Use of Schirmer strips and conjunctival swabs for virus detection on the ocular surface of adults: a scoping review

Sabage, Luís Expedito; Mazzo, Alessandra; Sabage, Josmar; Olivo, Taylor Endrigo Toscano; Santos, Carlos Ferreira; Lourençone, Luiz Fernando Manzoni

doi:10.5935/0004-2749.20230032

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REVIEW ARTICLE • Arq. Bras. Oftalmol. 86 (3) • May-Jun 2023 • https://doi.org/10.5935/0004-2749.20230032 copy

Use of Schirmer strips and conjunctival swabs for virus detection on the ocular surface of adults: a scoping review

Fitas de Schirmer e swab conjunctival para detecção de vírus na superfície ocular de adultos: scoping review

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Schirmer strips and conjunctival swabs are used in ophthalmology for the collection of tears and fluids. One of the biggest challenges during the COVID-19 pandemic has been accurate diagnosis and, in some cases, ocular manifestations are among the first symptoms. In this context, this study aimed to collect evidence to support the use of Schirmer strips and conjunctival swabs as a method of sample collection for viral analysis. A literature search was conducted following the Scoping Review protocol defined by The Joanna Briggs Institute. Studies were analyzed regarding virus research, collection methods, and sample analysis. The findings support that viruses can be detected on the ocular surface through analysis of Schirmer strips and conjunctival swabs. However, additional studies with larger samples and time data are necessary to confirm these conclusions.

Keywords:
Antigen, surface/isolation & purification; Conjunctiva; Tears; Eye protein/analysis; Specimen handling; Polymerase chain reaction/methods; COVID-19; Eye manifestations

Nº	Year	Country	Purpose	Methodology
1(¹⁷17 Uchio E, Aoki K, SaithoW, Itoh N, Ohno S. Rapid diagnosis of adenoviral conjunctivitis on conjunctival swabs by 10-minute immunochromatography. Ophthalmology. 1997;104(8):1294-9.)	1997	Japan	Compare IC and EIA tests for AdV detection	Experimental Quantitative Study
2(¹⁸18 Pring-Akerblom P, Adrian T, Köstler T. PCR-based detection and typing of human adenoviruses in clinical samples. Res Virol. 1997;148(3):225-31.)	1997	Germany	Evaluate type-specific primers for AdV	Experimental Quantitative Study
3(¹⁹19 Dalapathy S, Lily TK, Roy S, Madhavan HN. Development and use of nested polymerase chain reaction (PCR) for the detection of adenovirus from conjunctivitis specimens. J Clin Virol. 1998;11(1):77-84.)	1998	India	Develop and evaluate nested PCR as a tool for detecting AdV from conjunctival swabs	Descriptive Observational Study
4(⁴⁸48 Rodriguez LL, De Roo A, Guimard Y, Trappier SG, Sanchez A, Bressler D, et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999;179(Suppl 1):S170-6.)	1999	USA	Determine the genetic stability of EBO-Z, and whether additional strains of EBO virus were circulating during Kikwit outbreak	Experimental Quantitative Study
5(⁴⁷47 Liu JH, Hsu WM, Wong WW, Wang JJ, Liu WT, Liu CY, et al. Using conjunctival swab with polymerase chain reaction to aid diagnosis of cytomegalovirus retinitis in AIDS patients. Ophthalmologica. 2000;214(2):126-30.)	2000	China	Describe the application of conjunctival swab with PCR and virus culture to confirm the diagnosis of CMV retinitis in AIDS patients	Prospective Longitudinal Quantitative Study
6(²⁰20 Elnifro EM, Cooper RJ, Klapper PE, Yeo AC, Tullo AB. Multiplex polymerase chain reaction for diagnosis of viral and chlamydial keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2000;41(7):1818-22.)	2000	UK	Develop a multiplex PCR for the detection of AdV, HSV, and Chlamydia trachomatis in conjunctival swabs	Experimental Quantitative Study
7(²¹21 Chang CH, Sheu MM, Lin KH, Chen CW. Hemorrhagic viral keratoconjunctivitis in Taiwan caused by Adenovirus types 19 and 37: applicability of polymerase chain reaction-restriction fragment length polymorphism in detecting adenovirus genotypes. Cornea. 2001;20(3):295-300.)	2001	Taiwan	Evaluate the sensitivity and applicability of PCR and RT-PCR diagnoses for keratoconjunctivitis associated with viral infection	Experimental Quantitative Study
8(³⁰30 Zaal MJ, Völker-Dieben HJ, Wienesen M, D’Amaro J, Kijlstra A. Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus. Am J Ophthalmol. 2001;131(1):25-9.)	2001	Netherlands	Develop a longitudinal analysis of VZV DNA on the ocular surface of patients with herpes zoster ophthalmicus	Experimental Quantitative Study
9(³¹31 Willoughby CE, Baker K, Kaye SB, Carey P, O’Donnell N, Field A, et al. Epstein-barr virus (types 1 and 2) in the tear film in Sjogren’s Syndrome and HIV infection. J Med Virol. 2002;68(3):378-83.)	2002	UK	Determine whether ocular shedding of EBV in the tear film is peculiar to patients with Sjogren’s syndrome, and whether coinfection with EBV occurs in the tear film	Experimental Quantitative Study
10(²²22 Weitgasser U, Haller EM, El-Shabrawi Y. Evaluation of polymerase chain reaction for the detection of adenoviruses in conjunctival swab specimens using degenerate primers in comparison with direct immunofluorescence. Ophthalmologica. 2002;216(5):329-32.)	2002	Austria	Investigate a rapid and sensitive PCR-based assay for the detection of adenoviral infections	Experimental Quantitative Study
11(³²32 Robert PY, Traccard I, Adenis JP, Denis F, Ranger-Rogez S. Multiplex detection of herpesviruses in tear fluid using the “Stair Primers” PCR method: a prospective study of 93 patients. J Med Virol. 2002;66(4):506-11.)	2002	France	Use a multiplex PCR to detect herpes viruses in tears from normal subjects and from patients with pathological conditions	Descriptive Quantitative Observational Study
12(⁵²52 Leong HN, Chan KP, Khan AS, Oon L, Se-Thoe SY, Bai XL, et al. Virus-specific RNA and antibody from convalescent-phase SARS patients discharged from hospital. Emerg Infect Dis. 2004;10(10):1745-50.)	2004	Singapore	Determine the prevalence of virus in bodily excretions, and time of seroconversion in discharged patients with SARS	Experimental Quantitative Study
13(²³23 Mendes RM, Nogueira ML, Marques JT, Pereira MV, Machado MA, Cunha AS, et al. A rapid polymerase chain reaction protocol to detect adenovirus in eye swabs. Arq Bras Oftalmol. 2004;67(3):423-7.)	2004	Brazil	Develop a rapid protocol to detect AdV in eye swab	Descriptive Quantitative Observational Study
14(²⁴24 Kaye SB, Llyod M, Williams H, Yuen C, Scott JA, O’Donnell N, et al. Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis. J Med Virol. 2005;77(2):227-31.)	2005	UK	Determine if AdV persists on the ocular surface following adenoviral conjunctivitis	Experimental Quantitative Study
15(²⁵25 Miura-Ochiai R, Shimada Y, Konno T, Yamazaki S, Aoki K, Ohno S, et al. Quantitative detection and rapid identification of human adenoviruses. J Clin Microbiol. 2007;45(3):958-67.)	2007	Japan	Establish a method of quantitative detection and rapid identification of AdV	Observational Quantitative Study
16(²⁶26 Woo PC, Lao SK, Choi GK, Fung HT, Shek KC, Miao J, et al. Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis. J Clin Virol. 2010;47(3):282-5. Comment in: J Clin Virol. 2010;47(3):387.)	2010	China	Test if high-density resequencing microarray can be applied to detection of viruses in conjunctival swabs for patients with conjunctivitis	Experimental Quantitative Study
17(³³33 Morishige N, Yamada N, Morita Y, Nakamura Y, Nishida T, Sonoda KH. Detection of ICP0 protein in tear fluid of individuals with active herpetic epithelial keratitis. Jpn J Ophthalmol. 2011;55(6):591-4.)	2011	Japan	Investigate if ICP0 of HSV-1 is detectable in the tear fluid of patients with HEK	Observational Quantitative Study
18(³⁴34 Lee SY, Kim MJ, Kim MK, Wee WR. Comparative analysis of polymerase chain reaction assay for herpes simplex virus 1 detection in tear. Korean J Ophthalmol. 2013;27(5):316-21.)	2013	Korea	Analyze the methodological efficacy of the PCR assay for HSV-1 detection in tears	Experimental Quantitative Study
19(²⁷27 Moore C, Gatica L, Jones T, Mathews P, Watkins J, Tyson L, et al. Collect, boil and amplify - a simple approach for the detection of three common viruses associated with epidemic keratoconjunctivitis, conjunctivitis and dendritic ulcers. J Virol Methods. 2013;189(1):238-41.)	2013	UK	Validate and introduce a simple boil extraction on dry swabs followed by amplification and realtime detection using “in-house” assays for HSV and AdV with RNaseP as an internal control	Experimental Quantitative Study
20(³⁵35 Barrado L, Suarez MJ, Pérez-Blázquez E, Otero JR, Folgueira MD. Could polymerase chain reaction test on conjunctival swabs be useful to diagnose herpetic keratitis? Enferm Infecc Microbiol Clin. 2014;32(1):28-30.)	2014	Spain	Evaluate the usefulness of PCR as a rapid diagnostic method compared with the viral culture, and to assess if conjunctival swabs samples were equivalent to corneal scrapings to diagnose of HK	Experimental Quantitative Study
21(²⁸28 Kam KY, Ong HS, Bunce C, Ogunbowale L, Verma S. Sensitivity and specificity of the AdenoPlus point-of-care system in detecting adenovirus in conjunctivitis patients at an ophthalmic emergency department: a diagnostic accuracy study. Br J Ophthalmol. 2015;99(9):1186-9.)	2015	UK	Estimate the diagnostic accuracy of the AdenoPlus point-of-care AdV test compared to PCR	Prospective Diagnostic Accuracy Study
22(³⁶36 Shoji J, Sakimoto T, Inada N, Kamei Y, Matsubara M, Takamura E, et al. A diagnostic method for herpes simplex keratitis by simultaneous measurement of viral DNA and virus-specific secretory IgA in tears: an evaluation. Jpn J Ophthalmol. 2016;60(4):294-301.)	2016	Japan	Investigate diagnostic efficacy of PCR and ELISA for HSV in tears	Nonrandomized Prospective Cross-Sectional Study
23(²⁹29 Gopalkrishna V, Ganorkar NN, Patil PR. Identification and molecular characterization of adenovirus types (HAdV-8, HAdV-37, HAdV-4, HAdV-3) in a epidemic of keratoconjunctivitis occurred in Pune, Maharashtra, Western India. J Med Virol. 2016;88(12):2100-5.)	2016	India	Identify and characterize the viral etiological agents associated with keratoconjunctivitis	Retrospective Observational Study
24(⁴⁹49 Green E, Hunt L, Ross JC, Nissen NM, Curran T, Badhan A, et al. Viraemia and Ebola virus secretion in survivors of Ebola virus disease in Sierra Leone: a cross-sectional cohort study. Lancet Infect Dis. 2016;16(9):1052-6.)	2016	UK	Report EBO virus RT-PCR data for body site and fluid samples from a large cohort of EBO virus survivors at clinic follow-up	Cross-Sectional Observational Study
25(⁵¹51 Tan JJ, Balne PK, Leo YS, Tong L, Ng LF, Agrawal R. Persistence of Zika virus in conjunctival fluid of convalescence patients. Sci Rep. 2017;7(1):11194.)	2017	Singapore	Check if Zika virus could be detected in human tears after the first week of infection	Descriptive Observational Study
26(⁵⁰50 Chalkia AK, Derdas S, Bontzos G, Sourvinos G, Detorakis ET. Non-invasive detection of HPV DNA in exfoliative samples from ophthalmic pterygium: a feasibility study. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):193-8.)	2018	Germany	Evaluate a non-invasive detection method for HPV in ophthalmic pterygia	Observational Prospective Case Control Study
27(³⁷37 Brunner M, Somerville T, Corless CE, Myneni J, Rajhbeharrysingh T, Tiew S, et al. Use of a corneal impression membrane and PCR for the detection of herpes simplex virus type-1. J Med Microbiol. 2019;68(9):1324-9.)	2019	UK	Investigate the use of a corneal impression membrane for the detection of HSV-1	Experimental Quantitative Study
28(³⁹39 Chen L, Liu M, Zhang Z, Qiao K, Huang T, Chen M, et al. Ocular manifestations of a hospitalized patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol. 2020;104(6):748-51. Comment in: Br J Ophthalmol. 2020;104(6):741.)	2020	China	Report the ocular characteristics and the presence of viral RNA of SARS-CoV- 2 in conjunctival swab specimens in a patient with confirmed Covid-19	Prospective Observational Case Study
29(³⁸38 Hu Y, Chen T, Liu M, Zang L, Wang F, Zhao S, et al. Positive detection of SARS-CoV-2 combined HSV1 and HHV6B virus nucleic acid in tear and conjunctival secretions of a non-conjunctivitis COVID-19 patient with obstruction of common lacrimal duct. Acta Ophthalmol. 2020;98(8):859-63.)	2020	China	Detect SARS-CoV-2 in eye sample of one Covid-19 patient with obstruction of common lacrimal ducts	Prospective Observational Study
30(⁴⁰40 Kumar K, Prakash AA, Gangasagara SB, Rathod S, Ravi K, Rangaiah S, et al. Presence of viral RNA of SARS-CoV-2 in conjunctival swab specimens of COVID-19 patients. Indian J Ophthalmol. 2020;68(6):1015-7. Comment in: Indian J Ophthalmol. 2020;68(6):1018-9.)	2020	India	Detect the presence of viral RNA of SARS-CoV-2 in conjunctival swab specimens of Covid-19 patients	Experimental Quantitative Study
31(⁴¹41 Zhang X, Chen X, Chen L, Deng C, Zou X, Liu W, et al. The evidence of SARS-CoV-2 infection on ocular surface. Ocul Surf. 2020;18(3):360-2. Comment in: Travel Med Infect Dis. 2021;39:101955. Comment on: JAMA. 2020;323(11):1061-9.)	2020	China	Describe the clinical spectrum of ocular symptoms and laboratory test in conjunctival swab samples	Cross-Sectional Study
32(⁴²42 Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol. 2020;55(4):e125-e129. Comment in: Middle East Afr J Ophthalmol. 2020;27(1):1-3.)	2020	Canada	Present a case of Covid-19 with an initial medical presentation of keratoconjunctivitis	Descriptive Observational Case Study
33(⁴⁴44 Willcox MD, Walsh K, Nichols JJ, Morgan PB, Jones LW. The ocular surface, coronaviruses and COVID-19. Clin Exp Optom. 2020; 103(4):418-24.)	2020	USA	Understand evidence about SARS-CoV-2 and ocular infection	Narrative Review
34(⁴⁵45 Xie HT, Jiang SY, Xu KK, Liu X, Xu B, Wang L, et al. SARS-CoV-2 in the ocular surface of COVID-19 patients. Eye Vis (Lond). 2020;7:23.)	2020	China	Detect SARS-CoV-2 RNA in conjunctival swabs	Retrospective Observational Study
35(⁴⁶46 Navel V, Chiambarretta F, Dutheil F. Haemorrhagic conjunctivitis with pseudomembranous related to SARS-CoV-2. Am J Ophthalmol Case Rep. 2020;19:100735.)	2020	France	Describe the multiplicity of ocular manifestations of Covid-19 patients	Descriptive Observational Study
36(⁴³43 Güemes-Villahoz N, Burgos-Blasco B, Vilela AA, Arriola-Villalobos P, Rico-Luna CM, Cuiña-Sardiña R, et al. Detecting SARS-CoV-2 RNA in conjunctival secretions: is it a valuable diagnostic method of COVID-19?. J Med Virol. 2021;93(1):383-8.)	2021	Spain	Evaluate the presence SARS-CoV-2 RNA in conjunctival swabs of Covid-19 patients	Cross-Sectional Study

Nº	Virus	Method of collection	Method of analysis	Nº of Patients recruited	Nº of Samples	Result (+ or −)
1(¹⁷17 Uchio E, Aoki K, SaithoW, Itoh N, Ohno S. Rapid diagnosis of adenoviral conjunctivitis on conjunctival swabs by 10-minute immunochromatography. Ophthalmology. 1997;104(8):1294-9.)	AdV	CS	IC and EIA	130	130	+
2(¹⁸18 Pring-Akerblom P, Adrian T, Köstler T. PCR-based detection and typing of human adenoviruses in clinical samples. Res Virol. 1997;148(3):225-31.)	AdV	CS	PCR	68	68	+
3(¹⁹19 Dalapathy S, Lily TK, Roy S, Madhavan HN. Development and use of nested polymerase chain reaction (PCR) for the detection of adenovirus from conjunctivitis specimens. J Clin Virol. 1998;11(1):77-84.)	AdV/EV70/CA24v	CS	Direct smear, PCR and virus isolation	20	20	+/−/−
4(⁴⁸48 Rodriguez LL, De Roo A, Guimard Y, Trappier SG, Sanchez A, Bressler D, et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999;179(Suppl 1):S170-6.)	EBO	CS	RT-PCR	7	38	+
5(⁴⁷47 Liu JH, Hsu WM, Wong WW, Wang JJ, Liu WT, Liu CY, et al. Using conjunctival swab with polymerase chain reaction to aid diagnosis of cytomegalovirus retinitis in AIDS patients. Ophthalmologica. 2000;214(2):126-30.)	CMV	CS	Immunofluorescence and PCR	13	60	+
6(²⁰20 Elnifro EM, Cooper RJ, Klapper PE, Yeo AC, Tullo AB. Multiplex polymerase chain reaction for diagnosis of viral and chlamydial keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2000;41(7):1818-22.)	AdV/HSV	CS	PCR	541	805	+/+
7(²¹21 Chang CH, Sheu MM, Lin KH, Chen CW. Hemorrhagic viral keratoconjunctivitis in Taiwan caused by Adenovirus types 19 and 37: applicability of polymerase chain reaction-restriction fragment length polymorphism in detecting adenovirus genotypes. Cornea. 2001;20(3):295-300.)	AdV/EV70/CA24v	CS	PCR, RT-PCR, culture isolation, and neutralization test	113	113	+/−/−
8(³⁰30 Zaal MJ, Völker-Dieben HJ, Wienesen M, D’Amaro J, Kijlstra A. Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus. Am J Ophthalmol. 2001;131(1):25-9.)	VZV, HSV	CS	PCR	21	246	+/−
9(³¹31 Willoughby CE, Baker K, Kaye SB, Carey P, O’Donnell N, Field A, et al. Epstein-barr virus (types 1 and 2) in the tear film in Sjogren’s Syndrome and HIV infection. J Med Virol. 2002;68(3):378-83.)	EBV-1/EBV-2/CMV/VZV/HSV	ST	PCR	54	54	+/+/−/−/−
10(²²22 Weitgasser U, Haller EM, El-Shabrawi Y. Evaluation of polymerase chain reaction for the detection of adenoviruses in conjunctival swab specimens using degenerate primers in comparison with direct immunofluorescence. Ophthalmologica. 2002;216(5):329-32.)	AdV	CS	PCR	15	15	+
11(³²32 Robert PY, Traccard I, Adenis JP, Denis F, Ranger-Rogez S. Multiplex detection of herpesviruses in tear fluid using the “Stair Primers” PCR method: a prospective study of 93 patients. J Med Virol. 2002;66(4):506-11.)	HSV-1/HSV-2/VZV/CMV/ EBV/HHV-6	ST	PCR	93	186	+/+/+/+/+/+
12(⁵²52 Leong HN, Chan KP, Khan AS, Oon L, Se-Thoe SY, Bai XL, et al. Virus-specific RNA and antibody from convalescent-phase SARS patients discharged from hospital. Emerg Infect Dis. 2004;10(10):1745-50.)	SARS-CoV	CS	PCR	64	126	−
13(²³23 Mendes RM, Nogueira ML, Marques JT, Pereira MV, Machado MA, Cunha AS, et al. A rapid polymerase chain reaction protocol to detect adenovirus in eye swabs. Arq Bras Oftalmol. 2004;67(3):423-7.)	AdV	CS	PCR	7	7	+
14(²⁴24 Kaye SB, Llyod M, Williams H, Yuen C, Scott JA, O’Donnell N, et al. Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis. J Med Virol. 2005;77(2):227-31.)	AdV/HSV	ST and CS	PCR	30	90	+/−
15(²⁵25 Miura-Ochiai R, Shimada Y, Konno T, Yamazaki S, Aoki K, Ohno S, et al. Quantitative detection and rapid identification of human adenoviruses. J Clin Microbiol. 2007;45(3):958-67.)	AdV	CS	PCR	133	133	+
16(²⁶26 Woo PC, Lao SK, Choi GK, Fung HT, Shek KC, Miao J, et al. Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis. J Clin Virol. 2010;47(3):282-5. Comment in: J Clin Virol. 2010;47(3):387.)	AdV	CS	High-density resequencing microarray and PCR	38	114	+
17(³³33 Morishige N, Yamada N, Morita Y, Nakamura Y, Nishida T, Sonoda KH. Detection of ICP0 protein in tear fluid of individuals with active herpetic epithelial keratitis. Jpn J Ophthalmol. 2011;55(6):591-4.)	HSV-1	ST	Immunoblot analysis	18	18	+
18(³⁴34 Lee SY, Kim MJ, Kim MK, Wee WR. Comparative analysis of polymerase chain reaction assay for herpes simplex virus 1 detection in tear. Korean J Ophthalmol. 2013;27(5):316-21.)	HSV	ST	PCR	115	115	+
19(²⁷27 Moore C, Gatica L, Jones T, Mathews P, Watkins J, Tyson L, et al. Collect, boil and amplify - a simple approach for the detection of three common viruses associated with epidemic keratoconjunctivitis, conjunctivitis and dendritic ulcers. J Virol Methods. 2013;189(1):238-41.)	HSV-1/HSV-2/AdV	CS	PCR	541	541	+/+/+
20(³⁵35 Barrado L, Suarez MJ, Pérez-Blázquez E, Otero JR, Folgueira MD. Could polymerase chain reaction test on conjunctival swabs be useful to diagnose herpetic keratitis? Enferm Infecc Microbiol Clin. 2014;32(1):28-30.)	HSV	CS	PCR	188	188	+
21(²⁸28 Kam KY, Ong HS, Bunce C, Ogunbowale L, Verma S. Sensitivity and specificity of the AdenoPlus point-of-care system in detecting adenovirus in conjunctivitis patients at an ophthalmic emergency department: a diagnostic accuracy study. Br J Ophthalmol. 2015;99(9):1186-9.)	AdV	CS	PCR and point-of-care test	109	109	+
22(³⁶36 Shoji J, Sakimoto T, Inada N, Kamei Y, Matsubara M, Takamura E, et al. A diagnostic method for herpes simplex keratitis by simultaneous measurement of viral DNA and virus-specific secretory IgA in tears: an evaluation. Jpn J Ophthalmol. 2016;60(4):294-301.)	HSV	ST	PCR and ELISA	82	82	+
23(²⁹29 Gopalkrishna V, Ganorkar NN, Patil PR. Identification and molecular characterization of adenovirus types (HAdV-8, HAdV-37, HAdV-4, HAdV-3) in a epidemic of keratoconjunctivitis occurred in Pune, Maharashtra, Western India. J Med Virol. 2016;88(12):2100-5.)	AdV/EV	CS	PCR and RT-PCR	23	23	+/−
24(⁴⁹49 Green E, Hunt L, Ross JC, Nissen NM, Curran T, Badhan A, et al. Viraemia and Ebola virus secretion in survivors of Ebola virus disease in Sierra Leone: a cross-sectional cohort study. Lancet Infect Dis. 2016;16(9):1052-6.)	EBO	CS	RT-PCR	112	92	−
25(⁵¹51 Tan JJ, Balne PK, Leo YS, Tong L, Ng LF, Agrawal R. Persistence of Zika virus in conjunctival fluid of convalescence patients. Sci Rep. 2017;7(1):11194.)	Zika virus	CS	RT-PCR	29	58	+
26(⁵⁰50 Chalkia AK, Derdas S, Bontzos G, Sourvinos G, Detorakis ET. Non-invasive detection of HPV DNA in exfoliative samples from ophthalmic pterygium: a feasibility study. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):193-8.)	HPV	CS	PCR	21	42	+
27(³⁷37 Brunner M, Somerville T, Corless CE, Myneni J, Rajhbeharrysingh T, Tiew S, et al. Use of a corneal impression membrane and PCR for the detection of herpes simplex virus type-1. J Med Microbiol. 2019;68(9):1324-9.)	HSV-1	CS	PCR	110	220	+
28(³⁹39 Chen L, Liu M, Zhang Z, Qiao K, Huang T, Chen M, et al. Ocular manifestations of a hospitalized patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol. 2020;104(6):748-51. Comment in: Br J Ophthalmol. 2020;104(6):741.)	SARS-CoV-2	CS	RT-PCR	1	8	+
29(³⁸38 Hu Y, Chen T, Liu M, Zang L, Wang F, Zhao S, et al. Positive detection of SARS-CoV-2 combined HSV1 and HHV6B virus nucleic acid in tear and conjunctival secretions of a non-conjunctivitis COVID-19 patient with obstruction of common lacrimal duct. Acta Ophthalmol. 2020;98(8):859-63.)	SARS-CoV-2/HSV-1 HHV-6B	CS	RT-PCR and PCR	1	20	+/+/+
30(⁴⁰40 Kumar K, Prakash AA, Gangasagara SB, Rathod S, Ravi K, Rangaiah S, et al. Presence of viral RNA of SARS-CoV-2 in conjunctival swab specimens of COVID-19 patients. Indian J Ophthalmol. 2020;68(6):1015-7. Comment in: Indian J Ophthalmol. 2020;68(6):1018-9.)	SARS-CoV-2	CS	RT-PCR	45	45	+
31(⁴²42 Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol. 2020;55(4):e125-e129. Comment in: Middle East Afr J Ophthalmol. 2020;27(1):1-3.)	SARS-CoV-2	CS	RT-PCR	2	4	+
32(⁴²42 Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol. 2020;55(4):e125-e129. Comment in: Middle East Afr J Ophthalmol. 2020;27(1):1-3.)	SARS-CoV-2	CS	RT-PCR	1	2	+
33(⁴⁴44 Willcox MD, Walsh K, Nichols JJ, Morgan PB, Jones LW. The ocular surface, coronaviruses and COVID-19. Clin Exp Optom. 2020; 103(4):418-24.)	SARS-CoV-2			Narrative Review
34(⁴⁵45 Xie HT, Jiang SY, Xu KK, Liu X, Xu B, Wang L, et al. SARS-CoV-2 in the ocular surface of COVID-19 patients. Eye Vis (Lond). 2020;7:23.)	SARS-CoV-2	CS	RT-PCR	33	66	+
36(⁴⁶46 Navel V, Chiambarretta F, Dutheil F. Haemorrhagic conjunctivitis with pseudomembranous related to SARS-CoV-2. Am J Ophthalmol Case Rep. 2020;19:100735.)	SARS-CoV-2	CS	RT-PCR	1	2	+
33(⁴³43 Güemes-Villahoz N, Burgos-Blasco B, Vilela AA, Arriola-Villalobos P, Rico-Luna CM, Cuiña-Sardiña R, et al. Detecting SARS-CoV-2 RNA in conjunctival secretions: is it a valuable diagnostic method of COVID-19?. J Med Virol. 2021;93(1):383-8.)	SARS-CoV-2	CS	RT-PCR	36	72	+

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E-mail: abo@cbo.com.br

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[1] Corresponding author: Luís Expedito Sabage. E-mail: luis.sabage@usp.br