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Article

Uveitis and Other Ocular Complications Following COVID-19 Vaccination

1
Ocular Immunology Unit, Azienda USL-IRCCS, 42123 Reggio Emilia, Italy
2
Ophthalmology Unit, Azienda USL-IRCCS, 42123 Reggio Emilia, Italy
3
Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS, 42123 Reggio Emilia, Italy
4
Ophthalmology Unit, DIMES, Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy
5
Rheumatology Unit, Azienda USL-IRCCS, 42123 Reggio Emilia, Italy
6
Department of Surgery, Medicine, Dentistry and Morphological Sciences, with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(24), 5960; https://doi.org/10.3390/jcm10245960
Submission received: 19 November 2021 / Revised: 7 December 2021 / Accepted: 17 December 2021 / Published: 19 December 2021

Abstract

:
Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine.

1. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), a multisystemic disorder with medical and socioeconomic consequences that have led to public health crises worldwide. In an effort to alleviate the morbidity and mortality associated with COVID-19 and arrest viral transmission, different types of vaccinations have been developed. Among these vaccines are the inactivated vaccines (PiCoVacc, Sinovac [1]; BBIBP-CorV, Sinopharm [2]), the viral vector vaccines (Ad26.COV2, Janssen Johnson & Johnson [3]; ChAdOx1 nCoV-19/AZD1222, Oxford-AstraZeneca [4]), the messenger ribonucleic acid (mRNA)-based vaccines (BNT162b2, Pfizer-BioNTech [5]; mRNA-1273, ModernaTX [6]), and the protein subunit vaccine (NVX- CoV2373, Novavax [7]).
Common transient local and systemic post-vaccination reactions are pain, redness and/or swelling at the injection site, fatigue, headache, muscle pain, chills, fever, and nausea [4,5]. Although less common, other vaccine-related side effects include cutaneous reactions such as varicella zoster and herpes simplex flares [8].
Different types of ocular complications have also been reported after COVID-19 vaccination, including facial nerve palsy, abducens nerve palsy, new-onset Graves’ disease, episcleritis, anterior scleritis, anterior uveitis (AU), multifocal choroiditis, reactivation of Vogt-Koyanagi-Harada (VKH) disease, multiple evanescent white dot syndrome (MEWDS), acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy (PAAM), thrombosis, and central serous retinopathy (CSR) [9].
The aim of this study was to report uveitis and other cases of ocular complications following COVID-19 vaccination.

2. Materials and Methods

This retrospective study included patients with uveitis and other ocular complications following COVID-19 vaccination between January 2021 and October 2021 at the Ocular Immunology Unit, Azienda Unità Sanitaria Locale (AUSL)-IRCCS, Reggio Emilia, Italy.
Data collection consisted of demographic and clinical data. The demographic data included age, sex, general medical and ocular history, and medications. Clinical data included systemic and ocular symptoms post-vaccination, type of vaccine, time interval between vaccination (first and second dose) and symptom onset, laterality of eye disease, ocular findings, treatment, and outcome.
All patients underwent a complete ophthalmic examination with measurement of the best-corrected visual acuity (BCVA), anterior segment slit lamp biomicroscopy, fundus examination, and optical coherence tomography (OCT). Uveitis was graded and classified according to the Standardization of Uveitis Nomenclature (SUN) classification system [10]. In patients with a history of uveitis, the time interval from the last uveitis attack to current uveitis was calculated. In cases of de novo uveitis and no history of uveitis-related systemic disease, laboratory tests were performed at the discretion of the treating ophthalmologist with the aim of excluding other causes of ocular inflammation. These included complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Venereal Disease Research Laboratory test (VDRL), Treponema pallidum haemagglutination (TPHA), interferon-gamma release assay (QuantiFERON©-TB Gold test), serum angiotensin-converting enzyme (ACE), serum lysozyme, high-resolution computerized tomography (HRCT) of the chest, and magnetic resonance imaging (MRI) of the brain. In all patients, follow-up was carried out for a minimum of 3 months.
The study and data collection were conducted in agreement with the principles of the Declaration of Helsinki and approved by the local ethics committee (protocol n. 2021/0111389 Comitato Etico Provinciale di Reggio Emilia, Italy). Informed written consent was obtained from all patients.

3. Results

3.1. Demographics and Clinical Data

The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). Patients’ demographic data, medical history, type of vaccine, and systemic symptoms post-vaccination are reported in Table 1.

3.2. Uveitis and Other Ocular Complications

Mean time between vaccination and ocular complications onset was 9.4 days (median time 7 days, range 1–30 days). Ocular complications reported after the first dose of the vaccine occurred at a mean time of 7.5 days (median time 6.5 days, range 2–30 days), while ocular complications after the second dose of vaccine were reported at a mean time of 10.7 days (median time 7 days, range 1–30 days). Eleven patients had a known history of uveitis and 2 of scleritis, the median time from previous to current attack was 13 months (range 10–108 months). Four patients had a uveitis-related systemic disease: one patient had psoriatic arthritis (PsA), one patient had spondyloarthritis (SpA), and two patients had VKH disease.
The study included three cases of herpetic keratitis, two anterior scleritis, five AU, three toxoplasma retinochoroiditis, two cases of VKH disease reactivation, two pars planitis, two retinal vasculitis, one bilateral panuveitis, three MEWDS, one AMN, five retinal vein occlusion (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV), and an acute-onset bilateral CSR (Table 2).
Among the three cases of herpetic keratitis, one patient had a previous history of herpetic keratitis and had not been taking systemic antiviral treatment before vaccination. The other two patients that reported herpetic keratitis had a previous history of herpetic keratouveitis and had 1 g of oral valacyclovir once daily for prophylactic therapy during vaccination. The mean time between vaccination and herpetic keratitis onset was 6 days (range 5–7 days).
The five cases of AU included one patient with CMV AU and four with non-granulomatous anterior uveitis (NGAU). Among NGAU were three patients with human leukocyte antigen B27 (HLA-B27) + and three with a previous history of uveitis, two of whom with uveitis-related systemic disease (PsA and SpA) had not been taking systemic therapy at vaccination.
Three patients reported ocular toxoplasmosis, at a mean time of 7.3 days (range 7–8 days) after the vaccination, one patient had an initial episode, and two patients had a recurrence of Toxoplasma retinochoroiditis.
Two patients with bilateral intermediate uveitis had negative laboratory tests and normal chest HRTC and MRI of the brain. Pars planitis was diagnosed in both patients.
One patient presented bilateral panuveitis with retinal vasculitis, papillary oedema, and painful oral ulcers, followed by deep vein thrombosis of a lower extremity. Laboratory workup showed elevated CRP, elevated ESR, and positive pathergy test with a diagnosis of Behçet’s disease (BD).
The female patient who developed AMN 2 days after ChAdOx1 nCoV-19 vaccine was taking combined estrogen–progestin oral contraceptives at the time of vaccination, which were immediately suspended.
Five patients developed RVO: one central retinal vein occlusion (CRVO) and four branch retinal vein occlusion (BRVO). Of these patients, one was affected by diabetes mellitus (DM) and two by systemic arterial hypertension (SAH) (Table 1).
A female patient of 46 years old presented unilateral sectorial papillary oedema, no crowded disc was observed in the other eye. Automatic perimetry demonstrated a diffuse visual field loss. The patient had no clinical signs of giant cell arteritis (jaw claudication, headache, and scalp tenderness), and CRP and ESR were within the normal range. Brain imaging excluded an acute intracranial event, and the patient was diagnosed with NAION. Systemic risk factors associated with NAION such as SAH, DM, hyperlipidemia, and smoking were negative. A hypercoagulable state due to antiphospholipid antibodies was ruled out. Also, anticardiolipin and lupus anticoagulant were negative.
Three cases presented activation of quiescent CNV, secondary to myopia in one patient and secondary to uveitis in the other two. The myopic CNV and one uveitic CNV were never injected, while the other uveitic patient had the reactivation of a lesion treated with intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) drugs 1 year earlier.

3.3. Type of Vaccine

Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), seven after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), three after ModernaTX vaccination (mRNA-1273), and one after Janssen Johnson & Johnson vaccine (Ad26.COV2). Fourteen cases were reported after the first dose of the vaccine and 20 after the second dose (Table 2).

4. Discussion

Uveitis and other ocular adverse events have been described following vaccinations for hepatitis B virus (HBV), human papillomavirus (HPV), influenza virus, Bacille-Calmette-Guerin (BCG), varicella virus, measles-mumps-rubella (MMR), yellow fever, hepatitis A virus (HAV), and typhoid [11,12,13,14,15]. Different types of ocular complications have also been reported after COVID-19 vaccination. Pichi et al. reported one patient with episcleritis, two with anterior scleritis, two with AMN, one with PAAM, and one with subretinal fluid soon after receiving an inactivated COVID-19 vaccination (Sinopharm) [16].
A retrospective multicenter study collected 21 cases of unilateral or bilateral AU and 2 cases of MEWDS after the administration of the BNT162b2 mRNA vaccine [17]. Moreover, two case reports described bilateral multifocal choroiditis following COVID-19 vaccination [18,19]. Other cases of facial nerve palsy, abducens nerve palsy, new-onset Graves’ disease, VKH disease reactivation, AMN, PAAM, and thrombosis have been described [9].
This retrospective study reports uveitis and other ocular complications following COVID-19 vaccination. We observed three cases of herpes keratitis reactivation following COVID-19 vaccination.
Vaccines can result in varicella zoster virus (VZV) reactivation, as previously described in patients receiving inactivated vaccines for hepatitis A, influenza, rabies, and Japanese encephalitis. Fernandez-Nieto et al. described 15 cases of herpes simplex/zoster in patients infected with COVID-19 [20]. COVID-19 infection may represent a trigger for herpes reactivation, as recently reported. There are cases reported in the literature characterized by VZV reactivation after vaccination with the mRNA COVID-19 vaccine, including also herpes zoster ophthalmicus (HZO) [21,22,23,24]. It has been postulated that the stimulation of the immune system following vaccination induces a strong T-cell response with increased CD8+ T cell and T helper type 1 CD4+ T cells. Temporarily, VZV-specific CD8+ cells are not capable of controlling VZV after the massive shift of naïve CD8+ cells, which allows VZV to escape from its latent phase. Moreover, another possible explanation focuses on toll-like receptors (TLR) signaling. Abrogations in TLR expression among vaccinated individuals have been linked with marked induction of type I interferon (IFN-I) and potentiation of pro-inflammatory cytokines, which, although they promote T cell immunity and initiate an antibody-secreting memory B cell response, may negatively modulate antigen expression while potentially contributing to VZV reactivation [25].
As reported in the literature, the median time between COVID-19 diagnosis and the development of herpes zoster was 5.5 days [26]. Similarly, the VZV reactivation appeared 5 days after COVID-19 vaccination in a case report [23]. In our three cases, herpes keratitis reactivation occurred after a mean of 6 days (range 5–7 days) after COVID-19 vaccination.
A recent case report of a severe unilateral flare-up of a granulomatous hypertensive uveitis 5 days after the second dose of Moderna vaccine in a patient previously treated for herpes keratouveitis suggests that preventive antiviral treatment should be given in known herpes patients despite quiescent uveitis to avoid potential reactivation [27]. In two of our cases, herpes keratitis reactivation happened in patients with a history of previous herpetic keratouveitis although under systemic antiviral treatment with oral valacyclovir of 1 g once daily.
Episcleritis has been described as ocular manifestations in patients with COVID-19 [28,29,30]. Anterior scleritis has also been reported to manifest after COVID-19 [31]. In addition, scleritis and episcleritis have also been reported in three patients at a mean of 5 days after the first dose of the inactivated COVID-19 vaccine (Sinopharm) [16]. Consistent with the reported literature, our two cases of scleritis were mild and noted at a mean of 5.5 days after vaccination.
In accordance with other studies, we reported AU in patients with or without a history of previous uveitis and/or uveitis-related systemic disease [17,32]. The vaccine-induced increase in IFN-I secretion could potentially drive autoimmune manifestations in patients with a history of autoimmunity or with yet unknown susceptibility to develop one [17,33].
Among our cases, two patients had a recurrence of Toxoplasma retinochoroiditis and one patient an initial episode of Toxoplasma retinochoroiditis at a mean of 7.3 days (range 7–8 days) after the vaccination. The vaccination-induced CD8 T-cell exhaustion may lead to parasite reactivation [34].
Papasavvas I. and Herbort CP. reported a case of VKH disease reactivation 6 weeks after the second dose of the Pfizer anti-SARS-CoV-2 vaccine administration that had been completely under control with a maintenance treatment of infliximab every 10 weeks for 6 years. The patient presented with a severe reactivation of the disease almost as pronounced as during its initial onset [35]. In our study, two patients with VKH disease being treated with mycophenolate mofetil (2 g daily) presented a mild reactivation with choroidal granulomas on indocyanine green angiography (ICGA).
Cases of COVID-19 associated with systemic vasculitis, including retinal vasculitis and papillophlebitis, have been published [36,37]. In our study, two patients presented with bilateral intermediate uveitis and two patients with bilateral retinal vasculitis. These four patients underwent blood tests, chest HRCT, and MRI of the brain, all of which were negative.
A single case of clinical presentation consistent with new-onset BD or a BD-like adverse event following SARS-CoV-2 mRNA-1273 vaccination has been described [38]. Similarly, we reported a case of bilateral panuveitis with new-onset BD.
A multicenter study reported two cases of MEWDS occurring 5 and 30 days after BNT162b2 mRNA vaccination [17]. Our three cases of MEWDS were reported from 4 to 28 days after the first or second dose of BNT162b2 mRNA vaccination.
PAMM and AMN have been reported after H1N1 vaccination. Virgo and Mohamed reported two patients with new paracentral scotoma secondary to AMN and PAMM 16 days after confirmed COVID-19 infections [39]. Furthermore, four case reports described five cases of AMN in young women 2 days after receiving ChAdOx1 nCoV-19 vaccination [40,41,42,43]. Similarly, a case of AMN occurred in a young woman in our study that was taking combined estrogen–progestin oral contraceptives 2 days after ChAdOx1 nCoV-19 vaccination [40,42,43].
Artery or vein retinal occlusion have both been described during or following COVID-19 [44,45], which is thought to induce a systemic inflammatory response, endothelial dysfunction, and a hypercoagulative state, which predisposes patients to systemic thrombus formation [46].
Regarding post-vaccination thrombosis, rare cases of superior ophthalmic vein thrombosis and central retinal vein occlusion have been reported [47,48,49,50]. In this study were five cases of RVO (one CRVO and four BRVO), some of whom were affected by systemic comorbidities including DM or SAH. Moreover, a patient with no ocular or systemic risk factors reported unilateral NAION. So far, four cases of NAION associated with COVID-19 have been described in the literature [51,52,53,54].
Furthermore, three of our patients reported the activation or reactivation of a quiescent CNV secondary to myopia or uveitis
The literature reports a unilateral CSR 3 days after the injection of BNT162b2 mRNA COVID-19 vaccine occurred in a 33-year-old healthy Hispanic male without previous ocular history or pertinent medical history [55]. In our study, a case of acute-onset bilateral CSR in a male patient occurred 13 days after the second dose of BNT162b2 mRNA COVID-19 vaccination.
Most of the patients in our study (58.8%) developed ocular complications after the second dose of the vaccine.
The main limitation of this study was its retrospective design and relatively low number of cases. Previous multiple reports have shown ocular complications following COVID-19 vaccination, although a definitive association can be difficult to demonstrate. However, the close temporal association between vaccination and onset of uveitis or other ocular complications and the similarity to those reported in the literature are quite suggestive.

5. Conclusions

COVID-19 vaccination can be followed by herpetic keratitis reactivation in patients with previous herpetic keratitis or kerato-uveitis. The changes in the immune status, including lymphocyte exhaustion, may lead to herpes reactivation [25]. Therefore, prophylactic antiviral therapy with oral valacyclovir, at least for high-risk patients with several previous herpes uveitis episodes, may be considered.
COVID-19 vaccinations can also be followed by anterior scleritis; AU in patients with or without history of previous uveitis, and/or uveitis-related systemic disease; activation of Toxoplasma retinochoroiditis; VKH disease recurrences; pars planitis; retinal vasculitis; panuveitis in new-onset BD, MEWDS, and AMN; as well as RVO (CRVO or BRVO), NAION; activation of quiescent CNV secondary to myopia or uveitis; and CRS.
These complications could be related to the SARS-CoV-2 vaccines’ capacity to induce autoimmune manifestations or thromboembolic events.
Additional epidemiologic and clinical studies and longer follow-up of this cohort are needed to confirm the link between the COVID-19 vaccine and the recurrence or de novo development of uveitis and other ocular complications.

Author Contributions

Conceptualization, L.C. and E.B.; methodology, L.C. and E.B.; data curation, V.M.; formal analysis, S.C., M.B., L.B. and A.Z.; investigation, L.D.S., F.G. and C.A.; writing—original draft preparation, E.B. and D.I.; writing—review and editing, E.B. and D.I.; visualization, E.B., S.C. and M.B.; supervision L.F., C.S. and L.C.; project administration, L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the local Ethics Committee (protocol n. 2021/0111389 Comitato Etico Provinciale di Reggio Emilia, Italy, date of approval 7 September 2021).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Gao, Q.; Bao, L.; Mao, H.; Wang, L.; Xu, K.; Yang, M.; Li, Y.; Zhu, L.; Wang, N.; Lv, Z.; et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science 2020, 369, 77–81. [Google Scholar] [CrossRef] [PubMed]
  2. Xia, S.; Zhang, Y.; Wang, Y.; Wang, H.; Yang, Y.; Gao, G.F.; Tan, W.; Wu, G.; Xu, M.; Lou, Z.; et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect. Dis. 2021, 31, 39–51. [Google Scholar] [CrossRef]
  3. Sadoff, J.; Gray, G.; Vandebosch, A.; Cárdenas, V.; Shukarev, G.; Grinsztejn, B.; Goepfert, P.A.; Truyers, C.; Fennema, H.; Spiessens, B.; et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19. N. Engl. J. Med. 2021, 384, 2187–2201. [Google Scholar] [CrossRef] [PubMed]
  4. Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111. [Google Scholar] [CrossRef]
  5. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Marc, G.P.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
  6. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef]
  7. Heath, P.T.; Galiza, E.P.; Baxter, D.N.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D.R.; Clark, R.; Cosgrove, C.; Galloway, J.; et al. Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine. N. Engl. J. Med. 2021, 385, 1172–1183. [Google Scholar] [CrossRef]
  8. McMahon, D.E.; Amerson, E.; Rosenbach, M.; Lipoff, J.B.; Moustafa, D.; Tyagi, A.; Desai, S.R.; French, L.E.; Lim, H.W.; Thiers, B.H.; et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J. Am. Acad. Dermatol. 2021, 85, 46–55. [Google Scholar] [CrossRef]
  9. Ng, X.L.; Betzler, B.K.; Testi, I.; Ho, S.L.; Tien, M.; Ngo, W.K.; Zierhut, M.; Chee, S.P.; Gupta, V.; Pavesio, C.E.; et al. Ocular Adverse Events After COVID-19 Vaccination. Ocul. Immunol. Inflamm. 2021, 1–9. [Google Scholar] [CrossRef]
  10. The Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am. J. Ophthalmol. 2005, 140, 509–516. [Google Scholar] [CrossRef]
  11. Benage, M.; Fraunfelder, F.W. Vaccine-Associated Uveitis. 2016. Mo Med. 2016, 113, 48–52. [Google Scholar]
  12. Moorthy, R.S.; Moorthy, M.S.; Cunningham, E.T. Drug-induced uveitis. Curr. Opin. Ophthalmol. 2018, 29, 588–603. [Google Scholar] [CrossRef] [PubMed]
  13. Cunningham, E.T.; Moorthy, R.S.; Fraunfelder, F.W.; Zierhut, M. Vaccine-Associated Uveitis. Ocul. Immunol. Inflamm. 2019, 27, 517–520. [Google Scholar] [CrossRef] [PubMed]
  14. Cunningham, E.T.; Moorthy, R.S. Vaccine-Associated Posterior Uveitis. Retin. Cases Brief Rep. 2020, 40, 595–598. [Google Scholar]
  15. Cheng, J.Y.; Margo, C.E. Ocular adverse events following vaccination: Overview and update. Surv. Ophthalmol. 2021, in press. [Google Scholar] [CrossRef] [PubMed]
  16. Pichi, F.; Aljneibi, S.; Neri, P.; Hay, S.; Dackiw, C.; Ghazi, N.G. Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA Ophthalmol. 2021, 139, 1131–1135. [Google Scholar] [CrossRef]
  17. Rabinovitch, T.; Ben-Arie-Weintrob, Y.; Hareuveni-Blum, T.; Shaer, B.; Vishnevskia-Dai, V.; Shulman, S.; Newman, H.; Biadsy, M.; Masarwa, D.; Fischer, N.; et al. Uveitis following the BNT162b2 mRNA vaccination against SARS-CoV-2 infection. Retina 2021, 41, 2462–2471. [Google Scholar] [CrossRef]
  18. Goyal, M.; Murthy, S.I.; Annum, S. Bilateral Multifocal Choroiditis following COVID-19 Vaccination. Ocul. Immunol. Inflamm. 2021, 29, 753–757. [Google Scholar] [CrossRef]
  19. Mungmunpuntipantip, R.; Wiwanitkit, V. COVID-19 Vaccination and Bilateral Multifocal Choroiditis. Ocul. Immunol. Inflamm. 2021. [Google Scholar] [CrossRef] [PubMed]
  20. Fernandez-Nieto, D.; Ortega-Quijano, D.; Suarez-Valle, A.; Burgos-Blasco, P.; Jimenez-Cauhe, J.; Fernandez-Guarino, M. Comment on: “To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out. Characterization of herpetic lesions in hospitalized COVID-19 patients”. J. Am. Acad. Dermatol. 2020, 83, e257–e259. [Google Scholar] [CrossRef] [PubMed]
  21. Eid, E.; Abdullah, L.; Kurban, M.; Abbas, O. Herpes zoster emergence following mRNA COVID-19 vaccine. J. Med. Virol. 2021, 93, 5231–5232. [Google Scholar] [CrossRef]
  22. Rodríguez-Jiménez, P.; Chicharro, P.; Cabrera, L.M.; Seguí, M.; Morales-Caballero, Á.; Llamas-Velasco, M.; Sánchez-Pérez, J. Varicella-zoster virus reactivation after SARS-CoV-2 BNT162b2 mRNA vaccination: Report of 5 cases. JAAD Case Reports 2021, 12, 58–59. [Google Scholar] [CrossRef] [PubMed]
  23. Bostan, E.; Yalici-Armagan, B. Herpes zoster following inactivated COVID-19 vaccine: A coexistence or coincidence? J. Cosmet. Dermatol. 2021, 20, 1566–1567. [Google Scholar] [CrossRef] [PubMed]
  24. Papasavvas, I.; De Courten, C.; Herbort, C.P., Jr. Varicella-zoster virus reactivation causing herpes zoster ophthalmicus ( HZO ) after SARS-CoV-2 vaccination–report of three cases. J. Ophthalmic Inflamm. Infect. 2021, 11, 28. [Google Scholar] [CrossRef]
  25. Triantafyllidis, K.K.; Giannos, P.; Mian, I.T.; Kyrtsonis, G.; Kechagias, K.S. Varicella zoster virus reactivation following COVID-19 vaccination: A systematic review of case reports. Vaccines 2021, 9, 1013. [Google Scholar] [CrossRef]
  26. Tartari, F.; Spadotto, A.; Zengarini, C.; Zanoni, R.; Guglielmo, A.; Adorno, A.; Valzania, C.; Pileri, A. Herpes zoster in COVID-19-positive patients. Int. J. Dermatol. 2020, 59, 1028–1029. [Google Scholar] [CrossRef] [PubMed]
  27. Herbort, C.P., Jr.; Papasavvas, I. Effect of SARS-CoV-2 mRNA vaccination on ocular herpes simplex and varicella-zoster virus reactivation : Should preventive antiviral treatment be given in known herpes patients. Ocul Immunol Inflamm. J. Ophthalmic Inflamm. Infect. 2021, 11, 33. [Google Scholar] [CrossRef] [PubMed]
  28. Méndez Mangana, C.; Barraquer Kargacin, A.; Barraquer, R.I. Episcleritis as an ocular manifestation in a patient with COVID-19. Acta Ophthalmol. 2020, 98, e1056–e1057. [Google Scholar] [CrossRef]
  29. Bostanci Ceran, B.; Ozates, S. Ocular manifestations of coronavirus disease. Graefe’s Arch. Clin. Exp. Ophthalmol. 2020, 258, 1959–1963. [Google Scholar] [CrossRef]
  30. Fernández Alcalde, C.; Granados Fernández, M.; Nieves Moreno, M.; Calvo Rey, C.; Falces Romero, I.; Noval Martín, S. COVID-19 ocular findings in children: A case series. World J. Pediatr. Springer Singapore 2021, 17, 329–334. [Google Scholar] [CrossRef]
  31. Feizi, S.; Meshksar, A.; Naderi, A.; Esfandiari, H. Anterior Scleritis Manifesting After Coronavirus Disease 2019: A Report of Two Cases. Cornea 2021, 40, 1204–1206. [Google Scholar] [CrossRef] [PubMed]
  32. Renisi, G.; Lombardi, A.; Stanzione, M.; Invernizzi, A.; Bandera, A.; Gori, A. Anterior uveitis onset after bnt162b2 vaccination: Is this just a coincidence? Int. J. Infect. Dis. 2021, 110, 95–97. [Google Scholar] [CrossRef]
  33. Sprent, J.; King, C. COVID-19 vaccine side effects: The positives about feeling bad. Sci. Immunol. 2021, 6, 1–4. [Google Scholar] [CrossRef] [PubMed]
  34. Khan, I.A.; Ouellette, C.; Chen, K.; Moretto, M. Toxoplasma: Immunity and Pathogenesis. Curr. Clin. Microbiol. Reports 2019, 6, 44–50. [Google Scholar] [CrossRef] [PubMed]
  35. Papasavvas, I.; Herbort, C.P. Reactivation of Vogt-Koyanagi-Harada disease under control for more than 6 years, following anti-SARS-CoV-2 vaccination. J. Ophthalmic Inflamm. Infect. 2021, 11, 21. [Google Scholar] [CrossRef]
  36. Erdem, S.; Karahan, M.; Dursun, M.E.; Ava, S.; Hazar, L.; Katran, I.; Keklikci, U. Retinal Vasculitis Case Developing in the Early Period after COVID-19. Klin. Monbl. Augenheilkd. 2021. [Google Scholar] [CrossRef]
  37. Insausti-García, A.; Reche-Sainz, J.A.; Ruiz-Arranz, C.; López Vázquez, Á.; Ferro-Osuna, M. Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state. Eur. J. Ophthalmol. 2020. [Google Scholar] [CrossRef]
  38. Tagini, F.; Carrel, L.; Fallet, B.; Gachoud, D.; Ribi, C.; Monti, M. Behçet’s-like adverse event or inaugural Behçet’s disease after SARS-CoV-2 mRNA-1273 vaccination? Rheumatology 2021, 3–7. [Google Scholar] [CrossRef] [PubMed]
  39. Virgo, J.; Mohamed, M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye 2020, 34, 2352–2353. [Google Scholar] [CrossRef] [PubMed]
  40. Bøhler, A.D.; Strøm, M.E.; Sandvig, K.U.; Moe, M.C.; Jørstad, Ø.K. Acute macular neuroretinopathy following COVID-19 vaccination. Eye 2021, 1–2. [Google Scholar] [CrossRef] [PubMed]
  41. Book, B.A.J.; Schmidt, B.; Foerster, A.M.H. Bilateral Acute Macular Neuroretinopathy after Vaccination against SARS-CoV-19. JAMA Ophthalmol. 2021, 139, e212471. [Google Scholar] [CrossRef] [PubMed]
  42. Mambretti, M.; Huemer, J.; Torregrossa, G.; Ullrich, M.; Findl, O.; Casalino, G. Acute Macular Neuroretinopathy following Coronavirus Disease 2019 Vaccination. Ocul. Immunol. Inflamm. 2021, 29, 730–733. [Google Scholar] [CrossRef] [PubMed]
  43. Michel, T.; Stolowy, N.; Gascon, P.; Dupessey, F.; Comet, A.; Attia, R.; David, T.; Denis, D. Acute Macular Neuroretinopathy After COVID-19 Vaccine. J Ophthal Inflamm Infect. 2021, 1–9. [Google Scholar] [CrossRef]
  44. Sheth, J.U.; Narayanan, R.; Goyal, J.; Goyal, V. Retinal vein occlusion in COVID-19: A novel entity. Indian J. Ophthalmol. 2020, 68, 2291–2293. [Google Scholar] [CrossRef]
  45. Sen, M.; Honavar, S.G.; Sharma, N.; Sachdev, M.S. COVID-19 and eye: A review of ophthalmic manifestations of COVID-19. Indian J. Ophthalmol. 2021, 69, 488–509. [Google Scholar]
  46. Haematology, T.L. COVID-19 coagulopathy: An evolving story. Lancet Haematol. 2020, 7, e425. [Google Scholar] [CrossRef]
  47. Bayas, A.; Menacher, M.; Christ, M.; Behrens, L.; Rank, A.; Naumann, M. Bilateral superior ophthalmic vein thrombosis, ischaemic stroke, and immune thrombocytopenia after ChAdOx1 nCoV-19 vaccination. Lancet 2021, 397, e11. [Google Scholar] [CrossRef]
  48. Panovska-Stavridis, I.; Pivkova-Veljanovska, A.; Trajkova, S.; Lazarevska, M.; Grozdanova, A.; Filipche, V. A rare case of superior ophthalmic vein thrombosis and thrombocytopenia following ChAdOx1 nCoV-19 vaccine against SARS-CoV-19. Mediterr. J. Hematol. Infect. Dis. 2021, 13, e2021048. [Google Scholar] [CrossRef]
  49. Bialasiewicz, A.A.; Farah-Diab, M.S.; Mebarki, H.T. Central retinal vein occlusion occurring immediately after 2nd dose of mRNA SARS-CoV-2 vaccine. Int. Ophthalmol. 2021, 41, 3889–3892. [Google Scholar] [CrossRef]
  50. Endo, B.; Bahamon, S.; Martínez-Pulgarín, D. Central retinal vein occlusion after mRNA SARS-CoV-2 vaccination: A case report. Indian J. Ophthalmol. 2021, 69, 2865–2866. [Google Scholar] [CrossRef]
  51. Rho, J.; Dryden, S.C.; McGuffey, C.D.; Fowler, B.T.; Fleming, J. A Case of Non-Arteritic Anterior Ischemic Optic Neuropathy with COVID-19. Cureus 2020, 12, 10–12. [Google Scholar] [CrossRef] [PubMed]
  52. Moschetta, L.; Fasolino, G.; Kuijpers, R.W. Non-arteritic anterior ischaemic optic neuropathy sequential to SARS-CoV-2 virus pneumonia: Preventable by endothelial protection? BMJ Case Rep. 2021, 14, 1–5. [Google Scholar] [CrossRef] [PubMed]
  53. Clarke, K.M.; Riga, V.; Shirodkar, A.-L.; Meyer, J. Proning related bilateral anterior ischaemic optic neuropathy in a patient with COVID-19 related acute respiratory distress syndrome. BMC Ophthalmol. 2021, 21, 1–6. [Google Scholar] [CrossRef] [PubMed]
  54. Girbardt, C.; Busch, C.; Al-Sheikh, M.; Gunzinger, J.M.; Invernizzi, A.; Xhepa, A.; Unterlauft, J.D.; Rehak, M. Retinal Vascular Events after mRNA and Adenoviral-Vectored COVID-19 Vaccines—A Case Series. Vaccines 2021, 9, 1349. [Google Scholar] [CrossRef] [PubMed]
  55. Fowler, N.; Mendez Martinez, N.R.; Pallares, B.V.; Maldonado, R.S. Acute-onset central serous retinopathy after immunization with COVID-19 mRNA vaccine. Am. J. Ophthalmol. 2021, 23, 101136. [Google Scholar] [CrossRef] [PubMed]
Table 1. Patients’ demographics, medical history, type of vaccine, and systemic symptoms post vaccination.
Table 1. Patients’ demographics, medical history, type of vaccine, and systemic symptoms post vaccination.
Pt n°AgeGenderHistory
of Uveitis
Systemic
Disease
Treatment
at Vaccination
Time Interval
between the Last Uveitis Attack to Current Uveitis (Months)
Type of VaccineSystemic Symptoms
and Time of Appearance
After 1st Dose of Vaccine (Days)
Systemic Symptoms
and Time of Appearance
After 2nd Dose of Vaccine
(Days)
183M--- BNT162b2fever, weakness-
279Mkeratouveitis-oral valaciclovir 1g11ChAdOx1 nCoV-19pain at the injection sitepain at the injection site
365Fkeratouveitis-oral valaciclovir 1g13BNT162b2-chills, fever, weakness
442Fanterior scleritis--12ChAdOx1 nCoV-19chills, feverpain at the injection site
552Fanterior scleritis--13BNT162b2weakness, general fatiguefever, weakness
644MNGAU (HLA-B27-)--14BNT162b2pain at the injection site-
735FNGAU (HLA-B27+)PsA-108mRNA-1273fever, weaknesspain at the injection site
847MNGAU (HLA-B27+)SpA-10BNT162b2--
966F--- ChAdOx1 nCoV-19pain at the injection siteweakness, general fatigue
1044M--- BNT162b2-pain at the injection site
1153M--- BNT162b2pain at the injection site-
1258FToxoplasma
retinochoroiditis
--82BNT162b2pain at the injection site, weakness-
1352FToxoplasma
retinochoroiditis
--11Ad26.COV2fever, chills, weakness
1444FVKH diseaseVKH diseaseMMF 2g22BNT162b2pain at the injection sitepain at the injection site
1558FVKH diseaseVKH diseaseMMF 2g26BNT162b2-fever, weakness
1649F--- ChAdOx1 nCoV-19pain at the injection site-
1718F--- BNT162b2-fever
1841M--- mRNA-1273fever, chills, weaknesspain at the injection site
1959F--- BNT162b2-weakness
2042M--- BNT162b2weaknesspain at the injection site
2153M--- BNT162b2fever-
2218F--- BNT162b2pain at the injection sitepain at the injection site
2348M--- BNT162b2--
2425F--estrogen-progestin oral contraceptives ChAdOx1 nCoV-19pain at the injection site, fever, muscle pain
2539M--- mRNA-1273fever, chills, muscle painpain at the injection site
2653F-SAHoral bisoprolol and losartan ChAdOx1 nCoV-19pain at the injection site, weakness-
2761F--- ChAdOx1 nCoV-19pain at the injection siteweakness
2850M-DMoral metformin BNT162b2-weakness, fever
2948M-SAHoral doxazosin BNT162b2pain at the injection sitepain at the injection site
3046F--- BNT162b2pain at the injection site-
3147FToxoplasma
retinochoroiditis
--94BNT162b2pain at the injection site, chills, fever, weakness-
3268FSerpiginous
Choroiditis
--13BNT162b2pain at the injection site, weaknesspain at the injection site
3366F--- BNT162b2-pain at the injection site
3441M--- BNT162b2pain at the injection siteweakness, muscle pain
Pt: patient; M: male; F: female; -: none; blank cells: not applicable data; NGAU: non-granulomatous anterior uveitis; HLA-B27: human leukocyte antigen B27; PsA: psoriatic arthritis; SpA: spondyloarthritis; DM: diabetes mellitus; SAH: systemic arterial hypertension; MMF: mycophenolate mofetil.
Table 2. Uveitis and other ocular complications post vaccination.
Table 2. Uveitis and other ocular complications post vaccination.
Pt n°EyeOcular
Complication
History
of Uveitis
Ocular Complication Following 1st or 2nd Dose of VaccineTime Interval from Vaccine to Ocular Symptoms Onset (Days)Ocular
Symptoms
BCVA at Presentation (Snellen)BCVA at Last Follow Up (Snellen)Treatment Given
at Presentation
Outcome
1LEherpetic keratitis-2nd dose7redness, pain, blurred vision20/4020/25acyclovir ophthalmic ointmentcomplete resolution
2REherpetic keratitiskeratouveitis1st dose5pain,
blurred vision
20/4020/22oral valaciclovir 1g,
dexamethasone eye drops 2 mg/ml
complete resolution
3LEherpetic keratitiskeratouveitis2nd dose6redness, blurred vision20/5020/20oral valaciclovir 1g,
dexamethasone eye drops 2 mg/ml
complete resolution
4REanterior scleritisanterior scleritis2nd dose6redness, pain20/2020/20dexamethasone eye drops 2 mg/mlcomplete resolution
5REanterior scleritisanterior scleritis1st dose5redness, pain20/2020/20dexamethasone eye drops 2 mg/mlcomplete resolution
6LENGAU (HLA-B27-)NGAU (HLA-B27-)1st dose6photophobia20/2020/20dexamethasone eye drops 2 mg/mlcomplete resolution
7BENGAU (HLA-B27+)NGAU (HLA-B27+)2nd dose1redness, pain, blurred visionRE: 20/22
LE: 20/25
RE: 20/20
LE: 20/22
dexamethasone eye drops 2 mg/mlcomplete resolution
8LENGAU (HLA-B27+)NGAU (HLA-B27+)2nd dose6blurred vision20/2520/20dexamethasone eye drops 2 mg/mlcomplete resolution
9LENGAU (HLA-B27+)-1st dose30redness, pain, blurred vision20/3220/25dexamethasone eye drops 2 mg/mlcomplete resolution
10RECMV AU-2nd dose8blurred vision20/2820/20ganciclovir ophthalmic gel 0.15%, dexamethasone eye drops 2 mg/mlcomplete resolution
11LEToxoplasma
retinochoroiditis
-1st dose8blurred vision20/4020/20sulfadiazine and pyrimethamine
tablets, oral prednisone
complete resolution
12LEToxoplasma
retinochoroiditis
Toxoplasma
retinochoroiditis
2nd dose7blurred vision20/20020/20sulfadiazine and pyrimethamine
tablets, oral prednisone
complete resolution
13REToxoplasma
retinochoroiditis
Toxoplasma
retinochoroiditis
1st dose7blurred vision20/5020/20sulfadiazine and pyrimethamine
tablets, oral prednisone
complete resolution
14BEVKH diseaseVKH disease2nd dose12blurred visionRE: 20/22
LE: 20/25
RE: 20/20
LE: 20/20
MMF 2g, oral prednisonecomplete resolution
15BEVKH diseaseVKH disease2nd dose5blurred visionRE: 20/25
LE: 20/28
RE: 20/20
LE: 20/22
MMF 2g, oral prednisonecomplete resolution
16BEpars planitis-1st dose7blurred visionRE: 20/25
LE: 20/20
RE: 20/20
LE: 20/20
oral prednisonecomplete resolution
17BEpars planitis-2nd dose14blurred visionRE: 20/20
LE: 20/20
RE: 20/20
LE: 20/20
oral prednisonecomplete resolution
18BEretinal vasculitis-2nd dose5blurred visionRE: 20/66
LE: 20/20
RE: 20/20
LE: 20/20
oral prednisonecomplete resolution
19REretinal vasculitis-1st dose10blurred vision20/2820/20oral prednisonecomplete resolution
20BEpanuveitis in
new-onset BD
-2nd dose30redness, blurred visionRE: 20/28
LE: 20/32
RE: 20/25
LE: 20/22
oral prednisone, AZAcomplete resolution
21LEMEWDS-2nd dose28decreased VA, visual field defect20/2520/20-complete resolution
22REMEWDS-1st dose4blurred vision, visual field defect20/6620/20-complete resolution
23REMEWDS-1st dose7decreased VA20/40020/20-complete resolution
24BEAMN-1st dose2visual field defectRE: 20/20
LE: 20/20
RE: 20/20
LE: 20/20
-significant improvement
25RECRVO-2nd dose30decreased VA20/40020/100intravitreal anti-VEGFmild improvement
26LEBRVO-1st dose2decreased VA20/10020/40intravitreal anti-VEGFpartial improvement
27LEBRVO-2nd dose2decreased VA20/3220/25intravitreal anti-VEGFpartial improvement
28LEBRVO-2nd dose3decreased VA20/2220/20intravitreal anti-VEGFsignificant improvement
29LEBRVO-2nd dose23blurred vision20/2020/20intravitreal anti-VEGFsignificant improvement
30RENAION-1st dose2decreased VA, visual field defect20/4020/200oral prednisoneno improvement
31REuveitic CNVToxoplasma
retinochoroiditis
1st dose8decreased VA20/20020/40intravitreal anti-VEGFsignificant improvement
32REuveitic CNVSerpiginous
Choroiditis
2nd dose10decreased VA20/5020/32intravitreal anti-VEGFpartial improvement
33REmyopic CNV-2nd dose1blurred vision20/3220/25intravitreal anti-VEGFpartial improvement
34BECSR-2nd dose13blurred visionRE: 20/22
LE: 20/50
RE: 20/20
LE: 20/22
-complete resolution
BE: both eyes; LE: left eye; RE: right eye, NGAU: non-granulomatous anterior uveitis; HLA-B27: human leukocyte antigen B27; CMV: Citomegalovirus; AU: anterior uveitis; VKH: Vogt-Koyanagi-Harada; BD: Behçet’s disease; MEWDS: multiple evanescent white dot syndrome; AMN: acute macular neuroretinopathy; CNV: choroidal neovascularization; CRVO: central retinal vein occlusion; BRVO: branch retinal vein occlusion; NAION: non-arteritic ischemic optic neuropathy; CSR: central serous retinopathy; VA: visual acuity; BCVA: best corrected visual acuity; MMF: mycophenolate mofetil; AZA: Azathioprine; -: none; VEGF: vascular endothelial growth factor.
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Bolletta, E.; Iannetta, D.; Mastrofilippo, V.; De Simone, L.; Gozzi, F.; Croci, S.; Bonacini, M.; Belloni, L.; Zerbini, A.; Adani, C.; et al. Uveitis and Other Ocular Complications Following COVID-19 Vaccination. J. Clin. Med. 2021, 10, 5960. https://doi.org/10.3390/jcm10245960

AMA Style

Bolletta E, Iannetta D, Mastrofilippo V, De Simone L, Gozzi F, Croci S, Bonacini M, Belloni L, Zerbini A, Adani C, et al. Uveitis and Other Ocular Complications Following COVID-19 Vaccination. Journal of Clinical Medicine. 2021; 10(24):5960. https://doi.org/10.3390/jcm10245960

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Bolletta, Elena, Danilo Iannetta, Valentina Mastrofilippo, Luca De Simone, Fabrizio Gozzi, Stefania Croci, Martina Bonacini, Lucia Belloni, Alessandro Zerbini, Chantal Adani, and et al. 2021. "Uveitis and Other Ocular Complications Following COVID-19 Vaccination" Journal of Clinical Medicine 10, no. 24: 5960. https://doi.org/10.3390/jcm10245960

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