Association between Vaccination with

the BNT162b2 mRNA Coronavirus

Disease 2019 Vaccine and
Noninfectious Uveitis
Here is where this template begins
Prevention and treatment of coronavirus disease 2019 (COVID-
19)  leading issue in current global health care

BNT162b2 mRNA vaccine

• high efficacy in preventing severe acute respiratory syndrome coronavirus
2 infection, hospitalization, and related death

Safety profile
Good
↓
some increased risk of incident systemic
complications
↓
varicella zoster infection, lymphadenopathy, Guillain–Barré
syndrome, and myocarditis
Previous associations between vaccines and ocular complications

• Acute macular neuroretinopathy

• Central serous retinopathy

• Corneal graft rejection

• Cranial nerve palsies

• Particularly incident of uveitis

• Relapses of uveitis

Most uveitis cases

• Related to anterior uveitis

• Several reports  multiple evanescent white dot syndrome, Vogt–Koyanagi–Harada syndrome,
idiopathic panuveitis
 Previous reports This Study

◌ vaccine is related to temporal proximity large, population-based database of

◌ developed between 1 and 30 days after receiving individuals who received the BNT162b2
a vaccine dose vaccine

compared the rates of active

remains unclear noninfectious uveitis (NIU) requiring
treatment

◌ increase in the incidence of uveitis

◌ any populations are at higher risk. with rates both before and after the
COVID-19 pandemic
Methods
Study Design and Ethics Periods

Cohort Study (1) 2019 before the COVID-19 pandemic and

with a nonconcurrent historic vaccine introduction in Israel
comparative group (2) 2020 during the COVID-19 pandemic but before
introduction of the vaccine.
Participants

all patients who received at least 1 dose of Active NIU

the BNT162b2 vaccine.
December 20, 2020 ~ April 30, 2021.
Medical Record Documented a Diagnosis of NIU
CONFIRMED
an ophthalmic examination by ophthalmologist  newly
active or worsening inflammation and local or systemic
corticosteroids were initiated or increased

EXCLUSION CRITERIA

 not documented by an ophthalmologist

 full ophthalmic examination was not performed
 no signs of active inflammation were documented
 medical history of any infectious uveitis
 local or systemic corticosteroids were not initiated or increased.
 Additional variables Statistical Analysis

• Vaccine-related event 
time (days) after
A Observed cases after the first vaccine dose
vaccination
• Anatomic site of
inflammation December 20, 2020, and April 30, 2021
• Best-corrected visual
Observed cases after the second vaccine dose
acuity (BCVA)
0 B
• Uveitis definition
January 10, 2021, , and April 30, 2021

Standardized incidence ratios Attributable risk (AR) fraction among vaccinated

• (SIR – 1) / SIR
Poisson-based 95% confidence intervals (CIs).
• AR for 100 000 vaccinees  multiplying the risk
after each vaccine dose by the AR fraction

Cumulative incidence by time from vaccine dose

Kaplan–Meier method.
Results
2.602.557 people 2.441.719 people
2nd dose vaccine
average age of 46.8 ±
between January 10, 2021,
19.6 years and April 30, 2021

1st Dose of
BNT162b2 mRNA Previous diagnosis of NIU
COVID-19
Between December 20, 1st dose  18 236 people (0.7%)
2020, and April 30, 2021 2nd dose  17 250 people (0.7%)
 Noninfectious Uveitis after Vaccination

1st dose & 2nd

dose
↓
21-day overall
risk
↓
3.85 and 3.61
per 100.000 vaccinated

Standardized Incidence Ratios of Active Noninfectious Uveitis after First or

Second Vaccine Dose Stratified by Sex and Age Groups Using 2019 as the
Reference Population
 1st dose & 2nd dose
↓
median time to active NIU
↓
8.5 days and 10 days
↓
68 events (68.0%) and
59 events (67.0%)
↓
during the first 14 days

The cumulative incidence of active noninfectious uveitis by

dose.
 Comparison with Historical Cohorts
Incidence Rates of Active Noninfectious Uveitis after the First and
Second Vaccine Dose and in Reference Populations (2019 and 2020)

1st dose & 2nd dose

1st dose & 2nd dose ↓
↓ corresponding rate in the reference
overall incidence rate of active NIU population
↓ ↓
66.8 cases and 62.7 cases 45.7 cases and 45.1 cases
per 100.000 vaccinated
per 100.000 person  years 2020
 2019 data
↓ 1st dose & 2nd dose
1st dose & 2nd dose ↓
↓ AR
age- and sex-adjusted ↓
SIRs 1.12 events and 0.86 events
↓ per 100 000 vaccinees
1.41 and 1.31

Stratified analysis After 2nd dose After 2nd dose

↓ ↓ ↓
Male & Female Male Female
↓ ↓ ↓
Age-adjusted SIRs Age-adjusted SIRs Age-adjusted SIRs
1.48 and 1.35 1.46 1.46
↓ ↓ ↓
AR AR AR
1.16 and 1.07 1.13 1.13
per 100 000 vaccinees per 100 000 vaccinees
per 100 000 vaccinees
Subgroup Analysis by Past History of Uveitis

Adjusted Standardized Incidence Ratios of Active Noninfectious Uveitis after First

or Second Vaccine Dose Stratified by Past History of Uveitis Using 2019 as the
Reference Population
 1st dose & 2nd dose
↓
1st dose & 2nd dose 1st dose & 2nd dose
Age-adjusted SIRs for new-onset
↓ ↓
NIU
overall risk of new-onset NIU AR
1.3 and 1.57
↓ ↓
↓
1.63 and 1.98 events 1.12 events and 0.86 events
per 100.000 vaccinated per 100 000 vaccinees corresponding Ars
0.38 and 0.72
per 100 000 vaccinees

After 1st dose After 2nd dose

1st dose & 2nd dose 1st dose & 2nd dose
↓ ↓
↓ ↓
age- and sex- age- and sex-
no history of uveitis history of uveitis
adjusted SIR for adjusted SIR for
median time to active median time to active
NIU relapse 1.58 NIU relapse 1.16
NIU NIU
↓ ↓
↓ ↓
AR AR
8.5 days & 11 days 8.5 days & 10 days
116.94 31.27 per 100.000 vaccinated per 100.000 vaccinated
per 100 000 vaccinees per 100 000 vaccinees
 Clinical Characteristics of Active NIU after
Vaccination

● BCVA = best-corrected visual acuity; logMAR = logarithm of the minimum angle of

resolution.
Discussion
 BNT162b2 mRNA COVID-19
vaccine

Highly effective in preventing

• Severe infection with sars-cov-2
• Hospitalizations
• reduces morbidity rates

Possible systemic adverse effects

At ocular morbidity
 Current Reports  BNT162b2 mRNA COVID-19
• New onset or relapse of uveitis
vaccine
• Reactivations of herpes-related uveitis
• New episodes of NIU
occurrence within 30 days
after vaccination 1
Disparities in the findings of the 2 studies
2 population size, definition of active uveitis, and inclusion of people

Populations and results

not comparable 3
Our results
4 incidence of active NIU and the BNT162b2 vaccine compared with 2019 and 2020, with a
small AR  risk is outweighed by the impact of the vaccine
 Vaccines And Uveitis
patients with NIU are treated with immunosuppression
drugs  efficacy of the vaccine and potential disease
reactivation

increased incidence of active

o Overall AR  1 case/ 1000 vaccinated people
NIU among patients with a o 3 cases / 1000 vaccinated people in certain age groups
history of uveitis

o 90% of cases were anterior uveitis treated topically

o potential increased risk of relapse to patients with a history of uveitis
 Impact of This Additional do not support
advised of the
increased risk of Morbidity preventing symptoms of active
uveitis among outweighed by the reduced patients from uveitis
certain patient systemic COVID-19 morbidity • during 14 days after each dose
receiving the
populations achieved through vaccination • seek immediate ophthalmic care
vaccination
 sufficient for in line with the increases the
incidence of Other studies of
short-term window used by chance of other
active NIU vaccines
complications several studies unrelated factors

•during the first 21 days •without being too long •examine short-term •longer time frame •influencing new cases
after each of the first 2 to dilute the effect complications of a
doses. COVID-19 vaccine
 Limitation
Data extraction  errors and lack of data  nondifferential misclassification.

Large group with a previous diagnosis of uveitis (0.7%)  single events of

ocular inflammation who were not treated and followed up regularly

Unable to follow up No control for other risk

Adjustment was Only the risk of patients and ascertain factors for NIU  differ
limited only to active uveitis their final clinical and between vaccinated
age and sex. developing, visual outcomes after participants and the
treatment for uveitis. general population
 Conclusions
BNT162b2 mRNA COVID-19 vaccine may be associated with increased risk of NIU.

The small estimated ars suggest that the impact on public health is relatively minor.

Small effect size and study limitations  does not provide proof for a cause-and-effect relationship.

Future studies are needed to explore the association.

The benefits of vaccination outweigh the possible link to active uveitis

Support the continued use of the vaccine

Patients with known uveitis should be aware of the symptoms of relapse.

L
APPRAIS
AL
Population
• Two million six hundred two thousand five hundred fifty-seven people who
received the first vaccine dose between December 20, 2020, and April 30, 2021,
and 2 441 719 people who received the second vaccine dose between January
10, 2021, and April 30, 2021.
Intervention
• BNT126b2 vaccination

Comparison
•-

Outcome
• Uveitis Anterior
11
 Are the results of the study valid? (Internal Validity)
Was the defined representative sample of patients assembled at a
common (usually early) point in the course of their disease?

[ v ] YES [ ] NO [ ] UNCLEAR
Two million six hundred two thousand five hundred fifty-seven people who
received the first vaccine dose between December 20, 2020, and April 30,
2021, and 2 441 719 people who received the second vaccine dose between
January 10, 2021, and April 30, 2021.
Was patient follow-up sufficiently long and complete?

[ v ] YES [ ] NO [ ] UNCLEAR

between December 20, 2020, and April 30, 2021, and

January 10, 2021, and April 30, 2021.
 Are the results of the study valid? (Internal Validity)
Were outcome criteria either objective or applied in a ‘blind’ fashion?
[ ] YES [ ] NO [ v ] UNCLEAR
blinded determination of prognostic factors was not clearly defined in the
method section.

If subgroups with different prognoses are identified, did adjustment for important prognostic factors
take place?
[ ] YES [ ] NO [ v ] UNCLEAR
It is unclear if subgroups with different prognoses are identified and adjusted
 What are the results?
Overall, 100 and 88 events of active NIU were recorded within 21 days after the first and second vaccine
doses, respectively. Using the experience of the population in 2019 as a reference, after the first dose, the
estimated age- and sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15–1.71) along with a 21-day
attributable risk of 1.12 cases per 100 000 vaccinees. After the second dose, the SIR was 1.31 (95% CI,
1.05–1.62), with an estimated attributable risk of 0.86 cases per 100 000 vaccinees. Anterior uveitis was
the most common site of inflammation, occurring in 90.96% of eyes, and idiopathic uveitis was the most
common cause (56.38%).
What are the results?
VIA VALIDITAS
Apakah awal penelitian didefinisikan dengan jelas dan taat Ya
asas, misalnya saat diagnosis ditegakkan?

Apakah follow up dilakukan secara memadai? Ya

Apakah outcome dinilai dengan kriteria objektif, bila mungkin Ya

tersamar?
Apakah diidentifikasi kelompok dengan prognosis yang Ya
berbeda?
Apakah hasil sudah divalidasi pada kelompok subyek yang Ya
lain?

VALID
VIA IMPORTANCY

• Population in 2019 as a reference, after the first dose, the estimated age- and
sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15–1.71) along with a
21-day attributable risk of 1.12 cases per 100 000 vaccinees.
• After the second dose, the SIR was 1.31 (95% CI, 1.05–1.62), with an estimated
attributable risk of 0.86 cases per 100 000 vaccinees.
• Anterior uveitis was the most common site of inflammation, occurring in 90.96%
of eyes, and idiopathic uveitis was the most common cause (56.38%).

IMPORTANT
VIA APPLICABILITY

Apakah karakteristik pasien di sini mirip dengan subyek uji Ya, jumlah sampel sudah
klinis memadai

APPLICABLE
THANK
YOU