FormalPara Key Summary Points

We detail the case of a patient who had a hemispheric retinal vein occlusion 48 hours after receiving a second dose of the mRNA-1237 vaccine.

Published data on possible ocular adverse events potentially associated with SARS-Cov-2 mRNA-1237 vaccination are scarce.

SARS-Cov-2 mRNA-1237 vaccination should be considered to be the most likely explanation for the hemispheric retinal vein occlusion in our patient.

Introduction

Numerous case reports and studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have revealed the retinal manifestations of the disease, which include arterial and venous thrombosis associated with macular edema (ME), haemorrhages, microvascular alterations and acute macular neuroretinopathy [1,2,3,4,5]. In addition, SARS-CoV-2 viral particles were reported to be present in human retina specimens from deceased patients infected with the disease [6, 7]. However, it is unclear whether the reported findings are incidental, the result of systemic action of the virus or from direct retinal toxicity [8].

The introduction of liposome-encapsulated recombinant mRNA encoding the SARS-CoV-2 spike protein, i.e. the mRNA-1273 vaccine, has opened the way for primary prevention of the disease [9]. The remarkable efficacy of the vaccines based on these principles has been proven by the rarity of life-threatening adverse events and excellent safety profile.

Here, in the context of documenting all possible adverse events associated with SARS-CoV-2 vaccination, we present the case of unilateral hemispheric retinal vein occlusion potentially associated with vaccination with the second dose of the SARS-Cov-2 mRNA-1237 vaccine [10], in a patient receiving oral anticoagulant therapy for atrial fibrillation.

The study protocol complied with the tenets of the Declaration of Helsinki of 1964 and its later amendments. Informed consent was obtained from the patient for her case to be presented and discussed.

Observations

A 74-year-old woman presented with a painless vision loss in the right eye experienced 48 hours after receiving the second dose of the mRNA-1237 vaccine. Additional systemic symptoms included severe arthralgia, chills and swelling.

The patient denied any previous history of SARS-CoV2 infection, diabetes mellitus or poor glycemic control, blood hypertension and glaucoma. Past medical history was remarkable for breast cancer successfully treated with surgery and postoperative locoregional radiotherapy in 2017 achieving complete remission, and for current atrial fibrillation (AF) with a ventricular rate of 90 beats per minute (NYHA class II) that was managed with metoprolol 50 mg per day and oral anticoagulation with rivaroxaban 20 mg per day. The patient is a non-smoker, and the body mass index was within normal limits. The patient received the first vaccine dose without noteworthy side effects and completed the vaccination schedule after 4 weeks.

At presentation, the best-corrected visual acuity (BCVA) was 20/32 in the right eye. Ophthalmic examination, including fundus examination and structural optical coherence tomography (OCT), was performed. Ultra-wide field multicolour examination showed venous congestion and widespread blot haemorrhages in the inferior quadrants (Fig. 1a). Structural OCT revealed thickening of the occluded area (Fig. 1b). Based on these findings, the diagnosis of hemispheric retinal vein occlusion (RVO) was made. The fellow-eye was unremarkable. Intraocular pressure (IOP) and blood pressure (BP) were within normal range. No additional antithrombotic medication was administered since the patient was already receiving oral anticoagulation therapy. No additional laboratory/functional tests were performed at this point because the patient was under frequent supervision by her physician.

Fig. 1
figure 1

Baseline ultra-wide field multicolour image and structural optical coherence tomography (OCT) of the right eye. a Ultra-wide field multicolour examination showing venous congestion and widespread blot haemorrhages in the inferior quadrants. b Infrared reflectance and horizontal structural OCT passing through the fovea showing thickening of retinal layers nasally to the fovea

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At the 3-week follow-up, BCVA declined to 20/40 and structural OCT revealed the presence of cystoid ME with intraretinal fluid. No treatment was performed and fluorescein angiography (FA) was planned. At the 5-week examination, FA was performed, showing delayed vein filling, masking effect from intraretinal haemorrhages and vascular leakage in the inferior quadrants (Fig. 2). Structural OCT examination showed the extension of ME involving a large serous retinal detachment with intraretinal cysts (Fig. 2). This examination revealed disturbance in the platelet count, with a platelet count of 144 × 109/L. The patient was treated with two injections of intravitreal ranibizumab, which led to functional improvement of BCVA to 20/32 and regression of ME.

Fig. 2
figure 2

Baseline ultra-wide field multicolor image and structural OCT of the right eye. a Fundus photography showing the persistence of venous congestion and widespread blot haemorrhages in the inferior quadrants. b, c Early (36 s) and late (5 min and 10 s) phases of fluorescein angiography showing delayed vein filling, masking effect from intraretinal haemorrhages and vascular leakage in the inferior quadrants. d Infrared reflectance horizontal structural OCT passing through the fovea showing the presence of macular edema involving the fovea with a subfoveal neuroretinal detachment

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Discussion

Retinal vein occlusion is commonly associated with hypercoagulable states, hypertension, open-angle glaucoma, diabetes mellitus and a history of cardiovascular disease [11, 12]. The treatment of ME secondary to RVO is mainly based on repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections [13,14,15].

Here we report a case of retinal vein occlusion potentially associated with receiving the second dose of the mRNA-1237 vaccine, noting that our patient was currently receiving anticoagulant therapy for AF. Although a causal connection between the two events cannot be proven definitely, it should be noted that this was the first thrombotic episode experienced by our patient. Clinical assessment was not suggestive of alternative triggering causes for venous occlusion or underlying disease exhibiting thrombogenicity [16]. It was not possible to obtain a rivaroxaban-calibrated drug level, which is not performed routinely, but the patient claimed to adhere diligently to the prescribed therapeutic regimen.

Retinal vein occlusion has been reported earlier in a patient who received the BNT162b2 BioNTech/Pfizer vaccine [17] and has been declared an adverse event for mRNA vaccines on 37 occasions, as registered in the Global Database for Individual Case Safety Reports (VigiBase), an open-label databank provided by World Health Organization.

It has been well elucidated how vein thrombosis in unusual sites and thrombocytopenia may be adverse events associated with adenoviral vector vaccines [18]. Vaccine-induced thrombotic thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4) has been put forward to explain the pathogenesis of this condition [19]. These findings although anecdotal would provide an explanation of the possible—albeit extremely low−incidence associated with mRNA vaccines, namely PF4 antibodies can also occur after mRNA vaccination but are of minor clinical relevance in this group [20, 21].

In our case, we were not able to record a platelet count in the acute setting and, consequently, to determine the eventual timing of platelet nadir and recovery. However, a mild thrombocytopenia (i.e. 144 × 109/L) was observed 9 weeks after the vaccination. This finding is consistent with previous reports [22]. Additionally, differentiating between a vaccine-induced or coincidental thrombocytopenia in these patients can be challenging [22].

In conclusion, we report a case of retinal vein occlusion 48 hours after vaccination with the SARS-Cov-2 mRNA-1237 vaccine, but note that the relationship between these two events is unclear. In light of the global promotion of the third dose of mRNA-based vaccinations, further research is warranted to better document and understand the potential pathogenic link between retinal vascular events and vaccination. Finally, we speculate that patients with cardiovascular diseases (i.e. high-risk group) should be investigated in more detail before being vaccinated with SARS-Cov-2 vaccines.