. Central retinal artery occlusion following COVID-19 vaccine administration. Four patients experienced branch retinal artery occlusion 22.8 days on the average after the last vaccine dose application.9Ishibashi K Yatsuka H Haruta M Kimoto K Yoshida S Kubota T. Branch retinal artery occlusions, paracentralacute middle maculopathy and acute macular neuroretinopathy after COVID-19 vaccinations. In a study of 11 patients with visual complaints after SARS-CoV-2 vaccinations, 5 had retinal artery occlusion and four had retinal vein occlusion.10Silva LSCD Finamor LPS Andrade GC Lima LH Zett C Muccioli C Sarraf EP Marinho PM Peruchi J Oliveira RDL Giralt L Charcan I Fonollosa A Diaz JD Davis JL Nascimento H Belfort Jr., R Vascular retinal findings after COVID-19 vaccination in 11 cases: a coincidence or consequence?. Retinal arteriovenous occlusion was reported one day after the first dose of the AZV in a 77yo male.11Groselli S Gabka K Bechstein L Ulbig M. Retinaler arteriovenöser Gefäßverschluss nach COVID-Impfung mit Vaxzevria® (AstraZeneca) – Eine Impfkomplikation oder nicht? [Retinal arteriovenous vascular occlusion after COVID vaccination with Vaxzevria® (AstraZeneca)-A complication of vaccination or not?]. Two days after the second dose of the BPV a 38yo male developed branch retinal vein occlusion in the left eye.12Sugihara K Kono M Tanito M. Branch retinal vein occlusion after messenger RNA-based COVID-19 vaccine. A 34yo male presented with right retinal branch venous occlusion two days after the first BPV.13Pur DR Catherine Danielle Bursztyn LL Iordanous Y Branch retinal vein occlusion in a healthy young man following mRNA COVID-19 vaccination. Retinal vein occlusion has been also reported in 5 patients after the AZV (n=3) or the BPV (n=2) respectively.14Peters MC Cheng SSH Sharma A Moloney TP. Retinal vein occlusion following COVID-19 vaccination. Combined central retinal artery and vein occlusion together with ischemic optic neuropathy was reported in a 34yo male 10 days after the second BPV dose.15Lee S Sankhala KK Bose S Gallemore RP. Combined central retinal artery and vein occlusion with ischemic optic neuropathy after COVID-19 vaccination.The authors did not include several reports published before the 10th January 2022.16Shah PP Gelnick S Jonisch J Verma R. Central retinal vein occlusion following BNT162b2 (Pfizer-BioNTech)COVID-19 messenger RNA vaccine., 17Bolletta E Iannetta D Mastrofilippo V De Simone L Gozzi F Croci S Bonacini M Belloni L Zerbini A Adani C Fontana L Salvarani C Cimino L. Uveitis and other ocular complications following COVID-19 vaccination., 18Sonawane NJ Yadav D Kota AR Singh HV. Central retinal vein occlusion post-COVID-19 vaccination., 19Tanaka H Nagasato D Nakakura S Tanabe H Nagasawa T Wakuda H Imada Y Mitamura Y Tabuchi H. Exacerbation of branch retinal vein occlusion post SARS-CoV2 vaccination: Case reports., 20Sacconi R Simona F Forte P Querques G. Retinal vein occlusion following two doses of mRNA-1237 (Moderna) immunization for SARS-Cov-2: a case report., 21Ikegami Y Numaga J Okano N Fukuda S Yamamoto H Terada Y. Combined central retinal artery and vein occlusion shortly after mRNA-SARS-CoV-2 vaccination., 22Endo B Bahamon S Martínez-Pulgarín DF. Central retinal vein occlusion after mRNA SARS-CoV-2 vaccination: A case report., 23Bialasiewicz AA Farah-Diab MS Mebarki HT. Central retinal vein occlusion occurring immediately after 2nd dose of mRNA SARS-CoV-2 vaccine. It should be explained why these cases were not included in the review.No mention is made of Susac syndrome characterised by retinal vascular occlusions, cerebral micro-angiopathy and hypoacusis. Susac syndrome has not only been reported in association with SARS-CoV-2 vaccinations2Chen PJ Chang YS Lim CC Lee YK. Susac syndrome following COVID-19 vaccination: a case report. but also in a patient after smallpox vaccination.24Landa G Marcovich A Leiba H Springer A Bukelman A Pollack A. Multiple branch retinal arteriolar occlusions associated with smallpox vaccination.Hyper-viscosity syndrome (HVS) following SARS-CoV-2 vaccinations was not discussed as possibly pathophysiological mechanism explaining central retinal artery/vein occlusion.25Al-Kuraishy HM Al-Gareeb AI El-Bouseary MM Sonbol FI Batiha GE Hyperviscosity syndrome in COVID-19 and related vaccines: exploring of uncertainties. HVS is related to elevated levels of fibrinogen or immunoglobulins, to dehydration or exsiccosis, oxidative stress, or the inflammatory response to the vaccine.25Al-Kuraishy HM Al-Gareeb AI El-Bouseary MM Sonbol FI Batiha GE Hyperviscosity syndrome in COVID-19 and related vaccines: exploring of uncertainties.

Overall, the interesting study has some limitations that call the results and their interpretation into question. Clarifying these weaknesses would strengthen the conclusions and could improve the study. Retinal artery/vein occlusions following SARS-CoV-2 vaccinations is more common than anticipated.

Funding

no funding was received.

Author contribution

JF: design, literature search, discussion, first draft, critical comments, final approval.

Disclosures

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

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Clin Exp Med. : 1-10https://doi.org/10.1007/s10238-022-00836-xArticle InfoPublication History

Published online: June 26, 2022

Accepted: June 23, 2022

Received: June 11, 2022

Publication stageIn Press Corrected ProofIdentification

DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106617

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