Eye damage in COVID-19. Part 2: posterior segment complications, neuro-ophthalmic manifestations, vaccination and risk factors

Posterior eye segment involvement in COVID-19 has varied manifestations: vascular, inflammatory, and neuronal. All of them are triggered by SARS-CoV-2 virus but they cannot be viewed as exclusively specific to COVID-19. According to the literature, the mean age of the patients varies from 17 to 75 with the median of 50 years. The median duration between the appearance of ophthalmic symptoms and the detection of COVID-19 was 12 days. The disease affects both men and women equally. Direct exposure to the virus, immune-mediated tissue damage, activation of the coagulation system, the prothrombotic state caused by a viral infection, concomitant diseases and medications used in the treatment contribute to the development of eye pathologies. Ophthalmologists should be aware of the possible relations of posterior eye segment pathologies, orbit and neuro-ophthalmic disorders with SARS-CoV-2, as well as the possible exacerbation of chronic forms of inflammatory eye diseases and autoimmune disorders due to anti-COVID-19 vaccination.

1. Tao L., Qiu Y., Fu X., et al. Angiotensin-converting Enzyme 2 activator Diminazene Aceturate prevents lipopolysaccharide-induced inflammation by inhibiting MAPK and NF-kappaB pathways in human retinal pigment epithelium. J. Neuroinflammation. 2016; 13 (1): 35. https://doi.org/10.1186/s12974-016-0489-7

2. Reichhart N., Figura A., Skosyrski S., Strauß O. Control of the Retinal Local RAS by the RPE: An Interface to Systemic RAS Activity. Exp. Eye Res. 2019; 189: 107838. https://doi.org/10.1016/j.exer.2019.107838

3. Fletcher E.L., Phipps J.A., Ward M.M., et al. The Renin-Angiotensin system in retinal health and disease: its influence on neurons, glia and the vasculature. Prog. Retin. Eye Res. 2010; 29 (4): 284–311. https://doi.org/10.1016/j.preteyeres.2010.03.003

4. Zhang Y.H., Zhang Y., Dong X.F., et al. ACE2 and Ang-(1–7) protect endothelial cell function and prevent early atherosclerosis by inhibiting inflammatory response. Inflamm. Res. 2015; 64 (3–4): 253-60. https://doi.org/10.1007/s00011-015-0805-1

5. Seah I., Agrawal R. Can the Coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul. Immunol. Inflamm. 2020; 28 (3): 391–5. https://doi.org/10.1080/09273948.2020.1738501

6. Lovren F., Pan Y., Quan A., et al. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am. J. Physiol. Heart Circ Physiol. 2008; 295 (4): H1377-84. https://doi.org/10.1152/ajpheart.00331.2008

7. Holappa M., Valjakka J., Vaajanen A. Angiotensin(1-7) and ACE2, “The Hot Spots” of renin-angiotensin system, detected in the human aqueous humor. Open Ophthalmol. J. 2015; 9 (1): 28–32. https://doi.org/10.2174/1874364101509010028

8. Invernizzi A., Pellegrini M., Messenio D., et al. Impending central retinal vein occlusion in a patient with coronavirus disease 2019 (COVID-19). Ocul. Immunol. Inflamm. 2020; 28: 1290–2. doi: 10.1080/09273948.2020.1807023

9. Walinjkar J.A., Makhija S.C., Sharma H.R., Morekar S.R., Natarajan S. Central retinal vein occlusion with COVID-19 infection as the presumptive etiology. Indian J. Ophthalmol. 2020; 68: 2572–4. doi: 10.4103/ijo.IJO_2575_20

10. Sheth J.U., Narayanan R., Goyal J., Goyal V. Retinal vein occlusion in COVID-19: A novel entity. Indian J. Ophthalmol. 2020; 68 (10): 2291–3. doi: 10.4103/ijo.IJO_2380_20

11. Gaba W.H., Ahmed D., Al Nuaimi R.K., Al Dhahani A.A., Eatmadi H. Bilateral central retinal vein occlusion in a 40-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia. Am. J. Case Rep. 2020; 21: e927691. doi: 10.12659/AJCR.927691

12. Acharya S., Diamond M., Anwar S., Glaser A., Tyagi P. Unique case of central retinal artery occlusion secondary to COVID-19 disease. IDCases. 2020; 21: e00867. doi: 10.1016/j.idcr.2020.e00867

13. Dumitrascu O.M., Volod O., Bose S., et al. Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban. J. Stroke Cerebrovasc. Dis. 2020; 29: 104982. doi: 10.1016/j.jstrokecerebrovasdis.2020.104982

14. Gascon P., Briantais A., Bertrand E., et al. Covid-19-associated retinopathy: A case report. Ocul. Immunol. Inflamm. 2020; 28: 1293-7. doi: 10.1080/09273948.2020.1825751

15. Zamani G., Azimi S.A., Aminizadeh A., et al. Acute macular neuroretinopathy in a patient with acute myeloid leukemia and deceased by COVID-19: A case report. J. Ophthalmic Inflamm Infect. 2020; 10 (1): 39. doi: 10.1186/s12348-020-00231-1

16. Virgo J., Mohamed M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye (Lond). 2020; 34 (12): 2352–3. doi: 10.1016/j.preteyeres.2020.100884

17. Zago Filho L.A., Lima L.H., Melo G.B., Zett C., Farah M.E. Vitritis and outer retinal abnormalities in a patient with COVID-19. Ocul. Immunol. Inflamm. 2020; 28 (8): 1298–300. doi: 10.1080/09273948.2020.1821898

18. Gupta A., Dixit B., Stamoulas K., Akshikar R. Atypical bilateral acute retinal necrosis in a coronavirus disease 2019 positive immunosuppressed patient. Eur. J. Ophthalmol. 2022; 32 (1): NP94-NP96. doi: 10.1177/1120672120974941

19. Sen M., Honavar S.G., Sharma N., et al. COVID-19 and eye: A review of ophthalmic manifestations of COVID-19. Indian Journal of Ophthalmology. 2021; 69 (3): 488–509. doi: 10.4103/ijo.IJO_297_21

20. Pereira L.A., Soares L.C.M., Nascimento P.A., et al. Retinal findings in hospitalised patients with severe COVID-19. Br. J. Ophthal. 2022; 106 (1): 102–5. doi: 10.1136/bjophthalmol-2020-317576

21. Providência J., Fonseca C., Henriques F., Proença R. Serpiginous choroiditis presenting after SARS- CoV-2 infection: A new immunological trigger? Eur. J. Ophthalmol. 2022; 32 (1): NP97–NP101. doi: 10.1177/1120672120977817

22. Casagrande M., Fitzek A., Püschel K., et al. Detection of SARS-CoV-2 in human retinal biopsies of deceased COVID-19 patients. Ocul. Immunol. Inflamm. 2020; 28 (5): 721–5. doi: 10.1080/09273948.2020.1770301

23. Cavalcanti D.D., Raz E., Shapiro M., et al. Cerebral venous thrombosis associated with COVID-19. AJNR Am. J. Neuroradiol. 2020; 41 (8): 1370–6. doi: 10.3174/ajnr.A6644

24. de Souza E. C., de Campos V. E., Duker J. S. Atypical unilateral multifocal choroiditis in a COVID-19 positive patient. Am. J. Ophthalmol. Case Reports. 2021; 22: 101034. doi: 10.1016/j.ajoc.2021.101034

25. Marinho P.M., Marcos A.A., Romano A.C., Nascimento H., Belfort R. Retinal findings in patients with COVID-19. Lancet. 2020; 395 (10237): 1610. https://doi.org/10.1016/S0140-6736(20)31014-X

26. Zapata M.Á., García S.B., Sánchez-Moltalva A., et al. Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity. Br. J. Ophthalmol. 2022; 106 (4): 559–63. doi: 10.1136/bjophthalmol-2020-317953

27. Insausti-García A., Reche-Sainz J.A., Ruiz-Arranz C., Vázquez Á.L., Ferro-Osuna M. Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state. Eur. J. Ophthalmol. 2022; 32 (1): NP168-NP172. doi: 10.1177/1120672120947591

28. Sawalha K., Adeodokun S., Kamoga G.R. COVID-19-induced acute bilateral optic neuritis? J. Invest. Med. High. Impact. Case Rep. 2020; 8: 2324709620976018. doi: 10.1177/2324709620976018

29. Zhou S., Jones-Lopez E.C., Soneji D.J., Azevedo C.J., Patel V.R. Myelin oligodendrocyte glycoprotein antibody–associated optic neuritis and myelitis in COVID-19. J. Neuroophthalmol. 2020; 40 (3): 398–402. doi: 10.1097/WNO.0000000000001049

30. Méndez-Guerrero A., Laespada-García M.I., Gómez-Grande A., et al. Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection. Neurology. 2020; 95 (15): e2109–18. doi: 10.1212/WNL.0000000000010282

31. Ortiz-Seller A., Martínez Costa L., Hernández-Pons A., et al. Ophthalmic and neuro-ophthalmic manifestations of coronavirus disease 2019 (COVID-19). Ocul. Immunol. Inflamm. 2020; 28 (8): 1285–9. doi: 10.1080/09273948.2020.1817497

32. Tisdale A.K., Chwalisz B.K. Neuro-ophthalmic manifestations of coronavirus disease 19. Curr. Opin. Ophthalmol. 2020; 31: 489–94. doi: 10.1097/ICU.0000000000000707

33. Politi L.S., Salsano E., Grimaldi M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol. 2020; 77 (8): 1028–9. doi: 10.1001/jamaneurol.2020.2125

34. Dinkin M., Gao V., Kahan J., et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology. 2020; 95 (5): 221–3. doi: 10.1212/WNL.0000000000009700

35. Gutiérrez-Ortiz C., Méndez-Guerrero A., Rodrigo-Rey S., et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020; 95 (5): e601–5. doi: 10.1212/WNL.0000000000009619

36. Greer C.E., Bhatt J.M., Oliveira C.A., Dinkin M.J. Isolated cranial nerve 6 palsy in 6 patients with COVID19 infection. J Neuroophthalmol. 2020; 40 (4): 520–2. doi: 10.1097/WNO.0000000000001146

37. Falcone M.M., Rong A.J., Salazar H., et al. Acute abducens nerve palsy in a patient with the novel coronavirus disease (COVID-19) J AAPOS. 2020; 24 (4): 216–7. doi:10.1016/j.jaapos.2020.06.001

38. Belghmaidi S., Nassih H., Boutgayout S., et al. Third cranial nerve palsy presenting with unilateral diplopia and strabismus in a 24-year-old woman with COVID-19? Am. J. Case Rep. 2020; 21: e925897. doi: 10.12659/AJCR.925897

39. Theophanous C., Santoro J.D., Itani R. Bell's palsy in a pediatric patient with hyper IgM syndrome and severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Brain Dev. 2021; 43 (2): 357–9. doi: 10.1016/j.braindev.2020.08.017

40. Assini A., Benedetti L., Di Maio S., Schirinzi E., Del Sette M. New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: Two Italian cases. Neurol Sci. 2020; 41 (7): 1657–8. doi: 10.1007/s10072-020-04484-5

41. Huber M., Rogozinski S., Puppe W., et al. Postinfectious onset of myasthenia gravis in a COVID-19 patient? Front Neurol. 2020; 11: 576153. doi: 10.3389/fneur.2020.576153

42. Cyr D.G., Vicidomini C.M., Siu N.Y., Elmann S.E. Severe bilateral vision loss in 2 patients with coronavirus disease 2019. J. Neuroophthalmol. 2020; 40 (3): 403–5. doi: 10.1097/WNO.0000000000001039

43. Yang Y., Qidwai U., Burton B.J., Canepa C. Bilateral, vertical supranuclear gaze palsy following unilateral midbrain infarct. BMJ Case Reports. 2020; 13 (11): e238422. doi: 10.1136/bcr-2020-238422

44. McGill COVID19 Vaccine Tracker Team. 2020. Available at: https://covid19.trackvaccines.org/vaccines/. Accessed 31 Dec 2020.

45. Zhao J., Zhao S., Ou J., et al. COVID-19: coronavirus vaccine development updates. Front Immunol. 2020; 11: 602256. doi: 10.3389/fimmu.2020.602256

46. Petousis-Harris H. Assessing the safety of COVID-19 vaccines: a primer. Drug Saf. 2020; 43 (12): 1205–10. doi: 10.1007/s40264-020-01002-6

47. Sallusto F., Lanzavecchia A., Araki K., Ahmed R. From vaccines to memory and back. Immunity. 2010; 33 (4): 451–63. doi: 10.1016/j.immuni.2010.10.008

48. Perez V.L., Caspi R.R. Immune mechanisms in inflammatory and degenerative eye disease. Trends Immunol. 2015; 36 (6): 354–63. doi: 10.1016/j.it.2015.04.003

49. DeFrancesco L. Whither COVID-19 vaccines? Nat. Biotechnol. 2020; 38 (10): 1132–45. doi: 10.1038/s41587-020-0697-7

50. Thng Z.X., De Smet M.D., Lee C.S., et al. COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs. Br. J. Ophthalmol. 2021; 105 (3): 306–10. doi: 10.1136/bjophthalmol-2020-316586

51. Liang Y., Meng F.Y., Pan H.F., Ye D.Q. A literature review on the patients with autoimmune diseases following vaccination against infections. Hum. Vaccin. Immunother. 2015; 11 (9): 2274–80. doi: 10.1080/21645515.2015.1009337

52. Hung J.C.H., Li K.K.W. Implications of COVID-19 for uveitis patients: perspectives from Hong Kong. Eye. 2020; 34 (7): 1163–4. doi: 10.1038/s41433-020-0905-1

53. Agarwal A.K., Sudharshan S., Mahendradas P., et al. Impact of COVID-19 pandemic on uveitis patients receiving immunomodulatory and biological therapies (COPE STUDY). Br. J. Ophthalmol. 2022. 106 (1): 97–101. https://doi.org/10.1136/bjophthalmol-2020-317417

54. Furer V., Rondaan C., Heijstek M.W., et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann. Rheum. Dis. 2020; 79 (1): 39. doi: 10.1136/annrheumdis-2019-215882

55. Aggarwal K., Agarwal A., Jaiswal N., et al. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. PLoS One. 2020; 15 (11): e0241661. doi: 10.1371/journal.pone.0241661

56. Belser J.A., Rota P.A., Tumpey T.M. Ocular tropism of respiratory viruses. Microbiol Mol Biol Rev MMBR. 2013; 77 (1): 144–56. doi: 10.1128/MMBR.00058-12

57. Chen L., Deng C., Chen X., et al. Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study. Acta Ophthalmol. 2020; 98 (8): e951–9. doi: 10.1111/aos.14472