<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">glaucoma</journal-id><journal-title-group><journal-title xml:lang="ru">Национальный журнал Глаукома</journal-title><trans-title-group xml:lang="en"><trans-title>National Journal glaucoma</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2078-4104</issn><issn pub-type="epub">2311-6862</issn><publisher><publisher-name>Federal State Budgetary Institution of Science “Krasnov Research Institute of Eye Diseases”</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.25700/NJG.2020.01.10</article-id><article-id custom-type="elpub" pub-id-type="custom">glaucoma-277</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="ru"><subject>ОБЗОР ЛИТЕРАТУРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW OF LITERATURE</subject></subj-group></article-categories><title-group><article-title>Бесконсервантная терапия глаукомы</article-title><trans-title-group xml:lang="en"><trans-title>Non-preservative glaucoma treatment</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Еричев</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Erichev</surname><given-names>V. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, заведующий отделом глаукомы</p></bio><bio xml:lang="en"><p>Med.Sc.D., Professor, Head of Glaucoma Department</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Волжанин</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Volzhanin</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Волжанин Андрей Вячеславович, аспирант</p></bio><bio xml:lang="en"><p>postgraduate student</p></bio><email xlink:type="simple">avolzhanin@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБНУ «Научно-исследовательский институт глазных болезней»<country>Россия</country></aff><aff xml:lang="en">Scientific Research Institute of Eye Diseases<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>20</day><month>04</month><year>2020</year></pub-date><volume>19</volume><issue>1</issue><fpage>69</fpage><lpage>78</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Еричев В.П., Волжанин А.В., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Еричев В.П., Волжанин А.В.</copyright-holder><copyright-holder xml:lang="en">Erichev V.P., Volzhanin A.V.</copyright-holder><license 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.glaucomajournal.ru/jour/article/view/277">https://www.glaucomajournal.ru/jour/article/view/277</self-uri><abstract><p>Подавляющее большинство препаратов, применяемых для снижения внутриглазного давления (ВГД) при глаукоме, содержат консервант. Пожизненное применение капель создает условия для накопления и реализации его побочного действия. Одним из наиболее распространенных консервантов является бензалкония хлорид (БХ) — четвертичное аммониевое соединение, обладающее детергентными свойствами. Постоянная экспозиция БХ на передней поверхности глаза может приводить к функциональным и органическим изменениям тканей глаза, влияя как на качество жизни, так и на течение глаукомы и развитие сопутствующей патологии.</p><p>Учитывая невозможность создания «идеального консерванта» — активного по отношению к патогенным микроорганизмам, но интактного по отношению к тканям глаза, — а также малую распространенность и изученность других, более безвредных консервантов, актуальным является вопрос бесконсервантной гипотензивной терапии глаукомы. Полное исключение консервантов из принимаемых капель потенциально может намного улучшить приверженность лечению и сохранить зрение и качество жизни.</p><p>На сегодняшний день имеется большое количество исследований, подтверждающих лучшую переносимость бесконсервантных препаратов по сравнению с содержащими консервант. Вместе с тем бесконсервантная терапия также имеет ряд недостатков, наиболее важный среди которых — отсутствие долгосрочных исследований переносимости.</p></abstract><trans-abstract xml:lang="en"><p>The majority of hypotensive antiglaucoma drugs, designed for intraocular pressure (IOP) decrease, contain a preservative. A lifelong use of eyedrops provides the conditions for its accumulation with realization of its side effects. One of the most common preservatives is benzalkonium chloride — a quaternary ammonium compound with detergent properties. Its constant exposition on the eye surface can lead to functional and organic alterations of eye tissues, affecting both the quality of life and glaucoma progression with concomitant disease development.</p><p>As it is impossible to create an “ideal preservative”, active against the pathogen microorganisms, but that leaves the eye tissues intact — and taking into account a low prevalence and amount of studies of other, more harmless preservatives, an issue of non-preservative hypotensive glaucoma treatment is relevant. Complete absence of a preservative in the eyedrops can dramatically improve the treatment adherence and quality of life.</p><p>By now, there is a lot of data confirming better tolerance of non-preservative drugs, compared to the ones that contain preservative. Meanwhile, preservative-free therapy has also its drawbacks, with the most important of the bigger drug cost and absence of long-term tolerance studies.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>глаукома</kwd><kwd>консервант</kwd><kwd>бензалкония хлорид</kwd><kwd>переносимость</kwd></kwd-group><kwd-group xml:lang="en"><kwd>glaucoma</kwd><kwd>preservative</kwd><kwd>benzalkonium chloride</kwd><kwd>tolerance</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">Zimmerman T.J., Hahn S.R., Gelb L., Tan H., Kim E.E. The impact of ocular adverse effects in patients treated with topical prostaglandin analogs: changes in prescription patterns and patient persistence. J Ocul Pharmacol Ther. 2009; 25(2):145-152. doi:10.1089/jop.2008.0072</mixed-citation><mixed-citation xml:lang="en">Zimmerman T.J., Hahn S.R., Gelb L., Tan H., Kim E.E. The impact of ocular adverse effects in patients treated with topical prostaglandin analogs: changes in prescription patterns and patient persistence. J Ocul Pharmacol Ther. 2009; 25(2):145-152. doi:10.1089/jop.2008.0072</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">McCarty C.A., Bansal A.K., Livingston P.M., Stanislavsky Y.L., Taylor H.R. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology. 1998; 105(6):1114-1119. doi:10.1016/ S0161-6420(98)96016-X</mixed-citation><mixed-citation xml:lang="en">McCarty C.A., Bansal A.K., Livingston P.M., Stanislavsky Y.L., Taylor H.R. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology. 1998; 105(6):1114-1119. doi:10.1016/ S0161-6420(98)96016-X</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Schein O.D., Munoz B., Tielsch J.M., Bandeen-Roche K., West S. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997; 124(6):723-728. doi:10.1016/s0002-9394(14)71688-5</mixed-citation><mixed-citation xml:lang="en">Schein O.D., Munoz B., Tielsch J.M., Bandeen-Roche K., West S. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997; 124(6):723-728. doi:10.1016/s0002-9394(14)71688-5</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Palko J.R., Qi O., Sheybani A. Corneal alterations associated with pseudoexfoliation syndrome and glaucoma: a literature review. J Ophthalmic Vis Res. 2017; 12(3):312-324. doi:10.4103/jovr.jovr_28_17</mixed-citation><mixed-citation xml:lang="en">Palko J.R., Qi O., Sheybani A. Corneal alterations associated with pseudoexfoliation syndrome and glaucoma: a literature review. J Ophthalmic Vis Res. 2017; 12(3):312-324. doi:10.4103/jovr.jovr_28_17</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Erdogan H., Arici D.S., Toker M.I., Arici M.K., Fariz G., Topalkara A. Conjunctival impression cytology in pseudoexfoliative glaucoma and pseudoexfoliation syndrome. Clin Exp Ophthalmol. 2006; 34(2):108- 113. doi:10.1111/j.1442-9071.2006.01168.x</mixed-citation><mixed-citation xml:lang="en">Erdogan H., Arici D.S., Toker M.I., Arici M.K., Fariz G., Topalkara A. Conjunctival impression cytology in pseudoexfoliative glaucoma and pseudoexfoliation syndrome. Clin Exp Ophthalmol. 2006; 34(2):108- 113. doi:10.1111/j.1442-9071.2006.01168.x</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Kozobolis V.P., Christodoulakis E.V., Naoumidi I.I., Siganos C.S., Detorakis E.T., Pallikaris L.G. Study of conjunctival goblet cell morphology and tear film stability in pseudoexfoliation syndrome. Graefes Arch Clin Exp Ophthalmol. 2004; 242(6):478-483. doi:10.1007/ s00417-004-0865-3</mixed-citation><mixed-citation xml:lang="en">Kozobolis V.P., Christodoulakis E.V., Naoumidi I.I., Siganos C.S., Detorakis E.T., Pallikaris L.G. Study of conjunctival goblet cell morphology and tear film stability in pseudoexfoliation syndrome. Graefes Arch Clin Exp Ophthalmol. 2004; 242(6):478-483. doi:10.1007/ s00417-004-0865-3</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Kuppens E.V., de Jong C.A., Stolwijk T.R., de Keizer R.J., van Best J.A. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol. 1995; 79(4):339-342. doi:10.1136/ bjo.79.4.339</mixed-citation><mixed-citation xml:lang="en">Kuppens E.V., de Jong C.A., Stolwijk T.R., de Keizer R.J., van Best J.A. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol. 1995; 79(4):339-342. doi:10.1136/ bjo.79.4.339</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Asiedu K., Abu S.L. The impact of topical intraocular pressure lowering medications on the ocular surface of glaucoma patients: A review. J Curr Ophthalmol. 2019; 31(1):8-15. doi:10.1016/j.joco.2018.07.003</mixed-citation><mixed-citation xml:lang="en">Asiedu K., Abu S.L. The impact of topical intraocular pressure lowering medications on the ocular surface of glaucoma patients: A review. J Curr Ophthalmol. 2019; 31(1):8-15. doi:10.1016/j.joco.2018.07.003</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Erb C., Gast U., Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol. 2008; 246(11):1593-1601. doi:10.1007/ s00417-008-0881-9</mixed-citation><mixed-citation xml:lang="en">Erb C., Gast U., Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol. 2008; 246(11):1593-1601. doi:10.1007/ s00417-008-0881-9</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Ruangvaravate N., Prabhasawat P., Vachirasakchai V., Tantimala R. High prevalence of ocular surface disease among glaucoma patients in Thailand. J Ocul Pharmacol Ther. 2018; 34(5):387-394. doi:10.1089/ jop.2017.0104</mixed-citation><mixed-citation xml:lang="en">Ruangvaravate N., Prabhasawat P., Vachirasakchai V., Tantimala R. High prevalence of ocular surface disease among glaucoma patients in Thailand. J Ocul Pharmacol Ther. 2018; 34(5):387-394. doi:10.1089/ jop.2017.0104</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Wilson F.M., 2nd. Adverse external ocular effects of topical ophthalmic therapy: an epidemiologic, laboratory, and clinical study. Trans Am Ophthalmol Soc. 1983; 81:854-965.</mixed-citation><mixed-citation xml:lang="en">Wilson F.M., 2nd. Adverse external ocular effects of topical ophthalmic therapy: an epidemiologic, laboratory, and clinical study. Trans Am Ophthalmol Soc. 1983; 81:854-965.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Reardon G., Kotak S., Schwartz G.F. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: a systematic review. Patient Prefer Adherence. 2011; 5:441-463. doi:10.2147/PPA.S23780</mixed-citation><mixed-citation xml:lang="en">Reardon G., Kotak S., Schwartz G.F. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: a systematic review. Patient Prefer Adherence. 2011; 5:441-463. doi:10.2147/PPA.S23780</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Schwartz G.F., Quigley H.A. Adherence and persistence with glaucoma therapy. Surv Ophthalmol. 2008; 53: Suppl1:S57-68. doi:10.1016/j. survophthal.2008.08.002</mixed-citation><mixed-citation xml:lang="en">Schwartz G.F., Quigley H.A. Adherence and persistence with glaucoma therapy. Surv Ophthalmol. 2008; 53: Suppl1:S57-68. doi:10.1016/j. survophthal.2008.08.002</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Schwartz G.F. Compliance and persistency in glaucoma follow-up treatment. Curr Opin Ophthalmol. 2005; 16(2):114-121. doi:10.1097/ 01.icu.0000156139.05323.26</mixed-citation><mixed-citation xml:lang="en">Schwartz G.F. Compliance and persistency in glaucoma follow-up treatment. Curr Opin Ophthalmol. 2005; 16(2):114-121. doi:10.1097/ 01.icu.0000156139.05323.26.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Olthoff C.M., Schouten J.S., van de Borne B.W., Webers C.A. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005; 112(6):953-961. doi:10.1016/j.ophtha.2004.12.035</mixed-citation><mixed-citation xml:lang="en">Olthoff C.M., Schouten J.S., van de Borne B.W., Webers C.A. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005; 112(6):953-961. doi:10.1016/j.ophtha.2004.12.035</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Quigley H.A., Friedman D.S., Hahn S.R. Evaluation of practice patterns for the care of open-angle glaucoma compared with claims data: the Glaucoma Adherence and Persistency Study. Ophthalmology. 2007; 114(9):1599-1606. doi:10.1016/j.ophtha.2007.03.042</mixed-citation><mixed-citation xml:lang="en">Quigley H.A., Friedman D.S., Hahn S.R. Evaluation of practice patterns for the care of open-angle glaucoma compared with claims data: the Glaucoma Adherence and Persistency Study. Ophthalmology. 2007; 114(9):1599-1606. doi:10.1016/j.ophtha.2007.03.042</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Алексеев В.Н., Малеванная О.А., Надер Самил Ел Хаж. Причины низкой приверженности к лечению больных первичной открытоугольной глаукомы. Офтальмологические ведомости. 2010; 3(4):37-39.</mixed-citation><mixed-citation xml:lang="en">Alekseev V.N., Malevannaya O.A., Nader Samih El Haj. The reasons of low adherence in primary open-angle glaucoma patients treatment. Oftalmologicheskie vedomosti. 2010; 3(4):37-39.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 3: Treatment principles and options Supported by the EGS Foundation: Part 1: Foreword; Introduction; Glossary; Chapter 3 Treatment principles and options. Br J Ophthalmol. 2017; 101(6):130-195. doi:10.1136/bjophthalmol-2016-EGSguideline.003</mixed-citation><mixed-citation xml:lang="en">European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 3: Treatment principles and options Supported by the EGS Foundation: Part 1: Foreword; Introduction; Glossary; Chapter 3 Treatment principles and options. Br J Ophthalmol. 2017; 101(6):130-195. doi:10.1136/bjophthalmol-2016-EGSguideline.003</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Schiffman R.M., Christianson M.D., Jacobsen G., Hirsch J.D., Reis B.L. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118(5):615-621. doi:10.1001/archopht.118.5.615</mixed-citation><mixed-citation xml:lang="en">Schiffman R.M., Christianson M.D., Jacobsen G., Hirsch J.D., Reis B.L. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118(5):615-621. doi:10.1001/archopht.118.5.615</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Skalicky S.E., Goldberg I., McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012; 153(1):1-9e2. doi:10.1016/j.ajo.2011.05.033</mixed-citation><mixed-citation xml:lang="en">Skalicky S.E., Goldberg I., McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012; 153(1):1-9e2. doi:10.1016/j.ajo.2011.05.033</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Rossi G.C., Pasinetti G.M., Scudeller L., Bianchi P.E. Ocular surface disease and glaucoma: how to evaluate impact on quality of life. J Ocul Pharmacol Ther. 2013; 29(4):390-394. doi:10.1089/jop.2011.0159</mixed-citation><mixed-citation xml:lang="en">Rossi G.C., Pasinetti G.M., Scudeller L., Bianchi P.E. Ocular surface disease and glaucoma: how to evaluate impact on quality of life. J Ocul Pharmacol Ther. 2013; 29(4):390-394. doi:10.1089/jop.2011.0159</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Miljanovic B., Dana R., Sullivan D.A., Schaumberg D.A. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007; 143(3):409-415. doi:10.1016/j.ajo.2006.11.060</mixed-citation><mixed-citation xml:lang="en">Miljanovic B., Dana R., Sullivan D.A., Schaumberg D.A. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007; 143(3):409-415. doi:10.1016/j.ajo.2006.11.060</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Friedman N.J. Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol. 2010; 21(4):310-316. doi:10.1097/ ICU.0b013e32833a8c15</mixed-citation><mixed-citation xml:lang="en">Friedman N.J. Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol. 2010; 21(4):310-316. doi:10.1097/ ICU.0b013e32833a8c15</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Rahman M.Q., Tejwani D., Wilson J.A., Butcher I., Ramaesh K. Microbial contamination of preservative free eye drops in multiple application containers. Br J Ophthalmol. 2006; 90(2):139-141. doi:10.1136/ bjo.2005.078386</mixed-citation><mixed-citation xml:lang="en">Rahman M.Q., Tejwani D., Wilson J.A., Butcher I., Ramaesh K. Microbial contamination of preservative free eye drops in multiple application containers. Br J Ophthalmol. 2006; 90(2):139-141. doi:10.1136/ bjo.2005.078386</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Kim M.S., Choi C.Y., Kim J.M., Chang H.R., Woo H.Y. Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers. Br J Ophthalmol. 2008; 92(11):1518-1521. doi:10.1136/bjo.2008.144469</mixed-citation><mixed-citation xml:lang="en">Kim M.S., Choi C.Y., Kim J.M., Chang H.R., Woo H.Y. Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers. Br J Ophthalmol. 2008; 92(11):1518-1521. doi:10.1136/bjo.2008.144469</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Freeman P.D., Kahook M.Y. Preservatives in topical ophthalmic medications: historical and clinical perspectives. Expert Review Ophthalmol. 2009; 4:59–64.</mixed-citation><mixed-citation xml:lang="en">Freeman P.D., Kahook M.Y. Preservatives in topical ophthalmic medications: historical and clinical perspectives. Expert Review Ophthalmol. 2009; 4:59–64.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Basketter D.A., Marriott M., Gilmour N.J., White I.R. Strong irritants masquerading as skin allergens: the case of benzalkonium chloride. Contact Dermatitis. 2004; 50(4):213-217. doi:10.1111/j.0105- 1873.2004.00331.x</mixed-citation><mixed-citation xml:lang="en">Basketter D.A., Marriott M., Gilmour N.J., White I.R. Strong irritants masquerading as skin allergens: the case of benzalkonium chloride. Contact Dermatitis. 2004; 50(4):213-217. doi:10.1111/j.0105- 1873.2004.00331.x</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Prabhakaran S., Abu-Hasan M., Hendeles L. Benzalkonium chloride: a bronchoconstricting preservative in continuous albuterol nebulizer solutions. Pharmacotherapy. 2017; 37(5):607-610. doi:10.1002/ phar.1929</mixed-citation><mixed-citation xml:lang="en">Prabhakaran S., Abu-Hasan M., Hendeles L. Benzalkonium chloride: a bronchoconstricting preservative in continuous albuterol nebulizer solutions. Pharmacotherapy. 2017; 37(5):607-610. doi:10.1002/ phar.1929</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Ferk F., Misik M., Hoelzl C., Uhl M., Fuerhacker M., Grillitsch B., Parzefall W., Nersesyan A., Micieta K., Grummt T., Ehrlich V., Knasmuller S. Benzalkonium chloride (BAC) and dimethyldioctadecyl-ammonium bromide (DDAB), two common quaternary ammonium compounds, cause genotoxic effects in mammalian and plant cells at environmentally relevant concentrations. Mutagenesis. 2007; 22(6):363-370. doi:10.1093/mutage/gem027</mixed-citation><mixed-citation xml:lang="en">Ferk F., Misik M., Hoelzl C., Uhl M., Fuerhacker M., Grillitsch B., Parzefall W., Nersesyan A., Micieta K., Grummt T., Ehrlich V., Knasmuller S. Benzalkonium chloride (BAC) and dimethyldioctadecyl-ammonium bromide (DDAB), two common quaternary ammonium compounds, cause genotoxic effects in mammalian and plant cells at environmentally relevant concentrations. Mutagenesis. 2007; 22(6):363-370. doi:10.1093/mutage/gem027</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Reregistration eligibility decision for alkyl dimethyl benzyl ammonium chloride (ADBAC). EPA739-R-06-009. Washington, DC.: U.S. Environmental Protection Agency (EPA), 2006.</mixed-citation><mixed-citation xml:lang="en">Reregistration eligibility decision for alkyl dimethyl benzyl ammonium chloride (ADBAC). EPA739-R-06-009. Washington, DC.: U.S. Environmental Protection Agency (EPA), 2006.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Baudouin C., de Lunardo C. Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers. Br J Ophthalmol. 1998; 82(1):39-42. doi:10.1136/bjo.82.1.39</mixed-citation><mixed-citation xml:lang="en">Baudouin C., de Lunardo C. Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers. Br J Ophthalmol. 1998; 82(1):39-42. doi:10.1136/bjo.82.1.39</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Еричев В.П., Амбарцумян К.Г., Федоров А.А. Клинико-морфологические доказательства влияния консервантов на поверхность глаза при первичной открытоугольной глаукоме. Национальный журнал глаукома. 2014; 13(4):13-22.</mixed-citation><mixed-citation xml:lang="en">Erichev V.P., Ambartsumyan K.G., Fedorov A.A. Clinical and morphological evidence of the effect of preservatives on the eye surface in primary open-angle glaucoma. Natsional’nyi zhurnal glaukoma. 2014; 13(4):13-22. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">De Saint Jean M., Brignole F., Bringuier A.F., Bauchet A., Feldmann G., Baudouin C. Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci. 1999; 40(3):619-630.</mixed-citation><mixed-citation xml:lang="en">De Saint Jean M., Brignole F., Bringuier A.F., Bauchet A., Feldmann G., Baudouin C. Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci. 1999; 40(3):619-630.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Cha S.H., Lee J.S., Oum B.S., Kim C.D. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Exp Ophthalmol. 2004; 32(2):180-184. doi:10.1111/j.1442-9071.2004.00782.x</mixed-citation><mixed-citation xml:lang="en">Cha S.H., Lee J.S., Oum B.S., Kim C.D. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Exp Ophthalmol. 2004; 32(2):180-184. doi:10.1111/j.1442-9071.2004.00782.x</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Yalvac I.S., Gedikoglu G., Karagoz Y., Akgun U., Nurozler A., Koc F., Kasim R., Duman S. Effects of antiglaucoma drugs on ocular surface. Acta Ophthalmol Scand. 1995; 73(3):246-248. doi:10.1111/j.1600- 0420.1995.tb00277.x</mixed-citation><mixed-citation xml:lang="en">Yalvac I.S., Gedikoglu G., Karagoz Y., Akgun U., Nurozler A., Koc F., Kasim R., Duman S. Effects of antiglaucoma drugs on ocular surface. Acta Ophthalmol Scand. 1995; 73(3):246-248. doi:10.1111/j.1600- 0420.1995.tb00277.x</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Каменских Т.Г., Веселова Е.В., Колбенев И.О., Петрова Ю.В. Влияние различных консервантов на состояние роговицы при инстилляции аналогов простагландинов. Национальный журнал глаукома. 2015; 14(3):49-56.</mixed-citation><mixed-citation xml:lang="en">Kamenskikh T.G., Veselova E.V., Kolbenev I.O., Petrova Yu.V. Effect of different preservatives on the cornea during instillation of prostaglandin analogues. Natsional’nyi zhurnal glaukoma. 2015; 14(3):49-56. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Hopes M., Broadway D. Preservative-free treatment in glaucoma is a sensible and realistic aim for the future. European Ophthalmic Review. 2010; 4(1):23-28. doi:10.17925/EOR.2010.04.01.23</mixed-citation><mixed-citation xml:lang="en">Hopes M., Broadway D. Preservative-free treatment in glaucoma is a sensible and realistic aim for the future. European Ophthalmic Review. 2010; 4(1):23-28. doi:10.17925/EOR.2010.04.01.23</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Iester M., Telani S., Frezzotti P., Motolese I., Figus M., Fogagnolo P., Perdicchi A., Beta-Blocker Study G. Ocular surface changes in glaucomatous patients treated with and without preservatives beta-blockers. J Ocul Pharmacol Ther. 2014; 30(6):476-481. doi:10.1089/jop.2013.0216</mixed-citation><mixed-citation xml:lang="en">Iester M., Telani S., Frezzotti P., Motolese I., Figus M., Fogagnolo P., Perdicchi A., Beta-Blocker Study G. Ocular surface changes in glaucomatous patients treated with and without preservatives beta-blockers. J Ocul Pharmacol Ther. 2014; 30(6):476-481. doi:10.1089/jop.2013.0216</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Hamacher T., Airaksinen J., Saarela V., Liinamaa M.J., Richter U., Ropo A. Efficacy and safety levels of preserved and preservative-free tafluprost are equivalent in patients with glaucoma or ocular hypertension: results from a pharmacodynamics analysis. Acta Ophthalmol Suppl (Oxf). 2008; 242:14-19. doi:10.1111/j.1755-3768.2008.01381.x</mixed-citation><mixed-citation xml:lang="en">Hamacher T., Airaksinen J., Saarela V., Liinamaa M.J., Richter U., Ropo A. Efficacy and safety levels of preserved and preservative-free tafluprost are equivalent in patients with glaucoma or ocular hypertension: results from a pharmacodynamics analysis. Acta Ophthalmol Suppl (Oxf). 2008; 242:14-19. doi:10.1111/j.1755-3768.2008.01381.x</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Martone G., Frezzotti P., Tosi G.M., Traversi C., Mittica V., Malandrini A., Pichierri P., Balestrazzi A., Motolese P.A., Motolese I., Motolese E. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol. 2009; 147(4):725-735 e721. doi:10.1016/j.ajo.2008.10.019</mixed-citation><mixed-citation xml:lang="en">Martone G., Frezzotti P., Tosi G.M., Traversi C., Mittica V., Malandrini A., Pichierri P., Balestrazzi A., Motolese P.A., Motolese I., Motolese E. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol. 2009; 147(4):725-735 e721. doi:10.1016/j.ajo.2008.10.019</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Labbé A., Terry O., Brasnu E., Van Went C., Baudouin C. Tear film osmolarity in patients treated for glaucoma or ocular hypertension. Cornea. 2012; 31(9):994-999. doi:10.1097/ICO.0b013e31823f8cb6</mixed-citation><mixed-citation xml:lang="en">Labbé A., Terry O., Brasnu E., Van Went C., Baudouin C. Tear film osmolarity in patients treated for glaucoma or ocular hypertension. Cornea. 2012; 31(9):994-999. doi:10.1097/ICO.0b013e31823f8cb6</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Jaenen N., Baudouin C., Pouliquen P., Manni G., Figueiredo A., Zeyen T. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007; 17(3):341-349. doi:10.1177/ 112067210701700311</mixed-citation><mixed-citation xml:lang="en">Jaenen N., Baudouin C., Pouliquen P., Manni G., Figueiredo A., Zeyen T. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007; 17(3):341-349. doi:10.1177/ 112067210701700311</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Brignole-Baudouin F., Desbenoit N., Hamm G., Liang H., Both J.P., Brunelle A., Fournier I., Guerineau V., Legouffe R., Stauber J., Touboul D., Wisztorski M., Salzet M., Laprevote O., Baudouin C. A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits. PLoS One. 2012; 7(11):e50180. doi:10.1371/journal.pone.0050180</mixed-citation><mixed-citation xml:lang="en">Brignole-Baudouin F., Desbenoit N., Hamm G., Liang H., Both J.P., Brunelle A., Fournier I., Guerineau V., Legouffe R., Stauber J., Touboul D., Wisztorski M., Salzet M., Laprevote O., Baudouin C. A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits. PLoS One. 2012; 7(11):e50180. doi:10.1371/journal.pone.0050180</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Burstein N.L. Preservative cytotoxic threshold for benzalkonium chloride and chlorhexidine digluconate in cat and rabbit corneas. Invest Ophthalmol Vis Sci. 1980; 19(3):308-313.</mixed-citation><mixed-citation xml:lang="en">Burstein N.L. Preservative cytotoxic threshold for benzalkonium chloride and chlorhexidine digluconate in cat and rabbit corneas. Invest Ophthalmol Vis Sci. 1980; 19(3):308-313.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Stevens A.M., Kestelyn P.A., De Bacquer D., Kestelyn P.G. Benzalkonium chloride induces anterior chamber inflammation in previously untreated patients with ocular hypertension as measured by flare meter: a randomized clinical trial. Acta Ophthalmol. 2012; 90(3):e221-224. doi:10.1111/j.1755-3768.2011.02338.x</mixed-citation><mixed-citation xml:lang="en">Stevens A.M., Kestelyn P.A., De Bacquer D., Kestelyn P.G. Benzalkonium chloride induces anterior chamber inflammation in previously untreated patients with ocular hypertension as measured by flare meter: a randomized clinical trial. Acta Ophthalmol. 2012; 90(3):e221-224. doi:10.1111/j.1755-3768.2011.02338.x</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Baudouin C., Pisella P.J., Fillacier K., Goldschild M., Becquet F., De Saint Jean M., Bechetoille A. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999; 106(3):556-563. doi:10.1016/S0161- 6420(99)90116-1</mixed-citation><mixed-citation xml:lang="en">Baudouin C., Pisella P.J., Fillacier K., Goldschild M., Becquet F., De Saint Jean M., Bechetoille A. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999; 106(3):556-563. doi:10.1016/S0161- 6420(99)90116-1</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Baudouin C., Garcher C., Haouat N., Bron A., Gastaud P. Expression of inflammatory membrane markers by conjunctival cells in chronically treated patients with glaucoma. Ophthalmology. 1994; 101(3):454- 460. doi:10.1016/s0161-6420(94)31322-4</mixed-citation><mixed-citation xml:lang="en">Baudouin C., Garcher C., Haouat N., Bron A., Gastaud P. Expression of inflammatory membrane markers by conjunctival cells in chronically treated patients with glaucoma. Ophthalmology. 1994; 101(3):454- 460. doi:10.1016/s0161-6420(94)31322-4</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Nuzzi R., Vercelli A., Finazzo C., Cracco C. Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study. Graefes Arch Clin Exp Ophthalmol. 1995; 233(3):154-162. doi:10.1007/bf00166608</mixed-citation><mixed-citation xml:lang="en">Nuzzi R., Vercelli A., Finazzo C., Cracco C. Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study. Graefes Arch Clin Exp Ophthalmol. 1995; 233(3):154-162. doi:10.1007/bf00166608</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Baudouin C., Liang H., Hamard P., Riancho L., Creuzot-Garcher C., Warnet J.M., Brignole-Baudouin F. The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways. Ophthalmology. 2008; 115(1):109-115. doi:10.1016/j.ophtha.2007.01.036</mixed-citation><mixed-citation xml:lang="en">Baudouin C., Liang H., Hamard P., Riancho L., Creuzot-Garcher C., Warnet J.M., Brignole-Baudouin F. The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways. Ophthalmology. 2008; 115(1):109-115. doi:10.1016/j.ophtha.2007.01.036</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Miyake K., Ota I., Ibaraki N., Akura J., Ichihashi S., Shibuya Y., Maekubo K., Miyake S. Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia. Arch Ophthalmol. 2001; 119(3):387-394. doi:10.1001/archopht.119.3.387</mixed-citation><mixed-citation xml:lang="en">Miyake K., Ota I., Ibaraki N., Akura J., Ichihashi S., Shibuya Y., Maekubo K., Miyake S. Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia. Arch Ophthalmol. 2001; 119(3):387-394. doi:10.1001/archopht.119.3.387</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Datta S., Baudouin C., Brignole-Baudouin F., Denoyer A., Cortopassi G.A. The eye drop preservative benzalkonium chloride potently induces mitochondrial dysfunction and preferentially affects LHON mutant cells. Invest Ophthalmol Vis Sci. 2017; 58(4):2406-2412. doi:10.1167/iovs.16-20903</mixed-citation><mixed-citation xml:lang="en">Datta S., Baudouin C., Brignole-Baudouin F., Denoyer A., Cortopassi G.A. The eye drop preservative benzalkonium chloride potently induces mitochondrial dysfunction and preferentially affects LHON mutant cells. Invest Ophthalmol Vis Sci. 2017; 58(4):2406-2412. doi:10.1167/iovs.16-20903</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Costagliola C., Prete A.D., Incorvaia C., Fusco R., Parmeggiani F., Di Giovanni A. Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2001; 239(11):809-814. doi:10.1007/s004170100328</mixed-citation><mixed-citation xml:lang="en">Costagliola C., Prete A.D., Incorvaia C., Fusco R., Parmeggiani F., Di Giovanni A. Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2001; 239(11):809-814. doi:10.1007/s004170100328</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">De Saint Jean M., Debbasch C., Brignole F., Rat P., Warnet J.M., Baudouin C. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells. Curr Eye Res. 2000; 20(2):85-94. doi:10.1076/0271-3683(200002)20:2;1-d;ft085</mixed-citation><mixed-citation xml:lang="en">De Saint Jean M., Debbasch C., Brignole F., Rat P., Warnet J.M., Baudouin C. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells. Curr Eye Res. 2000; 20(2):85-94. doi:10.1076/0271-3683(200002)20:2;1-d;ft085</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Anders N., Wollensak J. [Ocular pseudopemphigoid after topical drug administration]. Klin Monbl Augenheilkd. 1994; 205(2):61-64. doi:10.1055/s-2008-1045493</mixed-citation><mixed-citation xml:lang="en">Anders N., Wollensak J. [Ocular pseudopemphigoid after topical drug administration]. Klin Monbl Augenheilkd. 1994; 205(2):61-64. doi:10.1055/s-2008-1045493</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Schwab I.R., Linberg J.V., Gioia V.M., Benson W.H., Chao G.M. Foreshortening of the inferior conjunctival fornix associated with chronic glaucoma medications. Ophthalmology. 1992; 99(2):197-202. doi:10.1016/s0161-6420(92)32001-9</mixed-citation><mixed-citation xml:lang="en">Schwab I.R., Linberg J.V., Gioia V.M., Benson W.H., Chao G.M. Foreshortening of the inferior conjunctival fornix associated with chronic glaucoma medications. Ophthalmology. 1992; 99(2):197-202. doi:10.1016/s0161-6420(92)32001-9</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Kashkouli M.B., Pakdel F., Hashemi M., Ghaempanah M.J., Rezaee R., Kaghaz-Kanani R., Ahadian A. Comparing anatomical pattern of topical anti-glaucoma medications associated lacrimal obstruction with a control group. Orbit. 2010; 29(2):65-69. doi:10.3109/01676830903324284</mixed-citation><mixed-citation xml:lang="en">Kashkouli M.B., Pakdel F., Hashemi M., Ghaempanah M.J., Rezaee R., Kaghaz-Kanani R., Ahadian A. Comparing anatomical pattern of topical anti-glaucoma medications associated lacrimal obstruction with a control group. Orbit. 2010; 29(2):65-69. doi:10.3109/01676830903324284</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Bouchemi M., Roubeix C., Kessal K., Riancho L., Raveu A.L., Soualmia H., Baudouin C., Brignole-Baudouin F. Effect of benzalkonium chloride on trabecular meshwork cells in a new in vitro 3D trabecular meshwork model for glaucoma. Toxicol In Vitro. 2017; 41:21-29. doi:10.1016/j.tiv.2017.02.006</mixed-citation><mixed-citation xml:lang="en">Bouchemi M., Roubeix C., Kessal K., Riancho L., Raveu A.L., Soualmia H., Baudouin C., Brignole-Baudouin F. Effect of benzalkonium chloride on trabecular meshwork cells in a new in vitro 3D trabecular meshwork model for glaucoma. Toxicol In Vitro. 2017; 41:21-29. doi:10.1016/j.tiv.2017.02.006</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Broadway D.C., Grierson I., O'Brien C., Hitchings R.A. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol. 1994; 112(11):1446-1454. doi:10.1001/ archopht.1994.01090230060021</mixed-citation><mixed-citation xml:lang="en">Broadway D.C., Grierson I., O'Brien C., Hitchings R.A. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol. 1994; 112(11):1446-1454. doi:10.1001/ archopht.1994.01090230060021</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Broadway D.C., Grierson I., O'Brien C., Hitchings R.A. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994; 112(11):1437-1445. doi:10.1001/ archopht.1994.01090230051020</mixed-citation><mixed-citation xml:lang="en">Broadway D.C., Grierson I., O'Brien C., Hitchings R.A. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994; 112(11):1437-1445. doi:10.1001/ archopht.1994.01090230051020</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Boimer C., Birt C.M. Preservative exposure and surgical outcomes in glaucoma patients: The PESO study. J Glaucoma. 2013; 22(9):730- 735. doi:10.1097/IJG.0b013e31825af67d</mixed-citation><mixed-citation xml:lang="en">Boimer C., Birt C.M. Preservative exposure and surgical outcomes in glaucoma patients: The PESO study. J Glaucoma. 2013; 22(9):730- 735. doi:10.1097/IJG.0b013e31825af67d</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Петров С.Ю., Сафонова Д.М. Консерванты в офтальмологических препаратах: от бензалкония хлорида к поликватернию. Национальный журнал глаукома. 2013; 12(4):82-96.</mixed-citation><mixed-citation xml:lang="en">Petrov S.Yu., Safonova D.M. Ophthalmic preservatives: from benzalkonium chloride to polyquaternium. Natsional’nyi zhurnal glaukoma. 2013; 12(4):82-96. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Becquet F., Goldschild M., Moldovan M.S., Ettaiche M., Gastaud P., Baudouin C. Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface. Curr Eye Res. 1998; 17(4):419-425. doi:10.1080/02713689808951223</mixed-citation><mixed-citation xml:lang="en">Becquet F., Goldschild M., Moldovan M.S., Ettaiche M., Gastaud P., Baudouin C. Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface. Curr Eye Res. 1998; 17(4):419-425. doi:10.1080/02713689808951223</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Tripathi B.J., Tripathi R.C. Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro. Lens Eye Toxic Res. 1989; 6(3):395-403.</mixed-citation><mixed-citation xml:lang="en">Tripathi B.J., Tripathi R.C. Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro. Lens Eye Toxic Res. 1989; 6(3):395-403.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Labbé A., Pauly A., Liang H., Brignole-Baudouin F., Martin C., Warnet J.M., Baudouin C. Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study. J Ocul Pharmacol Ther. 2006; 22(4):267-278. doi:10.1089/jop.2006.22.267</mixed-citation><mixed-citation xml:lang="en">Labbé A., Pauly A., Liang H., Brignole-Baudouin F., Martin C., Warnet J.M., Baudouin C. Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study. J Ocul Pharmacol Ther. 2006; 22(4):267-278. doi:10.1089/jop.2006.22.267</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Gazzard G., Konstantakopoulou E., Garway-Heath D., Garg A., Vickerstaff V., Hunter R., Ambler G., Bunce C., Wormald R., Nathwani N., Barton K., Rubin G., Buszewicz M., Li G.H.T.T.S.G. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019; 393(10180):1505-1516. doi:10.1016/ S0140-6736(18)32213-X</mixed-citation><mixed-citation xml:lang="en">Gazzard G., Konstantakopoulou E., Garway-Heath D., Garg A., Vickerstaff V., Hunter R., Ambler G., Bunce C., Wormald R., Nathwani N., Barton K., Rubin G., Buszewicz M., Li G.H.T.T.S.G. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019; 393(10180):1505-1516. doi:10.1016/ S0140-6736(18)32213-X</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Петров С.Ю., Зинина В.С., Волжанин А.В. Роль фиксированных комбинаций лекарственных средств в лечении открытоугольной глаукомы. Вестник офтальмологии. 2018; 134(4):100-107. doi:10.17116/oftalma2018134041100</mixed-citation><mixed-citation xml:lang="en">Petrov S.Yu., Zinina V.S., Volzhanin A.V. The role of fixed dose combinations in the treatment of primary open-angle glaucoma. Vestn oftalmol. 2018; 134(4):100-107. (In Russ.). doi:10.17116/oftalma2018134041100</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Бржеский В.В., Радхуан М. Глаукома и синдром «сухого глаза». Офтальмологические ведомости. 2014; 7(2):37-49</mixed-citation><mixed-citation xml:lang="en">Brjesky V.V., Radkhuan M. Glaucoma and the dry eye syndrome. Oftalmologicheskie vedomosti. 2014; 7(2):37-49. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Liu X., Yu F.F., Zhong Y.M., Guo X.X., Mao Z. Therapeutic effects of sodium hyaluronate on ocular surface damage induced by benzalkonium chloride Preserved Anti-glaucoma Medications. Chin Med J (Engl). 2015; 128(18):2444-2449. doi:10.4103/0366-6999.164927</mixed-citation><mixed-citation xml:lang="en">Liu X., Yu F.F., Zhong Y.M., Guo X.X., Mao Z. Therapeutic effects of sodium hyaluronate on ocular surface damage induced by benzalkonium chloride Preserved Anti-glaucoma Medications. Chin Med J (Engl). 2015; 128(18):2444-2449. doi:10.4103/0366-6999.164927</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Pauloin T., Dutot M., Warnet J.M., Rat P. In vitro modulation of preservative toxicity: high molecular weight hyaluronan decreases apoptosis and oxidative stress induced by benzalkonium chloride. Eur J Pharm Sci. 2008; 34(4-5):263-273. doi:10.1016/j.ejps.2008.04.006</mixed-citation><mixed-citation xml:lang="en">Pauloin T., Dutot M., Warnet J.M., Rat P. In vitro modulation of preservative toxicity: high molecular weight hyaluronan decreases apoptosis and oxidative stress induced by benzalkonium chloride. Eur J Pharm Sci. 2008; 34(4-5):263-273. doi:10.1016/j.ejps.2008.04.006</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Егорова Г.Б., Еричев В.П., Суббот А.М., Федоров А.А., Нестерова Т.В., Габашвили А.Н., Аверич В.В. Оценка возможностей снижения токсического действия антиглаукомного гипотензивного препарата, содержащего консервант бензалкония хлорид, на первичную культуру клеток лимба роговицы с помощью слезозаменителя Стиллавит® (экспериментальное исследование). Национальный журнал глаукома. 2017; 16(4):31-36.</mixed-citation><mixed-citation xml:lang="en">Egorova G.B., Erichev V.P., Subbot A.M., Fedorov A.A., Nesterova T.V., Gabashvili A.N., Averich V.V. Evaluation of Stillavit® artificial tears potential in reducing the toxic effect of benzalkonium chloridecontaining hypotensive instillations on primary cell culture of the corneal limbus (experimental study). Natsional’nyi zhurnal glaukoma. 2017; 16(4):31-36. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Uusitalo H., Chen E., Pfeiffer N., Brignole-Baudouin F., Kaarniranta K., Leino M., Puska P., Palmgren E., Hamacher T., Hofmann G., Petzold G., Richter U., Riedel T., Winter M., Ropo A. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol. 2010; 88(3):329-336. doi:10.1111/ j.1755-3768.2010.01907.x</mixed-citation><mixed-citation xml:lang="en">Uusitalo H., Chen E., Pfeiffer N., Brignole-Baudouin F., Kaarniranta K., Leino M., Puska P., Palmgren E., Hamacher T., Hofmann G., Petzold G., Richter U., Riedel T., Winter M., Ropo A. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol. 2010; 88(3):329-336. doi:10.1111/ j.1755-3768.2010.01907.x</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Januleviciene I., Derkac I., Grybauskiene L., Paulauskaite R., Gromnickaite R., Kuzmiene L. Effects of preservative-free tafluprost on tear film osmolarity, tolerability, and intraocular pressure in previously treated patients with open-angle glaucoma. Clin Ophthalmol. 2012; 6:103-109. doi:10.2147/OPTH.S28104</mixed-citation><mixed-citation xml:lang="en">Januleviciene I., Derkac I., Grybauskiene L., Paulauskaite R., Gromnickaite R., Kuzmiene L. Effects of preservative-free tafluprost on tear film osmolarity, tolerability, and intraocular pressure in previously treated patients with open-angle glaucoma. Clin Ophthalmol. 2012; 6:103-109. doi:10.2147/OPTH.S28104</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Cucherat M., Stalmans I., Rouland J.F. Relative efficacy and safety of preservative-free latanoprost (T2345) for the treatment of openangle glaucoma and ocular hypertension: an adjusted Indirect comparison meta-analysis of randomized clinical trials. J Glaucoma. 2014; 23(1):e69-75. doi:10.1097/IJG.0b013e3182a075e6</mixed-citation><mixed-citation xml:lang="en">Cucherat M., Stalmans I., Rouland J.F. Relative efficacy and safety of preservative-free latanoprost (T2345) for the treatment of openangle glaucoma and ocular hypertension: an adjusted Indirect comparison meta-analysis of randomized clinical trials. J Glaucoma. 2014; 23(1):e69-75. doi:10.1097/IJG.0b013e3182a075e6</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Rouland J.F., Traverso C.E., Stalmans I., Fekih L.E., Delval L., Renault D., Baudouin C., Group T.S. Efficacy and safety of preservative-free latanoprost eyedrops, compared with BAK-preserved latanoprost in patients with ocular hypertension or glaucoma. Br J Ophthalmol. 2013; 97(2):196-200. doi:10.1136/bjophthalmol-2012-302121</mixed-citation><mixed-citation xml:lang="en">Rouland J.F., Traverso C.E., Stalmans I., Fekih L.E., Delval L., Renault D., Baudouin C., Group T.S. Efficacy and safety of preservative-free latanoprost eyedrops, compared with BAK-preserved latanoprost in patients with ocular hypertension or glaucoma. Br J Ophthalmol. 2013; 97(2):196-200. doi:10.1136/bjophthalmol-2012-302121</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">British National Formulary (BNF). 72 ed. London: Pharmaceutical Press; BMJ Publishing Group; 2016. 1472 p.</mixed-citation><mixed-citation xml:lang="en">British National Formulary (BNF). 72 ed. London: Pharmaceutical Press; BMJ Publishing Group; 2016. 1472 p.</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru">Hollo G., Katsanos A., Boboridis K.G., Irkec M., Konstas A.G.P. Preservative-free prostaglandin analogs and prostaglandin/timolol fixed combinations in the treatment of glaucoma: efficacy, safety and potential advantages. Drugs. 2018; 78(1):39-64. doi:10.1007/s40265-017-0843-9</mixed-citation><mixed-citation xml:lang="en">Hollo G., Katsanos A., Boboridis K.G., Irkec M., Konstas A.G.P. Preservative-free prostaglandin analogs and prostaglandin/timolol fixed combinations in the treatment of glaucoma: efficacy, safety and potential advantages. Drugs. 2018; 78(1):39-64. doi:10.1007/s40265-017-0843-9</mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Konstas A.G., Hollo G. Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma. Expert Opin Pharmacother. 2016; 17(9):1271-1283. doi:10.1080/14656566. 2016.1182983</mixed-citation><mixed-citation xml:lang="en">Konstas A.G., Hollo G. Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma. Expert Opin Pharmacother. 2016; 17(9):1271-1283. doi:10.1080/14656566. 2016.1182983</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru">Konstas A.G., Quaranta L., Realini T. Overview of the Travoprost / timolol BAK-free fixed combination. Expert Opin Pharmacother. 2012; 13(5):757-766. doi:10.1517/14656566.2012.662485</mixed-citation><mixed-citation xml:lang="en">Konstas A.G., Quaranta L., Realini T. Overview of the Travoprost / timolol BAK-free fixed combination. Expert Opin Pharmacother. 2012; 13(5):757-766. doi:10.1517/14656566.2012.662485</mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Swymer C., Neville M.W. Tafluprost: the first preservative-free prostaglandin to treat open-angle glaucoma and ocular hypertension. Ann Pharmacother. 2012; 46(11):1506-1510. doi:10.1345/aph.1R229 80. Uusitalo H., Egorov E., Kaarniranta K., Astakhov Y., Ropo A. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials. Clin Ophthalmol. 2016; 10:445-454. doi:10.2147/OPTH.S91402 81. Hollo G. The side effects of the prostaglandin analogues. Expert Opin Drug Saf. 2007; 6(1):45-52. doi:10.1517/14740338.6.1.45</mixed-citation><mixed-citation xml:lang="en">Swymer C., Neville M.W. Tafluprost: the first preservative-free prostaglandin to treat open-angle glaucoma and ocular hypertension. Ann Pharmacother. 2012; 46(11):1506-1510. doi:10.1345/aph.1R229</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru">Dietlein T.S., Jordan J.F., Luke C., Schild A., Dinslage S., Krieglstein G.K. Self-application of single-use eyedrop containers in an elderly population: comparisons with standard eyedrop bottle and with younger patients. Acta Ophthalmol. 2008; 86(8):856-859. doi:10.1111/j.1755-3768.2007.01155.x</mixed-citation><mixed-citation xml:lang="en">Uusitalo H., Egorov E., Kaarniranta K., Astakhov Y., Ropo A. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials. Clin Ophthalmol. 2016; 10:445-454. doi:10.2147/OPTH.S91402</mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">Parkkari M., Latvala T., Ropo A. Handling test of eye drop dispenser – comparison of unit-dose pipettes with conventional eye drop bottles. J Ocul Pharmacol Ther. 2010; 26(3):273-276. doi:10.1089/ jop.2009.0111</mixed-citation><mixed-citation xml:lang="en">Hollo G. The side effects of the prostaglandin analogues. Expert Opin Drug Saf. 2007; 6(1):45-52. doi:10.1517/14740338.6.1.45</mixed-citation></citation-alternatives></ref><ref id="cit82"><label>82</label><citation-alternatives><mixed-citation xml:lang="ru">Stalmans I., Sunaric Megevand G., Cordeiro M.F., Hommer A., Rossetti L., Goni F., Heijl A., Bron A. Preservative-free treatment in glaucoma: who, when, and why. Eur J Ophthalmol. 2013; 23(4):518-525. doi:10.5301/ejo.5000270</mixed-citation><mixed-citation xml:lang="en">Dietlein T.S., Jordan J.F., Luke C., Schild A., Dinslage S., Krieglstein G.K. Self-application of single-use eyedrop containers in an elderly population: comparisons with standard eyedrop bottle and with younger patients. Acta Ophthalmol. 2008; 86(8):856-859. doi:10.1111/j.1755-3768.2007.01155.x</mixed-citation></citation-alternatives></ref><ref id="cit83"><label>83</label><citation-alternatives><mixed-citation xml:lang="ru">Herper M. The cost of creating a new drug now $5 billion, pushing big pharma to change: Forbes; 2013. Available from: https:// www.forbes.com/sites/matthewherper/2013/08/11/how-thestaggering-cost-of-inventing-new-drugs-is-shaping-the-future-ofmedicine/#310b7bb913c3</mixed-citation><mixed-citation xml:lang="en">Parkkari M., Latvala T., Ropo A. Handling test of eye drop dispenser – comparison of unit-dose pipettes with conventional eye drop bottles. J Ocul Pharmacol Ther. 2010; 26(3):273-276. doi:10.1089/ jop.2009.0111</mixed-citation></citation-alternatives></ref><ref id="cit84"><label>84</label><citation-alternatives><mixed-citation xml:lang="ru">Vicente A., Prud'homme S., Ferreira J., Abegao Pinto L., Stalmans I. Openangle glaucoma: drug development pipeline during the last 20 years (1995-2015). Ophthalmic Res. 2017; 57(4):201-207. doi:10.1159/000453527</mixed-citation><mixed-citation xml:lang="en">Stalmans I., Sunaric Megevand G., Cordeiro M.F., Hommer A., Rossetti L., Goni F., Heijl A., Bron A. Preservative-free treatment in glaucoma: who, when, and why. Eur J Ophthalmol. 2013; 23(4):518-525. doi:10.5301/ejo.5000270</mixed-citation></citation-alternatives></ref><ref id="cit85"><label>85</label><citation-alternatives><mixed-citation xml:lang="ru">Hay M., Thomas D.W., Craighead J.L., Economides C., Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014; 32(1):40-51. doi:10.1038/nbt.2786</mixed-citation><mixed-citation xml:lang="en">Herper M. The cost of creating a new drug now $5 billion, pushing big pharma to change: Forbes; 2013. Available from: https:// www.forbes.com/sites/matthewherper/2013/08/11/how-thestaggering-cost-of-inventing-new-drugs-is-shaping-the-future-ofmedicine/#310b7bb913c3</mixed-citation></citation-alternatives></ref><ref id="cit86"><label>86</label><citation-alternatives><mixed-citation xml:lang="ru">Tham Y.C., Li X., Wong T.Y., Quigley H.A., Aung T., Cheng C.Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013</mixed-citation><mixed-citation xml:lang="en">Vicente A., Prud'homme S., Ferreira J., Abegao Pinto L., Stalmans I. Openangle glaucoma: drug development pipeline during the last 20 years (1995-2015). Ophthalmic Res. 2017; 57(4):201-207. doi:10.1159/000453527</mixed-citation></citation-alternatives></ref><ref id="cit87"><label>87</label><citation-alternatives><mixed-citation xml:lang="ru">Hay M., Thomas D.W., Craighead J.L., Economides C., Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014; 32(1):40-51. doi:10.1038/nbt.2786</mixed-citation><mixed-citation xml:lang="en">Hay M., Thomas D.W., Craighead J.L., Economides C., Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014; 32(1):40-51. doi:10.1038/nbt.2786</mixed-citation></citation-alternatives></ref><ref id="cit88"><label>88</label><citation-alternatives><mixed-citation xml:lang="ru">Tham Y.C., Li X., Wong T.Y., Quigley H.A., Aung T., Cheng C.Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013</mixed-citation><mixed-citation xml:lang="en">Tham Y.C., Li X., Wong T.Y., Quigley H.A., Aung T., Cheng C.Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013</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>
