Retinal vascular occlusions in COVID-19 infection and vaccination: a literature review

Graefe's Archive for Clinical and Experimental Ophthalmology https://doi.org/10.1007/s00417-022-05953-7 MINI REVIEW Retinal vascular occlusions in COVID‑19 infection and vaccination: a literature review Suji Yeo1 · Hanju Kim2 · Jiwon Lee2 · Jeonghyun Yi2 · Yoo‑Ri Chung1 Received: 28 July 2022 / Revised: 8 December 2022 / Accepted: 21 December 2022 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023 Abstract Purpose Abnormal hypercoagulability and increased thromboembolic risk are common in patients with coronavirus disease (COVID-19). COVID-19 has been suggested to cause retinal vascular damage, with several studies on COVID-19 patients with retinal vascular occlusions. We reviewed and investigated studies on retinal vascular occlusions in patients diagnosed with COVID-19 and in those vaccinated for COVID-19. Methods Studies that reported retinal vascular occlusion in COVID-19 patients or in vaccinated people were identified using the terms “retinal occlusion,” together with “severe acute respiratory syndrome coronavirus 2”, “SARS-CoV-2,” “COVID-19,” “coronavirus,” and “vaccine,” through systematic searches of PubMed and Google Scholar databases until January 7, 2022. Results Thirteen cases of retinal artery occlusion (RAO) and 14 cases of retinal vein occlusion (RVO) were identified among patients diagnosed with COVID-19. Half of the patients with RAO or RVO revealed no systemic disorders except current or past COVID-19, and ocular symptoms were the initial presentation in five cases. Among patients with RAO, most presented with central RAO at 1–14 days of COVID-19 diagnosis, with abnormal coagulation and inflammatory markers. Among those with RVO, two-thirds presented with central RVO and one-third with RVO. Eleven cases with acute macular neuroretinopathy (AMN) and/or paracentral acute middle maculopathy (PAMM) were reported among patients with COVID-19, presenting scotoma resolved spontaneously in most cases. Among the 26 cases vaccinated with either mRNA or adenoviral vector vaccines for COVID-19 and presenting retinal vascular occlusions, there were more RVO cases than RAO cases, and ocular symptoms mostly occurred within 3 weeks after vaccination. One case presented bilateral AMN and PAMM after COVID-19 vaccination. Conclusion Retinal vascular occlusions might be a manifestation of COVID-19, although rare, especially in patients at risk of systemic hypercoagulability and thromboembolism. For COVID-19 vaccines, the causal relationship is controversial because there are few case reports of retinal vascular occlusions after COVID-19 vaccination. Keywords Coronavirus · COVID-19 · Retinal artery occlusion · Retinal vein occlusion · Vaccine Key messages Central retinal artery/vein occlusions are a frequent type of retinal vascular occlusion in patients with COVID-19. Retinal vascular occlusions might be one of the clinical manifestations of COVID-19, especially in patients at risk of systemic hypercoagulability and thromboembolism. There are only few case reports of retinal vascular occlusions associated with COVID-19 vaccination; therefore, the causality remains unknown. * Yoo‑Ri Chung Extended author information available on the last page of the article 13 Vol.:(0123456789) Graefe's Archive for Clinical and Experimental Ophthalmology Introduction A novel coronavirus was detected during an outbreak of pneumonia of unknown etiology in late 2019 in Wuhan, Hubei Province, China [1]. It is now officially known as severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and is responsible for the ongoing global pandemic [2]. Patients with coronavirus disease (COVID-19) caused by SARS-CoV-2 present with various systemic symptoms, including fever, cough, fatigue, breathing difficulties, and loss of smell and taste [2]. Besides respiratory symptoms, patients may also present with cardiovascular disorders including ischemic/inflammatory heart disease, arrhythmia, and thrombotic events [3]. Although relatively less involved, the nervous and gastrointestinal systems are also affected in COVID-19 [4, 5]. Meanwhile, important procoagulant mechanisms appear to be upregulated in COVID-19, leading to significant thrombotic complications [6, 7]. SARS-CoV-2 has distinctive spike proteins that show a higher affinity for the angiotensin-converting enzyme 2 (ACE2) receptor of host target cells [8]. This augments angiotensin II signaling and triggers the release of proinflammatory cytokines in the neighboring endothelia [8]. The prothrombotic pathway is also stimulated to lead to thrombotic angiopathy in multiple organs, including the lungs, legs, heart, and brain [6]. The most common thromboembolic complications are pulmonary thromboembolism and deep vein thrombosis, while the risk of venous thromboembolism remains high despite anticoagulation prophylaxis in COVID-19 [6]. Furthermore, vaccine-related side effects are of significant concern when associated with thromboembolism or thrombocytopenia [9]. Ocular manifestations have also been reported in patients admitted for treatment of COVID-19 [10, 11]. The prevalence of ocular manifestations is estimated to be 11%, with symptoms such as dry eye or foreign body sensation, redness, tearing, ocular pain, and discharge [11]. The involvement of the external eye is more common, presenting as follicular or pseudomembranous conjunctivitis, keratoconjunctivitis, and episcleritis [10]. There have also been reports of visual disturbances and ocular inflammation after COVID-19 vaccination [12]. Similar to the ocular manifestations reported with COVID-19 infection, most descriptions with COVID-19 vaccines are case reports with symptoms such as photophobia and blurred vision [12]. The retina, a highly vascularized tissue, is prone to thromboembolic disorders. Although less than external eye involvement, there have also been reports of manifestations in the posterior segment of the eyes of COVID-19 patients, especially in the retina. A report based on 12 13 patients diagnosed with COVID-19 revealed cotton wool spots and retinal hemorrhages on fundus examination and hyperreflective bands on optical coherence tomography (OCT) [13], although controversy remains as these findings can be identified in various disorders [14]. Retinal vascular occlusions have also been reported following COVID-19 vaccination, but their causality remains unclear [15, 16]. Retinal vascular occlusion is a common disorder that causes severe visual impairment and is associated with risk factors such as hypercoagulability and thrombotic disorders. In this review, we focus on retinal occlusive disorders, including retinal artery occlusions (RAO) and retinal vein occlusions (RVO), reported with COVID-19 infection and vaccines, and discuss the associated pathophysiologic mechanisms. Methods PubMed, Google Scholar, and Cochrane databases were last searched on January 7, 2022, using keywords such as “retinal occlusion,” (...truncated)