Purpose
To summarize the current evidence on COVID-19 vaccine-associated ocular adverse events.
Design
Narrative literature review.
Methods
The literature search was conducted in August 2021 using 4 electronic databases: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic Reviews. Population-based pharmacovigilance surveillance data were retrieved from all governmental agencies participating in the World Health Organization (WHO) Programme for International Drug Monitoring with publicly available online adverse event databases in English.
Results
A small number of case reports have documented uveitis flares and acute corneal graft rejection occurring within the first 3 weeks following immunization, while isolated cases of optic neuropathies, retinal conditions, scleritis, and herpetic eye disease have also been highlighted. However, data from population-based pharmacovigilance surveillance systems suggest that the prevalence of vaccination-associated ocular adverse events are very rare.
Conclusions
Vaccination-associated ocular adverse events are rare, and there is currently no substantive evidence to counterweigh the overwhelming benefits of COVID-19 immunization in patients with pre-existing ophthalmic conditions.
INTRODUCTION
T he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in December 2019 led to the devastating coronavirus disease 2019 (COVID-19) pandemic, which has become one of the largest global health threats to date. As of late August 2021, almost 220 million people had been infected worldwide, and more than 4.5 million lives claimed. However, the isolation of the SARS-CoV-2 virus and subsequent publication of its genome sequence in January 2020 ignited an unprecedented global response towards the accelerated development of preventative vaccine candidates, and mobilized multinational collaborative efforts between pharmaceutical corporations, academic institutions, and governmental agencies. , The expedited process culminated in 2 recombinant mRNA vaccines (Pfizer/BioNTech BNT162b2, and Moderna mRNA-1273) being granted emergency use authorization by the United States Food and Drug Administration in December 2020. A number of other immunizations, including 2 adenovirus vector-based vaccines (AstraZeneca ChAdOx1 nCoV-19 and Janssen Ad26.COV2.S), have subsequently been approved worldwide, and more than 5.3 billion COVID-19 vaccination doses have been administered globally to date.
Large phase 3 clinical trials have confirmed the high protective efficacy levels of several approved vaccines against serious COVID-19 infection, as well as demonstrating favorable safety profiles and low incidence rates of major adverse events. Nevertheless, the inherent methodological limitations of phase 3 clinical trials–including sample size, follow-up duration, and enrolment criteria restrictions–would preclude dedicated evaluation of rare and serious adverse vaccine-associated outcomes. Population-based pharmacovigilance surveillance systems have therefore become necessary to enable ongoing monitoring of vaccine safety. , A number of rare systemic adverse events following COVID-19 immunization have since garnered considerable attention, including: cerebral venous thrombosis, immune thrombocytopenia, and acute myocarditis. However, there is a significant paucity of scientific evidence evaluating the potential adverse effects of COVID-19 vaccines to the eye. Therefore, this narrative literature review aimed provide an overview of the current evidence on COVID-19 vaccine-associated ocular adverse events, as well as the clinical safety in patients with pre-existing ophthalmic conditions, using population-based pharmacovigilance surveillance systems and data reported in the peer-reviewed literature.
METHOD OF LITERATURE SEARCH
The literature search was conducted on August 31, 2021 ( Figure 1 ) using 4 electronic databases: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic Reviews. Appropriate keywords, subject headings, free text, and thesaurus search terms were used in order to maximize sensitivity for the search strategy, and included the following terms used in various combinations: “coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, vaccine, vaccination, immunization, eye, cornea, herpes simplex, herpes zoster, uveitis, scleritis, episcleritis, retina, retinopathy, retinal degeneration, macula, maculopathy, macular degeneration, optic nerve, optic neuropathy, optic neuritis, glaucoma”. No time range limits were set for the literature search. Published English abstracts for articles written in other languages were reviewed where available. The reference lists of retrieved articles were also reviewed for further identification of potentially relevant studies. A summary of all included studies from the peer-reviewed literature is provided in Table 1 .
| Study | Patients | Vaccine | Presentation | Clinical Outcomes |
|---|---|---|---|---|
| Ocular Inflammatory Disease | ||||
| ElSheikh et al. 2021 | 1 | BBIBP-CorV (Sinopharm): second dose administered 5 days earlier in a single patient. | Anterior uveitis in single patient with background of antinuclear, antibody-positive, oligoarticular, juvenile idiopathic arthritis, but no previous history of uveitis. | Initial treatment with 2-hourly topical prednisolone therapy and topical cyclopentolate 2 times daily was commenced. Complete resolution and return to baseline visual acuity occurred within 6 weeks. |
| Furer et al. 2021 | 2 | BNT162b2 (Pfizer/BioNTech): vaccination dose details not documented. | Uveitis in 2 patents with background of autoimmune inflammatory rheumatic diseases. Further clinical details not documented. | Not documented. |
| Goyal et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca): second dose administered 9 days earlier in a single patient. | Multifocal choroiditis with no previous history of systemic or ocular inflammatory conditions. | Initial treatment with oral prednisone 100 mg daily was commenced, with tapering course by 10 mg/week. Clinical outcome and follow-up not documented. |
| Mudie et al. 2021 | 1 | BBIBP-CorV (Sinopharm): second dose administered 3 days earlier in a single patient. | Panuveitis in a single patient. Past ocular and systemic history of the patient was not documented. | Initial treatment with topical difluprednate therapy 4 times daily and cycloplegia for anterior and intermediate uveitis. Commenced on oral prednisone 50 mg daily and 2-hourly topical difluprednate the following day for panuveitis. Oral prednisone subsequently tapered over 3 weeks with return of visual acuity to baseline. However, at 6-week follow-up, despite maintaining baseline visual acuity, the patient developed new floaters and recurrence of mild choroidal thickening, and was subsequently re-started on high-dose oral prednisone with plan for extended taper. |
| Papasavvas et al. 2021 | 1 | BBIBP-CorV (Sinopharm): second dose administered 6 weeks earlier in a single patient. | Vogt-Koyanagi-Harada disease reactivation in a single patient, with significant anterior segment inflammation, retinal folds, and subretinal fluid. The patient had previously been well controlled on maintenance treatment with 10-weekly infliximab for the past 6 years. | Initial treatment with a 5-day course of oral prednisone (1 mg/kg) and loading dose scheme of infliximab administered, with short-term clinical improvements recorded. |
| Pichi et al. 2021 | 3 | BBIBP-CorV (Sinopharm): unspecified dose administered 1 week earlier in 1 patient, and up to 15 days earlier in the other 2 patients with no further clinical details recorded. | Anterior scleritis in 2 patients, and episcleritis in 1 patient. One of the patients with anterior scleritis had a history of rheumatoid arthritis on sulfasalazine therapy. Clinical details not documented for the other 2 patients. | Initial treatment with 1-week tapering course of topical corticosteroid therapy of unspecified dose commenced in 1 patient, with clinical resolution occurring in 1 week, without the requirement for systemic corticosteroid treatment. No clinical follow-up details documented for the other 2 patients. |
| Rabinovitch et al. 2021 | 21 | BNT162b2 (Pfizer/BioNTech): first dose administered 1 to 14 days earlier in 8 patients, and second dose administered 1 to 30 days earlier in 13 patients. | Anterior uveitis in 18 patients, multiple evanescent white dot syndrome in 2 patients, anterior and intermediate uveitis with cystoid macular edema in 1 patient. Seven patients had previous history of anterior uveitis, and 1 patient had previous history of herpes zoster ophthalmicus keratouveitis. Three patients had ankylosing spondylitis, 1 patient had Crohn’s disease, and 1 patient had psoriasis. Twelve patients had no previous history of systemic or ocular inflammatory conditions. | Initial treatment with topical prednisolone (3-hourly to hourly) or dexamethasone (4 times daily to 2-hourly), and topical cyclopentolate (daily to 3 times daily) or tropicamide (daily to 3 times daily) was commenced in the 18 patients with anterior uveitis. Initial treatment with hourly topical prednisolone therapy and topical cyclopentolate 3 times daily was commenced in the patient with anterior and intermediate uveitis with cystoid macular edema, intravitreal dexamethasone injection (Ozurdex) was subsequently administered. The 2 patients with multiple evanescent white dot syndrome were managed conservatively. Complete resolution or significant improvement with return to baseline visual acuity occurred in all patients, although the time frame was not documented. |
| Renisi et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech): second dose administered 14 days earlier in a single patient. | Anterior uveitis in a single patient with no previous history of systemic or ocular inflammatory conditions. | Initial treatment with topical dexamethasone therapy 3 times daily and topical atropine twice daily was commenced, although topical dexamethasone was uptitrated to 6 times daily the following week before subsequent tapering. Complete resolution and return to baseline visual acuity occurred within 6 weeks. |
| Herpetic Eye Disease | ||||
| Furer et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech): first dose administered 4 days earlier in a single patient. | First episode of herpes zoster ophthalmicus with conjunctivitis in a patient with background of rheumatoid arthritis on tofacitinib therapy. | Initial treatment with 14-day course of oral acyclovir treatment and topical lubricant eye drops, and temporary discontinuation of tofacitinib therapy. Resolution occurred within 6 weeks. |
| Richardson-May et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca): first dose administered 1 day earlier in a single patient. | Recurrence of herpes simplex stromal keratitis in a patient with background of herpes zoster keratitis 40 years earlier. | Initial treatment with topical ganciclovir for herpes simplex epithelial keratitis. However, clinical deterioration noted at 7 days with geographical ulceration, corneal haze, and mild anterior chamber inflammation. Corneal scrape and viral PCR subsequently confirmed a diagnosis of herpes simplex stromal keratitis. Clinical improvements were observed with systemic antiviral and topical corticosteroid and antibiotic therapy, although residual corneal scarring was observed at 6-week follow-up. |
| Thimmanagari et al. 2021 | 2 | mRNA-1273 (Moderna): first dose administered 1 week earlier in first patient. Ad26.COV2.S (Janssen): administered 1 week earlier in second patient. | First episode herpes zoster ophthalmicus with conjunctivitis in first patient, and no ophthalmic involvement in second patient. Both patients had no previous history of systemic inflammatory conditions or immunosuppressant therapy. | Systemic antiviral therapy commenced in both patients, although medication dosage not documented. Resolution reported in both patients, although timeframe of clinical follow-up not documented. |
| Anterior Segment Conditions | ||||
| Crnej et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech): first dose administered 7 days earlier in a single patient. | Acute corneal graft rejection in a single patients with Descemet membrane endothelial keratoplasty for post-cataract surgery endothelial decompensation. | Initial treatment with 2-hourly topical dexamethasone therapy and oral valacyclovir 1 g 3 times daily was commenced in the patient. Significant improvements and return to baseline visual acuity occurred within 7 days. |
| Phylactou et al. 2021 | 2 | BNT162b2 (Pfizer/BioNTech): first dose administered 7 days earlier in the first patient, and second dose administered 3 weeks earlier in second patient. | Acute corneal graft rejection in 2 patients with Descemet membrane endothelial keratoplasty or Fuchs’ endothelial corneal dystrophy. | Initial treatment with hourly topical dexamethasone therapy was commenced in both patients. Significant improvements and return to baseline visual acuity occurred in both cases within 7 days. |
| Rallis et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech): first dose administered 4 days earlier in a single patient. | Acute corneal graft rejection in a single patient with penetrating keratoplasty for Fuchs’ endothelial corneal dystrophy. | Initial treatment with hourly topical dexamethasone therapy and 1-week course of oral acyclovir 400 mg 5 times daily was commenced in the patient. Significant improvements and return to baseline visual acuity occurred within 3 weeks. |
| Ravichandran et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca): first dose administered 3 weeks earlier in a single patient. | Acute corneal graft rejection in a single patient with penetrating keratoplasty for childhood corneal scar. | Not documented. |
| Wasser et al. 2021 | 2 | BNT162b2 (Pfizer/BioNTech): first dose administered 13 and 14 days earlier, respectively, in the 2 patients. | Acute corneal graft rejection in 2 patients with penetrating keratoplasty for keratoconus. | Initial treatment with topical dexamethasone therapy and oral prednisone 60 mg daily was commenced in both patients. Significant improvements and return to baseline visual acuity occurred within 7 days in the first patient, and 2 weeks in the second patient. |
| Retinal Conditions | ||||
| Book et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca): first dose administered 3 days earlier in a single patient. | Acute macular neuroretinopathy in a single patient with no significant past ocular history. | Not documented. |
| Bøhler et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca): first dose administered 2 days earlier in a single patient. | Acute macular neuroretinopathy in a single patient on combined desogestrel and ethinylestradiol contraceptive therapy, with no significant past ocular history. | Not documented. |
| Maleki et al. 2021 | 1 | mRNA-1273 (Moderna): second dose administered 10 days earlier in a single patient. | Acute zonal occult outer retinopathy in a single patient with background of pre-eclampsia and 1 previous unexplained miscarriage, but no significant past ocular history. | Treated with intravitreal dexamethasone implant, and combination azathioprine and cyclosporine therapy was considered, although further clinical follow-up details were not documented. |
| Mambretti et al. 2021 | 2 | ChAdOx1 nCoV-19 (AstraZeneca): first dose administered 2 days earlier in 2 patients. | Acute macular neuroretinopathy in 2 patients, both on long-term oral contraceptive therapy, with no significant past ocular history. | Not documented. |
| Pichi et al. 2021 | 4 | BBIBP-CorV (Sinopharm): unspecified dose administered 5 days earlier in 1 patient, and up to 15 days earlier in the other 3 patients with no further clinical details recorded. | Acute macular neuroretinopathy in 2 patients, paracentral acute middle maculopathy in 1 patient, subretinal fluid thought to represent forme fruste central serous chorioretinopathy in 1 patient. One of the patients with acute macular neuroretinopathy had previous ocular history of central serous chorioretinopathy, while the other patient with acute macular neuroretinopathy had no significant past ocular or systemic history. Clinical details were not documented for the other 2 patients. | One of the patients with acute macular neuroretinopathy was managed conservatively, and the optical coherence tomographic lesions were reported to resolve spontaneously at 2 months. No clinical follow-up details were documented for the remaining 3 patients. |
| Optic Neuropathy | ||||
| Helmchen et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca) vaccine: first dose administered 2 weeks earlier in a single patient. | Seronegative neuromyelitis optica spectrum disorder with bilateral optic neuritis with chiasmal involvement and longitudinal extensive transverse myelitis in a single patient with background of relapsing-remittent multiple sclerosis (on natalizumab therapy. | Initial treatment with intravenous methylprednisolone 2 g daily for 2 days, followed by plasmapheresis and immunoadsorption with mild improvement in visual acuities with recognition of motion. However, there was persistence of paraplegia, loss of sensory function below T5, and incontinence at 2 months |
| Leber et al. 2021 | 1 | CoronaVac (Sinovac) vaccine: second dose administered 12 hours earlier in single patients. | Myelin oligodendrocyte glycoprotein antibody-associated bilateral anterior optic neuritis and concurrent subacute thyroiditis in single patient. Past ocular and systemic history of the patient was not documented. | Initial treatment with intravenous methylprednisolone 1 g daily for 5 days, followed by tapering course of oral corticosteroids. Improvements in optic disc swelling, recovery of visual acuity and fields to baseline levels, and normalization of thyroid function occurred within 1 week. |
| Maleki et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech) vaccine: second dose administered 2 days earlier in a single patient | Temporal artery biopsy-positive bilateral arteritic anterior ischemic optic neuropathy in a single patient with no previous history of systemic or ocular inflammatory conditions. | Initial treatment with oral prednisone 60 mg daily and subcutaneous tocilizumab 162 mg weekly was commenced. Further clinical follow-up details were not documented. |
| Other Ophthalmic Conditions | ||||
| Bayas et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca) vaccine: first dose administered 10 days earlier in a single patient. | Vaccine-induced immune thrombotic thrombocytopenia with superior ophthalmic vein thrombosis in a single patient with no significant ocular or systemic history. | Initial treatment with intravenous dexamethasone and heparin. Developed left parietal lobe ischemic stroke 8 days following admission, followed by right-sided seizures controlled by levetiracetam and lacosamide. Heparin subsequently switched to phenprocoumon, and patient discharged 25 days following admission. |
| Burrows et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech) vaccine: first dose administered 5 days prior to right-sided Bell’s palsy, and second dose administered 2 days prior to left-sided Bell’s palsy. | Bilateral sequential Bell’s palsy in a single patient with a background of hypertension, hypercholesterolemia, and type 2 diabetes. | Initial treatment with oral prednisone 60 mg daily subsequently weaned over a 4-week period, with resolution of right-sided Bell’s palsy. Re-presented 2 days following second vaccine dose with left-sided Bell’s palsy, and treated with 7-day course of prednisone 60 mg daily and weaned over a 4-week period, with resolution of left-sided Bell’s palsy. |
| Colella et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech) vaccine: first dose administered 5 days earlier. | Unilateral Bell’s palsy in a single patient with no significant ocular or systemic history. | Initial treatment with oral prednisone 50 mg daily and artificial tears. Further details surrounding treatment taper not provided. At 1 month follow-up, partial improvement in facial mobility was observed, although pain sensation persisted. |
| El-Shitany et al. 2021 | 3 | BNT162b2 (Pfizer/BioNTech) vaccine: adverse events occurred in 3 cases following the first dose, further details not provided. | Bell’s palsy in 3 patients. Further clinical details not provided. | Not documented. |
| Iftikhar et al. 2021 | 1 | mRNA-1273 (Moderna) vaccine: second dose administered 2 days earlier. | Unilateral Bell’s palsy in a single patient with no significant ocular or systemic history. | Initial treatment with 7-day course of oral prednisone 60 mg daily and artificial tears. Improvements observed at 2 week follow-up, no further clinical follow-up details provided. |
| Mason et al. 2021 | 1 | mRNA-1273 (Moderna) vaccine: dose administered 4 weeks earlier, although unclear whether the first or second dose. | Bilateral sequential Bell’s palsy in a single patient with a background of migraine headaches. | Initial treatment plan for intravenous 500 mg twice daily for 3 days followed by oral prednisone taper, and oral acyclovir 400 mg 4 times daily for 10 days, after negative MRI brain and CT angiography. Four days later developed contralateral Bell’s palsy, with negative lumbar puncture and MRI brain with contrast. Re-commenced on 500 mg twice daily for 3 days with significant improvement and discharged on oral prednisone taper. |
| Martin-Villares et al. 2021 | 1 | mRNA-1273 (Moderna) vaccine: first dose administered 2 days earlier. | Unilateral Bells’ palsy in a single patient with 1 previous episode of Bell’s palsy during pregnancy 9 years ago. | Treatment details not provided. Full resolution of unilateral Bell’s palsy occurred at 3-week follow-up. |
| Panovska-Stavridis et al. 2021 | 1 | ChAdOx1 nCoV-19 (AstraZeneca) vaccine: first dose administered 10 days earlier in a single patient. | Vaccine-induced immune thrombotic thrombocytopenia with superior ophthalmic vein thrombosis in a single patient with no significant ocular or systemic history. | Initial treatment with a 2-day course of intravenous immunoglobulin followed by a tapering course of oral corticosteroid therapy, and commenced on rivaroxaban anticoagulation. Symptomatic resolution occurred within 5 days, platelet levels normalized in 1 week, and D-dimer levels normalized in 2 weeks. |
| Repajic et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech) vaccine: second dose administered 2 days earlier. | Unilateral Bells’ palsy in a single patient with a background of hypertension and recurrent Bell’s palsy. | Treatment details not provided. Clinical improvement in unilateral Bell’s palsy observed at 2-week follow-up. |
| Reyes-Capo et al. 2021 | 1 | BNT162b2 (Pfizer/BioNTech) vaccine: dose administered 2 days earlier, although unclear whether the first or second dose. | Isolated abducent nerve palsy in a single patient with no significant ocular or systemic history. | Not documented. |
| Shemer et al. 2021 | 21 | BNT162b2 (Pfizer/BioNTech) vaccine: further details regarding the timing of vaccination was not provided for the 21 patients. | Unilateral Bell’s palsy in 21 patients. Four patients had a background of hypertension, 3 patients had dyslipidemia, 2 patients had diabetes, 1 patient had small-fiber neuropathy, 1 patient had a cardiac pacemaker, 1 patient had obstructive sleep apnea, 1 patient had Meniere’s disease, 1 patient had asthma, 1 patient had hypothyroidism, 1 patient had thalassemia, 1 patient had prostate cancer, 1 patient had benign prostatic hypertrophy | Treatment details not provided. Partial recovery at last follow-up was documented in 9 patients. No clinical follow-up details were provided from the remaining 12 patients. |
| Wan et al. 2021 | 44 | CoronaVac (Sinovac) vaccine: first dose administered 1-42 days earlier in 19 patients, and second dose administered 1-17 days earlier in 9 patients. BNT162b2 (Pfizer/BioNTech): first dose administered 2-20 days earlier in 8 patients, and second dose administered 1-18 days earlier in 8 patients. | Unilateral Bell’s palsy in 44 patients. Previous ocular and systemic history not provided. | Treatment details not provided. Significant or full recovery at last follow-up was documented in 20 of 21 patients with details provided. No clinical follow-up details were provided from the remaining 23 patients. |
Population-based pharmacovigilance surveillance data were retrieved through searching the websites of all governmental agencies participating in the World Health Organization Programme for International Drug Monitoring with publicly available online adverse event databases in English ( Figure 2 ). Vaccine-associated adverse event data were extracted from the government agency websites on August 31, 2021, including the Australia Therapeutic Goods Administration Database of Adverse Event Notifications, the Canada Vigilance Adverse Reaction Database, the European Union Medicines Agency EudraVigilance System, the United Kingdom Medicines and Healthcare Products Regulatory Agency, and the United States Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. The numbers of ocular adverse events occurring following administration of each type of vaccine were recorded. Data on vaccination dose administration were retrieved from the University of Oxford Our World in Data website on August 31, 2021, which is compiled from official reports released by national public health agencies. Prevalence rates of ocular adverse events were calculated by dividing the number of events by the number of vaccine doses administered. A summary of population-based pharmacovigilance surveillance data is provided in Table 2 . It is acknowledged that data generated from population-based pharmacovigilance surveillance systems can be subjected to bias secondary to the unverified nature of suspected adverse event reporting conducted by individual clinicians and patients; therefore, causal relationships and direct association cannot be inferred.
| Adverse Ocular Event | Vaccine | European Union | United States | United Kingdom 1 | Canada | Australia 1 | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases | Prevalence (Cases Per Million Doses) | Cases | Prevalence (Cases Per Million Doses) | Cases | Prevalence (Cases Per Million Doses) | Cases | Prevalence (Cases Per Million Doses) | Cases | Prevalence (Cases Per Million Doses) | ||
| Ocular Inflammatory Disease | |||||||||||
| Uveitis | Pfizer/BioNTech | 121 | 0.3 | 39 | 0.2 | 37 | – | 1 | 0.02 | 5 | – |
| Moderna | 43 | 0.8 | 40 | 0.3 | 3 | – | 0 | 0 | – | – | |
| AstraZeneca | 53 | 0.8 | – | – | 42 | – | 0 | 0 | 7 | – | |
| Janssen | 3 | 0.2 | 3 | 0.2 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 220 | 0.4 | 82 | 0.2 | 82 | 0.9 | 1 | 0.02 | 12 | 0.6 | |
| Episcleritis | Pfizer/BioNTech | 25 | 0.07 | 19 | 0.09 | 7 | – | 0 | 0 | 0 | – |
| Moderna | 4 | 0.08 | 8 | 0.06 | 4 | – | 0 | 0 | – | – | |
| AstraZeneca | 6 | 0.09 | – | – | 18 | – | 0 | 0 | 2 | – | |
| Janssen | 1 | 0.07 | 0 | 0.00 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 36 | 0.07 | 27 | 0.07 | 29 | 0.3 | 0 | 0 | 2 | 0.1 | |
| Scleritis | Pfizer/BioNTech | 25 | 0.07 | 11 | 0.05 | 3 | – | 0 | 0 | 1 | – |
| Moderna | 11 | 0.2 | 8 | 0.06 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 16 | 0.2 | – | – | 13 | – | 0 | 0 | 0 | – | |
| Janssen | 1 | 0.07 | 1 | 0.07 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 53 | 0.1 | 20 | 0.05 | 16 | 0.2 | 0 | 0 | 1 | 0.05 | |
| Herpetic Eye Disease | |||||||||||
| Ophthalmic herpes zoster | Pfizer/BioNTech | 55 | 0.1 | 0 | 0 | 3 | – | 0 | 0 | 2 | – |
| Moderna | 23 | 0.4 | 0 | 0 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 37 | 0.5 | – | – | 10 | – | 0 | 0 | 4 | – | |
| Janssen | 2 | 0.1 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 117 | 0.2 | 0 | 0 | 13 | 0.1 | 0 | 0 | 6 | 0.3 | |
| Ophthalmic herpes simplex | Pfizer/BioNTech | 0 | 0 | 0 | 0 | 0 | – | 0 | 0 | 0 | – |
| Moderna | 0 | 0 | 0 | 0 | 1 | – | 0 | 0 | – | – | |
| AstraZeneca | 0 | 0 | – | – | 1 | – | 0 | 0 | 1 | – | |
| Janssen | 0 | 0 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 0 | 0 | 0 | 0 | 2 | 0.02 | 0 | 0 | 1 | 0.05 | |
| Anterior Segment Conditions | |||||||||||
| Corneal graft rejection | Pfizer/BioNTech | 10 | 0.03 | 1 | 0.005 | 5 | – | 0 | 0 | 0 | – |
| Moderna | 2 | 0.04 | 0 | 0 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 3 | 0.04 | – | – | 3 | – | 0 | 0 | 0 | – | |
| Janssen | 0 | 0 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 1 | – | – | – | – | – | |
| Total | 15 | 0.03 | 1 | 0.003 | 9 | 0.1 | 0 | 0 | 0 | 0 | |
| Retinal Conditions | |||||||||||
| Macular edema | Pfizer/BioNTech | 24 | 0.06 | 3 | 0.01 | 3 | – | 0 | 0 | 0 | – |
| Moderna | 10 | 0.2 | 6 | 0.04 | 1 | – | 1 | 0.06 | – | – | |
| AstraZeneca | 20 | 0.3 | – | – | 7 | – | 0 | 0 | 0 | – | |
| Janssen | 3 | 0.2 | 1 | 0.07 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 57 | 0.1 | 10 | 0.03 | 11 | 0.1 | 1 | 0.02 | 0 | 0 | |
| Macular degeneration | Pfizer/BioNTech | 17 | 0.05 | 11 | 0.05 | 3 | – | 0 | 0 | 0 | – |
| Moderna | 5 | 0.1 | 5 | 0.03 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 10 | 0.1 | 0 | – | 9 | – | 0 | 0 | 1 | – | |
| Janssen | 1 | 0.07 | 1 | 0.07 | – | – | – | – | – | ||
| Unspecified | – | – | – | – | 1 | – | – | – | – | – | |
| Total | 33 | 0.06 | 17 | 0.05 | 13 | 0.1 | 0 | 0 | 1 | 0.05 | |
| Maculopathy | Pfizer/BioNTech | 9 | 0.02 | 3 | 0.01 | 1 | – | 0 | 0 | 0 | – |
| Moderna | 3 | 0.06 | 0 | 0 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 7 | 0.1 | – | – | 2 | – | 0 | 0 | 0 | – | |
| Janssen | 0 | 0 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 19 | 0.04 | 3 | 0.008 | 3 | 0.03 | 0 | 0 | 0 | 0 | |
| Chorioretinopathy | Pfizer/BioNTech | 11 | 0.03 | 3 | 0.01 | 2 | – | 0 | 0 | 1 | – |
| Moderna | 5 | 0.1 | 2 | 0.01 | 1 | – | 0 | 0 | – | – | |
| AstraZeneca | 8 | 0.1 | – | – | 2 | – | 0 | 0 | 1 | – | |
| Janssen | 0 | 0 | 1 | 0.07 | – | – | – | – | – | ||
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 24 | 0.05 | 6 | 0.02 | 5 | 0.05 | 0 | 0 | 2 | 0.1 | |
| Acute zonal occult outer retinopathy | Pfizer/BioNTech | 0 | 0 | 0 | 0 | 0 | – | 0 | 0 | 0 | – |
| Moderna | 0 | 0 | 0 | 0 | 1 | – | 0 | 0 | – | – | |
| AstraZeneca | 0 | 0 | – | – | 1 | – | 0 | 0 | 0 | – | |
| Janssen | 0 | 0 | 0 | 0 | – | – | – | – | – | ||
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 0 | 0 | 0 | 0 | 2 | 0.02 | 0 | 0 | 0 | 0 | |
| Diabetic retinopathy | Pfizer/BioNTech | 1 | 0.003 | 0 | 0 | 0 | – | 0 | 0 | 0 | – |
| Moderna | 1 | 0.02 | 1 | 0.007 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 1 | 0.01 | – | – | 2 | – | 0 | 0 | 0 | – | |
| Janssen | 0 | 0 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 3 | 0.006 | 1 | 0.003 | 2 | 0.02 | 0 | 0 | 0 | 0 | |
| Optic Neuropathy | |||||||||||
| Optic neuritis | Pfizer/BioNTech | 136 | 0.4 | 44 | 0.2 | 24 | – | 0 | 0 | 4 | – |
| Moderna | 47 | 0.9 | 31 | 0.2 | 3 | – | 0 | 0 | – | – | |
| AstraZeneca | 96 | 1 | – | – | 51 | – | 0 | 0 | 7 | – | |
| Janssen | 7 | 0.5 | 7 | 0.5 | – | – | – | – | – | ||
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 286 | 0.6 | 82 | 0.2 | 78 | 0.9 | 0 | 0 | 11 | 0.6 | |
| Ischemic optic neuropathy | Pfizer/BioNTech | 51 | 0.1 | 10 | 0.05 | 2 | – | 0 | 0 | 0 | – |
| Moderna | 30 | 0.6 | 15 | 0.1 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 25 | 0.4 | – | – | 8 | – | 0 | 0 | 2 | – | |
| Janssen | 3 | 0.2 | 7 | 0.5 | – | – | – | – | – | – | |
| Unspecified | – | – | – | – | 0 | – | – | – | – | – | |
| Total | 109 | 0.2 | 32 | 0.09 | 10 | 0.1 | 0 | 0 | 2 | 0.1 | |
| Glaucoma | Pfizer/BioNTech 2 | 34 | 0.09 | 12 | 0.06 | 5 | – | 0 | 0 | 0 | – |
| Moderna | 10 | 0.2 | 9 | 0.06 | 0 | – | 0 | 0 | – | – | |
| AstraZeneca | 21 | 0.3 | – | – | 12 | – | 0 | 0 | 0 | – | |
| Janssen | 1 | 0.07 | 0 | 0 | – | – | – | – | – | – | |
| Unspecified | – | – | – | 0 | 0 | – | – | – | – | – | |
| Total | 66 | 0.1 | 21 | 0.06 | 17 | 0.2 | 0 | 0 | 0 | 0 | |
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