A Pediatric COVID-19 Study: Retinal Nerve Fiber Layer, Ganglion Cell Layer, and Alterations in Choroidal Thickness in Swept-Source OCT Measurements

Abstract

Purpose To investigate early covid measurements of central macular thickness (CMT), retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) thickness, and choroidal thickness (ChT) in children recovered from coronavirus disease 2019 (COVID-19).

Methods This cross-sectional study was carried out 4 weeks after completed COVID-19 treatment. The diagnosis of the Alpha variant COVID-19 was made by the polymerase chain reaction test after prediagnosis with clinical, laboratory, and radiological findings. A total of 46 children were included in the study. Pediatric patients who received COVID-19 treatment comprised the COVID-19 group (24 children), and healthy children were enrolled in the control group (22 children). Only the right eyes of the participants were enrolled in the study. All pediatric patients in the COVID-19 group required hospitalization without the need for intubation. Swept-source optical coherence tomography (SS-OCT) was used to measure CMT, RNFL, and GCL thickness, and ChT measurements.

Results The COVID-19 and control groups had similar mean values of visual acuity, intraocular pressure, spherical equivalent, axial length, and CMT (p > 0.05 for all). RNFL thickening, GCL, and choroidal thinning were observed in all SS-OCT measurements of COVID-19 children. However, RNFL thickening was significant only in the global and nasal peripapillary quadrants. GCL thinning was significant in the nasal/inferior sector (p < 0.002 for all). Some significant correlations were observed between the mean levels of inflammatory markers and OCT measurements (p < 0.002).

Conclusion This study may be among the first reports of SS-OCT examination of COVID-19 children. OCT measurements showed changes in retinal and ChT in the COVID-19 children as in adult patients.

Zusammenfassung

Zweck Untersuchung der frühen COVID-Messungen der zentralen Makuladicke (CMT), der retinalen Nervenfaserschicht (RNFL), der Dicke der Ganglienzellschicht (GCL) und der Aderhautdicke (ChT) bei Kindern, die sich von der Coronavirus-Krankheit 2019 (COVID-19) erholt haben.

Methoden Diese Querschnittsstudie wurde 4 Wochen nach der abgeschlossenen COVID-19-Behandlung durchgeführt. Die Diagnose der Alpha-Variante von COVID-19 wurde durch den Polymerase-Kettenreaktions-Test nach Vordiagnose mit klinischen, Labor- und radiologischen Befunden gestellt. Insgesamt wurden 46 Kinder in die Studie eingeschlossen. Pädiatrische Patienten, die eine COVID-19-Behandlung erhielten, bildeten die COVID-19-Gruppe (24 Kinder) und gesunde Kinder wurden in die Kontrollgruppe aufgenommen (22 Kinder). Nur das rechte Auge der Teilnehmer wurde in die Studie aufgenommen. Alle pädiatrischen Patienten in der COVID-19-Gruppe mussten ohne Intubation ins Krankenhaus eingeliefert werden. Die optische Kohärenztomografie mit Swept-Source (SS-OCT) wurde verwendet, um CMT-, RNFL-, GCL-Dicke- und ChT-Messungen zu messen.

Ergebnisse Die COVID-19- und die Kontrollgruppe hatten ähnliche Mittelwerte für Sehschärfe, Augeninnendruck, sphärisches Äquivalent, axiale Länge und CMT (p > 0,05 für alle). RNFL-Verdickung, GCL und Aderhautverdünnung wurden bei allen SS-OCT-Messungen von COVID-19-Kindern beobachtet. Die RNFL-Verdickung war jedoch nur in den globalen und nasalen peripapillären Quadranten signifikant. Die GCL-Verdünnung war im nasalen/unteren Bereich signifikant (p < 0,002 für alle). Einige signifikante Korrelationen wurden zwischen den mittleren Konzentrationen von Entzündungsmarkern und OCT-Messungen beobachtet (p < 0,002).

Schlussfolgerung Diese Studie gehört möglicherweise zu den ersten Berichten über die SS-OCT-Untersuchung von COVID-19-Kindern. OCT-Messungen zeigten bei den COVID-19-Kindern wie bei erwachsenen Patienten Veränderungen der Netzhaut- und Aderhautdicke.

Key words

pediatric COVID-19 - retinal neurodegeneration - swept-source - optical coherence tomography

Schlüsselwörter

pädiatrisches COVID-19 - Netzhautneurodegeneration - Swept-Source-optische Kohärenztomografie

Publikationsverlauf

Eingereicht: 23. Dezember 2021

Angenommen: 23. Februar 2022

Artikel online veröffentlicht:
14. April 2022

• References

• 1 World Health Organization. Coronavirus disease 2019 (COVID-19). Situation Report – 84. Accessed April 13, 2020 at: https://www.who.int/publications/m/item/situation-report-84
• 2 Zhu N, Zhang D, Wang W. et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 283: 727-733
• 3 Guan W, Ni Z, Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382: 1708-1720
• 4 Lu R, Zhao X, Li J. et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395: 565-574
• 5 Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323: 1239-1242
• 6 Chan JF, Kok KH, Zhu Z. et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020; 9: 221-236
• 7 Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020; 109: 102433
• 8 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506
• 9 Luers JC, Rokohl AC, Loreck N. et al. Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19). Clin Infect Dis 2020; 71: 2262-2264
• 10 Rokohl AC, Loreck N, Wawer Matos PA. et al. More than loss of taste and smell: burning watering eyes in coronavirus disease 19 (COVID-19). Clin Microbiol Infect 2020; 26: 1560.e5-1560.e8
• 11 Hoffmann M, Kleine-Weber H, Schroeder S. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271-280
• 12 Grajewski RS, Rokohl AC, Becker M. et al. A missing link between SARS-CoV-2 and the eye?: ACE2 expression on the ocular surface. J Med Virol 2021; 93: 78-79
• 13 Grajewski RS, Rokohl AC, Becker M. et al. Malignancy going viral: ACE2 and TMPRSS2 expression in conjunctival neoplastic diseases. Ann Anat 2021; 234: 151661
• 14 Becker R. COVID-19 update: Covid-19 associated coagulopathy. J Thromb Thrombolysis 2020; 50: 54-67
• 15 Seah IYJ, Anderson DE, Kang AEZ. et al. Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-19) patients. Ophthalmology 2020; 27: 977-979
• 16 Lu CW, Liu XF, Jia ZF. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet 2020; 395: e39
• 17 Marinho PM, Arcos AAA, Romano AC. et al. Retinal findings in patients with COVID-19. Lancet 2020; 395: 1610
• 18 Wu P, Duan F, Luo C. et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei province, China. JAMA Ophthalmol 2020; 138: 575-578
• 19 Rokohl AC, Grajewski RS, Matos PAW. et al. Ocular Involvement in COVID-19: Conjunctivitis and More. Klin Monbl Augenheilkd 2021; 238: 555-560
• 20 Valente P, Iarossi G, Federici M. et al. Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report. J AAPOS 2020; 24: 212-215
• 21 Choi SH, Kim HW, Kang JM. et al. Epidemiology and clinical features of coronavirus disease 2019 in children. Clin Exp Pediatr 2020; 63: 125-132
• 22 Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 2020; 109: 1088-1095
• 23 Virgo J, Mohamed M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye (Lond) 2020; 3: 1-2
• 24 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: 391-395
• 25 Marinho PM, Marcos AAA, Romano AC. et al. Retinal findings in patients with COVID-19. Lancet 2020; 395: 1610
• 26 Ortiz-Egea JM, Ruiz-Medrano J, Ruiz-Moreno JM. Retinal imaging study diagnoses in COVID-19: a case report. J Med Case Rep 2021; 15: 15
• 27 Savastano MC, Gambini G, Cozzupoli GM. et al. Gemelli Against COVID-19 Post-Acute Care Study Group. Retinal capillary involvement in early post-COVID-19 patients: a healthy controlled study. Graefes Arch Clin Exp Ophthalmol 2021; 259: 2157-2165
• 28 Vavvas DG, Sarraf D, Sadda SR. et al. Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication. Eye (Lond) 2020; 9: 1-2
• 29 Burgos-Blasco B, Güemes-Villahoz N, Morales-Fernandez L. et al. Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID-19: a cohort study. Arch Dis Child 2021; 107: 175-179
• 30 González-Zamora J, Bilbao-Malavé V, Gándara E. et al. Retinal Microvascular Impairment in COVID-19 Bilateral Pneumonia Assessed by Optical Coherence Tomography Angiography. Biomedicines 2021; 9: 247
• 31 Burgos-Blasco B, Güemes-Villahoz N, Donate-Lopez J. et al. Optic nerve analysis in COVID-19 patients. J Med Virol 2021; 93: 190-191
• 32 Burgos-Blasco B, Güemes-Villahoz N, Vidal-Villegas B. et al. Optic nerve and macular optical coherence tomography in recovered COVID-19 patients. Eur J Ophthalmol 2022; 32: 628-636
• 33 Savastano A, Crincoli E, Savastano MC. et al. Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients. J Clin Med 2020; 9: 2895
• 34 Cetinkaya T, Kurt MM, Akpolat C. Assessment of Retinal Neurodegeneration and Choroidal Thickness in COVID-19 Patients Using Swept-Source OCT Technology. Klin Monbl Augenheilkd 2021; 238: 1092-1097
• 35 Chen Y, Li J, Yan Y. et al. Diabetic macular morphology changes may occur in the early stage of diabetes. BMC Ophthalmol 2016; 16: 1-7
• 36 Sohn EH, van Dijk HW, Jiao C. et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A 2016; 113: E2655-E2664
• 37 Li S, Pan Y, Xu J. et al. Effects of physical exercise on macular vessel density and choroidal thickness in children. Sci Rep 2021; 11: 2015
• 38 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395: 1417-1418
• 39 Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med 2020; 58: 1131-1134
• 40 Zhang L, Yan X, Fan Q. et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020; 18: 1324-1329
• 41 Guemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B. et al. Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection. Med Clin (Barc) 2021; 156: 541-546