Eyedrop vaccination: an immunization route with promises for effective responses to pandemics

References

• Nabel GJ. Designing tomorrow’s vaccines. N Engl J Med. 2013;368(6):551–560.
   PubMed Web of Science ®Google Scholar
• Zheng Z, Diaz-Arevalo D, Guan H, et al. Noninvasive vaccination against infectious diseases. Hum Vaccin Immunother. 2018;14(7):1717–1733.
   PubMed Web of Science ®Google Scholar
• Azegami T, Yuki Y, Kiyono H. Challenges in mucosal vaccines for the control of infectious diseases. Int Immunol. 2014;26(9):517–528.
   PubMed Web of Science ®Google Scholar
• Nir Y, Paz A, Sabo E, et al. Fear of injections in young adults: prevalence and associations. Am J Trop Med Hyg. 2003;68(3):341–344.
   PubMed Web of Science ®Google Scholar
• Drucker E, Alcabes PG, Marx PA. The injection century: massive unsterile injections and the emergence of human pathogens. Lancet. 2001;358(9297):1989–1992.
   PubMed Web of Science ®Google Scholar
• Kermode M. Unsafe injections in low-income country health settings: need for injection safety promotion to prevent the spread of blood-borne viruses. Health Promot Int. 2004;19(1):95–103.
   PubMed Web of Science ®Google Scholar
• Fu YH, He JS, Wang XB, et al. A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus. Biochem Biophys Res Commun. 2010;395(1):87–92.
   PubMed Web of Science ®Google Scholar
• Dietrich G. Experience with registered mucosal vaccines. Vaccine. 2003;21(7–8):678–683.
   PubMed Web of Science ®Google Scholar
• Kim SH, Lee KY, Jang YS. Mucosal Immune System and M cell-targeting strategies for oral Mucosal vaccination. Immune Netw. 2012;12(5):165–175.
   PubMedGoogle Scholar
• Trombetta CM, Gianchecchi E, Montomoli E. Influenza vaccines: evaluation of the safety profile. Hum Vaccin Immunother. 2018;14(3):657–670.
   PubMed Web of Science ®Google Scholar
• Mutsch M, Zhou W, Rhodes P, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s Palsy in Switzerland. N Engl J Med. 2004;350(9):896–903.
   PubMed Web of Science ®Google Scholar
• Kim L, Liebowitz D, and Lin K, et al. Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial. JCI Insight. 2018; 3(13):e121077.
   PubMed Web of Science ®Google Scholar
• Seo KY, Han SJ, Cha HR, et al. Eye mucosa: an efficient vaccine delivery route for inducing protective immunity. J Immunol. 2010;185(6):3610–3619.
   PubMed Web of Science ®Google Scholar
• Fukuyama Y, Tokuhara D, Kataoka K, et al. Novel vaccine development strategies for inducing mucosal immunity. Expert Rev Vaccines. 2012;11(3):367–379.
   PubMed Web of Science ®Google Scholar
• Brandtzaeg P. Induction of secretory immunity and memory at mucosal surfaces. Vaccine. 2007;25(30):5467–5484.
   PubMed Web of Science ®Google Scholar
• Lamm ME. Current concepts in mucosal immunity. IV. How epithelial transport of IgA antibodies relates to host defense. Am J Physiol. 1998;274(4):G614–617.
   PubMedGoogle Scholar
• Wang S, Liu H, Zhang X, et al. Intranasal and oral vaccination with protein-based antigens: advantages. challenges and formulation strategies. Protein Cell. 2015;6:480–503.
   PubMed Web of Science ®Google Scholar
• Lamm ME, Phillips-Quagliata JM. Origin and homing of intestinal IgA antibody-secreting cells. J Exp Med. 2002;195(2):F5–8.
   PubMed Web of Science ®Google Scholar
• Macpherson AJ, McCoy KD, Johansen F-E, et al. The immune geography of IgA induction and function. Mucosal Immunol. 2008;1(1):11–22.
   PubMed Web of Science ®Google Scholar
• Mestecky J, Hue C, Russell MW. Selective transport of IgA. Cellular and molecular aspects. Gastroenterol Clin North Am. 1991;20(3):441–471.
   PubMed Web of Science ®Google Scholar
• Shakya AK, Chowdhury MYE, Tao W, et al. Mucosal vaccine delivery: current state and a pediatric perspective. J Control Release. 2016;240:394–413.
   PubMed Web of Science ®Google Scholar
• Lee E-Y, Kim J-Y, Lee D-K, et al. Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice. Microbiol Immunol. 2016;60(12):846–853.
   PubMed Web of Science ®Google Scholar
• Sabin AB. Oral poliovirus vaccine: history of its development and use and current challenge to eliminate poliomyelitis from the world. J Infect Dis. 1985;151(3):420–436.
   PubMed Web of Science ®Google Scholar
• Lundin BS, Johansson C, Svennerholm A-M. Oral immunization with a salmonella enterica serovar typhi vaccine induces specific circulating Mucosa-Homing CD4 + and CD8 +T Cells in Humans. Infect Immun. 2002;70(10):5622–5627.
   PubMed Web of Science ®Google Scholar
• Mosley JF 2nd, Smith LL, Brantley P, et al. The First FDA-approved cholera vaccination in the United States. P T. 2017;42(10):638–640.
   PubMedGoogle Scholar
• Buyse H, Vinals C, Karkada N, et al. The human rotavirus vaccine Rotarix in infants: an integrated analysis of safety and reactogenicity. Hum Vaccin Immunother. 2014;10(1):19–24.
   PubMed Web of Science ®Google Scholar
• Justino MCA, Araujo EC, van Doorn L-J, et al. Oral live attenuated human rotavirus vaccine (RotarixTM) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children. Mem Inst Oswaldo Cruz. 2012;107(7):846–853.
   PubMed Web of Science ®Google Scholar
• Fader HC, Phillips CN. Frequent-user patients: reducing costs while making appropriate discharges. Healthc Financ Manage. 2012;66(3):98–100, 102, 104 passim.
   PubMedGoogle Scholar
• Wong G, Richardson JS, Cutts T, et al. Intranasal immunization with an adenovirus vaccine protects Guinea pigs from Ebola virus transmission by infected animals. Antiviral Res. 2015;116:17–19.
   PubMed Web of Science ®Google Scholar
• Arnaboldi PM, Sambir M, D’Arco C, et al. Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague. Vaccine. 2016;34(47):5768–5776.
   PubMed Web of Science ®Google Scholar
• Malley R, Lipsitch M, Stack A, et al. Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci. Infect Immun. 2001;69(8):4870–4873.
   PubMed Web of Science ®Google Scholar
• Fan S, Gao Y, Shinya K, et al. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathog. 2009;5(5):e1000409.
   PubMed Web of Science ®Google Scholar
• Mallory RM, Malkin E, Ambrose CS, et al. Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials. PLoS One. 2010;5(10):e13755.
   PubMed Web of Science ®Google Scholar
• Beltran G, Hurley DJ, and Gogal RM Jr., et al. Immune responses in the eye-associated lymphoid tissues of chickens after ocular inoculation with vaccine and virulent strains of the respiratory infectious laryngotracheitis Virus (ILTV). Viruses. 2019;11(17):635–655.
   Google Scholar
• Fulton RM, Schrader DL, Will M. Effect of route of vaccination on the prevention of infectious laryngotracheitis in commercial egg-laying chickens. Avian Dis. 2000;44(1):8–16.
   PubMed Web of Science ®Google Scholar
• Shewen PE, Carrasco-Medina L, McBey BA, et al. Challenges in mucosal vaccination of cattle. Vet Immunol Immunopathol. 2009;128(1–3):192–198.
   PubMed Web of Science ®Google Scholar
• Adams A. Progress, challenges and opportunities in fish vaccine development. Fish Shellfish Immunol. 2019;90:210–214.
   PubMed Web of Science ®Google Scholar
• van Ginkel FW, Jackson RJ, Yuki Y, et al. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol. 2000;165(9):4778–4782.
   PubMed Web of Science ®Google Scholar
• Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356(7):685–696.
   PubMed Web of Science ®Google Scholar
• Pan L, Su Z, Song J, et al. Growth data and tumour risk of 32 Chinese children and adolescents with 45,X/46,XY mosaicism. BMC Pediatrics. 2019;19(1):143.
   PubMedGoogle Scholar
• Nochi T, Takagi H, Yuki Y, et al. Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination. Proc Natl Acad Sci U S A. 2007;104(26):10986–10991.
   PubMed Web of Science ®Google Scholar
• Brenneman KE, Willingham C, Kilbourne JA, et al. A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. PLoS One. 2014;9(1):e87411.
   PubMed Web of Science ®Google Scholar
• Marasini N, Skwarczynski M, Toth I. Oral delivery of nanoparticle-based vaccines. Expert Rev Vaccines. 2014;13(11):1361–1376.
   PubMed Web of Science ®Google Scholar
• Pavot V, Rochereau N, Genin C, et al. New insights in mucosal vaccine development. Vaccine. 2012;30:142–154.
   PubMed Web of Science ®Google Scholar
• Uddin AN, Bejugam NK, Gayakwad SG, et al. Oral delivery of gastro-resistant microencapsulated typhoid vaccine. J Drug Target. 2009;17(7):553–560.
   PubMed Web of Science ®Google Scholar
• Ogue S, Takahashi Y, Onishi H, et al. Preparation of double liposomes and their efficiency as an oral vaccine carrier. Biol Pharm Bull. 2006;29(6):1223–1228.
   PubMed Web of Science ®Google Scholar
• Kayama H, Takeda K. Regulation of intestinal homeostasis by innate and adaptive immunity. Int Immunol. 2012;24(11):673–680.
   PubMed Web of Science ®Google Scholar
• Manicassamy S, Reizis B, Ravindran R, et al. Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010;329(5993):849–853.
   PubMed Web of Science ®Google Scholar
• Choy EH, Scott DL, Kingsley GH, et al. Control of rheumatoid arthritis by oral tolerance. Arthritis Rheum. 2001;44(9):1993–1997.
   PubMed Web of Science ®Google Scholar
• Mestecky J, Russell MW, Elson CO. Perspectives on mucosal vaccines: is mucosal tolerance a barrier? J Immunol. 2007;179(9):5633–5638.
   PubMed Web of Science ®Google Scholar
• Li M, Wang Y, Sun Y, et al. Mucosal vaccines: strategies and challenges. Immunol Lett. 2020;217:116–125.
   PubMed Web of Science ®Google Scholar
• Azegami T, Yuki Y, Nakahashi R, et al. Nanogel-based nasal vaccines for infectious and lifestyle-related diseases. Mol Immunol. 2018;98:19–24.
   PubMed Web of Science ®Google Scholar
• Yuki Y, Byun Y, Fujita M, et al. Production of a recombinant hybrid molecule of cholera toxin-B-subunit and proteolipid-protein-peptide for the treatment of experimental encephalomyelitis. Biotechnol Bioeng. 2001;74(1):62–69.
   PubMed Web of Science ®Google Scholar
• Takahashi I, Marinaro M, Kiyono H, et al. Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin. J Infect Dis. 1996;173(3):627–635.
   PubMed Web of Science ®Google Scholar
• Eriksson AM, Schon KM, Lycke NY. The cholera toxin-derived CTA1-DD vaccine adjuvant administered intranasally does not cause inflammation or accumulate in the nervous tissues. J Immunol. 2004;173(5):3310–3319.
   PubMed Web of Science ®Google Scholar
• Seo H, Lu T, Mani S, et al. Adjuvant effect of enterotoxigenic Escherichia coli (ETEC) double-mutant heat-labile toxin (dmLT) on systemic immunogenicity induced by the CFA/I/II/IV MEFA ETEC vaccine: dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6). Hum Vaccin Immunother. 2020;16(2):419–425.
   PubMed Web of Science ®Google Scholar
• van Ginkel FW, Gulley SL, Lammers A, et al. Conjunctiva-associated lymphoid tissue in avian mucosal immunity. Dev Comp Immunol. 2012;36(2):289–297.
   PubMed Web of Science ®Google Scholar
• Kageyama M, Nakatsuka K, Yamaguchi T, et al. Ocular defense mechanisms with special reference to the demonstration and functional morphology of the conjunctiva-associated lymphoid tissue in Japanese monkeys. Arch Histol Cytol. 2006;69(5):311–322.
   PubMedGoogle Scholar
• Nagatake T, Fukuyama S, Kim DY, et al. Id2-, RORgammat-, and LTbetaR-independent initiation of lymphoid organogenesis in ocular immunity. J Exp Med. 2009;206(11):2351–2364.
   PubMed Web of Science ®Google Scholar
• Nagatake T, Fukuyama S, Sato S, et al. Central role of core binding factor beta2 in mucosa-associated lymphoid tissue organogenesis in mouse. PLoS One. 2015;10(5):e0127460.
   PubMed Web of Science ®Google Scholar
• Kim E-D, Han SJ, Byun Y-H, et al. Inactivated eyedrop influenza vaccine adjuvanted with Poly(I:C) Is safe and effective for inducing protective systemic and mucosal immunity. PLoS One. 2015;10(9):e0137608.
   PubMed Web of Science ®Google Scholar
• Choi KS, Kim SH, Kim ED, et al. Protection from hemolytic uremic syndrome by eyedrop vaccination with modified enterohemorrhagic E. coli outer membrane vesicles. PLoS One. 2014;9(7):e100229.
   PubMed Web of Science ®Google Scholar
• Yoon S, Kim E-D, Song M-S, et al. Eyedrop vaccination induced systemic and mucosal immunity against influenza virus in Ferrets. PLoS One. 2016;11(6):e0157634.
   PubMed Web of Science ®Google Scholar
• Jung BK, Kim ED, Song H, et al. Immunogenicity of exosomes from dendritic cells stimulated with toxoplasma gondii lysates in ocularly immunized mice. Korean J Parasitol. 2020;58(2):185–189.
   PubMed Web of Science ®Google Scholar
• Takamura K, Fukuyama S, Nagatake T, et al. Regulatory role of lymphoid chemokine CCL19 and CCL21 in the control of allergic rhinitis. J Immunol. 2007;179(9):5897–5906.
   PubMed Web of Science ®Google Scholar
• Song JH, Kim JI, Kwon HJ, et al. CCR7-CCL19/CCL21-regulated dendritic cells are responsible for effectiveness of sublingual vaccination. J Immunol. 2009;182(11):6851–6860.
   PubMed Web of Science ®Google Scholar
• Yamada M, Bingham J, Payne J, et al. Multiple routes of invasion of wild-type Clade 1 highly pathogenic avian influenza H5N1 virus into the central nervous system (CNS) after intranasal exposure in ferrets. Acta Neuropathol. 2012;124(4):505–516.
   PubMed Web of Science ®Google Scholar
• Tsubota K. Tear dynamics and dry eye. Prog Retin Eye Res. 1998;17(4):565–596.
   PubMed Web of Science ®Google Scholar
• Zhu H, Chauhan A. A mathematical model for ocular tear and solute balance. Curr Eye Res. 2005;30(10):841–854.
   PubMed Web of Science ®Google Scholar
• Ichinohe T, Watanabe I, Ito S, et al. Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection. J Virol. 2005;79(5):2910–2919.
   PubMed Web of Science ®Google Scholar
• Cholkar K, Patel SP, Vadlapudi AD, et al. Novel strategies for anterior segment ocular drug delivery. J Ocul Pharmacol Ther. 2013;29(2):106–123.
   PubMed Web of Science ®Google Scholar
• Gote V, Sikder S, Sicotte J, et al. Ocular drug delivery: Present innovations and future challenges. J Pharmacol Exp Ther. 2019;370(3):602–624.
   PubMed Web of Science ®Google Scholar
• Da Costa Martins R, Gamazo C, Sanchez-Martinez M, et al. Conjunctival vaccination against Brucella ovis in mice with mannosylated nanoparticles. J Control Release. 2012;162(3):553–560.
   PubMed Web of Science ®Google Scholar
• Adetunji Adeniran G, Ohore OG, Jarikre TA, et al. Humoral and mucosal immune responses in challenged chickens vaccinated with Infectious bursal disease vaccine using gums from Cedrela odorata and Khaya senegalensis as delivery agents. J Immunoassay Immunochem. 2019;40(6):630–641.
   PubMedGoogle Scholar
• Jayawardane GW, Spradbrow PB. Mucosal immunity in chickens vaccinated with the V4 strain of Newcastle disease virus. Vet Microbiol. 1995;46(1–3):69–77.
   PubMed Web of Science ®Google Scholar
• Jimenez de Bagues MP, Marin CM, Barberan M, et al. Responses of ewes to B. melitensis Rev1 vaccine administered by subcutaneous or conjunctival routes at different stages of pregnancy. Annales de recherches veterinaires. Annals of veterinary research. 1989;20(2):205–213.
   PubMedGoogle Scholar
• Blasco JM. A review of the use of B. melitensis Rev 1 vaccine in adult sheep and goats. Prev Vet Med. 1997;31(3–4):275–283.
   PubMed Web of Science ®Google Scholar
• McCluskie MJ, Brazolot Millan CLB, Gramzinski RA, et al. Ocular Drug delivery: present Innovations and Future Challenges. Mol Med. 1999;5(5):287–300.
   PubMed Web of Science ®Google Scholar
• Jackson CA, Hickey TL. Use of ferrets in studies of the visual system. Lab Anim Sci. 1985;35(3):211–215.
   PubMedGoogle Scholar
• Schulman JL. The use of an animal model to study transmission of influenza virus infection. Am J Public Health Nations Health. 1968;58(11):2092–2096.
   PubMed Web of Science ®Google Scholar
• Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med. 2002;347(22):1770–1782.
   PubMed Web of Science ®Google Scholar
• Milligan R, Paul M, Richardson M, et al. Vaccines for preventing typhoid fever. Cochrane Database Syst Rev. 2018;5:CD001261.
   PubMedGoogle Scholar
• Anwar E, Goldberg E, Fraser A, et al. Vaccines for preventing typhoid fever. Cochrane Database Syst Rev. 2014;1:CD001261. DOI:https://doi.org/10.1002/14651858.CD001261.pub3
   Google Scholar
• Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073–1086.
   PubMed Web of Science ®Google Scholar
• Kuehn MJ, Kesty NC. Bacterial outer membrane vesicles and the host–pathogen interaction. Genes Dev. 2005;19(22):2645–2655.
   PubMed Web of Science ®Google Scholar
• Kim SH, Kim KS, Lee SR, et al. Structural modifications of outer membrane vesicles to refine them as vaccine delivery vehicles. Biochim Biophys Acta. 2009;1788(10):2150–2159.
   PubMed Web of Science ®Google Scholar
• Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000;30(12–13):1217–1258.
   PubMed Web of Science ®Google Scholar
• Aline F, Bout D, Amigorena S, et al. Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect Immun. 2004;72(7):4127–4137.
   PubMed Web of Science ®Google Scholar
• Dubey JP. Toxoplasmosis in sheep–the last 20 years. Vet Parasitol. 2009;163(1–2):1–14.
   PubMed Web of Science ®Google Scholar
• Vagnozzi A, Zavala G, Riblet SM, et al. Protection induced by commercially available live-attenuated and recombinant viral vector vaccines against infectious laryngotracheitis virus in broiler chickens. Avian Pathol. 2012;41(1):21–31.
   PubMed Web of Science ®Google Scholar
• Tonetti MS. Periodontitis and risk for atherosclerosis: an update on intervention trials. J Clin Periodontol. 2009;36(Suppl 10):15–19.
   PubMed Web of Science ®Google Scholar
• Miyauchi S, Maekawa T, Aoki Y, et al. Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR-ApoEshl mice. J Periodontal Res. 2012;47(3):402–408.
   PubMed Web of Science ®Google Scholar
• Lockhart PB, Bolger AF, Papapanou PN, et al. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American heart association. Circulation. 2012;125(20):2520–2544.
   PubMed Web of Science ®Google Scholar
• Hajishengallis G. Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci. 2011;53(3):233–240.
   PubMedGoogle Scholar
• Olsen I, Yilmaz O. Modulation of inflammasome activity by Porphyromonas gingivalis in periodontitis and associated systemic diseases. J Oral Microbiol. 2016;8(1):30385.
   PubMed Web of Science ®Google Scholar
• Pussinen PJ, Alfthan G, Jousilahti P, et al. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007;193(1):222–228.
   PubMed Web of Science ®Google Scholar
• Maekawa T, Takahashi N, Tabeta K, et al. Chronic oral infection with Porphyromonas gingivalis accelerates atheroma formation by shifting the lipid profile. PLoS One. 2011;6(5):e20240.
   PubMed Web of Science ®Google Scholar
• Kesavalu L, Holt SC, Ebersole JL. Porphyromonas gingivalis virulence in a murine lesion model: effects of immune alterations. Microb Pathog. 1997;23(6):317–326.
   PubMed Web of Science ®Google Scholar
• Cheng X, Yu X, Ding YJ, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127(1):89–97.
   PubMed Web of Science ®Google Scholar
• Yang J, Wu J, Liu Y, et al. Porphyromonas gingivalis infection reduces regulatory T cells in infected atherosclerosis patients. PLoS One. 2014;9(1):e86599.
   PubMed Web of Science ®Google Scholar
• Ha H-S, Kim TY, Han SJ, et al. Anti-atherosclerotic vaccination against Porphyromonas gingivalis as a potential comparator of statin in mice. PeerJ. 2021;9:e11293.
   PubMed Web of Science ®Google Scholar
• Olsen I, Taubman MA, Singhrao SK. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease. J Oral Microbiol. 2016;8(1):33029.
   PubMed Web of Science ®Google Scholar
• Plotkin SA. Vaccines: the fourth century. Clin Vaccine Immunol. 2009;16(12):1709–1719.
   PubMedGoogle Scholar
• Vela Ramirez JE, Sharpe LA, Peppas NA. Current state and challenges in developing oral vaccines. Adv Drug Deliv Rev. 2017;114:116–131.
   PubMed Web of Science ®Google Scholar
• Billah MM, Zaman K, Estivariz CF, et al. Cold-chain adaptability during introduction of inactivated polio vaccine in Bangladesh, 2015. J Infect Dis. 2017;216(suppl_1):S114–S121.
   PubMedGoogle Scholar
• Mishima S, Gasset A, Klyce SD Jr., et al. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5(3):264–276.
   PubMedGoogle Scholar
• Davies NM. Biopharmaceutical considerations in topical ocular drug delivery. Clin Exp Pharmacol Physiol. 2000;27(7):558–562.
   PubMed Web of Science ®Google Scholar