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Klin Monbl Augenheilkd 2021; 238(12): 1305-1311
DOI: 10.1055/a-1579-0805
Klinische Studie

The Impact of Coronavirus Disease 2019 (COVID-19) on Retinal Microcirculation in Human Subjects

Auswirkungen der Coronavirus-Krankheit 2019 (COVID-19) auf die retinale Mikrozirkulation bei Menschen
Emre Aydemir 
1   Ophthalmology Department, Adıyaman University Training and Research Hospital, Adıyaman, Turkey
,
Gozde Aksoy Aydemir 
1   Ophthalmology Department, Adıyaman University Training and Research Hospital, Adıyaman, Turkey
,
Halil Ibrahim Atesoglu
2   Ophthalmology Department, Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
,
Yasin Sakir Goker
2   Ophthalmology Department, Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
,
Kazim Caglar Ozcelik
3   Surgical Oncology Department, Yıldırım Beyazıt University, Ankara, Turkey
,
Hasan Kiziltoprak
1   Ophthalmology Department, Adıyaman University Training and Research Hospital, Adıyaman, Turkey
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Abstract

Background The aim of the study was to assess retinal microcirculation in patients with coronavirus disease 2019 (COVID-19) through the use of optical coherence tomography angiography (OCT-A) and compare the results with those obtained in healthy controls.

Methods The study enrolled 39 patients who had fully recovered from COVID-19 and 40 healthy controls. OCT-A image acquisitions were obtained using AngioVue software (version 2017.1.0.151) and the RTVue XR Avanti imaging system (Optovue Inc., Fremont, CA, USA). Nonflow area in the superficial capillary plexus (SCP), foveal avascular zone (FAZ) area in the whole retinal vasculature, FAZ perimeter, acircularity index of FAZ, and foveal density were automatically obtained with the FAZ assessment tool. Vessel density (VD) at the SCP and deep capillary plexus were also measured.

Results Compared to the control group, the nonflow area and the FAZ area in the whole retina was greater in the COVID-19 group; however no statistically significant difference was observed (p > 0.05 respectively). As for vessel densities, all superficial parafoveal VD parameters were considerably higher in the COVID-19 group compared to the control group (p < 0.05 respectively). Despite the fact that the vessel densities in the remaining zones were lower in the COVID-19 group, those differences were not statistically significant (p > 0.05 respectively).

Conclusion VD at the parafoveal area of the SCP was significantly higher among patients in the late post-recovery period of COVID-19 disease compared to healthy controls. These findings show the impact of COVID-19 on the retinal microvasculature and its possible role as a risk factor for the development of ocular diseases.

Zusammenfassung

Hintergrund Ziel dieser Studie war es, die retinale Mikrozirkulation in von der Coronavirus-Krankheit 2019 (COVID-19) betroffenen Patienten mithilfe der optischen Kohärenztomografieangiografie (OCT-A) zu untersuchen und mit den Ergebnissen von gesunden Kontrollpersonen zu vergleichen.

Methoden In der Studie wurden 39 Patienten, die sich vollständig von der Coronavirus-Krankheit erholt hatten, und 40 gesunde Kontrollpersonen untersucht. Zur OCT-A-Bildakquisition wurde die AngioVue-Software (Version 2017.1.0.151) und das RTVue-XR-Avanti-Bildgebungssystem (Optovue Inc., Fremont, CA, USA) verwendet. Das FAZ-Bewertungstool ermittelt automatisch den Non-Flow-Bereich im oberflächlichen Kapillarplexus (SCP), im Bereich der fovealen avaskulären Zone (FAZ) und im gesamten retinalen Gefäßsystem sowie den FAZ-Perimeter, den FAZ-Azirkularitätsindex und die foveale Dichte. Die Gefäßdichte (VD) im SCP und im tiefen Kapillarplexus wurde auch gemessen.

Ergebnisse Auch wenn kein statistisch signifikanter Unterschied beobachtet wurde, war der Non-Flow-Bereich und der FAZ-Bereich in der gesamten Netzhaut in der COVID-19-Gruppe größer im Vergleich zur Kontrollgruppe (jeweils p > 0,05). Bezüglich der Gefäßdichten waren alle oberflächlichen parafovealen VD-Parameter in der COVID-19-Gruppe erheblich höher im Vergleich zur Kontrollgruppe (jeweils p < 0,05). Obwohl die Gefäßdichten in den verbleibenden Zonen in der COVID-19-Gruppe niedriger waren, waren diese Unterschiede statistisch nicht signifikant (jeweils p > 0,05).

Schlussfolgerung Die VD im parafovealen Bereich des SCP war bei Patienten im späten Rekonvaleszenzstadium der Coronavirus-Erkrankung signifikant höher verglichen mit gesunden Kontrollen. Diese Ergebnisse zeigen die Auswirkungen von COVID-19 auf die retinale Mikrovaskulatur und ihre mögliche Rolle als Risikofaktor für die Entwicklung von Augenerkrankungen auf.

Key words

coronavirus disease 2019 - retinal vascular structures - optical coherence tomography angiography - vessel density - retinal microcirculation

Schlüsselwörter

Coronavirus-Krankheit 2019 - Netzhautgefäßstrukturen - Gefäßdichte - retinale Mikrozirkulation - optische Kohärenztomografieangiografie


Publication History

Received: 20 May 2021

Accepted: 30 July 2021

Article published online:
29 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Wang C, Horby PW, Hayden FG. et al. A novel coronavirus outbreak of global health concern. Lancet 2020; 395: 470-473
    CrossrefPubMedGoogle Scholar
  • 2 Corman VM, Muth D, Niemeyer D. et al. Hosts and sources of endemic human coronaviruses. Adv Virus Res 2018; 100: 163-188
    CrossrefPubMedGoogle Scholar
  • 3 Shi X, Gong E, Gao D. et al. Severe Acute Respiratory Syndrome Associated Coronavirus Is Detected in Intestinal Tissues of Fatal Cases. Am J Gastroenterol 2005; 100: 169-176
    CrossrefPubMedGoogle Scholar
  • 4 Paules CI, Marston HD, Fauci AS. Coronavirus Infections-More Than Just the Common Cold. JAMA 2020; 323: 707-708
    CrossrefPubMedGoogle Scholar
  • 5 van der Hoek L, Pyrc K, Jebbink MF. et al. Identification of a new human coronavirus. Nat Med 2004; 10: 368-373
    CrossrefPubMedGoogle Scholar
  • 6 Chin MS, Hooper LC, Hooks JJ. et al. Identification of α-fodrin as an autoantigen in experimental coronavirus retinopathy (ECOR). J Neuroimmunol 2014; 272: 42-50
    CrossrefPubMedGoogle Scholar
  • 7 Hooks JJ, Wang Y, Detrick B. The critical role of IFN-gamma in experimental coronavirus retinopathy. Invest Ophthalmol Vis Sci 2003; 44: 3402-3408
    CrossrefPubMedGoogle Scholar
  • 8 Wang Y, Detrick B, Yu ZX. et al. The role of apoptosis within the retina of coronavirus infected mice. Invest Ophthalmol Vis Sci 2000; 41: 3011-3018
    PubMedGoogle Scholar
  • 9 Detrick B, Lee MT, Chin MS. et al. Experimental coronavirus retinopathy (ECOR): retinal degeneration susceptible mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early after virus infection. J Neuroimmunol 2008; 193: 28-37
    CrossrefPubMedGoogle Scholar
  • 10 Vinores SA, Wang Y, Vinores MA. et al. Blood-Retinal barrier breakdown in experimental coronavirus retinopathy: association with viral antigen, inflammation, and VEGF in sensitive and resistant strains. J Neuroimmunol 2001; 119: 175-182
    CrossrefPubMedGoogle Scholar
  • 11 Spaide RF, Fujimoto JG, Waheed NK. et al. Optical coherence tomography angiography. Prog Retin Eye Res 2018; 64: 1-55
    CrossrefPubMedGoogle Scholar
  • 12 Kashani AH, Chen CL, Gahm JK. et al. Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications. Prog Retin Eye Res 2017; 60: 66-100
    CrossrefPubMedGoogle Scholar
  • 13 Savastano A, Crincoli E, Savastano MC. et al. Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients. J Clin Med 2020; 9: 2895
    CrossrefPubMedGoogle Scholar
  • 14 Abrishami M, Emamverdian Z, Shoeibi N. et al. Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: a case-control study. Can J Ophthalmol 2020; 56: 24-30
    CrossrefPubMedGoogle Scholar
  • 15 Zapata MÁ, Banderas García S, Sánchez-Moltalvá A. et al. Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity. Br J Ophthalmol 2020; DOI: 10.1136/bjophthalmol-2020-317953.
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Collin J, Queen R, Zerti D. et al. Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. Ocul Surf 2020; 19: 190-200
    CrossrefPubMedGoogle Scholar
  • 18 Ma D, Chen CB, Jhanji V. et al. Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea. Eye (Lond) 2020; 34: 1212-1219
    CrossrefPubMedGoogle Scholar
  • 19 Zhou L, Xu Z, Castiglione GM. et al. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf 2020; 18: 537-544
    CrossrefPubMedGoogle Scholar
  • 20 Senanayake P, Drazba J, Shadrach K. et al. Angiotensin II and its receptor subtypes in the human retina. Invest Ophthalmol Vis Sci 2007; 48: 3301-3311
    CrossrefPubMedGoogle Scholar
  • 21 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: 28-32
    CrossrefPubMedGoogle Scholar
  • 22 Luhtala S, Vaajanen A, Oksala O. et al. Activities of angiotensin-converting enzymes ACE1 and ACE2 and inhibition by bioactive peptides in porcine ocular tissues. J Ocul Pharmacol Ther 2009; 25: 23-28
    CrossrefPubMedGoogle Scholar
  • 23 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: 721-725
    CrossrefPubMedGoogle Scholar
  • 24 Marinho PM, Marcos AAA, Romano AC. et al. Retinal findings in patients with COVID-19. Lancet 2020; 395: 1610
    CrossrefPubMedGoogle Scholar
  • 25 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; 34: 2153-2154
    CrossrefPubMedGoogle Scholar
  • 26 de Carlo TE, Romano A, Waheed NK. et al. A review of optical coherence tomography angiography (OCTA). Int J Retina Vitreous 2015; 1: 5
    CrossrefPubMedGoogle Scholar
  • 27 Turker IC, Dogan CU, Dirim AB. et al. Evaluation of Early and Late COVID-19-Induced Vascular Changes with Optical Coherence Tomography Angiography. Can J Ophthalmol 2021; DOI: 10.1016/j.jcjo.2021.05.001.
    CrossrefPubMedGoogle Scholar
  • 28 Cennamo G, Reibaldi M, Montorio D. et al. Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study. Am J Ophthalmol 2021; 227: 182-190
    CrossrefPubMedGoogle Scholar
  • 29 Marmor MF. COVID-19 and Chloroquine/Hydroxychloroquine: Is There Ophthalmological Concern?. Am J Ophthalmol 2020; 216: A1-A2
    CrossrefPubMedGoogle Scholar
  • 30 Goker YS, Ucgul Atılgan C, Tekin K. et al. The Validity of Optical Coherence Tomography Angiography as a Screening Test for the Early Detection of Retinal Changes in Patients with Hydroxychloroquine Therapy. Curr Eye Res 2019; 44: 311-315
    CrossrefPubMedGoogle Scholar