New findings from a study published in the American Journal of Ophthalmology offer new insight into the risk and development of non-infectious uveitis (NUI) following the COVID-19 vaccination.
Let’s hear some background first.
According to the World Health Organization (WHO) a total of 69.8% of the global population has received at least one dose of a COVID-19 vaccine.
Among these vaccinations, ophthalmic-related adverse events have been reported including (but not limited to):
- Facial nerve palsy
- Acute macular neuroretinopathy
- Corneal graft rejection
- Uveitis
So why focus on just uveitis?
Per the study investigators, “Uveitis is one of the most commonly reported ocular complications following COVID-19 vaccination.”
Further, previous research identified nearly 300 cases of vaccine-associated uveitis (VAU) linked to other vaccines, including those for hepatitis B virus (HBV), human papillomavirus (HPV), and influenza.
And lastly, past research has also found more than half of COVID-19 VAU cases involved anterior uveitis—with various cases of non-anterior uveitis or inflammatory diseases also reported.
Gotcha. Now talk about this research.
Investigators conducted a national, population-based, retrospective cohort study using customized data from the Korean National Health Insurance Service (NHIS) of South Korea.
There were a reported 44 million individuals—98% of the country’s population—who received at least one COVID-19 vaccination between January 1, 2020, and March 31, 2022. This data originated from 7,806,919 recipients who were selected via random sampling.
Of that, an analysis was done on patients’ medical records from January 1, 2016, to March 31, 2022.
What kind of data was collected?
The medical record information included:
- Demographic data
- Inpatient and outpatient healthcare visits
- Prescription medications
- Diagnoses
- Procedures (if applicable)
And which vaccines were administered to these patients?
The study assessed data from patients who received one of four vaccines:
- BNT162b2 (Pfizer-BioNTech)
- mRNA-1273 (Moderna)
- ChAdOx1 (AstraZeneca)
- Ad26.COV2.S (Janssen Biotech)
Any exclusions to know about?
Investigators excluded patients with missing personal info, those previously diagnosed with uveitis and received corticosteroids as treatment (within 1 year of the study), non-verified vaccination dates, those with less than 60 days of follow-up, and those who were infected with COVID-19.
How many patients were actually assessed?
Patients with one vaccine were split into two groups:
- Exposed (n = 5,185,153) (mean age = 33.44)
- Unexposed (n = 2,680,164) (mean age = 54.15)
The exposed group was assessed based on the index date of their first vaccination (before or by August 31, 2021); the unexposed group’s index date was set for before their vaccination (March 1, 2021).
to note, the unexposed group patients all received their first dose after September 1, 2021.
For long?
Each group was observed for 180 days (from their respective index dates), with investigators collecting baseline characteristics (age, sex, demographic area, etc.) and ocular history.
And the goal?
To determine the cumulative incidence and risk of developing NIU after a COVID-19 vaccination (along with any relevant risk factors).
Now the findings.
Throughout the observation period, NIU events were observed in 0.29% of patients in the exposed group and 0.14% in the unexposed group.
Overall, the cumulative incidence of NIU—including total, anterior, and non-anterior—was higher in the exposed group (0.29%, 0.24%, and 0.04%, respectively) than in the unexposed group (0.14%, 0.13%, and 0.02%, respectively).
Go on …
Multivariable analysis (age, sex, hypertension, etc.) found COVID-19 vaccination to be associated with an elevated risk of non-anterior uveitis within the initial 60 days of observation as well as between 61 to 180 days following the index date:
- Within 60 days(early event: Hazard Ratio [HR] = 1.27, 95% Confidence Interval [CI]: 1.03–1.55)
- Between 61 and 180 days(delayed event: HR = 1.39, 95% CI: 1.20–1.62)
However, vaccination “did not demonstrate a correlation with an augmented risk of anterior uveitis or when considering the combination of anterior and non-anterior uveitis,” the study authors reported.
Did gender play a factor?
Yes, actually …
The female sex was associated with an increased risk for early and delayed non-anterior uveitis—(HR = 1.44, 95% CI: 1.08-1.92; HR = 1.78, 95% CI: 1.43–2.20, respectively)—but not for anterior or total uveitis.
The male sex was not associated with any increased risk for uveitis.
What about type of vaccine?
The highest cumulative incidence of uveitis (including total and anterior, from Day 0 to 180) was associated with the ChAdOx1 vaccine (AstraZeneca), followed by (in descending order):
- BNT162b2 (Pfizer-BioNTech)
- mRNA-1273 (Moderna)
- Ad26.COV2.S (Janssen Biotech)
Between days 61 to 180, all vaccines (save for Ad26.COV2.S) were associated with an elevated risk for non-anterior uveitis.
Limitations?
The study authors noted that a bias may be present in the exposed group, leading to significant differences between the two groups and the low incidence of non-anterior and anterior uveitis in the unexposed group.
Conclusions?
The study authors concluded that, based on their observations, there is an increase in the cumulative incidence of NIU up to 180 days following COVID-19 vaccination.
They stated: “The data suggest that vaccination tends to be more closely associated with a modest increase in non-anterior uveitis, as opposed to anterior or total uveitis.”
Further, with females having an increased risk for non-anterior uveitis, “previous NIU seemed to be the most significant risk factor.”