To the Editor:
Since the first report of the novel coronavirus in Wuhan in December 2019, coronavirus disease 2019 (COVID-19) has been responsible for more than 3 million deaths worldwide. The development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in an unprecedented time. Long-term data on side effect profiles of SARS-CoV-2 vaccines are still developing and rare adverse events are still coming to light. Hence, it is essential to report these adverse events to document and understand the safety profile of the vaccines and enhance their use worldwide. We recently reviewed the article published in the latest volume entitled “COVID-19: Update on its ocular involvements, and complications from its treatments and vaccinations”; and would like to comment upon the pathophysiological perspectives reported by the respectable authors.1
There are limited data on the use of COVID-19 vaccines for patients with underlying ophthalmological diseases. Vaccine development typically takes 10 to 15 years. The expedited timeline may be attributed to the need for rapid deployment, generous funding, innovative trial designs, and multinational cooperation. Timely legislative changes by pharmaceutical regulatory bodies have also positively impacted the vaccine development process.2 The authors correctly emphasized that with more than 1.5 billion doses of COVID-19 vaccinations being administered worldwide, determining the causal relationship of every adverse event is not possible, as most of them could only be coincidental.1 However, they focused more on the expression of angiotensin-converting enzyme 2 and transmembrane protease, serine 2 whereas not implying probable pathophysiological responses behind ocular adverse events of COVID-19 vaccines that we intend to discuss in this letter.
The immunogenicity or the ability of the SARS-CoV-2 vaccines to induce an immune response constitutes an important endpoint for phase I and II clinical trials. The immu-nogenic profile for SARS-CoV-2 vaccines is estimated based on the titer of neutralizing antibodies and T-cell response. Like other vaccines, the immune response shows high interpersonal heterogeneity. Immunosenes-cence or immunosuppression are important factors driving variation in response. This immune response presents as symptoms commonly encountered in ophthalmology, such as redness, allergic reactions, and decreased visual acuity. Some patients may show deterioration in their prevaccine status, such as inducing flares in glaucoma, uveitis, and diabetic retinopathy patients.3 Immunosuppressive therapy is one of the treatment modalities used to manage ocular inflammation; a significant cause of ocular morbidity. It has been known that immunosuppressed individuals are at increased risk of infections, and more prone to severe diseases.4
Antibody-dependent enhancement (ADE) is a concern for the development of COVID-19 vaccines. The impact of immunological memory on endemic coronaviruses on SARS-CoV-2 infection and clinical outcomes remains unclear. ADE may lead to ocular or neuro-ophthalmological manifestations by molecular mimicry between the SARS-CoV-2 vaccine and ocular structures, leading to autoimmunity against eye structures. This autoimmune phenomenon may lead to retinitis, choroiditis, optic neuritis, and uveitis. Some studies showed a positive correlation between ADE and increased disease severity. However, the exact pathogenesis is still to be uncovered.5
COVID-19 vaccination has been accompanied by reports of inflammatory events (Supplementary Digital Content, Table 1, http://links.lww.com/APJO/A126). Some authors reported panuveitis presenting with choroidal thickening, accompanied by anterior chamber and vitreous inflammation.2 Anterior uveitis was also noted after the COVID-19 vaccination.3,6 The effect of the COVID-19 vaccine on the retina and the optic nerve is also reported. Bilateral multifocal choroiditis was associated with Oxford-AstraZeneca COVID-19 vaccine.4 In addition, acute-onset central serous retinopathy after COVID-19 mRNA vaccination was reported in a 33-year-old male 3 days post Pfizer-BioNTech COVID-19 vaccine.7 Neuro-ophthalmological manifestations have also been reported frequently. For instance, acute macular neuro-retinopathy presenting with the acute onset of 1 or multiple paracentral scotomas after COVID-19 vaccination was noted in a 27-year-old.8 Bell palsy after COVID-19 vaccination was reported in a 37-year-old White male post-COVID-19 vaccination. Bilateral superior ophthalmic vein thrombosis after ChAdOx1 nCoV-19 vaccinationwas seenina 55-year-old woman with conjunctival congestion, retro-orbital pain, and diplopia. Acute reduction of visual intensity and visual field defects after the Pfizer-BioNTech COVID-19 vaccine has been reported. Moreover, bilateral optic neuritis associated with COVID-19 vaccination has been documented.5 Macular hemorrhage was also reported after receiving Sinopharm COVID-19 vaccine.6
In conclusion, the global rollout ofthe COVID-19 vaccines is a crucial step in controlling the current pandemic. Ophthalmologists should be aware of any new ocular complaints after the COVID-19 vaccination. Timely diagnosis of adverse effects related to the COVID-19 vaccine with early management can improve the final visual outcome.
1. Lin TPH, Ko CN, Zheng K, et al. COVID-19: update on its ocular involvements, and complications from its treatments and vaccinations. Asia Pac J Ophthalmol (Phila). 2021;10:521–529.
2. Mudie LI, Zick JD, Dacey MS, Palestine AG. Panuveitis following vaccination for COVID-19. Ocul Immunol Injlamm. 2021;29:741–742.
3. ElSheikh RH, Haseeb A, Eleiwa TK, Elhusseiny AM. Acute uveitis following COVID-19 vaccination. Ocul Immunol Inflamm. 2021;1–3. doi: 10.1080/09273948.2021.1962917. Online ahead of print.
4. Goyal M, Murthy SI, Annum S. Bilateral multifocal choroiditis following COVID-19 vaccination. Ocul Immunol Inflamm. 2021;29:753–757.
5. Leber HM, Sant’Ana L, Konichi da Silva NR, et al. Acute thyroiditis and bilateral optic neuritis following SARS-CoV-2 vaccination with CoronaVac: a case report. Ocul Immunol Inflamm. 2021;1–7. doi: 10.1080/09273948.2021.1961815. Online ahead of print.
6. Pichi F, Aljneibi S, Neri P, et al. Association of ocular adverse events with inactivated COVID-19 vaccination in patients in Abu Dhabi. JAMA Ophthalmol. 2021;139:1131–1135.
7. Fowler N, Mendez Martinez NR, Pallares BV, et al. Acute-onset central serous retinopathy after immunization with COVID-19 mRNA vaccine. Am J Ophthalmol Case Rep. 2021;23:101136.
8. Bohler AD, Strom ME, Sandvig KU, et al. Acute macular neuroretinopathy following COVID-19 vaccination. Eye. 2021. doi: 10.1038/s41433-021-01610-1. Online ahead of print.