microcirculationРегионарное кровообращение и микроциркуляцияRegional blood circulation and microcirculation1682-66552712-9756Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1682-6655-2021-20-4-21-32microcirculation-1007Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ (КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ)ORIGINAL ARTICLES (CLINICAL INVESTIGATIONS)Исследование микрососудистого русла сетчатки и зрительного нерва методом оптической когерентной томографии-ангиографии у пациентов, перенесших COVID-19Study of the retina and optic nerve microvascular bed using optical coherence tomography-angiography in post-COVID-19 patientsТургельВ. А.TurgelV. А.

Тургель Вадим Алексеевич – аспирант кафедры офтальмологии с клиникой

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Turgel Vadim A. – postgraduate student of ophthalmology chair with clinic

6-8, L’va Tolstogo street, Saint Petersburg, 197022

zanoza194@gmail.comТульцеваС. Н.TultsevaS. N.

Тульцева Светлана Николаевна – д-р мед. наук, профессор кафедры офтальмологии с клиникой

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Tultseva Svetlana N. – MD, Dr. of Sci. (Med.), Professor of ophthalmology chair with clinic

6-8, L’va Tolstogo street, Saint Petersburg, 197022

tultceva@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian Federation2021090120222042132Copyright © Тургель В.А., Тульцева С.Н., 20222022Тургель В.А., Тульцева С.Н.Turgel V.А., Tultseva S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.microcirc.ru/jour/article/view/1007

Введение. Признаки ангиоретинопатии выявляются у 7–27,7 % пациентов, перенесших COVID-19. Прижизненную оценку микроциркуляторных изменений сетчатки у таких пациентов позволяет дать методика оптической когерентной томографии-ангиографии (ОКТА). Цель – изучение и сравнение основных показателей микроциркуляции капиллярных сплетений сетчатки и диска зрительного нерва с применением ОКТА у пациентов, перенесших COVID-19 разной степени тяжести. Материалы и методы. Основную группу составили 54 человека (108 глаз), перенесших COVID-19 в течение предшествующих 3 месяцев. В зависимости от тяжести течения COVID-19 пациенты были разделены на 3 подгруппы. Контрольную группу составили 22 здоровых добровольца (44 глаза). Всем пациентам проводилось стандартное офтальмологическое обследование, включая ОКТА. Оценивали плотность сосудов (VD) в целом и по секторам в пределах поверхностного (SCP) и глубокого (DCP) капиллярных сплетений, радиальных перипапиллярных капилляров (RPC) и в области фовеальной аваскулярной зоны (FAZ). Результаты. По всем исследованным показателям не выявлено значимых различий между пациентами контрольной группы и подгруппы пациентов с легким течением COVID-19. У пациентов со среднетяжелым течением COVID-19 выявлено значимое снижение VD SCP (P<0,01) и VD RPC (P<0,01). У пациентов с тяжелым и крайнетяжелым течением заболевания наблюдалось снижение VD DCP в области фовеа (P=0,016) и VD FAZ (P<0,01). Показатели VD коррелируют с толщиной слоев сетчатки, в которых эти сосудистые сплетения залегают. Ни в одной из подгрупп не наблюдалось статистически значимого расширения площади FAZ и структурных изменений диска зрительного нерва. Заключение. У пациентов, перенесших COVID-19, имеются признаки редукции капиллярного кровотока сетчатки в SCP и RPC, пропорциональные тяжести COVID-19. Ассоциированная микроангиопатия является значимым офтальмологическим проявлением COVID-19. Микросудистые изменения сетчатки могут выступать в роли нового биомаркера, отражающего тяжесть возникающего при COVID-19 поражения сосудистой системы организма.

Introduction. Signs of angioretinopathy are revealed in 7–27.7 % of post-COVID-19 patients. Optical coherence tomographyangiography (OCT-A) allows performing life-time evaluation of structural and microvascular retinal changes in patients after the new coronavirus infection. Aim. To investigate and to compare main microcirculatory parameters of capillary retinal and optic nerve plexuses using OCT-A in patients after COVID-19 of different severity degree. Materials and methods. The main group consisted of 54 people (108 eyes), who recovered from COVID-19 during 3 preceding months. According to the COVID-19 course severity degree, patients were divided into 3 sub-groups. 22 healthy volunteers (44 eyes) were included in the control group. All patients underwent OCT-A. In the angiography regimen, entire vascular density (VD) and that of every sector in the limits of superficial (SCP) and deep (DCP) capillary plexuses, radial peripapillary capillaries (RPC), and in the foveal avascular zone (FAZ). Results. All over parameters investigated no significant differences between control group patients and those of the sub-group with mild COVID-19 course. In patients with moderately severe infectious process course a significant decrease in VD SCP (P<0.01), as well as decrease in VD RPC (P<0.01). In patients with severe and critically severe disease course there was an decrease of VD DCP in the foveal area (P=0.016) and VD FAZ (P<0.01). VD indices correlations with thickness of retinal layers, in which these vascular plexuses are located. In any of the groups, there was no statistically significant enlargement of the FAZ area and no structural optic disc changes. Conclusion. In post-COVID-19 patients, there are signs of capillary blood flow reduction in retinal SCP and RPC, which is proportional to the prior infection severity degree. Associated to COVID-19 microangiopathy is a significant ophthalmologic sign of the new coronavirus infection. Microvascular changes of the retina could play a role of of a new biomarker reflecting the severity degree of the entire vascular system impairment in COVID-19.

COVID-19коронавирусная инфекцияоптическая когерентная томография-ангиографияповерхностное капиллярное сплетение сетчаткиглубокое капиллярное сплетение сетчаткирадиальные перипапиллярные капиллярыаваскулярная зона сетчаткислой нервных волокон сетчаткикомплекс ганглиозных клеток сетчаткиCOVID-19coronavirus infectionoptical coherence tomography-angiographysuperficial capillary plexus of the retinadeep capillary plexus of the retinaradial peripapillary capillariesfoveal avascular zone of the retinaretinal nerve fiber layerganglion-cell complexReferencesWorld Health Organization (WHO). Coronavirus disease (COVID-19) pandemic. ttps://www.who.int/emergencies/diseases/novel-coronavirus-2019 (accessed: 30.10.2021).World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic. ttps://www.who.int/emergencies/diseases/novel-coronavirus-2019 (accessed: 30.10.2021).WHO Coronavirus (COVID-19) Dashboard. Available atL https://covid19.who.int/ (accessed: 30.10.2021).WHO Coronavirus (COVID-19) Dashboard. Available atL https://covid19.who.int/ (accessed: 30.10.2021).Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection: a narrative review // Ann Intern Med. 2020;173(5):362–367.Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection: a narrative review // Ann Intern Med. 2020;173(5):362–367.Becker RC. COVID-19 update: Covid-19-associated coagulopathy // J Thromb Thrombolysis. 2020;50(1):54–67. Doi: 10.1007/s11239-020-02134-3.Becker RC. COVID-19 update: Covid-19-associated coagulopathy // J Thromb Thrombolysis. 2020;50(1):54–67. Doi: 10.1007/s11239-020-02134-3.Klok FA, Kruip MJHA, van der Meer NJM. Incidence of thrombotic complications in critically ill ICU patients with COVID-19 // Thromb Res 2020;(191):145–147.Klok FA, Kruip MJHA, van der Meer NJM. Incidence of thrombotic complications in critically ill ICU patients with COVID-19 // Thromb Res 2020;(191):145–147.Artifoni M, Danic G, Gautier G, Gicquel P, Boutoille D, Raffi F. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors // J Thrombosis Thrombolysis. 2020;(50):211–216. Doi: 10.1007/s11239-020-02146-z.Artifoni M, Danic G, Gautier G, Gicquel P, Boutoille D, Raffi F. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors // J Thrombosis Thrombolysis. 2020;(50):211–216. Doi: 10.1007/s11239-020-02146-z.Aggarwal G, Lippi G, Michael Henry B. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019. (COVID-19): a pooled analysis of published literature // Int J Stroke. 2020;(15):385–389. Doi: 10.1177/1747493020921664.Aggarwal G, Lippi G, Michael Henry B. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019. (COVID-19): a pooled analysis of published literature // Int J Stroke. 2020;(15):385–389. Doi: 10.1177/1747493020921664.Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, Lantos J, Schenck EJ, Goyal P, Bruce SS, Kahan J, Lansdale KN, LeMoss NM, Murthy SB, Stieg PE, Fink ME, Iadecola C, Segal AZ, Cusick M, Campion TR Jr, Diaz I, Zhang C, Navi BB. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza //JAMA Neurol. 2020 Jul 2;77(11):1–7. Doi: 10.1001/jamaneurol.2020.2730.Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, Lantos J, Schenck EJ, Goyal P, Bruce SS, Kahan J, Lansdale KN, LeMoss NM, Murthy SB, Stieg PE, Fink ME, Iadecola C, Segal AZ, Cusick M, Campion TR Jr, Diaz I, Zhang C, Navi BB. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza //JAMA Neurol. 2020 Jul 2;77(11):1–7. Doi: 10.1001/jamaneurol.2020.2730.Melmed KR, Boehme A, Ironside N, Murthy S, Park S, Agarwal S. Respiratory and blood stream infections are associated with subsequent venous thromboembolism after primary intracerebral hemorrhage // Neurocritical Care. 2020. Doi: 10.1007/s12028-020-00974-8.Melmed KR, Boehme A, Ironside N, Murthy S, Park S, Agarwal S. Respiratory and blood stream infections are associated with subsequent venous thromboembolism after primary intracerebral hemorrhage // Neurocritical Care. 2020. Doi: 10.1007/s12028-020-00974-8.Li Y, Li M, Wang M. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study // Stroke Vasc Neurol 2020. Doi: 10.1136/svn-2020-000431.Li Y, Li M, Wang M. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study // Stroke Vasc Neurol 2020. Doi: 10.1136/svn-2020-000431.Pranata R, Huang I, Lim MA, Wahjoepramono EJ, July J. Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19–systematic review, meta-analysis, and meta-regression // J Stroke Cerebrovascular Dis. 2020;(29):104949. Doi: 10.1016/j.jstrokecerebrovasdis.2020.104949.Pranata R, Huang I, Lim MA, Wahjoepramono EJ, July J. Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19–systematic review, meta-analysis, and meta-regression // J Stroke Cerebrovascular Dis. 2020;(29):104949. Doi: 10.1016/j.jstrokecerebrovasdis.2020.104949.Atum M, Boz AAE, Çakır B, Karabay O, Köroglu M, Ögütlü A, Alagöz G. Evaluation of Conjunctival Swab PCR Results in Patients with SARS-CoV-2 Infection // Ocul. Immunol. Inflamm. 2020;(22):1–4.Atum M, Boz AAE, Çakır B, Karabay O, Köroglu M, Ögütlü A, Alagöz G. Evaluation of Conjunctival Swab PCR Results in Patients with SARS-CoV-2 Infection // Ocul. Immunol. Inflamm. 2020;(22):1–4.Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Ueffng M, Schindler M, Thaler S. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues // Am. J. Ophthalmol. CaseRep. 2020;(19):100805.Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Ueffng M, Schindler M, Thaler S. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues // Am. J. Ophthalmol. CaseRep. 2020;(19):100805.Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS // J Virol. 2020. epubaheadofprint. Doi: 10.1128/JVI.00127-20.Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS // J Virol. 2020. epubaheadofprint. Doi: 10.1128/JVI.00127-20.Alenina N, Bader M. ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models // Neurochem Res. 2019;44(6):1323–1329. Doi: 10.1007/s11064018-2679-4.Alenina N, Bader M. ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models // Neurochem Res. 2019;44(6):1323–1329. Doi: 10.1007/s11064018-2679-4.Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis // J Pathol. 2004;203(2):631–637. Doi: 10.1002/path.1570.Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis // J Pathol. 2004;203(2):631–637. Doi: 10.1002/path.1570.Senanayake P, Drazba J, Shadrach K. et al. Angiotensin II and its receptor subtypes in the human retina // Invest Ophthalmol Vis Sci. 2007;48(7):3301–3311. Doi: 10.1167/iovs.06-1024.Senanayake P, Drazba J, Shadrach K. et al. Angiotensin II and its receptor subtypes in the human retina // Invest Ophthalmol Vis Sci. 2007;48(7):3301–3311. Doi: 10.1167/iovs.06-1024.Copin MC, Parmentier E, Duburcq T, Poissy J, Mathieu D; Lille COVID-19 ICU and Anatomopathology Group. Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection // Intensive Care Med. 2020:1–3. Doi: 10.1007/s00134-020-06057-8.Copin MC, Parmentier E, Duburcq T, Poissy J, Mathieu D; Lille COVID-19 ICU and Anatomopathology Group. Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection // Intensive Care Med. 2020:1–3. Doi: 10.1007/s00134-020-06057-8.Becker R. COVID-19 update: Covid-19-associated coagulopathy // J Thromb Thrombolysis. Epub ahead of print 15 May 2020. Doi: 10.1007/s11239-020-02134-3.Becker R. COVID-19 update: Covid-19-associated coagulopathy // J Thromb Thrombolysis. Epub ahead of print 15 May 2020. Doi: 10.1007/s11239-020-02134-3.Huertas A, Montani D, Savale L. et al. Endothelial Cell Dysfunction: A Major Player in SARS-CoV-2 Infection (COVID-19)? // Eur Respir J. 2020; Jun 18. Doi: 10.1183/13993003.01634-2020.Huertas A, Montani D, Savale L. et al. Endothelial Cell Dysfunction: A Major Player in SARS-CoV-2 Infection (COVID-19)? // Eur Respir J. 2020; Jun 18. Doi: 10.1183/13993003.01634-2020.Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures // J Anat. 2005;206(4):319–348. Doi: 10.1111/j.1469-7580.2005.00395.x.Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures // J Anat. 2005;206(4):319–348. Doi: 10.1111/j.1469-7580.2005.00395.x.Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease // Prog Retin Eye Res. 2012;31(5):377–406. Doi: 10.1016/j.preteyeres.2012.04.004.Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease // Prog Retin Eye Res. 2012;31(5):377–406. Doi: 10.1016/j.preteyeres.2012.04.004.Marinho PM, Marcos AAA, Romano AC, et al. Retinal findings in patients with COVID-19 // Lancet 2020; 395(10237):1610.Marinho PM, Marcos AAA, Romano AC, et al. Retinal findings in patients with COVID-19 // Lancet 2020; 395(10237):1610.Invernizzi A, Torre A, Parrulli S, Zicarelli F, Schiuma M, Colombo V, Giacomelli A, Cigada M, Milazzo L, Ridolfo A, Faggion I, Cordier L, Oldani M, Marini S, Villa P, Rizzardini G, Galli M, Antinori S, Staurenghi G, Meroni L. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study // EClinical Medicine. 2020;(20):100550. Doi: 10.1016/j.eclinm.2020.100550.Invernizzi A, Torre A, Parrulli S, Zicarelli F, Schiuma M, Colombo V, Giacomelli A, Cigada M, Milazzo L, Ridolfo A, Faggion I, Cordier L, Oldani M, Marini S, Villa P, Rizzardini G, Galli M, Antinori S, Staurenghi G, Meroni L. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study // EClinical Medicine. 2020;(20):100550. Doi: 10.1016/j.eclinm.2020.100550.Hagag AM, Gao SS, Jia Y, Huang D. Optical coherence tomography angiography: Technical principles and clinical applications in ophthalmology // Taiwan J Ophthalmol. 2017;7(3):115–129. Doi: 10.4103/tjo.tjo_31_17.Hagag AM, Gao SS, Jia Y, Huang D. Optical coherence tomography angiography: Technical principles and clinical applications in ophthalmology // Taiwan J Ophthalmol. 2017;7(3):115–129. Doi: 10.4103/tjo.tjo_31_17.Campbell JP, Zhang M, Hwang TS, Bailey ST, Wilson DJ, Jia Y, Huang D. Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography // Sci Rep. 2017;10(7):42201. Doi: 10.1038/srep42201. PMID: 28186181; PMCID: PMC5301488.Campbell JP, Zhang M, Hwang TS, Bailey ST, Wilson DJ, Jia Y, Huang D. Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography // Sci Rep. 2017;10(7):42201. Doi: 10.1038/srep42201. PMID: 28186181; PMCID: PMC5301488.Cennamo G, Reibaldi M, Montorio D, D’Andrea L, Fallico M, Triassi M. Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study // Am J Ophthalmol. 2021;(227):182–190. Doi: 10.1016/j.ajo.2021.03.015.Cennamo G, Reibaldi M, Montorio D, D’Andrea L, Fallico M, Triassi M. Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study // Am J Ophthalmol. 2021;(227):182–190. Doi: 10.1016/j.ajo.2021.03.015.Ashraf M, Sampani K, Clermont A. Vascular density of deep, intermediate and superficial vascular plexuses are differentially affected by diabetic retinopathy severity // Invest Ophthalmol Vis Sci. 2020;61(12):53.Ashraf M, Sampani K, Clermont A. Vascular density of deep, intermediate and superficial vascular plexuses are differentially affected by diabetic retinopathy severity // Invest Ophthalmol Vis Sci. 2020;61(12):53.Coscas F, Glacet-Bernard A, Miere A. Optical coherence tomography angiography in retinal vein occlusion: evaluation of superficial and deep capillary plexa // Am J Ophthalmol. 2016;161(10):160–171.Coscas F, Glacet-Bernard A, Miere A. Optical coherence tomography angiography in retinal vein occlusion: evaluation of superficial and deep capillary plexa // Am J Ophthalmol. 2016;161(10):160–171.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.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.Savastano A, Crincoli E, Savastano MC, Younis S, Gambini G, De Vico U, Cozzupoli GM, Culiersi C, Rizzo S, Gemelli. Against COVID-19 Post-Acute Care Study Group. Peripapillary Retinal Vascular Involvement in Early Post- COVID-19 Patients // J. Clin. Med. 2020, 9, 2895.Savastano A, Crincoli E, Savastano MC, Younis S, Gambini G, De Vico U, Cozzupoli GM, Culiersi C, Rizzo S, Gemelli. Against COVID-19 Post-Acute Care Study Group. Peripapillary Retinal Vascular Involvement in Early Post- COVID-19 Patients // J. Clin. Med. 2020, 9, 2895.Guemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B. et al. Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography // Graefes Arch ClinExpOphthalmol. 2021;259(8):2243–2249.Guemes-Villahoz N, Burgos-Blasco B, Vidal-Villegas B. et al. Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography // Graefes Arch ClinExpOphthalmol. 2021;259(8):2243–2249.Guemes-Villahoz Noemi et al. Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection // Medicinaclinica. 2021;156(11):541–546. Doi: 10.1016/j.medcli.2020.12.006.Guemes-Villahoz Noemi et al. Reduced retinal vessel density in COVID-19 patients and elevated D-dimer levels during the acute phase of the infection // Medicinaclinica. 2021;156(11):541–546. Doi: 10.1016/j.medcli.2020.12.006.Oren B, AksoyAydemır G, Aydemır E. et al. Quantitative assessment of retinal changes in COVID-19 patients // Clin Exp Optom. 2021;104(6):717–722.Oren B, AksoyAydemır G, Aydemır E. et al. Quantitative assessment of retinal changes in COVID-19 patients // Clin Exp Optom. 2021;104(6):717–722.Abrishami M, Emamverdian Z, Shoeibi N, Omidtabrizi A, Daneshvar R, SaeidiRezvani T, Saeedian N, Eslami S, Mazloumi M, Sadda S, Sarraf D. Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: a case-control study // Can J Ophthalmol. 2021;56(1):24–30. Doi: 10.1016/j.jcjo.2020.11.006. PMID: 33249111; PMCID: PMC7666612.Abrishami M, Emamverdian Z, Shoeibi N, Omidtabrizi A, Daneshvar R, SaeidiRezvani T, Saeedian N, Eslami S, Mazloumi M, Sadda S, Sarraf D. Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: a case-control study // Can J Ophthalmol. 2021;56(1):24–30. Doi: 10.1016/j.jcjo.2020.11.006. PMID: 33249111; PMCID: PMC7666612.Zapata MÁ, Banderas García S, Sánchez-Moltalvá A. et al Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity // British Journal of Ophthalmology Published Online First. 2020. 16 Dec. Doi: 10.1136/bjophthalmol-2020-317953.Zapata MÁ, Banderas García S, Sánchez-Moltalvá A. et al Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity // British Journal of Ophthalmology Published Online First. 2020. 16 Dec. Doi: 10.1136/bjophthalmol-2020-317953.Hazar L, Karahan M, Vural E. et al. Macular vessel density in patients recovered from COVID-19 // Photodiagnosis Photodyn Ther. 2021;(34):102267.Hazar L, Karahan M, Vural E. et al. Macular vessel density in patients recovered from COVID-19 // Photodiagnosis Photodyn Ther. 2021;(34):102267.Turker IC, Dogan CU, Guven D, Kutucu OK, Gul C. Optical coherence tomographyangiography findings in patients with COVID-19 // Can J Ophthalmol. 2021. PMID: 33497612Turker IC, Dogan CU, Guven D, Kutucu OK, Gul C. Optical coherence tomographyangiography findings in patients with COVID-19 // Can J Ophthalmol. 2021. PMID: 33497612Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19 // Lancet 2020; (395):1417–1418.Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19 // Lancet 2020; (395):1417–1418.Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia // J Thromb Haemost. 2020;(18):844.8Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia // J Thromb Haemost. 2020;(18):844.8Roberts KA, Colley L, Agbaedeng TA, Ellison-Hughes GM, Ross MD. Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction // Front Cardiovasc Med. 2020;26(7):598400. Doi: 10.3389/fcvm.2020.598400. PMID: 33195487; PMCID: PMC7649150.Roberts KA, Colley L, Agbaedeng TA, Ellison-Hughes GM, Ross MD. Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction // Front Cardiovasc Med. 2020;26(7):598400. Doi: 10.3389/fcvm.2020.598400. PMID: 33195487; PMCID: PMC7649150.Gavriilaki E, Brodsky RA. Severe COVID-19 infection and thrombotic microangiopathy: success does not come easily // Br J Haematol. 2020;189(6):E227–E230.Gavriilaki E, Brodsky RA. Severe COVID-19 infection and thrombotic microangiopathy: success does not come easily // Br J Haematol. 2020;189(6):E227–E230.Sheth JU, Narayanan R, Goyal J, Goyal V. Retinal vein occlusion in COVID-19: A novel entity // Indian J Ophthalmol 2020;(68):2291–2293.Sheth JU, Narayanan R, Goyal J, Goyal V. Retinal vein occlusion in COVID-19: A novel entity // Indian J Ophthalmol 2020;(68):2291–2293.Montesel A, Bucolo C, Mouvet V, Moret E and Eandi CM (2020) Case Report: Central Retinal Artery Occlusion in a COVID-19 Patient // Front. Pharmacol. 11:588384. Doi: 10.3389/fphar.2020.588384.Montesel A, Bucolo C, Mouvet V, Moret E and Eandi CM (2020) Case Report: Central Retinal Artery Occlusion in a COVID-19 Patient // Front. Pharmacol. 11:588384. Doi: 10.3389/fphar.2020.588384.Dumitrascu OM, Volod O, Bose S, Wang Y, Biousse V, and Lyden PD. (2020). Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban // J Stroke Cerebrovasc. Dis. 29, 2–4. Doi: 10.1016/j.jstrokecerebrovasdis.2020.104982.Dumitrascu OM, Volod O, Bose S, Wang Y, Biousse V, and Lyden PD. (2020). Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban // J Stroke Cerebrovasc. Dis. 29, 2–4. Doi: 10.1016/j.jstrokecerebrovasdis.2020.104982.Tal Yahalomi, Joseph Pikkel, Roee Arnon, and Yuval Pessach. Central retinal vein occlusion in a young healthy COVID-19 patient: A case report // Am J Ophthalmol Case Rep. 2020;20: 100992. Doi: 10.1016/j.ajoc.2020.100992.Tal Yahalomi, Joseph Pikkel, Roee Arnon, and Yuval Pessach. Central retinal vein occlusion in a young healthy COVID-19 patient: A case report // Am J Ophthalmol Case Rep. 2020;20: 100992. Doi: 10.1016/j.ajoc.2020.100992.

The authors declare that there are no conflicts of interest present.