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Review

The Characteristics of COVID-19 Vaccine-Associated Uveitis: A Summative Systematic Review

by
Yasmine Yousra Sadok Cherif
1,†,
Chakib Djeffal
1,†,
Hashem Abu Serhan
2,3,
Ahmed Elnahhas
2,4,
Hebatallah Yousef
2,5,
Basant E. Katamesh
2,4,
Basel Abdelazeem
2,6,7 and
Abdelaziz Abdelaal
2,4,8,9,*
1
Faculty of Medicine, University of Algiers, Algiers 16311, Algeria
2
Tanta Research Team, El-Gharbia 31516, Egypt
3
Department of Ophthalmology, Hamad Medical Corporations, Doha 576214, Qatar
4
Faculty of Medicine, Tanta University, Tanta 31527, Egypt
5
Ophthalmology Department, Kafr Ash Shaykh Ophthalmology Hospital, Kafr Ash Shaykh 33511, Egypt
6
McLaren Health Care, Flint, MI 48532, USA
7
Internal Medicine Department, Michigan State University, East Lansing, Michigan, MI 48824, USA
8
Harvard Medical School, Postgraduate Medical Education, Boston, MA 02115, USA
9
Doheny Eye Institute, University of California, Los Angeles, CA 90033, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2023, 11(1), 69; https://doi.org/10.3390/vaccines11010069
Submission received: 13 November 2022 / Revised: 14 December 2022 / Accepted: 24 December 2022 / Published: 28 December 2022
(This article belongs to the Special Issue Ophthalmic Adverse Events following SARS-CoV-2 Vaccination)
Browse Figure
Review Reports Versions Notes

Abstract

:
Numerous complications following COVID-19 vaccination has been reported in the literature, with an increasing body of evidence reporting vaccination-associated uveitis (VAU). In this systematic review, we searched six electronic databases for articles reporting the occurrence of VAU following COVID-19 vaccination. Data were synthesized with emphasis on patients’ characteristics [age, gender], vaccination characteristics [type, dose], and outcome findings [type, nature, laterality, course, location, onset, underlying cause, and associated findings]. Data are presented as numbers (percentages) for categorical data and as mean (standard deviation) for continuous data. Sixty-five studies were finally included [43 case reports, 16 case series, four cohort, one cross-sectional, and one registry-based study]. VAU occurred in 1526 cases, most commonly in females (68.93%) and middle-aged individuals (41–50 years: 19.71%), following the first dose (49.35%) of vaccination, especially in those who received Pfizer (77.90%). VAU occurred acutely (71.77%) as an inflammatory reaction (88.29%) in unilateral eyes (77.69%), particularly in the anterior portion of the uvea (54.13%). Importantly, most cases had a new onset (69.92%) while only a limited portion of cases had a reactivation of previous uveitis condition. In conclusion, although rare, uveitis following COVID-19 vaccination should be considered in new-onset and recurrent cases presenting with either acute or chronic events.

1. Introduction

Following the declaration of the COVID-19 pandemic, healthcare systems all over the globe were burdened by the increased number of daily diagnosed cases and associated deaths. This urged the need to develop effective vaccines within a short time period. During the past two years, a number of vaccines received emergency authorization and were then disseminated globally. Currently, over 12.6 billion doses have been distributed, including messenger RNA vaccines (the Pfizer-BioNTech and the Moderna), vector vaccines (Johnson & Johnson, AstraZeneca), and protein subunit vaccine (Novavax). Although these vaccines were effective in limiting the spread of the disease and limiting the occurrence of severe forms, several adverse events were reported, particularly those involving the eye [1,2].
Uveitis is a potentially vision-threatening condition that involves intraocular inflammation. It accounts for 10–15% of blindness cases worldwide [3]. It has incidence and prevalence rates of 50.45 and 9–730 per 100,000 cases, respectively. The etiology of uveitis is multifactorial, which can be autoimmune, systemic (60.1%), infectious (30–50%), or idiopathic (20–40%) in origin [3]. That being said, uveitis can occur postvaccination. Vaccination-related uveitis, although uncommon, has been reported during previous Hepatitis B virus (40%), human papillomavirus (15%), hepatitis A virus, influenza virus, Bacille-Calmette-Guerin, varicella virus, and measles-mumps-rubella vaccination programs [4]. In this context, the hypothesis of COVID-19 vaccine-associated uveitis (VAU) has emerged, with several reports highlighting the magnitude of this problem [1,5,6]. For instance, non-infectious uveitis has been reported in 66.8 and 62.7 cases per 100,000 person-years following the first and second doses of the BNT162b2 mRNA vaccine, respectively [7].
In light of COVID-19 VAU, the level of evidence has shifted. Instead of being based solely on case reports, a number of new cohort and cross-sectional studies have been published in this regard, all of which highlight the magnitude of this newly emerging observation. Therefore, we conducted a systematic review to summarize available evidence on COVID-19 vaccine-associated uveitis with a particular focus on vaccines’ information [type, dose, duration], patients’ characteristics [sociodemographic and clinical], and disease-associated outcomes [origin, type, location, presentation, management, and outcomes].

2. Materials and Methods

2.1. Study Protocol and Database Search

This research was carried out in accordance with the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA) recommendations. In July 2022, our protocol was registered on PROSPERO [registration number: CRD42022358117]. Meanwhile, on 26–27 July 2022, we searched six electronic databases [PubMed, Scopus, EMBASE, Web of Science, CENTRAL, and Google Scholar] to retrieve all studies that reported the occurrence of VAU following COVID-19 vaccination using the following keywords: COVID-19 AND vaccin* AND uveitis. Medical Subject Headings (MESH) terms were also added whenever applicable to retrieve all relevant studies based on their indexed terms in included databases. Of note, only the first 200 records from Google Scholar were retrieved and screened as per the recent recommendations [8]. The detailed search strategy for each database is provided in Table A1. It is worth noting that an updated database search was carried out on 11 September 2022, to include any newly published studies before the official synthesis of collected data.
Additionally, on 1 September 2022, after finishing the screening process, we conducted a manual search of references to identify any relevant studies that we could not identify through the original database search. This search was conducted through: (1) the reference list of included studies, (2) “similar article” of included papers on PubMed, and (3) Google by using these keywords: “COVID-19” + “uveitis” + “vaccine”.

2.2. Eligibility Criteria

We included original research papers that discussed the occurrence of VAU following COVID-19 vaccination. We included all of the following study designs: case reports and series, cohorts, and cross-sectional studies. Studies were included regardless of the type and/or dose of vaccine, history or location of uveitis, or the language of publication. Meanwhile, studies were excluded if they: (1) recruited individuals (healthy or infected with COVID-19) who did not receive COVID-19 vaccines, (2) were not original (reviews, editorials, commentaries, books, etc.), (3) included duplicated records, (4) did not have a full text, or (5) reported other types of ocular/ophthalmic complications other than uveitis.

2.3. Screening and Study Selection

Retrieved records from the database search were exported into EndNote software for duplicate removal before the beginning of the screening phase. Records were then imported into an Excel (Microsoft, Rochester, MN, USA) Sheet for screening. The screening was divided into two steps: title and abstract screening and full-text screening. The full texts of eligible articles were then retrieved for screening before being finally included in the review. Both steps were carried out by three reviewers (HY, HA, AE). Any differences between reviewers were solved through group discussions, and the senior authors (YYSC, CD) were consulted if reviewers could not reach an agreement.

2.4. Data Extraction

The data extraction was performed by three reviewers [HY, HA, AE] through a data extraction sheet that was formatted through Excel (Microsoft, Rochester, MN, USA). This sheet consisted of six parts. The first part included the baseline characteristics of included studies (title, authors’ names, year of publication, country, and study design) and patients as well [sample size, age, and gender]—only those with evidence VAU. The second part included data on the administered vaccines (type and dose), while the third part included information regarding VAU cases’ medical history (systemic, immunological, and ocular diseases). The fourth part included patients’ clinical presentation and examination findings (symptoms, signs, and intraocular pressure (IOP)), while the fifth part included data on the main outcome of interest—VAU (type, location, laterality, interval between vaccination and symptom onset, nature, underlying cause, and associated findings). The final part included the management approach in such cases and reported outcomes (resolution, improvement, complications, recurrence, etc.).

2.5. Data Synthesis

All of the included studies were qualitatively analyzed as per our plan in priori. Additionally, since data were provided on a per-case basis, we performed several descriptive analyses to detect patterns on the occurrence of VAU based on: age, gender, type and dose of vaccination, presenting symptoms, laterality (right, left, unilateral, bilateral), type of uveitis (new-onset, reactivation), longevity (acute, chronic), location (anterior, intermediate, posterior, panuveitis), duration of vaccination to symptom onset, associated findings [macular edema, glaucoma, synechiae], and management outcomes (resolution, improvement, recurrence, complications). Data are presented as mean/standard deviation (SD) for continuous variables and as numbers/percentages for categorical ones.

3. Results

3.1. Search Results

The results of the database search and screening phases are presented in Figure 1. The initial database search yielded 538 articles, of which 209 duplicates were removed through EndNote. Following the screening of 329 articles, the full texts of 65 articles were retrieved for full-text screening, of which 11 articles were excluded. The manual search resulted in 10 articles, and an updated database search revealed one additional article, resulting in a total number of relevant eligible studies of 65.

3.2. Baseline Characteristics of Studies Reporting COVID-19 VAU

A total of 65 studies were both qualitatively and quantitatively analyzed (Table 1) [1,5,7,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69], out of which 43 were case reports, 16 were case series, four were retrospective cohort, one was cross-sectional, and one was a registry-based study. The sample size of included patients with VAU ranged from 1 to 1094, with an overall sample size of 1526 VAU cases. Most reports were from India (n = 9), followed by China (n = 7), Israel (n = 7), Korea (n = 6), Italy (n = 4), and USA (n = 4), respectively.

3.3. Sociodemographic and Clinical Characteristics of VAU Cases

3.3.1. Age and Gender

COVID-19 vaccine-associated uveitis was twice more likely to occur in females than in males (68.93% vs. 31.06%). Patients’ age ranged from 8 to 95 years (mean of 48.18 and standard deviation of 18.94). The peak of vaccine-associated uveitis occurred in middle-aged patients (41–50 years of age) with a declining trend as it comes nearer to both extremes (0–10 or ≥91 years) [Table 2].

3.3.2. Medical History

A minority of VAU cases reported having either systemic, ocular, or immunological diseases [Table 3]. SARS-CoV-2 infection occurred in a very limited number of patients (0.93%), while only 0.59% and 0.42% reported having hypertension or diabetes, respectively. More than one-tenth of VAU cases reported having uveitis in the past (13.51%). Although cases reported a wide variety of previous ocular conditions, none of them seems to be correlated with VAU due to their rare occurrence (below 0.50%). In terms of immunological diseases, autoimmune diseases (AIDS) were the most frequent among VAU cases, accounting for 1.19% of cases.

3.4. Vaccine- and Outcome-Related Characteristics

3.4.1. Type and Dose of COVID-19 Vaccines

The majority of cases were documented in those who took the Pfizer-BioNTech vaccine (77.9%), followed by Moderna (15.54%), and AstraZeneca (3.01%), respectively [Table 2]. Most cases were more likely to occur following the first dose of the vaccine (49.35%), and the occurrence of vaccine-related uveitis was remarkedly minimized following the third and fourth booster doses (7.84% and 0.37%), respectively.

3.4.2. Clinical Presentation

The majority of patients presented with redness (72.99%), followed by diminished vision (23.53%), photophobia (10.48%), and blurry vision (5.28%), respectively [Table 4]. Although infrequent, some VAU cases presented with floaters (2.22%) and vision loss (1.07%). The IOP was measured in 38 and 17 right and left eyes of VAU cases, respectively. IOP ranged from 9 to 55 and from 8 to 60 mmHg in the left and right eyes, with a mean IOP of 17.93 (SD = 11.03) and 17.3 (SD = 9.38) mmHg, respectively.

3.4.3. The Nature of the Reported VAU and Disease Laterality

Out of 1526 VAU cases, only 1476 cases had the type of intraocular inflammation documented [Table 5]. The most common type was uveitis (97.56%), followed by VKH (1.08%) and retinochoroiditis (0.20%), respectively. The mean interval from COVID-19 vaccination to the occurrence of uveitis was 9.61 (SD = 8.07) days, ranging from 1 to 42 days post-vaccination. VAU was twice more likely to occur in one eye/unilaterally (77.69%) than in both eyes/bilaterally (22.05%). The rate of VAU occurrence in the right and left eyes was comparable (32.3% vs. 34.61%), respectively [Table 5].

3.4.4. Disease Course, Location, Nature, and Underlying Cause of VAU

The course of VAU was acute in more than two-thirds of the population (71.77%) as compared to chronic cases (28.22%) [Table 5]. Among VAU cases where the location was determined, the anterior segment of the uveal tract in more than half the population was affected (54.13%). Surprisingly, panuveitis was more likely to occur than posterior uveitis by almost two-fold (10.02% vs. 5.28%). Of note, the majority of VAU cases did not have a history of uveitis and experienced an episode of uveitis for the first time (69.92%), while only one-third of VAU cases had prior episodes of uveitis (30.08%). VAU was inflammatory in nature in most cases (88.29%) and infectious in 8.36% of them. The underlying cause of VAU was idiopathic in almost half the population (43.26%), while VKH (7.34%) accounted for the most commonly reported cause among other causes [Table 5].

3.5. Management and Treatment Outcomes

A detailed description of the management plan that was carried out per each patient is provided in Table A2. Of note, the majority (90.15%) of VAU cases showed complete resolution following treatment, while only 9.85% had partial improvement. In studies that assessed complications following the treatment of VAU cases, 21.68% of cases had at least one complication, the most common of which being transient elevation in IOP (non-serious) and nummular corneal lesions in 3.61% of cases [Table 6].

4. Discussion

Since the emergence of COVID-19 vaccines, many adverse events have been recognized globally. Of these adverse events, uveitis was one of the most commonly reported ocular events. Specifically, a recent study, using the CDC-VAERS registry, reported that VAU was evident in 1094 VAU cases across 40 countries with a crude incidence rate of 0.57 cases per million doses of the COVID-19 Pfizer vaccine [71].
The exact pathophysiology of VAU is unclear, but it is believed to be mediated through an autoimmune reaction by the vaccines [72]. Additionally, it could be due to a combination of mechanisms such as molecular mimicry, the production of specific autoantibodies, hypersensitivity reactions, and the role of some vaccine adjuvants [73,74]. Vaccines provoke an inflammatory cascade by expression of type 1 interferon, resulting in a host immune response. On the other hand, they may also induce the production of autoantibodies, which can potentially trigger an autoimmune reaction [73]. Rabinovitch et al. [55] suggested that VAU caused by mRNA vaccines is a type I autoimmune reaction resulting in spiked levels of type 1 interferon. Cunningham et al. [75] attributed VAU to type 4 hypersensitivity reaction due to molecular mimicry between uveal self-peptides and vaccine peptides. Nevertheless, the postulated mechanisms that lead to VAU following COVID-19 vaccinations are mainly hypothetical and warrant additional studies. Due to the autoimmunity nature of VAU, it tends to occur more frequently in females [76]. Although the underlying cause of this trend is uncertain, the latest evidence has shown that sex hormones have an impact on the immune reaction, with estrogen enhancing it and androgens repressing it [77]. Furthermore, recent research has demonstrated that estrogen is essential for the development and function of Th17 cells in addition to IL-17 generation [78]. Our findings coincide with this, showing that COVID-19 VAU was twice more likely to occur in females than in males (68.93% vs. 31.06%). In addition, AIDS was the most frequent among VAU cases, accounting for 1.19% of cases, which strengthens the hypothesis of autoimmunity.
Our study supports the hypothesis that uveitis can occur following COVID-19 vaccination either as new-onset (the majority of cases) or as an exacerbation or reactivation of a previous uveitis. The peak of vaccine-associated uveitis occurred in middle-aged individuals (41–50 years of age), which is parallel to findings made by Darrell et al. [79]. The majority of cases were documented in those who took the Pfizer-BioNTech vaccine (77.9%), followed by Moderna (15.54%), and AstraZeneca (3.01%), respectively. This could be explained by the fact that Pfizer–BioNTech COVID-19 vaccine elicits an additional CD8 T-cell immune response, providing additional protection against SARS-CoV2 infection—however, also triggering autoimmune reactions [80,81]. This could also be attributed to the dominance of Pfizer-BioNTech vaccine over other COVID-19 vaccine type in the number of administered doses. For instance, up to December 2022, 656.90 million Pfizer doses have been administered followed by Moderna (153.82 million), AstraZeneca (67.03 million), Jhonshon&Jhonson (18.93 million), Sinopharm (2.32 million), and Sputnik (1.85 million), respectively. Other vaccines (Sinovac, Novavax, and Covaxin) have been administered at a much lower rate (below 1 million doses) [82]. These findings were also observed in Singh RB et al. [71]’s registry analysis. Most cases were more likely to occur following the first dose of the vaccine (49.35%), and the occurrence of vaccine-related uveitis was remarkedly minimized following the third and fourth booster doses (7.84% and 0.37%), respectively. Oberhardt V et al. [83] found that the first dose of COVID-19 vaccines is associated with inducing a significantly higher level of anti-spike IgG protein, resulting in a proportionately higher number of naive and transitional B cells, as well as functional spike-specific CD8+ T cells, which is parallel to findings observed by Singh RB et al. [71]. The mean interval from COVID-19 vaccination till to the occurrence of uveitis was 9.61 (SD = 8.07) days. This might be explained by the fact that the highest immune response usually occurs during the first ten days [84]. Unfortunately, given the small sample size, we could not determine the interval time from vaccination to symptom onset per each vaccine type. That being said, the previous study [71] indicated that the interval is significantly longer in those who received the Moderna vaccine as compared to those who received either Pfizer or AstraZeneca (p < 0.0001). However, no conclusive, clinically applicable evidence can be drawn from such observations given the non-normal distribution of analyzed data (standard deviation was larger than the mean).
Moreover, the occurrence of VAU following COVID-19 vaccination did not follow a specific pattern regarding the location of uveitis or the course of the disease. However, in our study, VAU was more likely to occur as an acute inflammatory (non-infectious) reaction involving mainly the anterior portion of the uveal tract. The majority of VAU cases did not have a history of uveitis and experienced an episode of uveitis for the first time (69.92%), while only one-third of VAU cases had prior episodes of uveitis (30.08%). This necessitates the importance of early recognition of symptoms of uveal tract involvement especially diminished vision, photophobia, and blurry vision. Similar to any uveitis, the management of COVID-19 VAU is an exclusion diagnosis. Therefore, identifying an underlying cause whilst also ruling out infections is critical. In addition to the standard uveitis questionnaires for previous uveitis, medical history, and constitutional health symptoms during the COVID-19 pandemic, clinicians should inquire about COVID-19 vaccination status.

5. Conclusions

Our review summarizes the occurrence of COVID-19 vaccination-associated uveitis, which is more likely to occur among middle-aged females. This event occurs either as a new onset of the disease or a reactivation of previous uveitis, most commonly after vaccination with Pfizer vaccine. Although it commonly occurs after the first and then second doses of the vaccines, it can occur after the first and second booster doses as well. It usually involves the anterior part of the uveal tract as an inflammatory event in an acute form.

Author Contributions

Conceptualization, Y.Y.S.C., C.D. and A.A.; methodology, Y.Y.S.C., C.D., B.A., H.A.S., H.Y. and A.E.; software, A.A.; validation, Y.Y.S.C., C.D. and A.A.; formal analysis, A.A.; investigation, Y.Y.S.C., C.D. and A.A.; resources, A.A.; data curation, Y.Y.S.C., C.D. and A.A.; writing—original draft preparation, A.A., H.A.S., Y.Y.S.C. and C.D.; writing—review and editing, B.A. and B.E.K.; visualization, Y.Y.S.C., C.D. and A.A.; supervision, A.A.; project administration, B.E.K.; funding acquisition, not applicable. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data provided in this manuscript can be provided upon reasonable request by contacting the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A

Table
Table A1. The detailed search strategy used in our review.
Table A1. The detailed search strategy used in our review.
DatabaseNo.Search QueryResults
PubMed [date of search: 27 July 2022]
#1(“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh] OR 2019-ncov*[tiab] OR 2019ncov*[tiab] OR 2019-novel-cov*[tiab] OR coronavirus-2*[tiab] OR coronavirus-disease-19*[tiab] OR corona-virus-disease-19*[tiab] OR coronavirus-disease-20*[tiab] OR corona-virus-disease-20*[tiab] OR COVID-19*[tiab] OR COVID19*[tiab] OR COVID-20*[tiab] OR COVID20*[tiab] OR ncov-2019*[tiab] OR ncov2019*[tiab] OR new-coronavirus[tiab] OR new-corona-virus[tiab] OR novel-coronavirus[tiab] OR novel-corona-virus[tiab] OR SARS-2*[tiab] OR SARS2*[tiab] OR SARS-CoV-19*[tiab] OR SARS-CoV19*[tiab] OR SARSCoV19*[tiab] OR SARSCoV-19*[tiab] OR SARS-CoV-2*[tiab] OR SARS-CoV2*[tiab] OR SARSCoV2*[tiab] OR SARSCoV-2*[tiab] OR ((“Coronavirus”[mh] OR “Coronavirus Infections”[mh] OR betacoronavirus[tiab] OR beta-coronavirus[tiab] OR beta-corona-virus[tiab] OR corona-virus[tiab] OR coronavirus[tiab] OR SARS*[tiab] OR severe-acute-respiratory*[tiab]) AND (2019[tiab] OR 2020[tiab] OR wuhan*[tiab] OR hubei*[tiab] OR china*[tiab] OR chinese*[tiab] OR outbreak*[tiab] OR epidemic*[tiab] OR pandemic*[tiab]))) AND 2019/12:3000[dp]276,477
#2Uveiti* OR choroiditis OR iritis OR iridocyclitis OR “Uveitis”[Mesh] OR “Choroiditis”[Mesh] OR “Iritis”[Mesh] OR “Iridocyclitis”[Mesh]92,380
#3Pfizer-BioNTech OR BTN162b2 OR Sinopharm OR Sinovac OR Moderna OR AstraZeneca OR ChAdOx1 OR AZD1222 OR Janssen OR “Johnson & Johnson” OR Novavax OR CoronaVac OR Covaxin OR Convidecia OR Sputnik OR Zifivax OR Corbevax OR COVIran OR SCB-2019 OR vaccin* OR “COVID-19 Vaccines”[Mesh] 564,424
#4#1 AND #2 AND #3 95
Scopus [date of search: 27 July 2022]
#1(TITLE-ABS-KEY (COVID-19) OR TITLE-ABS-KEY (SARS-CoV-2) OR TITLE-ABS-KEY (2019-ncov*) OR TITLE-ABS-KEY (2019ncov*) OR TITLE-ABS-KEY (2019-novel-cov*) OR TITLE-ABS-KEY (coronavirus-2*) OR TITLE-ABS-KEY (coronavirus-disease-19*) OR TITLE-ABS-KEY (corona-virus-disease-19*) OR TITLE-ABS-KEY (coronavirus-disease-20*) OR TITLE-ABS-KEY (corona-virus-disease-20*) OR TITLE-ABS-KEY (COVID-19*) OR TITLE-ABS-KEY (COVID19*) OR TITLE-ABS-KEY (COVID-20*) OR TITLE-ABS-KEY (COVID20*) OR TITLE-ABS-KEY (ncov-2019*) OR TITLE-ABS-KEY (ncov2019*) OR TITLE-ABS-KEY (new-coronavirus) OR TITLE-ABS-KEY (new-corona-virus) OR TITLE-ABS-KEY (novel-coronavirus) OR TITLE-ABS-KEY (novel-corona-virus) OR TITLE-ABS-KEY (sars-2*) OR TITLE-ABS-KEY (sars2*) OR TITLE-ABS-KEY (SARS-CoV-19*) OR TITLE-ABS-KEY (SARS-CoV19) OR TITLE-ABS-KEY (SARSCoV19*) OR TITLE-ABS-KEY (SARSCoV-19*) OR TITLE-ABS-KEY (SARS-CoV-2*) OR TITLE-ABS-KEY (SARS-CoV2*) OR TITLE-ABS-KEY (SARSCoV2*) OR TITLE-ABS-KEY (SARSCoV-2*) OR TITLE-ABS-KEY (coronavirus) OR TITLE-ABS-KEY (coronavirus AND infections) OR TITLE-ABS-KEY (betacoronavirus) OR TITLE-ABS-KEY (beta-coronavirus) OR TITLE-ABS-KEY (beta-corona-virus) OR TITLE-ABS-KEY (corona-virus) OR TITLE-ABS-KEY (coronavirus) OR TITLE-ABS-KEY (sars*))414,003
#2(TITLE-ABS-KEY (uveiti) OR TITLE-ABS-KEY (choroiditis) OR TITLE-ABS-KEY (iritis) OR TITLE-ABS-KEY (iridocyclitis))43,658
#3(TITLE-ABS-KEY (pfizer-biontech) OR TITLE-ABS-KEY (btn162b2) OR TITLE-ABS-KEY (sinopharm) OR TITLE-ABS-KEY (sinovac) OR TITLE-ABS-KEY (moderna) OR TITLE-ABS-KEY (astrazeneca) OR TITLE-ABS-KEY (chadox1) OR TITLE-ABS-KEY (azd1222) OR TITLE-ABS-KEY (janssen) OR TITLE-ABS-KEY (johnson AND & AND johnson) OR TITLE-ABS-KEY (novavax) OR TITLE-ABS-KEY (coronavac) OR TITLE-ABS-KEY (covaxin) OR TITLE-ABS-KEY (convidecia) OR TITLE-ABS-KEY (sputnik) OR TITLE-ABS-KEY (zifivax) OR TITLE-ABS-KEY (corbevax) OR TITLE-ABS-KEY (coviran) OR TITLE-ABS-KEY (scb-2019) OR TITLE-ABS-KEY (vaccin*) OR TITLE-ABS-KEY (COVID-19 AND vaccines))659,050
#4#1 AND #2 AND #3 92
EMBASE [date of search: 27 July 2022]
#1COVID 19’:ti,ab,kw OR ‘SARS CoV 2’:ti,ab,kw OR ‘2019 ncov’:ti,ab,kw OR 2019ncov:ti,ab,kw OR ‘2019 novel cov’:ti,ab,kw OR ‘coronavirus 2’:ti,ab,kw OR ‘coronavirus disease 19*’:ti,ab,kw OR ‘corona virus disease 19*’:ti,ab,kw OR ‘coronavirus disease 20*’:ti,ab,kw OR ‘corona virus disease 20*’:ti,ab,kw OR ‘COVID 19*’:ti,ab,kw OR COVID19*:ti,ab,kw OR ‘COVID 20*’:ti,ab,kw OR COVID20*:ti,ab,kw OR ‘ncov 2019*’:ti,ab,kw OR ncov2019*:ti,ab,kw OR ‘new coronavirus’:ti,ab,kw OR ‘new coronavirus’:ti,ab,kw OR ‘novel coronavirus’:ti,ab,kw OR ‘novel corona virus’:ti,ab,kw OR ‘sars 2*’:ti,ab,kw OR sars2*:ti,ab,kw OR ‘SARS CoV 19*’:ti,ab,kw OR ‘SARS CoV19*’:ti,ab,kw OR SARSCoV19*:ti,ab,kw OR ‘SARSCoV 19*’:ti,ab,kw OR ‘SARS CoV2*’:ti,ab,kw OR SARSCoV2*:ti,ab,kw OR ‘SARSCoV 2*’:ti,ab,kw OR ‘coronavirus infections’:ti,ab,kw OR betacoronavirus:ti,ab,kw OR ‘beta coronavirus’:ti,ab,kw OR ‘beta coronavirus’:ti,ab,kw OR ‘corona virus’:ti,ab,kw OR coronavirus:ti,ab,kw302,489
#2coronavirus disease 2019’/exp OR ‘severe acute respiratory syndrome coronavirus 2’/exp OR ‘coronavirinae’/exp280,492
#3#1 OR #2333,874
#4pfizer biontech’:ti,ab,kw OR btn162b2:ti,ab,kw OR sinopharm:ti,ab,kw OR sinovac:ti,ab,kw OR moderna:ti,ab,kw OR astrazeneca:ti,ab,kw OR chadox1:ti,ab,kw OR azd1222:ti,ab,kw OR janssen:ti,ab,kw OR ‘johnson & johnson’:ti,ab,kw OR novavax:ti,ab,kw OR coronavac:ti,ab,kw OR covaxin:ti,ab,kw OR convidecia:ti,ab,kw OR sputnik:ti,ab,kw OR zifivax:ti,ab,kw OR corbevax:ti,ab,kw OR coviran:ti,ab,kw OR ‘scb 2019’:ti,ab,kw OR vaccin*:ti,ab,kw OR ‘COVID-19 vaccines’:ti,ab,kw492,172
#5SARS-CoV-2 vaccine’/exp OR ‘pfizer biontech’/exp OR ‘covilo’/exp OR ‘coronavac’/exp OR ‘elasomeran’/exp OR ‘vaxzevria’/exp OR ‘ad26.cov2.s vaccine’/exp OR ‘nvx-cov2373 vaccine’/exp OR ‘covaxin’/exp OR ‘convidecia’/exp OR ‘zifivax’/exp OR ‘corbevax’/exp OR ‘coviran barekat’/exp21,790
#6#4 OR #5494,823
#7uveiti:ti,ab,kw OR choroiditis:ti,ab,kw OR iridocyclitis:ti,ab,kw OR uveitis:ti,ab,kw34,836
#8uveitis’/exp OR ‘choroiditis’/exp OR ‘iritis’/exp OR ‘iridocyclitis’/exp71,059
#9#7 OR #875,142
#10#3 AND #6 AND #9148
Web of Science [date of search: 27 July 2022]
#1COVID-19 (All Fields) or SARS-CoV-2 (All Fields) or 2019-ncov* (All Fields) or 2019ncov* (All Fields) or 2019-novel-cov* (All Fields) or coronavirus-2* (All Fields) or coronavirus-disease-19* (All Fields) or corona-virus-disease-19* (All Fields) or oronavirus-disease-20* (All Fields) or corona-virus-disease-20* (All Fields) or COVID-19* (All Fields) or COVID19* (All Fields) or COVID-20* (All Fields) or COVID20* (All Fields) or ncov-2019* (All Fields) or ncov2019* (All Fields) or new-coronavirus (All Fields) or new-corona-virus (All Fields) or novel-coronavirus (All Fields) or novel-corona-virus (All Fields) or sars-2* (All Fields) or sars2* (All Fields) or SARS-CoV-19* (All Fields) or SARS-CoV19* (All Fields) or SARSCoV19* (All Fields) or SARSCoV-19* (All Fields) or SARS-CoV-2* (All Fields) or SARS-CoV2* (All Fields) or SARSCoV2* (All Fields) or SARSCoV-2* (All Fields) or Coronavirus (All Fields) or Coronavirus Infections (All Fields) or betacoronavirus (All Fields) or beta-coronavirus (All Fields) or beta-corona-virus (All Fields) or corona-virus (All Fields) or coronavirus (All Fields) or sars* (All Fields)371,351
#2PfizerBioNTech (All Fields) or BTN162b2 (All Fields) or Sinopharm (All Fields) or Sinovac (All Fields) or Moderna (All Fields) or AstraZeneca (All Fields) or ChAdOx1 (All Fields) or AZD1222 (All Fields) or Janssen (All Fields) or Johnson Johnson (All Fields) or Novavax (All Fields) or CoronaVac (All Fields) or Covaxin (All Fields) or Convidecia (All Fields) or Sputnik (All Fields) or Zifivax (All Fields) or Corbevax (All Fields) or COVIran (All Fields) or SCB-2019 (All Fields) or vaccin (All Fields) or COVID19 Vaccines (All Fields)766,301
#3Uveiti (All Fields) or choroiditis (All Fields) or iritis (All Fields) or iridocyclitis (All Fields)3452
#4#1 AND #2 AND #33
CENTRAL [date of search: 27 July 2022]
#1(COVID-19):ti,ab,kw OR (SARS-CoV-2):ti,ab,kw OR (“coronavirus infection”):ti,ab,kw OR (novel-coronavirus):ti,ab,kw OR (sars-2):ti,ab,kw11,673
#2(Coronavirus Infections):ti,ab,kw OR (betacoronavirus):ti,ab,kw AND (COVID20):ti,ab,kw AND (new-coronavirus):ti,ab,kw AND (SARSCoV2):ti,ab,kw1291
#3#1 OR #211,710
#4(“uveitis”):ti,ab,kw OR (choroiditis):ti,ab,kw OR (iritis):ti,ab,kw OR (iridocyclitis):ti,ab,kw1596
#5(Pfizer-BioNTech):ti,ab,kw OR (BTN162b2):ti,ab,kw OR (Sinopharm):ti,ab,kw OR (Sinovac):ti,ab,kw OR (Moderna):ti,ab,kw331
#6(AstraZeneca):ti,ab,kw OR (ChAdOx1):ti,ab,kw OR (AZD1222):ti,ab,kw OR (Janssen):ti,ab,kw OR (Johnson & Johnson):ti,ab,kw3752
#7(Novavax):ti,ab,kw OR (CoronaVac):ti,ab,kw OR (Covaxin):ti,ab,kw OR (Convidecia):ti,ab,kw OR (Sputnik):ti,ab,kw104
#8(Zifivax):ti,ab,kw OR (Corbevax):ti,ab,kw OR (COVIran):ti,ab,kw OR (SCB-2019):ti,ab,kw OR (COVID-19 Vaccines):ti,ab,kw663
#9#5 OR #6 OR #7 OR #84582
#10#3 AND #4 AND #90
Google Scholar [date of search: 26 July 2022]
With all of the wordsCOVID vaccine
With the exact phrase
With at least one of the wordsUveitis choroiditis iritis iridocyclitis
Total 200
Table
Table A2. The management strategy of COVID-19 vaccine-associated uveitis reported in the literature.
Table A2. The management strategy of COVID-19 vaccine-associated uveitis reported in the literature.
Author (YOP)NTTreatment
Accorinti (2022)11Oral, IV, and periocular corticosteroids
Achiron (2022)11Bulbar triamcinolone (40 mg/mL; 1 mL) + systemic prednisolone (starting from 60 mg and tapering down 10 mg every 2–3 days)/topical prednisolone acetate eye drops (10 mg/mL)/cyclopentolate eye drops/prednisolone eye gel
Al-Allaf (2022)11Triamcinolone drops and Azathioprine (50 mg)
Alhamazani (2022)11Topical prednisolone acetate 1% + cyclopentolate
Brunet de Courssou (2022)11Peribulbar injections of dexamethasone 8 mg + 3 intravenous pulses of methylprednisolone 15 mg/kg/day/ + oral prednisone
Chen (2022a)11Periocular injections of triamcinolone acetonide 40 mg
De Carvalho (2022)11Steroid
De Domingo (2022)11Steroid
Ishay (2021)11Pulse intravenous prednisolone + topical steroid therapy
Duran (2022)11Topical 0.1% dexamethasone 8 × 1, 1% cycloplegic drops 3 × 1 and 0.1% dexamethasone ointment 1 × 1 nightly were started.
ElSheikh (2021)11Topical prednisolone acetate 1% every 2 h and cyclopentolate hydrochloride three times daily.
Lee (2022)111g of intravenous methylprednisolone daily for 3 days, followed by oral prednisolone with a tapering dosage
Gedik (2022)11Topical steroid eye drops, cycloplegin eye drops and anti-glaucomata eye drops
Goyal (2021)11oral prednisolone 100 mg daily
Hébert (2022)11Prednisolone 1%, cyclopentolate, timolol, dexamethasone ointment, oral prednisone
Hwang (2022)11Topical dexamethasone, atropine sulfate eye drops, and systemic prednisone
Jain (2021)11Topical steroids and cycloplegics.
K. Joo (2022)11Oral prednisolone
Kim (2022)11Installation of 0.5%loteprednol etabonate + steroid pulse therapy
Koong (2021)11Pulsed intravenous methylprednisolone
Papasavvas (2021)11Capsaicin
Ding (2022)11Steroid
Lee (2022)11Systemic prednisone and mycophenolate mofetil
Sai (2022)11Topical difluprednate four times a day with gradual taper over 6 weeks with continued bimonthly dose of 40 mg adalimumab and weekly dose of 25 mg methotrexate
Matsuo (2022)110.1% betamethasone eye drops + oral prednisolone 20 mg daily
Mishra (2021)11Oral corticosteroids Tablets. Prednisolone 40 mg/day and was added then Table Prednisolone was tapered over a period of 6 weeks.
Mudie (2021)1150 mg/day of oral prednisone and her difluprednate was increased to every 2 h
Pan (2021)11Triamcinolone acetonide (40 mg, periocular injection) and oral prednisone (20 mg once a day).
Papasavvas (2021)115 days of oral prednisone (1 mg/kg) and Infliximab was administered following again a loading dose scheme with positive short-term evolution
Reddy (2021)11High-dose oral steroids of 70 mg per day which was tapered gradually. After reactivation: ongoing steroids of 20 mg per day. Her systemic steroid dosage is stepped up with the addition of topical steroids and cycloplegic
Renisi (2021)11Dexamethasone eye drops with a cycloplegic agent (atropine 1%)
Sangoram (2022)11Topical steroids and a cycloplegic agent.
Santiago (2021)11Prednisone and azathioprine
Saraceno (2021)11oral systemic prednisone (1.5 mg/kg/day)
Singh (2022a)11Oral steroids (prednisolone 1 mg/kg/day) with slow tapering over 6 weeks.
Yalçinkaya (2022)11IVIG (2 g/kg) and methylprednisolone (2 mg/kg)
Yamaguchi (2022)11IV methylprednisolone (1000 mg/day) for 3 days followed by oral prednisolone (60 mg/day)
Shilo (2022)11Oral prednisone which was tapered to a lower dose, and azathioprine treatment was initiated for a long-term effect.
Kakarla (2022)11Topical prednisolone
Numakura (2022)11Subcapsular injection of steroids
Murgova (2022)11Steroids, and anti-glaucoma therapy
Patel (2022)33Oral prednisone and topical difluorinated steroid therapy
Lawson-Tovey (2022)22Intravitreal injection dexamethasone
Arora (2022)-1-
Choi (2022)33Steroid and methotrexate
Ortiz-Egea (2022)22Topical acyclovir, oral valaciclovir, cycloplegic, and moxifloxacin
Nanji (2022)12Topical prednisolone acetate 1% and cyclogyl 1%
Pang (2022)12One-time periocular triamcinolone acetonide injection and oral prednisone
12Topical application of prednisolone acetate and oral prednisone
Ren (2022)12Systemic corticosteroid administered orally at a dose of 1 mg/kg per day
12Topical steroid (prednisolone acetate), tropicamide and pirprofen eye drops
Cohen (2022)14Oral valacyclovir, topical dexamethasone eye
24Topical dexamethasone and tropicamide
14Systemic corticosteroids (prednisone), topical dexamethasone and cycloplegic eye drops (0.5% tropicamide)
Aguiar (2022)22Dexamethasone, prednisolone ointment and cycloplegic agent (cyclopentolate)
Ferreira (2022)14Systemic corticosteroid/methotrexate
34Systemic corticosteroid/azathioprine
Chen (2022b)15Topical and periocular steroid
25Systemic steroids
25Periocular steroids
Chew (2022)46Steroid
26Sulfadiazine, Folinic acid, Pyrimethamine, Clindamycin
Rallis (2022)77Topical ganciclovir, oral acyclovir, and topical steroids
Li (2022)-9-
Sim (2022)1111Topical 1% prednisolone acetate eye drops and systemic prednisolone
Rabinovitch (2021)-21-
Bolletta (2021)413Dexamethasone eye drops 2 mg/mL
113Ganciclovir ophthalmic gel 0.15%, dexamethasone eye drops 2 mg/mL
313Sulfadiazine and pyrimethamine tablets, and oral prednisone
513Oral prednisone
Ferrand (2022)1425Topical steroid
1225Systemic steroid
225Acyclovir
125Azathioprine
325Methotrexate
425Tocilizumab/natalizumab/Ixekizumab
125Dimethyl fumarate
Ozdede (2022)-5-
Testi (2022)3750Topical Corticosteroids
850Systemic Corticosteroids
550Antivirals
050NSAID
450Antibiotics
Tomkins-Netzer (2022)-188-
Barda (2021)-26-
Singh (2022b)-1094-
IV: Intravenous; YOP: Year of Publication; NSAID: Non-steroidal anti-inflammatory drug; IVIG: Intravenous Immunoglobulins.

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Vaccines 11 00069 g001 550
Figure 1. A PRISMA flow diagram showing the database search and screening results.
Figure 1. A PRISMA flow diagram showing the database search and screening results.
Vaccines 11 00069 g001
Table
Table 1. The baseline characteristics of studies reporting COVID-19 vaccine-associated uveitis cases.
Table 1. The baseline characteristics of studies reporting COVID-19 vaccine-associated uveitis cases.
Author (YOP)CountryDesignGenderAgeTypeDose
Case Reports
Accorinti (2022) [9]ItalyCase ReportFemale54Pfizer-BioNTechFirst
Achiron (2022) [10]FinlandCase ReportMale17Pfizer-BioNTech-
Al-Allaf (2022) [11]QatarCase ReportMale46Pfizer-BioNTechFirst
Alhamazani (2022) [12]Saudi ArabiaCase ReportMale37Pfizer-BioNTechFirst
Brunet de Courssou (2022) [16]FranceCase ReportFemale57Pfizer-BioNTechFirst
Chen (2022a) [18] ChinaCase ReportMale19SinovacFirst
De Carvalho (2022) [22]BrazilCase ReportMale51Oxford/AstraZenecaFirst
De Domingo (2022) [23]SpainCase ReportFemale46Pfizer-BioNTechSecond
Ishay (2021) [32]IsraelCase ReportMale28Pfizer-BioNTechFirst
Duran (2022) [25]IsraelCase ReportFemale54Pfizer-BioNTechFirst
ElSheikh (2021) [26]EgyptCase ReportFemale18SinopharmFirst
Lee (2022) [39]South KoreaCase ReportFemale83Pfizer-BioNTechSecond
Gedik (2022) [28]TurkeyCase ReportMale47Pfizer-BioNTechSecond
Goyal (2021) [29]IndiaCase ReportMale34Oxford/AstraZenecaSecond
Hébert (2022) [30]CanadaCase ReportMale41Pfizer-BioNTechFirst
Hwang (2022) [31]South KoreaCase ReportFemale21Pfizer-BioNTechSecond
Jain (2021) [33]IndiaCase ReportMale27Oxford/AstraZenecaFirst
Joo (2022) [34]South KoreaCase ReportFemale50ModernaFirst
Kim (2022) [36]South KoreaCase ReportFemale72Oxford/AstraZenecaFirst
Koong (2021) [37]SingaporeCase ReportMale54Pfizer-BioNTechFirst
Papasavvas (2021) [53]SwitzerlandCase ReportFemale73ModernaFirst
Ding (2022) [24]ChinaCase ReportMale33SinopharmFirst
Lee (2022) [40]USACase ReportFemale25ModernaSecond
Mahendradas (2022) [42]IndiaCase ReportFemale19CovaxinSecond
Matsuo (2022) [43]Japan Case ReportMale34Pfizer-BioNTechSecond
Mishra (2021) [44]IndiaCase ReportMale71Oxford/AstraZenecaFirst
Mudie (2021) [45]SpainCase ReportFemale43Pfizer-BioNTechSecond
Pan (2021) [51]ChinaCase ReportFemale50Sinopharm
Papasavvas (2021) [53]SwitzerlandCase ReportFemale43Pfizer-BioNTechSecond
Reddy (2021) [57]IndiaCase ReportFemale30Oxford/AstraZenecaSecond
Renisi (2021) [59]ItalyCase ReportMale23Pfizer-BioNTechSecond
Sangoram (2022) [60]IndiaCase ReportFemale40Oxford/AstraZenecaSecond
Santiago (2021) [61]Puerto RicoCase ReportMale32Pfizer-BioNTechSecond
Saraceno (2021) [62]BrazilCase ReportFemale62Oxford/AstraZeneca-
Singh (2022a) [64]IndiaCase ReportMale29Oxford/AstraZenecaFirst
Yalçinkaya (2022) [67]TurkeyCase ReportMale12 Pfizer-BioNTechFirst
Yamaguchi (2022) [68]JapanCase ReportFemale30Pfizer-BioNTechSecond
Shilo (2022) [70]IsraelCase ReportMale20Pfizer-BioNTechFirst
Kakarla (2022) [35]India Case ReportFemale15CovaxinFirst
Numakura (2022) [48]Japan Case ReportMale61Pfizer-BioNTechFirst
Murgova (2022) [46]BulgariaCase ReportFemale89Pfizer-BioNTechSecond
Patel (2022) [54]USACase ReportMale79Pfizer-BioNTechSecond
Lawson-Tovey (2022) [38]ItalyCase ReportFemale--Second
Case Series
Author (YOP)CountryCasesGenderAgeTypeDose
Arora (2022) [13]IndiaCase 1Female20Oxford/AstraZenecaFirst
Case 2Male26Oxford/AstraZenecaFirst
Choi (2022) [20]KoreaCase 1Male62Oxford/AstraZenecaFirst
Case 2Female79Pfizer-BioNTechFirst
Case 3Female55Pfizer-BioNTechFirst
Ortiz-Egea (2022) [49]SpainCase 1Female92Pfizer-BioNTechFirst
Case 2Female85Pfizer-BioNTechFirst
Nanji (2022) [47]USACase 1Female58ModernaFirst
Case 2Female60ModernaFirst
Pang (2022) [52]ChinaCase 1Female50SinopharmFirst
Case 2Female34SinopharmSecond
Ren (2022) [58]ChinaCase 1Female46SinovacFirst
Case 2Female26SinovacFirst
Cohen (2022) [21]IsraelCase 1Female81Pfizer-BioNTechSecond
Case 2Female64Pfizer-BioNTechSecond
Case 3Male74Pfizer-BioNTechThird
Case 4Male63Pfizer-BioNTechThird
Aguiar (2022) [17]PortugalCase 1Female21Pfizer-BioNTechFirst
Case 2Male70Pfizer-BioNTechSecond
De Queiroz Tavares Ferreira (2022) [5]BrazilCase 1Female27Oxford/AstraZenecaFirst
Case 2Male39Oxford/AstraZenecaFirst
Case 3Female38Pfizer-BioNTechFirst
Case 4Female32SinovacSecond
Chen (2022b) [19]ChinaCase 1Male33SinopharmFirst
Case 2Female57Sinovac Second
Case 3Male21SinovacFirst
Case 4Female30SinovacSecond
Case 5Female28SinopharmFirst
Chew (2022) [1]SingaporeCase 1Female64Pfizer-BioNTechSecond
Case 2Male74SinopharmSecond
Case 3Female31Pfizer-BioNTechSecond
Case 4Female71Pfizer-BioNTechSecond
Case 5Female32Pfizer-BioNTechSecond
Case 6Female28Pfizer-BioNTechSecond
Rallis (2022) [56]UKCase 1Female47Oxford/AstraZenecaFirst
Case 2Female48Oxford/AstraZenecaFirst
Case 3Male44Oxford/AstraZenecaFirst
Case 4Female59Oxford/AstraZenecaFirst
Case 5Male65Oxford/AstraZenecaFirst
Case 6Male95Pfizer-BioNTechFirst
Case 7Male68Pfizer-BioNTechFirst
Li (2022) [41]ChinaCase 1Female48SinovacFirst
Case 2Male41SinovacThird
Case 3Male8SinovacFirst
Case 4Female52SinovacSecond
Case 5Female55SinovacFirst
Case 6Female67SinovacFirst
Case 7Female46SinovacFirst
Case 8Female57SinovacFirst
Case 9Male22SinovacFirst
Sim (2022) [63]KoreaCase 1Female51Pfizer-BioNTechSecond
Case 2Female21Pfizer-BioNTechSecond
Case 3Male50Pfizer-BioNTechSecond
Case 4Female52Pfizer-BioNTechThird
Case 5Male32Johnson & JohnsonSecond
Case 6Male72Oxford/AstraZenecaSecond
Case 7Female67Oxford/AstraZenecaThird
Case 8Male54Pfizer-BioNTechSecond
Case 9Female61Pfizer-BioNTechThird
Case 10Female63Pfizer-BioNTechSecond
Case 11Female47Pfizer-BioNTechThird
Rabinovitch (2021) [55]IsraelCase 1Female43Pfizer-BioNTechFirst
Case 2Male34Pfizer-BioNTechFirst
Case 3Female34Pfizer-BioNTechFirst
Case 4Male78Pfizer-BioNTechSecond
Case 5Male53Pfizer-BioNTechFirst
Case 6Male64Pfizer-BioNTechFirst
Case 7Male68Pfizer-BioNTechFirst
Case 8Female61Pfizer-BioNTechFirst
Case 9Male59Pfizer-BioNTechSecond
Case 10Male72Pfizer-BioNTechSecond
Case 11Male51Pfizer-BioNTechSecond
Case 12Female42Pfizer-BioNTechSecond
Case 13Male74Pfizer-BioNTechSecond
Case 14Male39Pfizer-BioNTechSecond
Case 15Female64Pfizer-BioNTechSecond
Case 16Female50Pfizer-BioNTechSecond
Case 17Female23Pfizer-BioNTechSecond
Case 18Female65Pfizer-BioNTechFirst
Case 19Male36Pfizer-BioNTechSecond
Case 20Male41Pfizer-BioNTechSecond
Case 21Female28Pfizer-BioNTechSecond
Bolletta (2021) [15]ItalyCase 1Male79Oxford/AstraZenecaSecond
Case 2Female65Pfizer-BioNTechSecond
Case 3Female42Oxford/AstraZenecaSecond
Case 4Female52Pfizer-BioNTechSecond
Case 5Male44Pfizer-BioNTechFirst
Case 6Female35ModernaSecond
Case 7Male47Pfizer-BioNTechFirst
Case 8Female58Pfizer-BioNTechFirst
Case 9Female52Oxford/AstraZenecaFirst
Case 10Female44Pfizer-BioNTechSecond
Case 11Female58Pfizer-BioNTechSecond
Case 12Female47Pfizer-BioNTechFirst
Case 13Female68Pfizer-BioNTechSecond
Observational Studies
Author (YOP)CountryDesignMale/TotalAge
Mean (SD)		Type [N]Dose [N]
Ferrand (2022) [27]GermanyRetrospective Cohort6/2543.2 (13.9)Pfizer-BioNTech [15]; Oxford/AstraZeneca [6]; Moderna [3]; Covaxin [1]First [6]; Second [19]
Ozdede (2022) [50]IstanbulCross-Sectional-/5-Sinovac [3]; Pfizer-BioNTech [2]-
Testi (2022)UKRetrospective Cohort22/5041.3 (13.9)Pfizer-BioNTech [24]; Oxford/AstraZeneca [16]; Moderna [8]; Sinopharm [1]; Covaxin [1]First [28]; Second [22]
Tomkins-Netzer (2022) [7]IsraelRetrospective Cohort--Pfizer-BioNTech [188]First [100]; Second [88]
Barda (2021) [14]IsraelRetrospective Cohort-/26-Pfizer-BioNTech [26]-
Singh (2022b) [71]USARetrospective registry-based322/109446.24 (16.93)Pfizer-BioNTech [853]; Moderna [220]; Johnson & Johnson [21]First [452]; Second [373]; Third [97]; Fourth [5]
YOP: Year of Publication; UK: United Kingdom; USA: United States of America; N: Number of Cases; SD: Standard Deviation.
Table
Table 2. Patients’ and COVID-19 vaccines’ characteristics.
Table 2. Patients’ and COVID-19 vaccines’ characteristics.
VariableSubgroupNumber%
Gender
Male40631.06
Female90168.93
Age
1–1010.73
11–2085.84
21–302014.6
31–401913.87
41–502719.71
51–602316.79
61–702014.6
71–80139.49
81–9042.92
≥9121.46
Vaccine Type
Covaxin40.26
Johnson & Johnson221.44
Moderna23715.54
Oxford/AstraZeneca463.01
Pfizer-BioNTech118877.9
Sinovac110.72
Sinopharm171.11
Vaccine Dose
First65449.35
Second56242.41
Third1047.84
Fourth50.37
Table
Table 3. The systemic, ocular, and immunologic history of vaccine-associated uveitis cases.
Table 3. The systemic, ocular, and immunologic history of vaccine-associated uveitis cases.
Author (YOP)Medical HistoryTotal
Systemic [N]Ocular [N]Immunological [N]
Accorinti (2022)None--1
Achiron (2022)-Uveitis [1]—RVO [1]—Iridis Rubeosis [1]-1
Al-Allaf (2022)HTN--1
Alhamazani (2022)---1
Brunet de Courssou (2022)---1
Chen (2022a)NoneNoneNone1
De Carvalho (2022)ASUveitis [1]HLA-B27 [1]1
De Domingo (2022)-NoneNone1
Ishay (2021)Bechet’s diseaseNoneBechet’s disease [1]1
Duran (2022)DMNone-1
ElSheikh (2021)-NoneJIA [1]1
Lee (2022)HTN—LipidemiaNone-1
Gedik (2022)---1
Goyal (2021)NoneNoneNone1
Hébert (2022)NoneNoneNone1
Hwang (2022)NoneNoneNone1
Jain (2021)-Uveitis [1]JIA [1]1
K. Joo (2022)NoneAllergic conjunctivitis [1]None1
Kim (2022)---1
Koong (2021)DM—LipidemiaNoneNone1
Papasavvas (2021)NoneCataract [1]None1
Ding (2022)HTNNoneNone1
Lee (2022)--None1
Sai (2022)-Uveitis [1]JIA [1]1
Matsuo (2022)---1
Mishra (2021)DM—HTN--1
Mudie (2021)---1
Pan (2021)---1
Papasavvas (2021)-VKH [1]None1
Reddy (2021)---1
Renisi (2021)NoneNoneNone1
Sangoram (2022)NoneNoneNone1
Santiago (2021)NoneNoneNone1
Saraceno (2021)NoneNoneNone1
Singh (2022a)NoneNoneNone1
Yalçinkaya (2022)NoneNoneNone1
Yamaguchi (2022)NoneNoneNone1
Shilo (2022)NoneNoneNone1
Kakarla (2022)NoneNoneNone1
Numakura (2022)NoneNoneNone1
Murgova (2022)-CRVO [1]—Cataract [1]—Glaucoma [1]—Herpetic uveitis [1]-1
Patel (2022)NoneCataract [1]—RD [1]—ERM [1]None1
Lawson-Tovey (2022)---1
Arora (2022)-Uveitis [2]—SLC [1]-2
Choi (2022)HTN [2]—DM [1]—Asthma [1]Uveitis [2]—BRVO [1]HLAB51 [1]3
Ortiz-Egea (2022)-AMD [1]-2
Nanji (2022)-Uveitis [1]—OU [1]-2
Pang (2022)---2
Ren (2022)---2
Cohen (2022)NoneHZO [1]—Uveitis [1]Psoriasis [1]—RA [1]4
Aguiar (2022)Epilepsy [1]—Asthma [1]—DM [1]—HTN [1]—Rhinitis [1]NoneNone2
Ferreira (2022)COVID-19 [2]—HTN [1]NoneNone4
Chen (2022b)AS [1]--5
Chew (2022)NoneUveitis [3]—Cataract [1]—PACG [1]—HSK [4]HLAB51 [1]6
Rallis (2022)---7
Li (2022)---9
Sim (2022)---11
Rabinovitch (2021)AS [3]—Psoriasis [2]—Crohn’s disease [1]—Spondylarthritis [1]Uveitis [8]—HZO [1]-21
Bolletta (2021)Spondylarthritis [1]—Psoriatic arthritis [1]Uveitis [3]—VKH [2]—Toxoplasma Retinochoroiditis [2]-13
Ferrand (2022)-Uveitis [19]—VKH [1]HLAB27 [2]—MS [2]—JIA [1]25
Ozdede (2022)--Bechet’s syndrome [1]5
Testi (2022)-Uveitis [20]—Glaucomatocyclitic Crisis [3]50
Tomkins-Netzer (2022)---188
Barda (2021)---26
Singh (2022b)COVID-19 [9]Uveitis [106]AIDs [14]1094
Summary of the History of VAU Cases
CategoryDiseaseNumberTotal%
Systemic Diseases
HTN711780.59
DM511780.42
AS511780.42
Lipidemia211780.16
Asthma211780.16
Epilepsy111780.08
Rhinitis111780.08
COVID-191111780.93
Ocular Diseases
Uveitis170125813.51
VKH412580.32
HZO212580.16
Toxoplasma Retinochoroiditis212580.16
Glaucoma512580.39
Cataract412580.32
HSK412580.32
SLC112580.07
BRVO112580.07
RVO112580.07
Iridis Rubeosis112580.07
OU112580.07
CRVO112580.07
ERM112580.07
RD112580.07
Conjunctivitis112580.07
AMD112580.07
Immunological Diseases
HLA-B27311700.26
JIA411700.34
Psoriasis311700.26
HLAB51211700.17
MS211700.17
Bechet’s disease311700.26
AIDs1411701.19
RA111700.08
Crohn’s disease211700.17
Spondylarthritis111700.08
AS: Ankylosing Spondylitis; AMD: Age-related Macular Degeneration; BRVO: Branch Retinal Vein Occlusion; CRVO: Central Retinal Vein Occlusion; ERM: Epiretinal Membrane; HTN: Hypertension; HSK: Herpes-Simplex Keratitis; HZO: Herpes-Zoster Ophthalmicus; JIA: Juvenile Idiopathy Arthritis; OU: Optic Disc Vasculitis; PACG: Primary Angle-Closure Glaucoma; RD: Retinal Detachment; SLC: Serpiginous-like Choroiditis; VAU: Vaccine-Associated Uveitis; VKH: Vogt-Koyanagi-Harada.
Table
Table 4. The clinical presentation of COVID-19 vaccine-associated uveitis.
Table 4. The clinical presentation of COVID-19 vaccine-associated uveitis.
Author (YOP)Eye Symptoms/Signs [N]Total
Accorinti (2022)Central scotoma [1]1
Achiron (2022)Vision loss [1]1
Al-Allaf (2022)Pain [1]—Erythema [1]—Photophobia [1]—Blurry vision [1]1
Alhamazani (2022)Pain [1]—Photophobia [1]—Redness [1]—Diminished Vision [1]1
Brunet de Courssou (2022)Headache [1]—Blurry vision [1]1
Chen (2022a)Headache [1]—Blurry vision [1]—Fatigue [1]1
De Carvalho (2022)Pain [1]—Redness [1]—Foreign Body Sensation [1]1
De Domingo (2022)Blurry vision [1]1
Ishay (2021)Pain [1]—Redness [1]—Blurry vision [1]1
Duran (2022)Blurry vision [1]—Redness [1]—Headache [1]1
ElSheikh (2021)Blurry vision [1]—Photophobia [1]1
Lee (2022)Vision loss [1]1
Gedik (2022)Pain [1]—Diminished vision [1]1
Goyal (2021)Vision loss [1]1
Hébert (2022)Vision loss [1]—Floaters [1]1
Hwang (2022)Erythema [1]1
Jain (2021)Pain [1]—Redness [1]1
K. Joo (2022)Pain [1]—Blurry vision [1]—Headache [1]—Eyelid swelling [1]1
Kim (2022)Vision loss [1]—Headache [1]1
Koong (2021)Blurry vision [1]1
Papasavvas (2021)Pain [1]1
Ding (2022)Vision loss [1]1
Lee (2022)Pain [1]—Blurry vision [1]1
Sai (2022)Blurry vision [1]—Floaters [1]1
Matsuo (2022)Blurry vision [1]1
Mishra (2021)Pain [1]—Diminished vision [1]1
Mudie (2021)Pain [1]—Photophobia [1]—Redness [1]—Vision loss [1] 1
Pan (2021)Vision loss [1]1
Papasavvas (2021)Pain [1]—Diminished vision [1]—Photophobia [1]1
Reddy (2021)Blurry vision [1]1
Renisi (2021)Pain [1]—Redness [1]—Diminished vision [1]—Photophobia [1]1
Sangoram (2022)Blurry vision [1]—Pain [1]1
Santiago (2021)Redness [1]1
Saraceno (2021)Vision loss [1]1
Singh (2022a)Diminished vision [1]1
Yalçinkaya (2022)Redness [1]1
Yamaguchi (2022)Metamorphopsia [1]—Diminished vision [1]1
Shilo (2022)Photophobia [1]—Vision loss [1]1
Kakarla (2022)Blurry vision [1]—Headache [1]1
Numakura (2022)Blurry vision [1]1
Murgova (2022)Metamorphopsia [1]1
Patel (2022)Pain [1]—Blurry vision [1]—Floaters [1]1
Lawson-Tovey (2022)-1
Arora (2022)Diminished vision [1]—Floaters [1]2
Choi (2022)Diminished vision [3]3
Ortiz-Egea (2022)Pain [2]—Redness [1]2
Nanji (2022)Pain [2]—Redness [2]2
Pang (2022)Blurry vision [1]2
Ren (2022)Diminished vision [1]—Blurry vision [1]—Redness [1]—Pain [1]2
Cohen (2022)Pain [1]—Photophobia [1]—Diminished vision [1]—Floaters [1]4
Aguiar (2022)Redness [2]—Photophobia [2]—Pain [1]—Diminished vision [1]2
Ferreira (2022)Vision loss [3]—Headache [4]—Blurry vision [1]—Hyperemia [1]4
Chen (2022b)Blurry vision [5]—Redness [3]5
Chew (2022)Blurry vision [6]—Redness [3]—Pain [1]6
Rallis (2022)Diminished vision [7]—Pain [7]7
Li (2022)-9
Sim (2022)-11
Rabinovitch (2021)Redness [21]—Pain [21]—Blurry vision [21]—Photophobia [21]—Photopsia [2]—Diminished vision [2]21
Bolletta (2021)Blurry vision [12]—Redness [3]—Pain [2]—Photophobia [1]13
Ferrand (2022)-25
Ozdede (2022)-5
Testi (2022)-50
Tomkins-Netzer (2022)-188
Barda (2021)-26
Singh (2022b)Pain [270]—Redness [839]—Diminished vision [262]—Photophobia [95]—Floaters [21]—Lacrimation [22]1094
Summary of Symptoms/Signs of VAU
PresentationNumberTotal%
Central Scotoma112110.08
Vision Loss1312111.07
Pain5312114.37
Erythema212110.16
Photophobia127121110.48
Blurry vision6412115.28
Redness884121172.99
Diminished vision285121123.53
Headache1012110.82
Foreign Body Sensation112110.08
Floaters2712112.22
Eyelid swelling112110.08
Photopsia212110.16
Metamorphopsia212110.16
YOP: Year of Publication; VAU: Vaccine-Associated Uveitis; N: Number.
Table
Table 5. The type, laterality, course, location, onset, nature, and underlying cause of vaccine-associated uveitis.
Table 5. The type, laterality, course, location, onset, nature, and underlying cause of vaccine-associated uveitis.
OutcomeCategoryNumberTotal%
Type of VAU
VKH1614761.08
Choroiditis914760.6
Iridocyclitis114760.06
Iritis214760.13
Kerato-uveitis114760.06
Retinitis214760.13
Uveitis1440147697.56
Retinochoroiditis314760.2
Pars planitis214760.13
Laterality
Right12639032.3
Left13539034.61
Unilateral30339077.69
Bilateral8639022.05
Course
Acute23432671.77
Chronic9232628.22
Location
Anterior799147654.13
Intermediate1414760.94
Posterior7814765.28
Panuveitis148147610.02
Onset
New-onset24434969.92
Reactivation10534930.08
Nature
Autoimmune42991.34
Granulomatous62992.01
Inflammatory [non-infectious]26429988.29
Infectious252998.36
Underlying Cause
Behcet’s disease42451.63
CMV12450.4
HSV-192453.67
HZO32451.22
JIA42451.63
MIS-C12450.4
Retinal vasculitis12450.4
Sarcoidosis32451.22
Toxoplasma42451.63
VKH182457.34
VZV32451.22
Psoriasis12450.4
Spondylarthritis12450.4
Idiopathic10624543.26
HLA B27122454.89
Fuchs heterochromic iridocyclitis22450.81
Posner–Schlossman syndrome12450.4
Duration from vaccination to uveitis attack (days)
Mean—SD9.618.07
Min—Max142
Observations108
Table
Table 6. The outcomes and complications following the treatment of vaccine-associated uveitis.
Table 6. The outcomes and complications following the treatment of vaccine-associated uveitis.
OutcomeCategoryNumberTotal %Duration (days)
Complications
CME2832.4160
Choroidal depigmentation2832.4114
Inflammatory glaucoma1831.2-
Peripheral neovascularization1831.2135
Retinal necrosis1831.2-
Recurrence of choroidal thickening1831.221
ME2832.41180
Uveitis exacerbation1831.2-
Vitritis1831.2-
Transient IOP elevation3833.61-
Nummular Corneal Lesions3833.61-
Treatment Outcome
Complete Resolution17419390.15-
Partial Improvement191939.85-
CME: Cystoid Macular Edema; ME: Macular Edema; IOP: Intraocular Pressure.
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Cherif, Y.Y.S.; Djeffal, C.; Abu Serhan, H.; Elnahhas, A.; Yousef, H.; Katamesh, B.E.; Abdelazeem, B.; Abdelaal, A. The Characteristics of COVID-19 Vaccine-Associated Uveitis: A Summative Systematic Review. Vaccines 2023, 11, 69. https://doi.org/10.3390/vaccines11010069

AMA Style

Cherif YYS, Djeffal C, Abu Serhan H, Elnahhas A, Yousef H, Katamesh BE, Abdelazeem B, Abdelaal A. The Characteristics of COVID-19 Vaccine-Associated Uveitis: A Summative Systematic Review. Vaccines. 2023; 11(1):69. https://doi.org/10.3390/vaccines11010069

Chicago/Turabian Style

Cherif, Yasmine Yousra Sadok, Chakib Djeffal, Hashem Abu Serhan, Ahmed Elnahhas, Hebatallah Yousef, Basant E. Katamesh, Basel Abdelazeem, and Abdelaziz Abdelaal. 2023. "The Characteristics of COVID-19 Vaccine-Associated Uveitis: A Summative Systematic Review" Vaccines 11, no. 1: 69. https://doi.org/10.3390/vaccines11010069

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