{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:37:43Z","timestamp":1771540663085,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vision"],"abstract":"<jats:p>Purpose of review: to provide a prospective on the current mechanisms by which SARS-CoV-2 enters cells and replicates, and its implications for ocular transmission. The literature was analyzed to understand ocular transmission as well as molecular mechanisms by which SARS-CoV-2 enters cells and replicates. Analysis of gene expression profiles from available datasets, published immunohistochemistry, as well as current literature was reviewed, to assess the likelihood that ocular inoculation of SARS-CoV-2 results in systemic infection. Recent findings: The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2. In addition to direct ocular infection, virus carried by tears through the nasolacrimal duct to nasal epithelium represent a means of ocular inoculation. Summary: There is evidence that SARS-CoV-2 may either directly infect cells on the ocular surface, or virus can be carried by tears through the nasolacrimal duct to infect the nasal or gastrointestinal epithelium.<\/jats:p>","DOI":"10.3390\/vision4030040","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T14:21:10Z","timestamp":1598970070000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Potential of Ocular Transmission of SARS-CoV-2: A Review"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8301-404X","authenticated-orcid":false,"given":"Brad P.","family":"Barnett","sequence":"first","affiliation":[{"name":"NVISION Eye Centers\u2014South Sacramento, 7501 Hospital Dr. Suite 105, Sacramento, CA 95823, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-8304","authenticated-orcid":false,"given":"Karl","family":"Wahlin","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doran","family":"Spencer","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Welsbie","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Afshari","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Chao","sequence":"additional","affiliation":[{"name":"Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1056\/NEJMra032498","article-title":"The severe acute respiratory syndrome","volume":"349","author":"Peiris","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Raboud, J., Shigayeva, A., McGeer, A., Bontovics, E., Chapman, M., Gravel, D., Henry, B., Lapinsky, S., Loeb, M., and McDonald, L.C. (2010). Risk factors for SARS transmission from patients requiring intubation: A multicentre investigation in Toronto, Canada. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010717"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ajo.2009.07.030","article-title":"Ocular surface reconstruction with autologous nasal mucosa in cicatricial ocular surface disease","volume":"149","author":"Kim","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/09273948.2020.1772314","article-title":"Ocular Surface Expression of SARS-CoV-2 Receptors","volume":"28","author":"Leonardi","year":"2020","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ulrich, H., and Pillat, M.M. (2020). CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement. Stem Cell Rev. Rep.","DOI":"10.1007\/s12015-020-09976-7"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11876","DOI":"10.1073\/pnas.0505577102","article-title":"Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry","volume":"102","author":"Simmons","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhou, L., Xu, Z., Castiglione, G.M., Soiberman, U.S., Eberhart, C.G., and Duh, E.J. (2020). ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Biorxiv.","DOI":"10.1101\/2020.05.09.086165"},{"key":"ref_12","first-page":"E011","article-title":"[Expression analysis of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues]","volume":"56","author":"Zhang","year":"2020","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1128\/JVI.02202-13","article-title":"TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein","volume":"88","author":"Heurich","year":"2014","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Asselta, R., Paraboschi, E.M., Mantovani, A., and Duga, S. (2020). ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Medrxiv.","DOI":"10.1101\/2020.03.30.20047878"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jmb.2011.04.060","article-title":"The retinal specific CD147 Ig0 domain: From molecular structure to biological activity","volume":"411","author":"Redzic","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.ajpath.2011.05.036","article-title":"EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: Implications in dry eye disease","volume":"179","author":"Huet","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Joung, C., Noh, H., Jung, J., Song, H.Y., Bae, H., Pahk, K., and Kim, W.K. (2020). A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082990"},{"key":"ref_18","unstructured":"Mission, W.-C.J. (2020). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), World Health Organization."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/S0140-6736(20)31014-X","article-title":"Retinal findings in patients with COVID-19","volume":"395","author":"Marinho","year":"2020","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Aakalu, V.K., Parameswaran, S., Maienschein-Cline, M., Bahroos, N., Shah, D., Ali, M., and Krishnakumar, S. (2017). Human Lacrimal Gland Gene Expression. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169346"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.celrep.2016.04.020","article-title":"OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition","volume":"15","author":"Kitazawa","year":"2016","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e100811","DOI":"10.15252\/embj.2018100811","article-title":"A single-cell transcriptome atlas of the adult human retina","volume":"38","author":"Lukowski","year":"2019","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/02713680600932290","article-title":"Immunolocalization of EMMPRIN (CD147) in the human eye and detection of soluble form of EMMPRIN in ocular fluids","volume":"31","author":"Maatta","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1038\/s41467-019-12780-8","article-title":"Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration","volume":"10","author":"Menon","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3727\/105221609788681231","article-title":"Comparison of gene expression profiles of conjunctival cell lines with primary cultured conjunctival epithelial cells and human conjunctival tissue","volume":"14","author":"Tong","year":"2009","journal-title":"Gene Expr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1167\/iovs.06-0998","article-title":"Comparative analysis of human conjunctival and corneal epithelial gene expression with oligonucleotide microarrays","volume":"48","author":"Turner","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24100","DOI":"10.1073\/pnas.1914143116","article-title":"Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration","volume":"116","author":"Voigt","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.4049\/jimmunol.0901623","article-title":"Acquisition of T regulatory function in cathepsin L-inhibited T cells by eye-derived CTLA-2alpha during inflammatory conditions","volume":"183","author":"Sugita","year":"2009","journal-title":"J. Immunol."},{"key":"ref_29","first-page":"1883","article-title":"Ocular tropisms of murine coronavirus (strain JHM) after inoculation by various routes","volume":"32","author":"Robbins","year":"1991","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1177\/0300985810378760","article-title":"Studies of severe acute respiratory syndrome coronavirus pathology in human cases and animal models","volume":"47","author":"Nagata","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/425915a","article-title":"Virology: SARS virus infection of cats and ferrets","volume":"425","author":"Martina","year":"2003","journal-title":"Nature"},{"key":"ref_32","first-page":"1372","article-title":"Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis virus infection in pigs after oronasal inoculation","volume":"41","author":"Andries","year":"1980","journal-title":"Am. J. Vet. Res."},{"key":"ref_33","first-page":"417","article-title":"Ocular manifestations of feline infectious peritonitis","volume":"159","author":"Doherty","year":"1971","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_34","first-page":"538","article-title":"Keratoconjunctivitis associated with sialodacryoadenitis in rats","volume":"15","author":"Lai","year":"1976","journal-title":"Investig. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1016\/S0140-6736(20)30313-5","article-title":"2019-nCoV transmission through the ocular surface must not be ignored","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","author":"Kar","year":"2019","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1906-x","article-title":"scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation","volume":"21","author":"Madissoon","year":"2019","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e105114","DOI":"10.15252\/embj.20105114","article-title":"SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells","volume":"39","author":"Lukassen","year":"2020","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Deprez, M., Zaragosi, L.-E., Truchi, M., Garcia, S.R., Arguel, M.-J., Lebrigand, K., Paquet, A., Pee\u2019r, D., Marquette, C.-H., and Leroy, S. (2019). A single-cell atlas of the human healthy airways. Biorxiv.","DOI":"10.1101\/2019.12.21.884759"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3201\/eid2211.160920","article-title":"Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Healthcare Personnel","volume":"22","author":"Alraddadi","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.cmi.2016.07.017","article-title":"Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: Incidence and risk factors of MERS-CoV seropositivity","volume":"22","author":"Kim","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5365\/wpsar.2018.9.3.002","article-title":"Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in public health workers responding to a MERS outbreak in Seoul, Republic of Korea, in 2015","volume":"10","author":"Ryu","year":"2019","journal-title":"West. Pac. Surveill. Response J."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, W.Q., Ling, W.H., Lu, C.Y., Hao, Y.T., Lin, Z.N., Ling, L., Huang, J., Li, G., and Yan, G.M. (2009). Which preventive measures might protect health care workers from SARS?. BMC Public Health, 9.","DOI":"10.1186\/1471-2458-9-81"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1873-9598(09)70018-3","article-title":"Mortality Factor Survey of Severe Acute Respiratory Syndrome in Taiwan","volume":"3","author":"Liu","year":"2009","journal-title":"Int. J. Gerontol."},{"key":"ref_46","first-page":"271","article-title":"Investigation of the influencing factors on severe acute respiratory syndrome among health care workers","volume":"38","author":"Pei","year":"2006","journal-title":"Beijing Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_47","first-page":"18","article-title":"Effectiveness of personal protective measures in prevention of nosocomial transmission of severe acute respiratory syndrome","volume":"25","author":"Yin","year":"2004","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/BF03021815","article-title":"Intubation of SARS patients: Infection and perspectives of healthcare workers","volume":"53","author":"Caputo","year":"2006","journal-title":"Can. J. Anaesth."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12262","DOI":"10.1073\/pnas.1608147113","article-title":"Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism","volume":"113","author":"Park","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3201\/eid1002.030746","article-title":"Lack of SARS transmission and U.S. SARS case-patient","volume":"10","author":"Peck","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Burke, R.M., Balter, S., Barnes, E., Barry, V., Bartlett, K., Beer, K.D., Benowitz, I., Biggs, H.M., Bruce, H., and Bryant-Genevier, J. (2020). Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States. Medrxiv.","DOI":"10.1371\/journal.pone.0238342"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0140-6736(20)31142-9","article-title":"Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: A systematic review and meta-analysis","volume":"395","author":"Chu","year":"2020","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bhaskar, M.E., and Arun, S. (2020). SARS-CoV-2 Infection Among Community Health Workers in India Before and After Use of Face Shields. J. Am. Med. Aossc.","DOI":"10.1001\/jama.2020.15586"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/S2213-2600(18)30236-4","article-title":"Tropism, replication competence, and innate immune responses of influenza virus: An analysis of human airway organoids and ex-vivo bronchus cultures","volume":"6","author":"Hui","year":"2018","journal-title":"Lancet Respir Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dai, H., Zhang, X., Xia, J., Zhang, T., Shang, Y., Huang, R., Liu, R., Wang, D., Li, M., and Wu, J. (2020). High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China. Int. J. Infect. Dis.","DOI":"10.1016\/j.ijid.2020.04.003"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e05098","DOI":"10.7554\/eLife.05098","article-title":"In vitro generation of human pluripotent stem cell derived lung organoids","volume":"4","author":"Dye","year":"2015","journal-title":"Elife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41286","DOI":"10.1038\/srep41286","article-title":"Cornea organoids from human induced pluripotent stem cells","volume":"7","author":"Foster","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.cell.2020.04.004","article-title":"Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2","volume":"e7","author":"Monteil","year":"2020","journal-title":"Cell"}],"container-title":["Vision"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2411-5150\/4\/3\/40\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:39Z","timestamp":1760177139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2411-5150\/4\/3\/40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["vision4030040"],"URL":"https:\/\/doi.org\/10.3390\/vision4030040","relation":{},"ISSN":["2411-5150"],"issn-type":[{"value":"2411-5150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}