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Ocular inflammatory events following COVID-19 vaccination: a multinational case series

Ocular inflammatory events following COVID-19 vaccination: a multinational case series Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome. Keywords: Uveitis, Ocular inflammation, Immunomodulatory, Coronavirus disease, COVID-19, SARS-CoV-2, Vaccination The most common ocular manifestation of COVID-19, prevention of 2019 coronavirus disease, whereas the the disease cause by SARS-CoV-2, includes conjunctiv- Oxford-AstraZeneca COVID-19 vaccine was authorised itis, with reported cases of keratitis, keratoconjunctivitis, by the European Medicines Agency (EMA) soon after in episcleritis, uveitis, posterior ischemic optic neuropathy January 2021. Currently, there are four types of COVID- and retinal vascular involvement [1–4]. In December 19 vaccines available, including the messenger RNA 2020, the Food and Drug Administration (FDA) released (mRNA) vaccines (Pfizer-BioNTech and Moderna); the the emergency use authorisation for the Pfizer- protein subunit vaccines (Novavax); the vector vaccines BioNTech and Moderna COVID-19 vaccine for the (Janssen Johnson & Johnson and Oxford-AstraZeneca), and the whole virus vaccines (Sinovac13, Sinopharm14 * Correspondence: c.pavesio@nhs.net and Covaxin). Inflammatory adverse events, including Department of Uveitis, Moorfields Eye Hospital, NHS Foundation Trust, myocarditis and pericarditis, have been reported to London, UK Full list of author information is available at the end of the article occur following COVID-19 vaccination [5, 6]. The © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 2 of 6 objective of this study is to describe the spectrum and corresponding phenotypes is described in Table 1 with outcome of ocular inflammatory events associated with the details of ocular inflammatory events in Table 2. the administration of COVID-19 vaccination. Forty-one patients had anterior uveitis after vaccin- ation, of which nine (22.0%) had history of HLA-B27 as- Methods sociated uveitis (one was on secukinumab and one on Case series of patients diagnosed with an ocular in- infliximab plus methotrexate), six (14.6%) had idiopathic flammatory event after receiving COVID-19 vaccin- anterior uveitis, three (7.3%) had glaucomatocyclitic cri- ation collected from 40 international centres over a 3 sis (one on topical corticosteroids), two (4.9%) with her- month period in 2021 (see group information). The petic anterior uveitis, one (2.4%) of juvenile idiopathic study was conducted with ethical approval obtained arthritis associated uveitis (on adalimumab), one (2.4%) by the leading centre from its local institutional ethics of Cytomegalovirus (CMV) uveitis and one (2.4%) of sys- committee (ethics approval: 2021/00438). The diagno- temic lupus erythematosus uveitis (on hydroxychloro- sis of COVID-19 vaccination related-ocular inflamma- quine). All the events after vaccination in these patients tion was established based on the onset of the event were similar to their previous ones. Two patients (4.9%) within 14 days following COVID-19 vaccination and presented with herpetic anterior uveitis for the first time the patients who satisfied this specific criteria were and no other new diagnosis was made for any other pa- only recruited for this report. A form for data collec- tient. Two patients (4.9%) had persistent visual loss on tion was sent to all International Ocular Inflammation the last follow-up, one (2.4%) due to cystoid macular Society (IOIS) and International Uveitis Study Group oedema (visual acuity (VA) reduced ≤3 lines) and one (IUSG) members. Clinicians who observed an ocular (2.4%) due to nummular corneal lesions (VA reduced > inflammatory event within 14 days following COVID- 3 lines). 19 vaccination filled out the form. The following in- Nine patients had posterior uveitis after vaccination, of formation were retrieved from patients’ medical which 2 (22.2%) had history of ocular toxoplasmosis, records: type of COVID-19 vaccination, timing of the and one (11.1%) of acute zonal occult outer retinopathy events, including date of vaccination and date of on- (AZOOR). The patients with history of ocular toxoplas- set of uveitis, past ocular history, type of ocular in- mosis presented with recurrence of lesions and the pa- flammatory event, including scleritis, episcleritis, tient with AZOOR had a different presentation from anterior uveitis, posterior uveitis, intermediate uveitis, previous events, with multifocal choroiditis. Three pa- panuveitis, and optic neuritis, local and systemic tients (33.3%) presented with ocular toxoplasmosis, two treatment history, therapeutic management and (22.2%) presented with retinal vasculitis, and one (11.1%) outcome. presented with choroiditis for the first time. One patient (11.1%) with ocular toxoplasmosis, and one (11.1%) with Data collection occlusive retinal vasculitis had persistent visual loss on A purpose built data entry platform was created to col- the last follow-up due to macular scarring. lect the ocular inflammatory adverse reactions to Seven patients had anterior scleritis after vaccination, COVID-19 vaccination. The secure encrypted web-based of which four (57.1%) had history of idiopathic anterior platform was programmed by CP, RA and IT. Given the scleritis, and one (14.3%) of idiopathic posterior scleritis observational and retrospective nature of the data, mul- (on methotrexate and prednisolone). All the events after tiple imputations were not allowed. Ninety-four cases vaccination in these patients were similar to their previ- were collected, however, 24 had the event, 2 weeks after ous ones. Two patients (28.6%) presented anterior scler- the vaccination and were excluded from the analysis, itis for the first time. All patients had unaffected visual resulting in 70 cases. Statistical analysis was done using acuity after the event. the software R v 4.1.1 [R Core Team (2021). R: A lan- Other events (N = 13, 18.6%) included panuveitis (N = guage and environment for statistical computing. R 3, 4.3%), optic neuritis (N = 2, 2.9%), episcleritis (N = 2, Foundation for Statistical Computing, Vienna, Austria]. 2.9%), intermediate uveitis (N = 2, 2.9%), paracentral Continuous variables were described as median [range] acute middle maculopathy (N = 1, 1.4%), giant cell arter- while binary variables were described as number (%). itis (N = 1, 1.4%), periocular skin herpes zoster (N = 1, 1.4%), and unspecific blurriness of vision (N = 1, 1.4%). Results Among these patients, one (7.7%) had history of inter- Seventy patients presented with ocular inflammatory mediate uveitis (was on mycophenolic acid), one (7.7%) events within 14 days following COVID-19 vaccination, of idiopathic panuveitis (was on azathioprine), one and the most common were anterior uveitis (n = 41, (7.7%) of optic neuritis, one (7.7%) of CMV anterior uve- 58.6%), posterior uveitis (n = 9, 12.9%), and anterior itis, and one (7.7%) of episcleritis. The events after vac- scleritis (n = 7, 10.0%). The study population and the cination in these patients were similar to their previous Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 3 of 6 Table 1 Description of the study population by the type of event (n = 70) Variable Total (%) Anterior Uveitis Posterior Uveitis Scleritis Others (%) (%) (%) (%) Demographics Number of Patients 70 (100.0) 41 (58.6) 9 (12.9) 7 (10.0) 13 (18.6) Age (years) 51 [19–84] 55 [19–84] 40 [28–61] 48 [40–52] 54 [25–79] Gender = Female 35 (56.5) 19 (52.8) 4 (44.4) 6 (85.7) 6 (60) Gender = Male 27 (43.5) 17 (47.2) 5 (55.6) 1 (14.3) 4 (40) History of Previous COVID-19 1 (1.4) 1 (2.4) 0 (0.0) 0 (0.0) 0 (0.0) Vaccine Pfizer 40 (57.1) 20 (48.8) 4 (44.4) 5 (71.4) 11 (84.6) Astra-Zeneca 17 (24.3) 12 (29.3) 4 (44.4) 1 (14.3) 0 (0) Moderna 10 (14.3) 7 (17.1) 1 (11.1) 1 (14.3) 1 (7.7) Sinopharm 2 (2.9) 1 (2.4) 0 (0) 0 (0.0) 1 (7.7) Covaxin 1 (1.4) 1 (2.4) 0 (0) 0 (0.0) 0 (0) Event After First Dose Number of Patients 43 (61.4) 22 (53.7) 6 (66.7) 4 (57.1) 11 (84.6) Time After First Dose [days] 6[1–14] 5.5 [1–14] 6.5 [1–14] 4.5 [1–9] 8 [1–14] Received Another Dose 18 (41.9) 11 (50) 3 (50) 1 (25) 3 (27.3) Recurrence After Second Dose 6/18 5 / 11 (45.5) 0 (0.0) 1 / 4 (25.0) 0 (0.0) (33.3) Event After Second Number 27 (39.6) 19 (46.3) 3 (33.3) 3 (42.9) 2 (15.4) Dose Time After Second Dose 5[1–14] 5 [1–14] 8 [2–9] 4 [2–14] 7 [2–12] [days] Missing Data for Age and Gender: Total = 8, Anterior Uveitis = 5, Others = 3 ones, except for the patient with history of CMV anter- this study. A search of Medline, using PubMed and ior uveitis, who presented with intermediate uveitis after Google Scholar, performed in August 2021, using the vaccination. One patient (7.7%) had persistent visual loss following keywords: ‘uveitis’, ‘vaccination’, ‘COVID- on the last follow-up due to cystoid macular oedema in 19’, revealed six case reports and two national case intermediate uveitis (VA reduced ≤3 lines). series describing presumed COVID-19 vaccine-related Regarding the management of the events, 39 patients uveitis have been reported so far, including new onset (55.7%) received only topical corticosteroids, 13 (18.6%) of bilateral juvenile idiopathic arthritis (JIA)-associated received systemic corticosteroids (five of them also re- anterior uveitis, unilateral anterior uveitis, bilateral ceived topical corticosteroids and four antibiotics), 10 choroiditis complicated by subretinal fluid, bilateral (14.3%) did not require any treatment, six (8.6%) re- panuveitis with choroidal thickening and vascular ceived antivirals (two of them with topical corticoste- leakage, and recurrence of Vogt Koyanagi Harada roids), and two (2.8%) received topical corticosteroids (VKH) [19–26]. Rabinovitch et al. reported twenty with oral non-steroidal anti-inflammatory drugs (NSAI one cases of uveitis after COVID-19 vaccination in Ds). Three patients (4.3%) required IOP lowering medi- Israel, of which nineteen were diagnosed with anterior cations (two with glaucomatocyclitic crisis and one with uveitis and two developed multiple evanescent white CMV anterior uveitis) and one (1.4%) initiated metho- dot syndrome (MEWDS) [24]. Recently, Pichi et al. trexate after the episode (giant cell arteritis). described seven patients diagnosed with episcleritis (1), anterior scleritis (2), acute macular neuroretinopa- Discussion thy (AMN) (2), paracentral acute middle maculopathy Although rare, development of uveitis after administra- (PAMM) (1), and subretinal fluid (1) after COVID-19 tion of vaccine is a known event. Cases of vaccine- vaccination [25]. None of these studies was a multi- associated uveitis have been reported with almost all the central case series. Similarly to the findings of Rabi- vaccines currently administered, including vaccines novitch et al., we found that anterior uveitis was the against hepatitis A and B virus, human papillomavirus, most common ocular inflammatory event observed influenza virus, bacillus Calmette-Guerin, measles- after COVID-19 vaccination, with more than 50% of mumps-rubella, varicella virus, yellow fever and Neis- the patients having a known history of uveitis. The seria meningitides [7–18]. majority of the episodes we reported occurred after Ocular inflammatory events after COVID-19 vaccin- the Pfizer vaccine. These findings are probably based ation from a multinational case series are described in on the number of the administered doses. Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 4 of 6 Table 2 Ocular Inflammatory Events Description Variable Total Anterior Uveitis Posterior Uveitis Scleritis Others (%) (%) (%) (%) (%) (N = (N = 41) (N = 9) (N =7) (N = 13) 70) Previous Ocular Inflammatory Number of patients 36 23 (56.1) 3 (33.3) 5 (71.4) 5 (38.5) Events (51.4) Controlled more than 3 28 17 (81.0) 3 (100) 3 (60.0) 5 (100) months (82.4) On Topical Anti-inflammatory 1 (2.8) 1 (4.3) 0 (0.0) 0 (0.0) 0 (0.0) On Systemic Anti- 7 (19.4) 4 (17.4) 0 (0.0) 1 (20.0) 2 (15.4) inflammatory Event similar to previous 34 23 (100.0) 2 (66.7) 5 (100.0) 4 (80) events (94.4) Presentation Unilateral 60 33 (80.5) 8 (88.9) 7 (100) 12 (92.3) (85.7) Bilateral 10 8 (19.5) 1 (11.1) 0 (0.0) 1 (7.7) (14.3) VA Unaffected 38 22 (53.7) 2 (22.2) 6 (85.7) 8 (61.5) (54.3) VA reduced ≤ 3 lines 18 10 (24.4) 4 (44.4) 1 (14.3) 3 (23.1) (25.7) VA reduced > 3 lines 14 9 (22.0) 3 (33.3) 0 (0.0) 2 (15.4) (20.0) Management Topical Corticosteroids 48 34 (82.9) 3 (33.3) 6 (85.7) 5 (38.5) (68.6) Systemic Corticosteroids 13 2 (4.9) 6 (66.7) 1 (14.3) 4 (30.8) (18.6) Antivirals 6 (8.6) 5 (12.2) 0 (0.0) 0 (0.0) 1 (7.7) NSAIDs 2 (2.9) 0 (0.0) 0 (0.0) 1 (14.3) 1 (7.7) Antibiotics 4 (5.7) 0 (0.0) 4 (44.4) 0 (0.0) 0 (0.0) Visual Outcomes VA Unaffected 65 39 (95.1) 7 (77.8) 7 (100) 12 (92.3) (92.9) VA reduced ≤ 3 lines 2 (2.9) 1 (2.4) 0 (0.0) 0 (0.0) 1 (7.7) VA reduced > 3 lines 3 (4.3) 1 (2.4) 2 (22.2) 0 (0.0) 0 (0.0) Complications Transient IOP elevation 3 (4.3) 3 (7.3) 0 (0.0) 0 (0.0) 0 (0.0) Nummular Corneal Lesions 1 (1.4) 1 (2.4) 0 (0.0) 0 (0.0) 0 (0.0) Cystoid Macular Oedema 2 (2.9) 1 (2.4) 0 (0.0) 0 (0.0) 1 (7.7) Macular Scarring 2 (2.9) 0 (0.0) 2 (22.2) 0 (0.0) 0 (0.0) The potential mechanism underlying the ocular in- specificity, (4) temporality, (5) biological gradient, (6) flammation response following COVID-19 vaccination is plausibility, (7) coherence, (8) experiment, and analogy not known. Commonly proposed mechanisms include (9) [31]. The design of this study guarantees temporality, (1) molecular mimicry secondary to resemblance be- since there was a short interval of time following vaccin- tween uveal peptides and vaccine peptide fragments, (2) ation and the onset of the events. The fact that among antigen-specific cell and antibody-mediated hypersensi- 18 patients who had an event following the first dose tivity reactions, (3) inflammatory damage induced by ad- and still received a second dose, 6 (33.3%) presented juvants included the vaccines stimulating innate similar events following the second dose, as well as dif- immunity through endosolic or cytoplasmic nucleic acid ferent observations in different regions from different receptors [18, 27–30]. people, supports consistency (reproducibility) between The Bradford-Hill criteria include nine aspects to con- exposure and outcome. The causality is plausible as sider when inferring causality between events: (1) some biological mechanisms have already been pro- strength of the association, (2) consistency, (3) posed. Finally, the events after COVID-19 vaccination Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 5 of 6 are analogous to those reported following other Medicine, Chicago, IL, USA; Nima Ghadiri, Liverpool University Hospital, Liver- pool, UK; Alex Fonollosa Calduch, Hospital Universitario Cruces, Universidad vaccines. del País Vasco, Instituto Oftalmológico Bilbao, Bilbao, Spain; Gabriel Costa de From our study it emerged that most of the inflamma- Andrade; Padmamalini Mahendradas, Narayana Nethralaya, Bangalore, India; tory episodes were not severe, and patients were mainly Julio J González-López, Hospital Ramón y Cajal, Madrid, Spain; Ester Carreño, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Rola N Hamam, managed with topical corticosteroids or observation only American University of Beirut, Lebanon; Nicole Stübiger, Universitätsklinikum (70%), with unaffected final visual acuity (92.9%). Very Hamburg-Eppendorf, Augenklinik, Germany; Bahram Bodaghi, Sorbonne Uni- few patients developed ocular complications resulting in versité, Hôpital de la Pitié-Salpêtrière, Paris, France; Yu-Jang Chao, Cheng Hsin General Hospital, Taipei, Taiwan; Masaru Takeuchi, National Defense Medical tissue damage and visual loss (7.1%), including corneal College, Namiki Tokorozawa Saitama, Japan; Mei-Ling Tay-Kearney, Lions Eye opacity, cystoid macular oedema and macular scarring. Institute, Royal Perth Hospital, Perth, WA, USA; Alejandro Portero, Hospital Study limitations include its observational and non- Universitario La Zarzuela, Madrid, Spain; Hiroshi Keino, Kyorin University School of Medicine, Tokyo, Japan; Padmamalini Mahendradas, Narayana controlled nature, that cannot be used to infer causality Nethralaya, Bangalore; Mar Esteban-Ortega, Hospital Infanta Sofia, San Sebas- because it does not allow to stablish strength of the asso- tian de los Reyes, Madrid, Spain; Joanna Przeździecka-Dołyk, Wrocław Medical ciation, specificity, biological gradient, coherence, nor University, Wroclaw, Poland; Aleksandra Radosavljević, University Clinical Cen- ter of Serbia, Belgrade, Serbia; Ian Paredes, Legaspi Eye Center, Legaspi, Bicol, experiment. Additionally, there is a potential sample bias Philippines and Chua Eye Center, Angeles, Pampanga, Philippines; Rupesh due to the form of data collection, and the data collected Agrawal, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, might not be representative of all population, although Singapore; Ho Su Ling, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; Wei Kiong, National Healthcare Group Eye Institute, the multicentre nature of the study need to be consid- Tan Tock Seng Hospital, Singapore; Melissa Tien, National Healthcare Group ered as it may reduce the bias. Eye Institute, Tan Tock Seng Hospital, Singapore; Xin Le Ng, National Health- care Group Eye Institute, Tan Tock Seng Hospital, Singapore; Carlos Pavesio, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; Ilaria Testi, Moor- Conclusion fields Eye Hospital, NHS Foundation Trust, London, UK; Soon Phaik Chee, Hereby we report a large multinational case series of Singapore National Eye Centre, Singapore; Jay Siak, Singapore National Eye ocular inflammatory events occurred following COVID- Centre, Singapore; Ines Hernanz-Rodriguez, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Victor Menezo, Institut Catala de Retina, Barce- 19 vaccination, based on a temporal and multicentrical lona, Spain; Christoph Tappeiner, Department of Ophthalmology, Pallas Klini- association, but not proving causality. Even in the possi- ken, Olten, Switzerland; Franz Marie Cruz, Peregrine Eye and Laser Institute, bility of of a causal association, most of the events were Makati, Philippines; Peter Addison, London, UK; Robert Kuijpers, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; Daniel Vitor mild and had a good visual outcome. Therefore, there is Vasconcelos-Santos, Universidade Federal de Minas Gerais, Belo Horizonte, no evidence from this study to suggest that individuals Brazil. should avoid getting vaccinated because of ophthalmic- Authors’ contributions related adverse events. It is not the aim of the authors to Conception and design: Pavesio, Testi, Agrawal. Analysis and interpretation: impede or curtail the vaccination efforts, but rather to Brandão-de-Resende, Pavesio, Testi, Agrawal. Overall responsibility: Pavesio, educate physicians and patients about rare but potential Testi, Agrawal, Brandão-de-Resende. The authors read and approved the final manuscript. ocular inflammatory events after the COVID-19 vaccination. Funding None. Abbreviations FDA: Food and drug administration; EMA: European medicines agency; Availability of data and materials mRNA: Messenger RNA; AZOOR: Acute zonal occult outer retinopathy; All the data pertaining to the cases are available with the corresponding VA: Visual acuity; CMV: Cytomegalovirus; NSAIDs: Non-steroidal anti- author. inflammatory drugs; JIA: Juvenile idiopathic arthritis; VKH: Vogt Koyanagi Harada; MEWDS: Multiple evanescent white dot syndrome; AMN: Acute Declarations macular neuroretinopathy; PAMM: Paracentral acute middle maculopathy Consent for publication Acknowledgements The IRB/ethics committee approved this study. All research adhered to the We would like to acknowledge the International Ocular Inflammation Society tenets of the Declaration of Helsinki. The requirement for informed consent (IOIS) and International Uveitis Study Group (IUSG) for supporting the was waived because of the retrospective nature of the study. project. *Group Information. Competing interests The COVID-19 Vaccination Ocular Inflammatory Events Study Group The authors have no relevant affiliations or financial involvement with any members are: Laura Steeples, Manchester Royal Eye Hospital, Manchester, UK; organization or entity with a financial interest in or financial conflict with the Balini Balasubramaniam, Queen Elizabeth Hospital, Birmingham, UK; Peter subject matter or materials discussed in the manuscript. This includes McCluskey, The University of Sydney, Save Sight Institute, Sydney, Australia; employment, consultancies, honoraria, stock ownership or options, expert Francesco Pichi, Cleveland Clinic Abu Dhabi, UAE; Aniruddha Agarwal, testimony, grants or patents received or pending, or royalties. Cleveland Clinic Abu Dhabi, UAE; Carl Herbort, COS, Lausanne, Switzerland; Luca Cimino, Arcispedale S. Maria Nuova, Reggio Emila, Italy; Salam Iriqat, St Author details John of Jerusalem Eye Hospital, Jerusalem, Israel; Jennifer E. Thorne, Wilmer Department of Uveitis, Moorfields Eye Hospital, NHS Foundation Trust, Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, London, UK. Clinical Research Facility, Moorfields Eye Hospital, NHS USA; Jose Echegaray, Case Western Reserve University in Cleveland, OH, USA; Foundation Trust, London, UK. National Healthcare Group Eye Institute, Tan Kalpana Babu, Prabha eye clinic and research centre & Vittala Institute of Tock Seng Hospital, Singapore, Singapore. Singapore Eye Research Institute, Ophthalmology, Bangalore, India; Alexander Arthur Bialasiewicz, Al-Ahli Hos- Singapore, Singapore. Lee Kong Chian School of Medicine, Nanyang pital, Doha, Qatar; Debra A. 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Papasavvas I, Herbort CP Jr (2021) Reactivation of Vogt-Koyanagi-Harada disease under control for more than 6 years, following anti-SARS-CoV-2 vaccination. J Ophthalmic Inflamm Infect 11(1):21. https://doi.org/10.1186/ s12348-021-00251-5 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Ophthalmic Inflammation and Infection Springer Journals

Ocular inflammatory events following COVID-19 vaccination: a multinational case series

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Abstract

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome. Keywords: Uveitis, Ocular inflammation, Immunomodulatory, Coronavirus disease, COVID-19, SARS-CoV-2, Vaccination The most common ocular manifestation of COVID-19, prevention of 2019 coronavirus disease, whereas the the disease cause by SARS-CoV-2, includes conjunctiv- Oxford-AstraZeneca COVID-19 vaccine was authorised itis, with reported cases of keratitis, keratoconjunctivitis, by the European Medicines Agency (EMA) soon after in episcleritis, uveitis, posterior ischemic optic neuropathy January 2021. Currently, there are four types of COVID- and retinal vascular involvement [1–4]. In December 19 vaccines available, including the messenger RNA 2020, the Food and Drug Administration (FDA) released (mRNA) vaccines (Pfizer-BioNTech and Moderna); the the emergency use authorisation for the Pfizer- protein subunit vaccines (Novavax); the vector vaccines BioNTech and Moderna COVID-19 vaccine for the (Janssen Johnson & Johnson and Oxford-AstraZeneca), and the whole virus vaccines (Sinovac13, Sinopharm14 * Correspondence: c.pavesio@nhs.net and Covaxin). Inflammatory adverse events, including Department of Uveitis, Moorfields Eye Hospital, NHS Foundation Trust, myocarditis and pericarditis, have been reported to London, UK Full list of author information is available at the end of the article occur following COVID-19 vaccination [5, 6]. The © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 2 of 6 objective of this study is to describe the spectrum and corresponding phenotypes is described in Table 1 with outcome of ocular inflammatory events associated with the details of ocular inflammatory events in Table 2. the administration of COVID-19 vaccination. Forty-one patients had anterior uveitis after vaccin- ation, of which nine (22.0%) had history of HLA-B27 as- Methods sociated uveitis (one was on secukinumab and one on Case series of patients diagnosed with an ocular in- infliximab plus methotrexate), six (14.6%) had idiopathic flammatory event after receiving COVID-19 vaccin- anterior uveitis, three (7.3%) had glaucomatocyclitic cri- ation collected from 40 international centres over a 3 sis (one on topical corticosteroids), two (4.9%) with her- month period in 2021 (see group information). The petic anterior uveitis, one (2.4%) of juvenile idiopathic study was conducted with ethical approval obtained arthritis associated uveitis (on adalimumab), one (2.4%) by the leading centre from its local institutional ethics of Cytomegalovirus (CMV) uveitis and one (2.4%) of sys- committee (ethics approval: 2021/00438). The diagno- temic lupus erythematosus uveitis (on hydroxychloro- sis of COVID-19 vaccination related-ocular inflamma- quine). All the events after vaccination in these patients tion was established based on the onset of the event were similar to their previous ones. Two patients (4.9%) within 14 days following COVID-19 vaccination and presented with herpetic anterior uveitis for the first time the patients who satisfied this specific criteria were and no other new diagnosis was made for any other pa- only recruited for this report. A form for data collec- tient. Two patients (4.9%) had persistent visual loss on tion was sent to all International Ocular Inflammation the last follow-up, one (2.4%) due to cystoid macular Society (IOIS) and International Uveitis Study Group oedema (visual acuity (VA) reduced ≤3 lines) and one (IUSG) members. Clinicians who observed an ocular (2.4%) due to nummular corneal lesions (VA reduced > inflammatory event within 14 days following COVID- 3 lines). 19 vaccination filled out the form. The following in- Nine patients had posterior uveitis after vaccination, of formation were retrieved from patients’ medical which 2 (22.2%) had history of ocular toxoplasmosis, records: type of COVID-19 vaccination, timing of the and one (11.1%) of acute zonal occult outer retinopathy events, including date of vaccination and date of on- (AZOOR). The patients with history of ocular toxoplas- set of uveitis, past ocular history, type of ocular in- mosis presented with recurrence of lesions and the pa- flammatory event, including scleritis, episcleritis, tient with AZOOR had a different presentation from anterior uveitis, posterior uveitis, intermediate uveitis, previous events, with multifocal choroiditis. Three pa- panuveitis, and optic neuritis, local and systemic tients (33.3%) presented with ocular toxoplasmosis, two treatment history, therapeutic management and (22.2%) presented with retinal vasculitis, and one (11.1%) outcome. presented with choroiditis for the first time. One patient (11.1%) with ocular toxoplasmosis, and one (11.1%) with Data collection occlusive retinal vasculitis had persistent visual loss on A purpose built data entry platform was created to col- the last follow-up due to macular scarring. lect the ocular inflammatory adverse reactions to Seven patients had anterior scleritis after vaccination, COVID-19 vaccination. The secure encrypted web-based of which four (57.1%) had history of idiopathic anterior platform was programmed by CP, RA and IT. Given the scleritis, and one (14.3%) of idiopathic posterior scleritis observational and retrospective nature of the data, mul- (on methotrexate and prednisolone). All the events after tiple imputations were not allowed. Ninety-four cases vaccination in these patients were similar to their previ- were collected, however, 24 had the event, 2 weeks after ous ones. Two patients (28.6%) presented anterior scler- the vaccination and were excluded from the analysis, itis for the first time. All patients had unaffected visual resulting in 70 cases. Statistical analysis was done using acuity after the event. the software R v 4.1.1 [R Core Team (2021). R: A lan- Other events (N = 13, 18.6%) included panuveitis (N = guage and environment for statistical computing. R 3, 4.3%), optic neuritis (N = 2, 2.9%), episcleritis (N = 2, Foundation for Statistical Computing, Vienna, Austria]. 2.9%), intermediate uveitis (N = 2, 2.9%), paracentral Continuous variables were described as median [range] acute middle maculopathy (N = 1, 1.4%), giant cell arter- while binary variables were described as number (%). itis (N = 1, 1.4%), periocular skin herpes zoster (N = 1, 1.4%), and unspecific blurriness of vision (N = 1, 1.4%). Results Among these patients, one (7.7%) had history of inter- Seventy patients presented with ocular inflammatory mediate uveitis (was on mycophenolic acid), one (7.7%) events within 14 days following COVID-19 vaccination, of idiopathic panuveitis (was on azathioprine), one and the most common were anterior uveitis (n = 41, (7.7%) of optic neuritis, one (7.7%) of CMV anterior uve- 58.6%), posterior uveitis (n = 9, 12.9%), and anterior itis, and one (7.7%) of episcleritis. The events after vac- scleritis (n = 7, 10.0%). The study population and the cination in these patients were similar to their previous Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 3 of 6 Table 1 Description of the study population by the type of event (n = 70) Variable Total (%) Anterior Uveitis Posterior Uveitis Scleritis Others (%) (%) (%) (%) Demographics Number of Patients 70 (100.0) 41 (58.6) 9 (12.9) 7 (10.0) 13 (18.6) Age (years) 51 [19–84] 55 [19–84] 40 [28–61] 48 [40–52] 54 [25–79] Gender = Female 35 (56.5) 19 (52.8) 4 (44.4) 6 (85.7) 6 (60) Gender = Male 27 (43.5) 17 (47.2) 5 (55.6) 1 (14.3) 4 (40) History of Previous COVID-19 1 (1.4) 1 (2.4) 0 (0.0) 0 (0.0) 0 (0.0) Vaccine Pfizer 40 (57.1) 20 (48.8) 4 (44.4) 5 (71.4) 11 (84.6) Astra-Zeneca 17 (24.3) 12 (29.3) 4 (44.4) 1 (14.3) 0 (0) Moderna 10 (14.3) 7 (17.1) 1 (11.1) 1 (14.3) 1 (7.7) Sinopharm 2 (2.9) 1 (2.4) 0 (0) 0 (0.0) 1 (7.7) Covaxin 1 (1.4) 1 (2.4) 0 (0) 0 (0.0) 0 (0) Event After First Dose Number of Patients 43 (61.4) 22 (53.7) 6 (66.7) 4 (57.1) 11 (84.6) Time After First Dose [days] 6[1–14] 5.5 [1–14] 6.5 [1–14] 4.5 [1–9] 8 [1–14] Received Another Dose 18 (41.9) 11 (50) 3 (50) 1 (25) 3 (27.3) Recurrence After Second Dose 6/18 5 / 11 (45.5) 0 (0.0) 1 / 4 (25.0) 0 (0.0) (33.3) Event After Second Number 27 (39.6) 19 (46.3) 3 (33.3) 3 (42.9) 2 (15.4) Dose Time After Second Dose 5[1–14] 5 [1–14] 8 [2–9] 4 [2–14] 7 [2–12] [days] Missing Data for Age and Gender: Total = 8, Anterior Uveitis = 5, Others = 3 ones, except for the patient with history of CMV anter- this study. A search of Medline, using PubMed and ior uveitis, who presented with intermediate uveitis after Google Scholar, performed in August 2021, using the vaccination. One patient (7.7%) had persistent visual loss following keywords: ‘uveitis’, ‘vaccination’, ‘COVID- on the last follow-up due to cystoid macular oedema in 19’, revealed six case reports and two national case intermediate uveitis (VA reduced ≤3 lines). series describing presumed COVID-19 vaccine-related Regarding the management of the events, 39 patients uveitis have been reported so far, including new onset (55.7%) received only topical corticosteroids, 13 (18.6%) of bilateral juvenile idiopathic arthritis (JIA)-associated received systemic corticosteroids (five of them also re- anterior uveitis, unilateral anterior uveitis, bilateral ceived topical corticosteroids and four antibiotics), 10 choroiditis complicated by subretinal fluid, bilateral (14.3%) did not require any treatment, six (8.6%) re- panuveitis with choroidal thickening and vascular ceived antivirals (two of them with topical corticoste- leakage, and recurrence of Vogt Koyanagi Harada roids), and two (2.8%) received topical corticosteroids (VKH) [19–26]. Rabinovitch et al. reported twenty with oral non-steroidal anti-inflammatory drugs (NSAI one cases of uveitis after COVID-19 vaccination in Ds). Three patients (4.3%) required IOP lowering medi- Israel, of which nineteen were diagnosed with anterior cations (two with glaucomatocyclitic crisis and one with uveitis and two developed multiple evanescent white CMV anterior uveitis) and one (1.4%) initiated metho- dot syndrome (MEWDS) [24]. Recently, Pichi et al. trexate after the episode (giant cell arteritis). described seven patients diagnosed with episcleritis (1), anterior scleritis (2), acute macular neuroretinopa- Discussion thy (AMN) (2), paracentral acute middle maculopathy Although rare, development of uveitis after administra- (PAMM) (1), and subretinal fluid (1) after COVID-19 tion of vaccine is a known event. Cases of vaccine- vaccination [25]. None of these studies was a multi- associated uveitis have been reported with almost all the central case series. Similarly to the findings of Rabi- vaccines currently administered, including vaccines novitch et al., we found that anterior uveitis was the against hepatitis A and B virus, human papillomavirus, most common ocular inflammatory event observed influenza virus, bacillus Calmette-Guerin, measles- after COVID-19 vaccination, with more than 50% of mumps-rubella, varicella virus, yellow fever and Neis- the patients having a known history of uveitis. The seria meningitides [7–18]. majority of the episodes we reported occurred after Ocular inflammatory events after COVID-19 vaccin- the Pfizer vaccine. These findings are probably based ation from a multinational case series are described in on the number of the administered doses. Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 4 of 6 Table 2 Ocular Inflammatory Events Description Variable Total Anterior Uveitis Posterior Uveitis Scleritis Others (%) (%) (%) (%) (%) (N = (N = 41) (N = 9) (N =7) (N = 13) 70) Previous Ocular Inflammatory Number of patients 36 23 (56.1) 3 (33.3) 5 (71.4) 5 (38.5) Events (51.4) Controlled more than 3 28 17 (81.0) 3 (100) 3 (60.0) 5 (100) months (82.4) On Topical Anti-inflammatory 1 (2.8) 1 (4.3) 0 (0.0) 0 (0.0) 0 (0.0) On Systemic Anti- 7 (19.4) 4 (17.4) 0 (0.0) 1 (20.0) 2 (15.4) inflammatory Event similar to previous 34 23 (100.0) 2 (66.7) 5 (100.0) 4 (80) events (94.4) Presentation Unilateral 60 33 (80.5) 8 (88.9) 7 (100) 12 (92.3) (85.7) Bilateral 10 8 (19.5) 1 (11.1) 0 (0.0) 1 (7.7) (14.3) VA Unaffected 38 22 (53.7) 2 (22.2) 6 (85.7) 8 (61.5) (54.3) VA reduced ≤ 3 lines 18 10 (24.4) 4 (44.4) 1 (14.3) 3 (23.1) (25.7) VA reduced > 3 lines 14 9 (22.0) 3 (33.3) 0 (0.0) 2 (15.4) (20.0) Management Topical Corticosteroids 48 34 (82.9) 3 (33.3) 6 (85.7) 5 (38.5) (68.6) Systemic Corticosteroids 13 2 (4.9) 6 (66.7) 1 (14.3) 4 (30.8) (18.6) Antivirals 6 (8.6) 5 (12.2) 0 (0.0) 0 (0.0) 1 (7.7) NSAIDs 2 (2.9) 0 (0.0) 0 (0.0) 1 (14.3) 1 (7.7) Antibiotics 4 (5.7) 0 (0.0) 4 (44.4) 0 (0.0) 0 (0.0) Visual Outcomes VA Unaffected 65 39 (95.1) 7 (77.8) 7 (100) 12 (92.3) (92.9) VA reduced ≤ 3 lines 2 (2.9) 1 (2.4) 0 (0.0) 0 (0.0) 1 (7.7) VA reduced > 3 lines 3 (4.3) 1 (2.4) 2 (22.2) 0 (0.0) 0 (0.0) Complications Transient IOP elevation 3 (4.3) 3 (7.3) 0 (0.0) 0 (0.0) 0 (0.0) Nummular Corneal Lesions 1 (1.4) 1 (2.4) 0 (0.0) 0 (0.0) 0 (0.0) Cystoid Macular Oedema 2 (2.9) 1 (2.4) 0 (0.0) 0 (0.0) 1 (7.7) Macular Scarring 2 (2.9) 0 (0.0) 2 (22.2) 0 (0.0) 0 (0.0) The potential mechanism underlying the ocular in- specificity, (4) temporality, (5) biological gradient, (6) flammation response following COVID-19 vaccination is plausibility, (7) coherence, (8) experiment, and analogy not known. Commonly proposed mechanisms include (9) [31]. The design of this study guarantees temporality, (1) molecular mimicry secondary to resemblance be- since there was a short interval of time following vaccin- tween uveal peptides and vaccine peptide fragments, (2) ation and the onset of the events. The fact that among antigen-specific cell and antibody-mediated hypersensi- 18 patients who had an event following the first dose tivity reactions, (3) inflammatory damage induced by ad- and still received a second dose, 6 (33.3%) presented juvants included the vaccines stimulating innate similar events following the second dose, as well as dif- immunity through endosolic or cytoplasmic nucleic acid ferent observations in different regions from different receptors [18, 27–30]. people, supports consistency (reproducibility) between The Bradford-Hill criteria include nine aspects to con- exposure and outcome. The causality is plausible as sider when inferring causality between events: (1) some biological mechanisms have already been pro- strength of the association, (2) consistency, (3) posed. Finally, the events after COVID-19 vaccination Testi et al. Journal of Ophthalmic Inflammation and Infection (2022) 12:4 Page 5 of 6 are analogous to those reported following other Medicine, Chicago, IL, USA; Nima Ghadiri, Liverpool University Hospital, Liver- pool, UK; Alex Fonollosa Calduch, Hospital Universitario Cruces, Universidad vaccines. del País Vasco, Instituto Oftalmológico Bilbao, Bilbao, Spain; Gabriel Costa de From our study it emerged that most of the inflamma- Andrade; Padmamalini Mahendradas, Narayana Nethralaya, Bangalore, India; tory episodes were not severe, and patients were mainly Julio J González-López, Hospital Ramón y Cajal, Madrid, Spain; Ester Carreño, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Rola N Hamam, managed with topical corticosteroids or observation only American University of Beirut, Lebanon; Nicole Stübiger, Universitätsklinikum (70%), with unaffected final visual acuity (92.9%). Very Hamburg-Eppendorf, Augenklinik, Germany; Bahram Bodaghi, Sorbonne Uni- few patients developed ocular complications resulting in versité, Hôpital de la Pitié-Salpêtrière, Paris, France; Yu-Jang Chao, Cheng Hsin General Hospital, Taipei, Taiwan; Masaru Takeuchi, National Defense Medical tissue damage and visual loss (7.1%), including corneal College, Namiki Tokorozawa Saitama, Japan; Mei-Ling Tay-Kearney, Lions Eye opacity, cystoid macular oedema and macular scarring. Institute, Royal Perth Hospital, Perth, WA, USA; Alejandro Portero, Hospital Study limitations include its observational and non- Universitario La Zarzuela, Madrid, Spain; Hiroshi Keino, Kyorin University School of Medicine, Tokyo, Japan; Padmamalini Mahendradas, Narayana controlled nature, that cannot be used to infer causality Nethralaya, Bangalore; Mar Esteban-Ortega, Hospital Infanta Sofia, San Sebas- because it does not allow to stablish strength of the asso- tian de los Reyes, Madrid, Spain; Joanna Przeździecka-Dołyk, Wrocław Medical ciation, specificity, biological gradient, coherence, nor University, Wroclaw, Poland; Aleksandra Radosavljević, University Clinical Cen- ter of Serbia, Belgrade, Serbia; Ian Paredes, Legaspi Eye Center, Legaspi, Bicol, experiment. Additionally, there is a potential sample bias Philippines and Chua Eye Center, Angeles, Pampanga, Philippines; Rupesh due to the form of data collection, and the data collected Agrawal, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, might not be representative of all population, although Singapore; Ho Su Ling, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; Wei Kiong, National Healthcare Group Eye Institute, the multicentre nature of the study need to be consid- Tan Tock Seng Hospital, Singapore; Melissa Tien, National Healthcare Group ered as it may reduce the bias. Eye Institute, Tan Tock Seng Hospital, Singapore; Xin Le Ng, National Health- care Group Eye Institute, Tan Tock Seng Hospital, Singapore; Carlos Pavesio, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; Ilaria Testi, Moor- Conclusion fields Eye Hospital, NHS Foundation Trust, London, UK; Soon Phaik Chee, Hereby we report a large multinational case series of Singapore National Eye Centre, Singapore; Jay Siak, Singapore National Eye ocular inflammatory events occurred following COVID- Centre, Singapore; Ines Hernanz-Rodriguez, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Victor Menezo, Institut Catala de Retina, Barce- 19 vaccination, based on a temporal and multicentrical lona, Spain; Christoph Tappeiner, Department of Ophthalmology, Pallas Klini- association, but not proving causality. Even in the possi- ken, Olten, Switzerland; Franz Marie Cruz, Peregrine Eye and Laser Institute, bility of of a causal association, most of the events were Makati, Philippines; Peter Addison, London, UK; Robert Kuijpers, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; Daniel Vitor mild and had a good visual outcome. Therefore, there is Vasconcelos-Santos, Universidade Federal de Minas Gerais, Belo Horizonte, no evidence from this study to suggest that individuals Brazil. should avoid getting vaccinated because of ophthalmic- Authors’ contributions related adverse events. It is not the aim of the authors to Conception and design: Pavesio, Testi, Agrawal. Analysis and interpretation: impede or curtail the vaccination efforts, but rather to Brandão-de-Resende, Pavesio, Testi, Agrawal. Overall responsibility: Pavesio, educate physicians and patients about rare but potential Testi, Agrawal, Brandão-de-Resende. The authors read and approved the final manuscript. ocular inflammatory events after the COVID-19 vaccination. Funding None. Abbreviations FDA: Food and drug administration; EMA: European medicines agency; Availability of data and materials mRNA: Messenger RNA; AZOOR: Acute zonal occult outer retinopathy; All the data pertaining to the cases are available with the corresponding VA: Visual acuity; CMV: Cytomegalovirus; NSAIDs: Non-steroidal anti- author. inflammatory drugs; JIA: Juvenile idiopathic arthritis; VKH: Vogt Koyanagi Harada; MEWDS: Multiple evanescent white dot syndrome; AMN: Acute Declarations macular neuroretinopathy; PAMM: Paracentral acute middle maculopathy Consent for publication Acknowledgements The IRB/ethics committee approved this study. All research adhered to the We would like to acknowledge the International Ocular Inflammation Society tenets of the Declaration of Helsinki. The requirement for informed consent (IOIS) and International Uveitis Study Group (IUSG) for supporting the was waived because of the retrospective nature of the study. project. *Group Information. Competing interests The COVID-19 Vaccination Ocular Inflammatory Events Study Group The authors have no relevant affiliations or financial involvement with any members are: Laura Steeples, Manchester Royal Eye Hospital, Manchester, UK; organization or entity with a financial interest in or financial conflict with the Balini Balasubramaniam, Queen Elizabeth Hospital, Birmingham, UK; Peter subject matter or materials discussed in the manuscript. This includes McCluskey, The University of Sydney, Save Sight Institute, Sydney, Australia; employment, consultancies, honoraria, stock ownership or options, expert Francesco Pichi, Cleveland Clinic Abu Dhabi, UAE; Aniruddha Agarwal, testimony, grants or patents received or pending, or royalties. Cleveland Clinic Abu Dhabi, UAE; Carl Herbort, COS, Lausanne, Switzerland; Luca Cimino, Arcispedale S. Maria Nuova, Reggio Emila, Italy; Salam Iriqat, St Author details John of Jerusalem Eye Hospital, Jerusalem, Israel; Jennifer E. Thorne, Wilmer Department of Uveitis, Moorfields Eye Hospital, NHS Foundation Trust, Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, London, UK. Clinical Research Facility, Moorfields Eye Hospital, NHS USA; Jose Echegaray, Case Western Reserve University in Cleveland, OH, USA; Foundation Trust, London, UK. National Healthcare Group Eye Institute, Tan Kalpana Babu, Prabha eye clinic and research centre & Vittala Institute of Tock Seng Hospital, Singapore, Singapore. Singapore Eye Research Institute, Ophthalmology, Bangalore, India; Alexander Arthur Bialasiewicz, Al-Ahli Hos- Singapore, Singapore. Lee Kong Chian School of Medicine, Nanyang pital, Doha, Qatar; Debra A. 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Journal

Journal of Ophthalmic Inflammation and Infection – Springer Journals

Published: Jan 4, 2022

Keywords: Uveitis; Ocular inflammation; Immunomodulatory; Coronavirus disease; COVID-19; SARS-CoV-2; Vaccination

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