Reported ocular adverse events with three COVID‐19 vaccines

Editor: R ecent anecdotal reports have alluded to the risk of potential ocular adverse events with various COVID-19 vaccines. Although ocular adverse events including conjunctivitis have been reported in patients with COVD-19 (Cheema et al. 2020, Ozturker 2021), data on ocular adverse events related to the different COVID19 vaccines are scant. In one of the randomized trials of mRNA-1273 SARS-CoV-2 vaccine (Baden et al. 2021) (Moderna), the risk of allergic conjunctivitis was reported as less than 0.1% (Baden et al. 2021). However randomized trials are often not powered to detect rare adverse events and to date, data on ocular adverse events with COVID-19 vaccines have not been systematically quantified. To better quantify ocular adverse events associated with COVID-19 vaccines, we undertook a disproportionality analysis (DA). DA is a signal detection tool often used by drug regulatory agencies to detect safety signals with prescriptions drugs. This approach compares the reported adverse event of interest with a drug or vaccine under question to the same events with all other drugs. A reported measure of effect such as the reported odds ratio (ROR) is computed for signal quantification. We sought individual ocular adverse events and corresponding RORs (and 95% confidence intervals) for ocular adverse events with the three COVID-19 vaccines (BNT162b2 mRNA vaccine (Pfizer-BioNTech), mRNA-1273 SARS-CoV-2 vaccine (Moderna) and ChAdOx1 nCoV-19 vaccine (AstraZeneca) from VigiBase, the World Health Organization (WHO) global database of individual case safety reports (ICSRs). RORs for the influenza vaccine were also ascertained to be used as a control vaccine. Specifically, RORs for the following events were sought: conjunctival haemorrhage, eye haemorrhage, eye swelling (composite end point of either periorbital oedema, periorbital swelling or eye swelling), eye pain, blurred vision, increased ocular pressure and visual impairment. All RORs are presented in Table 1. A signal was defined as an OR of greater than 1.00. All four vaccines showed a signal for eye pain with AstraZeneca being the highest (OR = 4.99, 95% CI: 4.83–5.15) (Table 1). The AstraZeneca vaccine also showed a signal for conjunctival haemorrhage (OR = 2.60, 95% CI: 2.26– 2.99) and blurred vision (OR = 1.71, 95% CI: 1.65–1.77). For Moderna, a signal was also detected for blurred vision (OR = 1.26, 95% CI: 1.18–1.34) and eye swelling (OR = 1.12, 95% CI: 1.04–1.21). The Pfizer-BioNTech vaccine showed a signal for conjunctival haemorrhage (OR = 1.92, 95% CI: 1.62–2.27) and blurred vision (OR = 1.28, 95% CI: 1.23–1.34). Eye pain appears to be associated with all four vaccines which might suggest an immune response common to all vaccines which might not be specific to a particular type of vaccine (Joachim et al. 2013). Indication of a signal does not necessarily indicate a causal link as these associations should be further investigated in well-designed pharmacoepidemiologic studies. Moreover, reported cases might represent an under estimation of the true risk for these events. Finally, disproportionality analysis is a signal detection analysis and does not show a causal link, thus highlighting a need for future large welldesigned epidemiological studies. Previous studies have shown ocular adverse events with the influenza vaccine which are either inactivated or live-attenuated vaccines (Jun & Fraunfelder 2017). More research is needed to examine the incidence and the type of ocular adverse events with the newer mRNA or adenovirus-based vaccines.