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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">sechenov</journal-id><journal-title-group><journal-title xml:lang="en">Sechenov Medical Journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Сеченовский вестник</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2218-7332</issn><issn pub-type="epub">2658-3348</issn><publisher><publisher-name>Сеченовский Университет</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47093/2218-7332.2020.11.2.40-49</article-id><article-id custom-type="elpub" pub-id-type="custom">sechenov-240</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>COVID-19</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>COVID-19</subject></subj-group></article-categories><title-group><article-title>Frequency of retinal changes in patients with COVID-19: an observational study</article-title><trans-title-group xml:lang="ru"><trans-title>Частота ретинальных изменений у пациентов, перенесших заболевание COVID-19: обсервационное исследование</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6220-1401</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Илларионова</surname><given-names>А. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Illarionova</surname><given-names>A. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Илларионова Алла Рудольфовна, канд. мед. наук, зав. офтальмологическим отделением </p><p>ул. 2-я Фрунзенская, д. 4, г. Москва, 119146</p></bio><bio xml:lang="en"><p>Alla R. Illarionova, MD, PhD, Head of Ophthalmology Department, Polyclinic No. 2</p><p>4, 2nd Frunzenskaya str., Moscow, 119146</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0957-5236</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Потапова</surname><given-names>О. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Potapova</surname><given-names>O. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Потапова Ольга Михайловна, зав. офтальмологическим отделением  </p><p>пер. Сивцев Вражек, д. 26/28, г. Москва, 119002</p></bio><bio xml:lang="en"><p>Olga M. Potapova, Head of Ophthalmology Department, Polyclinic No. 1</p><p>26/28, Sivtsev Vrazhek lane, Moscow, 119002</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5319-0520</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Косарева</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kosareva</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Косарева Ольга Александровна, офтальмолог офтальмологического отделения </p><p>ул. 2-я Фрунзенская, д. 4, г. Москва, 119146</p></bio><bio xml:lang="en"><p>Olga A. Kosareva, ophthalmologist, Ophthalmology Department, Polyclinic No. 2</p><p>4, 2nd Frunzenskaya str., Moscow, 119146</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8165-4094</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузнецова</surname><given-names>Ю. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuznetsova</surname><given-names>Yu. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кузнецова Юлия Рашитовна, офтальмолог офтальмологического отделения </p><p>ул. 2-я Фрунзенская, д. 4, г. Москва, 119146</p></bio><bio xml:lang="en"><p>Yulia R. Kuznetsova, ophthalmologist, Ophthalmology Department, Polyclinic No. 2</p><p>4, 2nd Frunzenskaya str., Moscow, 119146</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Поликлиника № 2» Управления делами Президента РФ</institution><country>Россия</country></aff><aff xml:lang="en"><institution>FSBI Polyclinic No. 2 of the Directorate of the President of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБУ «Поликлиника № 1» Управления делами Президента РФ</institution><country>Россия</country></aff><aff xml:lang="en"><institution>FSBI Polyclinic No. 1 of the Directorate of the President of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>06</day><month>12</month><year>2020</year></pub-date><volume>11</volume><issue>2</issue><issue-title>Special Issue: COVID-19</issue-title><fpage>40</fpage><lpage>49</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Illarionova A.R., Potapova O.M., Kosareva O.A., Kuznetsova Y.R., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Илларионова А.Р., Потапова О.М., Косарева О.А., Кузнецова Ю.Р.</copyright-holder><copyright-holder xml:lang="en">Illarionova A.R., Potapova O.M., Kosareva O.A., Kuznetsova Y.R.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.sechenovmedj.com/jour/article/view/240">https://www.sechenovmedj.com/jour/article/view/240</self-uri><abstract><p>In order to enter cells, SARS-CoV-2 virus uses the angiotensin-converting enzyme 2 receptor that is also expressed in retina.</p><sec><title>Aim</title><p> Aim. Determination of the frequency and nature of retinal changes, evaluation of visual functions in patients who have got over COVID-19.</p></sec><sec><title>Materials and methods</title><p> Materials and methods. This observational research includes 31 patients aged from 28 to 79 that got over COVID-19 (with severity according to computed tomography (CT): 1–3) in the period from 15 to 40 days before the research. Standard ophthalmological examination and optical coherence tomography (OCT) were performed; visual acuity measurement and threshold static perimetry were used to assess visual functions.</p></sec><sec><title>Results</title><p>Results. Pathology of the ocular surface wasn’t detected. Ophthalmoscopy revealed retinal changes in only one patient. At OCT, 27 (87%) patients proved to have de novo changes in the retinal neuroepithelium at the level of the internal plexiform layer and the retinal ganglion cell layer in the form of hyper-reflective polymorphic foci with clear borders; 18 (67%) patients had monocular lesions. The maximum corrected visual acuity didn’t differ from the previously defined one; no violations of retinal light sensitivity were detected. No association was found between the severity of CT lung changes and retinal changes. The detected retinal changes weren’t associated with symptoms of anosmia (hyposmia) and ageusia. OCT repeated after 12–15 days showed no dynamics of hyperreflective foci: they remained unchanged in their shape, echogenicity and size.</p></sec><sec><title>Conclusion</title><p> Conclusion. De novo changes in retinal neuroepithelium at the level of the inner plexiform layer and the retinal ganglion cell layer were detected according to OCT data in 87% of patients who had undergone COVID-19. Anatomical changes in the retina weren’t manifested by functional visual disturbances. There is no association of retinal changes with lesions of I and IX cranial nerve pairs.</p></sec></abstract><trans-abstract xml:lang="ru"><p>Для проникновения в клетки SARS-CoV-2 использует рецептор ангиотензинпревращающего фермента 2, который экспрессируется в том числе в сетчатке.</p><sec><title>Цель</title><p> Цель. Определить частоту и характер ретинальных изменений, оценить зрительные функции у пациентов, перенесших COVID-19.</p></sec><sec><title>Материалы и методы</title><p> Материалы и методы. В наблюдательное исследование включен 31 пациент в возрасте от 28 до 79 лет, перенесший COVID-19 (степень тяжести по данным компьютерной томографии (КТ): 1–3) в сроки от 15 до 40 дней до момента исследования. Проведено стандартное офтальмологическое обследование, оптическая когерентная томография (ОКТ); для оценки зрительных функций использовалась визометрия и пороговая статическая периметрия.</p></sec><sec><title>Результаты</title><p> Результаты. Патологии поверхности глаза не выявлено. При офтальмоскопии изменения сетчатки были выявлены только у одного пациента. При проведении ОКТ у 27 (87%) пациентов отмечены изменения de novo в ретинальном нейроэпителии на уровне внутреннего плексиформного слоя и слоя ганглиозных клеток сетчатки в виде гиперрефлективных полиморфных очагов с четкими границами; у 18 (67%) отмечалось монокулярное поражение. Максимально корригированная острота зрения не отличалась от фиксированной ранее; нарушений световой чувствительности сетчатки не выявлено. Ассоциации между степенью тяжести КТ изменений легких и изменениями сетчатки не выявлено. Обнаруженные изменения сетчатки не были ассоциированы с симптомами аносмии (гипосмии) и агевзии. На повторной ОКТ через 12–15 дней динамики гиперрефлективных очагов отмечено не было: они оставались не измененными по своей форме, эхогенности и размерам.</p></sec><sec><title>Заключение</title><p> Заключение. Изменения de novo в ретинальном нейроэпителии на уровне внутреннего плексиформного слоя и слоя ганглиозных клеток сетчатки обнаруживаются по данным ОКТ у 87% пациентов, перенесших COVID-19. Анатомические изменения сетчатки не проявляются функциональными зрительными нарушениями. Отсутствует ассоциация изменений сетчатки с поражением I и IX пар черепно-мозговых нервов.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>сетчатка</kwd><kwd>ретинальная патология</kwd><kwd>исследования сетчатки</kwd><kwd>оптическая когерентная томография</kwd><kwd>ОКТ</kwd><kwd>COVID-19</kwd><kwd>ватообразные очаги</kwd><kwd>геморрагии</kwd><kwd>SARS-CoV-2</kwd><kwd>обсервационное исследование</kwd></kwd-group><kwd-group xml:lang="en"><kwd>retina</kwd><kwd>retinal pathology</kwd><kwd>retinal research</kwd><kwd>optical coherence tomography</kwd><kwd>ОСТ</kwd><kwd>COVID-19</kwd><kwd>cotton wool spots</kwd><kwd>hemorrhages</kwd><kwd>SARS-CoV-2</kwd><kwd>observational study</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Временные методические рекомендации Минздрава РФ по профилактике, диагностике лечению коронавирусной инфекции (COVID-19), версия 7.0 от 03.06.2020.</mixed-citation><mixed-citation xml:lang="en">Vremennye metodicheskie rekomendatsii Minzdrava RF poprofilaktike, diagnostike i lecheniyu koronavirusnoi infektsii (COVID-19). Versiia 7 (03.06.2020). [Clinical recommendations of the Russian Federation for the prevention, diagnosis and treatment of coronavirus infection (COVID-19) of the Ministry of Health. Version 7 (03.06.2020)]. 166 р. (In Russian). URL: https://static-0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_COVID-19_ v7.pdf (accessed 03.06.2020).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">static-0.rosminzdrav.ru › 03062020_МR_COVID-19_v7</mixed-citation><mixed-citation xml:lang="en">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 Mar 31; 138(5): 575–8. https://doi.org/10.1001/jamaophthalmol.2020.1291 PMID: 32232433</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">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; published online March 31. DOI:10.1001/jamaophthalmol.2020.1291.</mixed-citation><mixed-citation xml:lang="en">Майчук Д.Ю., Атлас С.Н., Лошкарева А.О. Глазные проявления коронавирусной инфекции COVID-19 (клиническое наблюдение). Вестник офтальмологии. 2020; 136(4): 118–23.https://doi.org/10.17116/oftalma2020136041118</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Майчук Д.Ю., Атлас С.Н., Лошкарева А.О. Глазные проявления коронавирусной инфекции COVID-19 (клиническое наблюдение). Вестник офтальмологии. 2020;136(4): 118-123. 10.17116/oftalma2020136041118</mixed-citation><mixed-citation xml:lang="en">Khavandi S., Tabibzadeh E., Naderan M., Shoar S. Corona virus disease-19 (COVID-19) presenting as conjunctivitis: atypically high-risk during a pandemic. Cont Lens Anterior Eye. 2020 Jun; 43(3): 211–2. https://doi.org/10.1016/j.clae.2020.04.010. PMID: 32354654</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Khavandi S, Tabibzadeh E, Naderan M, Shoar S. Corona virus disease-19 (COVID-19) presenting as conjunctivitis: atypically high-risk during a pandemic. Contact Lens and Anterior Eye: the Journal of the British Contact Lens Association. 2020;43(3):211-212. https://doi.org/10.1016/j.clae.2020.04.010.</mixed-citation><mixed-citation xml:lang="en">Li J.O., Lam D.S.C., Chen Y., Ting D.S.W. Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. Br J Ophthalmol. 2020 Mar; 104(3): 297–8. https://doi.org/10.1136/ bjophthalmol-2020-315994 PMID: 32086236</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Li JO, Lam DSC, Chen Y, Ting DSW. Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. The British Journal of Ophthalmology. 2020; 104(3):297-298. https://doi.org/10.1136/bjophthalmol-2020-315994</mixed-citation><mixed-citation xml:lang="en">Insausti-García A., Reche-Sainz J.A., Ruiz-Arranz С., et al. Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state. Eur J Ophthalmol. 2020 Jul 30. https://doi. org/10.1177/1120672120947591 PMID: 32735134</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Insausti-García A, Reche-Sainz J A, Ruiz-Arranz С, Vázquez Á L, Ferro-Osuna M. Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state. Eur J Ophthalmol. 2020 Jul 30 : 1120672120947591. Published online 2020 Jul 30. doi: 10.1177/1120672120947591</mixed-citation><mixed-citation xml:lang="en">Zhang H., Penninger J.M., Li Y., et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr; 46(4): 586–90. https://doi.org/10.1007/s00134-020-05985-9. PMID: 32125455</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang H, Penninger JM, Li Y, et al. Angiotensin‐converting enzyme 2 (ACE2) as a SARS‐CoV‐2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020; 46: 586–90.</mixed-citation><mixed-citation xml:lang="en">Verma A., Shan Z., Lei B., et al. ACE2 and Ang-(1–7) confer protection against development of diabetic retinopathy. Mol Ther. 2012 Jan; 20(1): 28–36. https://doi.org/10.1038/mt.2011.155. PMID: 21792177</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Verma A, Shan Z, Lei B et al. ACE2 and Ang‐(1–7) confer protection against development of diabetic retinopathy. Mol Ther 2012; 20: 28–36.</mixed-citation><mixed-citation xml:lang="en">Landecho M.F., Gándara E. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med. 2020 Jul 30. https://doi.org/10.1111/joim.13156 PMID: 32729633</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Landecho M F, Gándara E. COVID‐19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? Journal of Internal Medicine First published: 30 July 2020. https://doi.org/10.1111/joim.13156</mixed-citation><mixed-citation xml:lang="en">Marinho P., Marcos А., Romano А., et al. Retinal findings in patients with COVID-19. Lancet. 2020 May 23; 395(10237): 1610. https://doi.org/10.1016/S0140-6736(20)31014-X PMID: 32405105</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Marinho P, Marcos А, Romano А, et al.. Retinal findings in patients with COVID-19. The Lancet. 2020 May 23;395(10237):1610. doi: 10.1016/S0140-6736(20)31014-X. PMID: 32405105. PMCID: PMC7217650.</mixed-citation><mixed-citation xml:lang="en">Casagrande M., Fitzek A., Püschel K., et al. Detection of SARSCoV-2 in Human Retinal Biopsies of Deceased COVID-19 Patients. Ocul Immunol Inflamm. 2020 Jul 3; 28(5): 721–5. https://doi.org/10.1080/09273948.2020.1770301 PMID: 32469258</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">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 Jul 3;28(5):721-725. doi: 1080/09273948.2020.1770301.Epub 2020 May 29.</mixed-citation><mixed-citation xml:lang="en">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 Apr; 28(3): 391– 5. https://doi.org/10.1080/09273948.2020.1738501 PMID: 32175797</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">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: 391–95.</mixed-citation><mixed-citation xml:lang="en">Hooks J.J., Percopo C., Wang Y., Detrick B. Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy. J Immunol. 1993 Sep; 151(6): 3381–9. PMID: 8397257</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Hooks JJ, Percopo C, Wang Y, Detrick B. Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy. J Immunol. 1993;151:3381–3389. [PubMed]</mixed-citation><mixed-citation xml:lang="en">Kazaryan A.A., Ponomareva E.N. SluchaĬ glaznykh proyavleniĬ toksicheskogo vozdeĬstviya gidroksikhlorokhina. [Cases of ocular manifestations of toxic effects of hydroxychloroquine]. Klinicheskaya praktika. 2011; (2): 12–21 (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Казарян А.А., Пономарева Е.Н. Случай глазных проявлений токсического воздействия гидроксихлорохина. Клиническая практика. 2011 (2): 12-21.</mixed-citation><mixed-citation xml:lang="en">Gonzalez-Noriega A., Grubb J.H., Talkad V., Sly W.S. Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J Cell Biol. 1980 Jun; 85(3): 839–52. https://doi.org/10.1083/jcb.85.3.839 PMID: 7190150</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Gonzalez Noriega A., Grubb J.H., Talkad V., Sly W.S. Chloroquine inhibits lysosomal enzyme pinocyto sis and enhances lysosomal enzyme secretion by impair ing receptor recycling // J. Cell Biol. 1980. Vol. 85. P. 839 852.</mixed-citation><mixed-citation xml:lang="en">Gonzalez Noriega A., Grubb J.H., Talkad V., Sly W.S. Chloroquine inhibits lysosomal enzyme pinocyto sis and enhances lysosomal enzyme secretion by impair ing receptor recycling // J. Cell Biol. 1980. Vol. 85. P. 839 852.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
