J Korean Med Sci.  2023 Mar;38(12):e95. 10.3346/jkms.2023.38.e95.

Non-Arteritic Ischemic Optic Neuropathy Following COVID-19 Vaccination in Korea: A Case Series

• Moon Y
• Jung JH
• Shin HJ
• Choi DG
• Park KA
• Jeon H
• Lee BJ
• Kim SJ
• Oh SY
• Ahn H
• Chung SA
• Kim US
• Lee HJ
• Lee JY
• Choi YJ
• Korean NeuroOphthalmology Society

• KMID: 2541041
• DOI: http://doi.org/10.3346/jkms.2023.38.e95

Abstract

Background
To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea.
Methods
This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION.
Results
The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43–77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1–41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/ disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit.
Conclusion
Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.

Keyword

Coronavirus Disease 2019 (COVID-19); Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Vaccination; Non-Arteritic Anterior Ischemic Optic Neuropathy

Figure

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  Fig. 1 Images of the fundus and visual field maps. (A) Fundus photograph and corresponding horizontal cross-sectional optical coherence tomography scan in a patient with non-arteritic anterior ischemic optic neuropathy following coronavirus disease 2019 vaccination. Severe optic disc edema and peripapillary sub-retinal fluid (white arrow) are seen. (B) Visual field test results (grayscale map, total deviation probability map, and pattern deviation probability map) of the patients show the inferior altitudinal defect.

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  Fig. 2 Line chart showing the changes of visual acuity.NLP = no light perception, LP = light perception, HM = hand motion, CF = count finger.aTwo eyes showed the same changes.

Reference

1. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020; 324(8):782–793. PMID: 32648899.

2. Woolf SH, Masters RK, Aron LY. Effect of the COVID-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. BMJ. 2021; 373:n1343. PMID: 34162598.

3. Alderson J, Batchelor V, O'Hanlon M, Cifuentes L, Richter FC, Kopycinski J, et al. Overview of approved and upcoming vaccines for SARS-CoV-2: a living review. Oxf Open Immunol. 2021; 22(1):iqab010.

4. Cai C, Peng Y, Shen E, Huang Q, Chen Y, Liu P, et al. A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther. 2021; 29(9):2794–2805. PMID: 34365034.

5. Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA. 2021; 326(14):1390–1399. PMID: 34477808.

6. Li X, Ostropolets A, Makadia R, Shaoibi A, Rao G, Sena AG, et al. Characterising the background incidence rates of adverse events of special interest for COVID-19 vaccines in eight countries: multinational network cohort study. BMJ. 2021; 373:n1435. PMID: 35727911.

7. Gee J, Marquez P, Su J, Calvert GM, Liu R, Myers T, et al. First month of COVID-19 vaccine safety monitoring - United States, December 14, 2020-January 13, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(8):283–288. PMID: 33630816.

8. Haseeb AA, Solyman O, Abushanab MM, Abo Obaia AS, Elhusseiny AM. Ocular complications following vaccination for COVID-19: a one-year retrospective. Vaccines (Basel). 2022; 10(2):342. PMID: 35214800.

9. Wang MT, Niederer RL, McGhee CN, Danesh-Meyer HV. COVID-19 vaccination and the eye. Am J Ophthalmol. 2022; 240:79–98. PMID: 35227700.

10. Ng XL, Betzler BK, Ng S, Chee SP, Rajamani L, Singhal A, et al. The eye of the storm: COVID-19 vaccination and the eye. Ophthalmol Ther. 2022; 11(1):81–100. PMID: 34914035.

11. Park HS, Byun Y, Byeon SH, Kim SS, Kim YJ, Lee CS. Retinal hemorrhage after SARS-CoV-2 vaccination. J Clin Med. 2021; 10(23):5705. PMID: 34884407.

12. Chung SA, Yeo S, Sohn SY. Non-arteritic anterior ischemic optic neuropathy following COVID-19 vaccination. Korean J Ophthalmol. 2022; 36(2):168–170. PMID: 35067014.

13. Song MY, Koh KM, Hwang KY, Kwon YA, Kim KY. Relapsed disciform stromal herpetic keratitis following mRNA COVID-19 vaccination: a case report. Korean J Ophthalmol. 2022; 36(1):80–82. PMID: 34823340.

14. Kim SY, Kang MS, Kwon HJ. Bilateral panuveitis mimicking Vogt-Koyanagi-Harada disease following the first dose of ChAdOx1 nCoV-19 vaccine. Ocul Immunol Inflamm. 2022; 30(5):1218–1221. PMID: 35113750.

15. Frontera JA, Tamborska AA, Doheim MF, Garcia-Azorin D, Gezegen H, Guekht A, et al. Neurological events reported after COVID-19 vaccines: an analysis of VAERS. Ann Neurol. 2022; 91(6):756–771. PMID: 35233819.

16. Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, et al. Safety of the BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. N Engl J Med. 2021; 385(12):1078–1090. PMID: 34432976.

17. The IONDT Research Group. The ischemic optic neuropathy decompression trial (IONDT): design and methods. Control Clin Trials. 1998; 19(3):276–296. PMID: 9620811.

18. Lee JW, Lai JS, Yick DW, Tse RK. Retrospective case series on the long-term visual and intraocular pressure outcomes of phacomorphic glaucoma. Eye (Lond). 2010; 24(11):1675–1680. PMID: 20689570.

19. Kawasaki A, Purvin VA, Tang R. Bilateral anterior ischemic optic neuropathy following influenza vaccination. J Neuroophthalmol. 1998; 18(1):56–59. PMID: 9532544.

20. Manasseh G, Donovan D, Shao EH, Taylor SR. Bilateral sequential non-arteritic anterior ischaemic optic neuropathy following repeat influenza vaccination. Case Rep Ophthalmol. 2014; 5(2):267–269. PMID: 25298770.

21. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res. 2009; 28(1):34–62. PMID: 19063989.

22. Nachbor KM, Naravane AV, Adams OE, Abel AS. Nonarteritic anterior ischemic optic neuropathy associated with COVID-19 vaccination. J Neuroophthalmol. 2021.

23. Vlachopoulos C, Dima I, Aznaouridis K, Vasiliadou C, Ioakeimidis N, Aggeli C, et al. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation. 2005; 112(14):2193–2200. PMID: 16186422.

24. Jain S, Khera R, Corrales-Medina VF, Townsend RR, Chirinos JA. “Inflammation and arterial stiffness in humans”. Atherosclerosis. 2014; 237(2):381–390. PMID: 25463062.

25. Terentes-Printzios D, Gardikioti V, Solomou E, Emmanouil E, Gourgouli I, Xydis P, et al. The effect of an mRNA vaccine against COVID-19 on endothelial function and arterial stiffness. Hypertens Res. 2022; 45(5):846–855. PMID: 35273351.

26. Afshar ZM, Barary M, Babazadeh A, Hosseinzadeh R, Alijanpour A, Miri SR, et al. SARS-CoV-2-related and COVID-19 vaccine-induced thromboembolic events: A comparative review. Rev Med Virol. 2022; 32(4):e2327. PMID: 35112763.

27. Girbardt C, Busch C, Al-Sheikh M, Gunzinger JM, Invernizzi A, Xhepa A, et al. Retinal vascular events after mRNA and adenoviral-vectored COVID-19 vaccines-a case series. Vaccines (Basel). 2021; 9(11):1349. PMID: 34835280.

28. Elnahry AG, Al-Nawaflh MY, Gamal Eldin AA, Solyman O, Sallam AB, Phillips PH, et al. COVID-19 vaccine-associated optic neuropathy: a systematic review of 45 patients. Vaccines (Basel). 2022; 10(10):1758. PMID: 36298623.

29. Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol. 1996; 114(11):1366–1374. PMID: 8906027.

30. Kupersmith MJ, Sibony PA, Dave S. Nonarteritic anterior ischemic optic neuropathy induced retinal folds and deformations. Invest Ophthalmol Vis Sci. 2017; 58(10):4286–4291. PMID: 28846776.

31. Beck RW, Servais GE, Hayreh SS. Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology. 1987; 94(11):1503–1508. PMID: 3684223.

32. Hayreh SS, Zimmerman MB. Nonarteritic anterior ischemic optic neuropathy: refractive error and its relationship to cup/disc ratio. Ophthalmology. 2008; 115(12):2275–2281. PMID: 19041480.

33. The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA. 1995; 273(8):625–632. PMID: 7844872.

34. Mojon DS, Hedges TR 3rd, Ehrenberg B, Karam EZ, Goldblum D, Abou-Chebl A, et al. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002; 120(5):601–605. PMID: 12003609.