Chapter 1: Overview of the Study

A recent study published in the esteemed journal NPJ Vaccines has raised eyebrows regarding the safety of mRNA vaccines. The research, titled "Risk assessment of retinal vascular occlusion after COVID-19 vaccination," analyzed data from over 6 million patients and revealed a 2.19-fold increased risk of retinal vascular occlusion (RVO) in vaccinated individuals compared to those who were not vaccinated.

Retinal vascular occlusion, a leading cause of vision impairment, occurs when blood vessels in the eye become blocked due to various factors, including vascular inflammation, damaged vessel walls, or blood clots. Common risk factors include diabetes, hypertension, obesity, and cardiovascular diseases. This raises a significant question: Is this study a legitimate concern regarding the safety of COVID-19 vaccines, or is it merely overblown? The answer is not straightforward, as it relies on one's interpretation of the findings. However, it is crucial to note that this study does not indicate widespread cases of blindness caused by mRNA vaccines.

Last month, several commentators highlighted that some readers might misinterpret the study if they don't read to the conclusion. Therefore, it is essential to clarify the article’s main takeaway.

Chapter 2: Study Methodology and Findings

Li et al., a group of researchers from Taiwan and the U.S., utilized the TriNetX network database, which holds extensive medical records from over 90 million people in the U.S. After excluding individuals under 18, those with a history of RVO in the past six months, patients who were prescribed specific medications four weeks prior, and those with a history of COVID-19, the researchers were left with 745,041 vaccinated individuals and 3,874,458 unvaccinated individuals.

They then matched 739,066 vaccinated individuals to unvaccinated individuals in a 1:1 ratio, ensuring that both groups were similar in terms of age, sex, and other baseline characteristics. This matching process aimed to ensure that any observed outcomes were due to vaccination rather than other confounding factors.

The study yielded two main results:

1. The vaccinated group exhibited a 3.54-fold and 2.19-fold higher risk of RVO compared to the unvaccinated group at 12 weeks and 2 years of follow-up, respectively. This association remained significant across all RVO subtypes, unaffected by factors like age, sex, or race.
2. Subgroup analyses revealed that the risk of RVO increased significantly after both the first and second doses of Pfizer's or Moderna's mRNA vaccines over a two-year follow-up. However, no significant association was found with the Johnson & Johnson vaccine.

Chapter 3: Understanding the Mechanisms

Despite the alarming findings, the underlying mechanisms linking mRNA vaccines to RVO are not well understood. Li et al. speculate that the mechanism might resemble vaccine-induced thrombotic thrombocytopenia (VITT), which involves the activation of platelet factor 4 (PF4) by the vaccine. This theory is plausible, given that both RVO and VITT are vascular complications. However, VITT has primarily been associated with AstraZeneca and Johnson & Johnson vaccines, not mRNA types.

Several large cohort studies have reported no significant risk of thrombotic or thrombocytopenic events from mRNA vaccines. Therefore, the biological basis for the association between RVO and mRNA vaccination remains unclear, casting doubt on the validity of the findings.

Chapter 4: Potential Confounding Factors

If the mechanistic basis is uncertain, one must consider other factors that could explain the observed increase in RVO risk among vaccinated individuals. One potential issue is unmeasured confounding, which refers to variables not accounted for in the study that might influence the results.

A known example is the "healthy vaccinee bias," where healthier individuals are more likely to receive vaccinations. Conversely, those with health issues may delay vaccination until their condition improves. This could lead to a vaccinated population that is generally healthier, potentially skewing the results.

Li et al. acknowledged this limitation, stating that while they accounted for multiple confounding variables, residual confounding might still exist, affecting the results. This limitation highlights the need for caution when interpreting observational studies, which cannot definitively establish cause-and-effect relationships.

Chapter 5: Examining Effect Size

It is also possible that the observed association is genuine, indicating that mRNA vaccines may elevate the risk of RVO. This hypothesis gains support from another significant study conducted by Dorney et al., published in JAMA Ophthalmology, which found a 2.25-fold increased risk of RVO following the second dose of the mRNA vaccine compared to the first dose.

Both studies utilized the TriNetX database, suggesting they could be viewed as part of a single dataset. However, Dorney et al. found no difference in RVO risk among individuals receiving the first dose of the mRNA vaccine compared to those receiving other vaccines. This inconsistency raises questions about the validity of the findings and merits further investigation.

When examining the effect sizes, Li et al.'s study identified substantial risk increases. However, the absolute numbers indicate that only a small percentage of vaccinated individuals developed RVO, leading to the conclusion that the risk may not be as significant as it appears.

To summarize, both studies suggest that one excess case of RVO may occur for every 13,150 vaccinated individuals, a relatively small risk when weighed against the benefits of vaccination.

Chapter 6: Conclusion

In conclusion, the potential risk of RVO following mRNA vaccination must be evaluated against the substantial benefits of vaccination, particularly in preventing severe COVID-19 and its long-term complications. While emerging data indicates a possible risk of RVO associated with mRNA vaccines, the limitations of the studies and the lack of a clear mechanistic understanding make it premature to draw definitive conclusions.

Ultimately, even if a connection exists between mRNA vaccines and RVO, the overall risk appears minimal compared to the benefits of vaccination, especially for populations vulnerable to severe COVID-19 outcomes.

Thank you for reading. If you found this information valuable, consider subscribing to my Medium email list. You can also support my work through my referral link for unlimited access to Medium or by tipping me directly. Your support is greatly appreciated!