State of corneal nerve fibers in patients with glaucoma recovered from the coronavirus infection

PURPOSE. To evaluate the structural changes in the corneal nerve fibers (CNF) in patients with primary open-angle glaucoma (POAG) who have recovered from the coronavirus infection (COVID-19).

METHODS. The study examined 66 patients (132 eyes), who were divided into the main group with stage I–III POAG (38 patients, 76 eyes) and the control group of healthy volunteers (28 patients, 56 eyes). The groups were divided into subgroups based on the history of coronavirus infection. All patients underwent confocal microscopy of the cornea and analysis of the subbasal layer of corneal nerve fibers using special software (programs Liner 1.2.S and Liner Calculate).

RESULTS. Analysis of confocal images of patients who recovered from COVID-19 showed significant differences with healthy individuals with no distinctions in their medical history (p=0.02). The group with POAG showed pronounced changes in corneal nerve fibers compared with the control group (p<0.01). When comparing the indicators between the subgroups of the main group, no significant differences were found. A positive correlation was found between the severity of changes in the subbasal nerve plexus, and the stage of glaucoma and the duration of the glaucomatous process since the time of diagnosis. CONCLUSION. The study revealed the effect of coronavirus infection on the state of the subbasal layer of corneal nerve fibers in healthy individuals without visible ophthalmic pathologies. The neurodegenerative effect of glaucoma on the nerve tissue of the cornea has been proven. The relationship between the stage of glaucoma and the duration of glaucoma optic neuropathy, and the severity of pathological changes on confocal images of the patients was revealed. However, it was not possible to diagnose the effect of coronavirus infection on corneal nerve fibers of patients with POAG due to the presence of pronounced glaucomatous changes in them.><0.01). When comparing the indicators between the subgroups of the main group, no significant differences were found. A positive correlation was found between the severity of changes in the subbasal nerve plexus, and the stage of glaucoma and the duration of the glaucomatous process since the time of diagnosis.

CONCLUSION. The study revealed the effect of coronavirus infection on the state of the subbasal layer of corneal nerve fibers in healthy individuals without visible ophthalmic pathologies. The neurodegenerative effect of glaucoma on the nerve tissue of the cornea has been proven. The relationship between the stage of glaucoma and the duration of glaucoma optic neuropathy, and the severity of pathological changes on confocal images of the patients was revealed. However, it was not possible to diagnose the effect of coronavirus infection on corneal nerve fibers of patients with POAG due to the presence of pronounced glaucomatous changes in them.

1. Mohamadian M, Chiti H, Shoghli A, Biglari S, Parsamanesh N, Esmaeilzadeh A. COVID-19: Virology, biology and novel laboratory diagnosis. J Gene Med. 2021; 23(2):e3303. doi: 10.1002/jgm.3303

2. Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol. 2020; 41(12):1100-1115. doi: 10.1016/j.it.2020.10.004

3. Xintian Xu, Ping Chen, Jingfang Wang, Jiannan Feng, Hui Zhou. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. SCIENCE CHINA Life Sciences. 2020; 63:457-460. doi:10.1007/s11427-020-1637-5

4. Shchelkanov M.Yu., Popova A.Yu., Dedkov V.G., Akimkin V.G., Maleev V.V. History of study and modern classification of coronaviruses (Nidovirales: Coronaviridae). Infection and immunity. 2020; 10(2):221-246. doi:10.15789/2220-7619-HOI-1412

5. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052

6. Xintian Xu, Ping Chen, Jingfang Wang, Jiannan Feng, Hui Zhou. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. SCIENCE CHINA Life Sciences. 2020; 63: 457-460. doi:10.1007/s11427-020-1637-5

7. Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013; 495(7440):251-4. doi: 10.1038/nature12005

8. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, Duh EJ. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf. 2020; 18(4):537-544. doi: 10.1016/j.jtos.2020.06.007

9. Aggarwal K, Agarwal A, Jaiswal N, Dahiya N, Ahuja A, Mahajan S, Tong L, Duggal M, Singh M, Agrawal R, Gupta V. 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

10. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol. 2020; 92(6):589-594. doi: 10.1002/jmv.25725

11. Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 14; 495(7440):251-4. doi: 10.1038/nature12005

12. Takeshi Moriguchi, Norikazu Harii, Junko Goto eds. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International Journal of Infectious Diseases. 2020; 94(1):55-58. doi: 10.1016/j.ijid.2020.03.062.

13. Avetisov S.E., Surnina Z.V., Ahmedzhanova L.T., Georgiev S. First results of clinical diagnostic analysis of post-COVID peripheral neuropathy. Vestnik Oftal’mologii. 2021; 137(4):58-64. doi: 10.17116/oftalma202113704158

14. Erie JC, McLaren JW, Patel SV. Confocal microscopy in ophthalmology. Am J Ophthalmol. 2009; 148(5):639-46. doi: 10.1016/j.ajo.2009.06.022.

15. Ranno S., Fogagnolo P., Rossetti L., Orzalesi N., Nucci P. Changes in corneal parameters at confocal microscopy in treated glaucoma patients. Clin Ophthalmol. 2011; 5:1037-1042. doi: 10.2147/OPTH.S22874

16. Mastropasqua L, Agnifili L, Mastropasqua R, Fasanella V, Nubile M, Toto L, Carpineto P, Ciancaglini M. In vivo laser scanning confocal microscopy of the ocular surface in glaucoma. Microsc Microanal. 2014; 20(3):879-94. doi: 10.1017/S1431927614000324.

17. Strakhov V.V., Surnina Z.V., Malakhova A.I., Klimova O.N., Popova A.A. Degenerative changes of the corneal nerves in patients with primary open-angle glaucoma. Natsional’nyi zhurnal glaukoma. 2017; 16(4):52-68. (In Russ.)

18. Erichev V.P., Ermolaev A.P., Antonov A.A., Grigoryan G.L., Kosova D.V. New possibilities for studying the visual field. Vestnik Oftal’mologii. 2018; 2(134):66-72. (In Russ.) doi: 10.17116/oftalma2018134266-72

19. Alekseev I.B., Strakhov V.V., Melnikova N.V., Popova A.A. Changes in the fibrous tunic of the eye in patients with newly diagnosed primary open-angle glaucoma. Natsional’nyi zhurnal glaukoma. 2016; 15(1):13-24. (In Russ.)

20. Malakhova A.I., Deev L.A., Molchanov V.V. Cornea changes at patients with primary open-angle glaucoma. Natsional’nyi zhurnal glaukoma. 2015; 14(1):84-93. (In Russ.)