Ocular Adverse Reactions after Receiving COVID-19 Vaccine
The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of July 31, 2022, there have been over 570 million confirmed cases of COVID-19 and over 6 million deaths worldwide. COVID-19 vaccinations are highly effective at preventing severe, symptomatic disease. Although modest reductions in vaccine effectiveness have been observed with the emergence of variants, booster doses can provide adequate levels of protection. Despite the efficacy of COVID-19 vaccines, vaccine hesitancy remains high with a global vaccine acceptance rate ranging from 54% to 86%. Many of the concerns stem from perceived harms of receiving the vaccination. Indeed, uncommon but potentially fatal complications such as immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis have been reported following COVID-19 vaccination. Ocular adverse events following COVID-19 vaccines, although exceedingly rare, have also been documented. The immune response induced by the vaccine is considered a pathophysiological mechanism of ocular adverse reaction following the COVID-19 vaccination.  In this article, we summarize the various ocular adverse events following COVID-19 vaccination reported in the peer-reviewed literature.
Ocular Inflammatory Diseases
Multiple case reports have documented anterior uveitis following both the first and second doses of COVID-19 vaccines. Although some patients had a previous history of uveitis-related diseases that may have predisposed them to this phenomenon, many notably did not. Cases of scleritis, episcleritis, and multiple evanescent white dot syndrome, following COVID-19 vaccination have also been reported.. Most of these cases resolved with topical, intravitreal, and/or systemic corticosteroid therapy with complete recovery to baseline best corrected visual acuity (BCVA). Both recurrent and new onset cases of Vogt-Koyanagi-Harada disease following COVID-19 vaccination have also been reported. These events resolved with oral and periocular steroids, respectively. Panuveitis, choroiditis, and central serous chorioretinopathy impacting the choroid were also reported reactions associated with COVID-19 vaccination. Patients were treated with steroids and most were able to reach their baseline BCVA . A case series of 3 cases with orbital inflammation following mRNA vaccines were described and all cases were successfully treated with oral prednisolone. 
Published literature to date demonstrates very few post-COVID-vaccination cases of optic neuritis and ischemic optic neuropathy. Optic neuritis cases typically resolved after several days of intravenous methylprednisolone therapy to near-baseline visual acuity. A case of arteritic anterior ischemic optic neuropathy (AAION) and a case of non-arteritic anterior ischemic optic neuropathy (NA-AION) were reported after the second and first mRNA vaccine doses, respectively. AAION was treated with high-dose oral corticosteroids and tocilizumab therapy , while the NA-AION resolved without treatment. It should be noted that there are no peer-reviewed cases of adverse COVID-19 vaccination effects in glaucoma patients.
Anterior Segment Conditions
Cases of Herpes zoster ophthalmicus have been reported after both the first and second doses of COVID-19 vaccines. Very few cases reported a previous history of herpes zoster ophthalmicus and many documented a notable lack of vesicular rash accompanying ocular manifestations . All cases resolved with steroid and antiviral treatment. Further, corneal graft rejections were also associated with COVID-19 vaccines. Several patients notably had prior histories of Descemet membrane endothelial keratoplasty (DMEK) or penetrating keratoplasty (PKP). Common findings consisted of corneal edema, corneal neovascularization, and keratic precipitates. Steroid treatment was initiated for patients, with mixed results ranging from improved corneal graft clarity and visual acuity to lasting corneal defects . Keratitis has also been reported as an adverse event following COVID-19 vaccines. One case of a patient with a previous history of PKP further described a reactivation of herpes simplex keratitis shortly after vaccination. Antibiotics and corticosteroid treatment were used to resolve symptoms and visual acuity improved to near baseline levels. One case of bilateral immune-mediated keratolysis was associated with vaccination, which was treated with tectonic penetrating keratoplasty and post-operative steroid antibiotics.
Acute macular neuroretinopathy, central retinal artery occlusion, central retinal vein occlusion, central serous chorioretinopathy, paracentral acute middle maculopathy, and retinal hemorrhage have all been reported in the peer-reviewed literature following COVID-19 vaccination. Disease courses ranged from complete resolution with return to BCVA to permanent vision loss, depending on the severity of disease. Many of these patients lacked medical comorbidities that may have predisposed them to these conditions, although hormone-based birth control was noted in a few patients. However, population-based adverse event reporting systems show that vaccination-associated retinal conditions are exceedingly rare, making it difficult to ascertain the causative nature of COVID-19 vaccination on subsequent retinal pathologies.
Discussions and Conclusion
COVID-19 vaccines are widely recommended to the general public for prevention of severe disease courses. However, ophthalmologists should be aware of the rare side effects in the eye and should carefully monitor patients with pre-existing conditions that have been associated with the development of ophthalmologic side effects.
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