glaucomaНациональный журнал ГлаукомаNational Journal glaucoma2078-41042311-6862Federal State Budgetary Institution of Science “Krasnov Research Institute of Eye Diseases”glaucoma-155Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEW OF LITERATUREЦиклоспорин А в хирургическом лечении глаукомы: перспективы и возможностиCyclosporine A in glaucoma surgery: perspectives and opportunitiesГермановаВ. Н.GermanovaV. N.

клинический ординатор, кафедра офтальмологии,

443068, Самара, ул. Ново-Садовая, 158

Resident, Ophthalmology Department,

158 Novo-Sadovaya str., Samara, 443068

ВолжанинА. В.VolzhaninA. V.

ординатор,

119021,  Москва, ул. Россолимо, 11А

 

Resident,

11A Rossolimo st., Moscow, 119021

ЗолотаревА. В.ZolotarevA. V.

д.м.н., доцент, заведующий кафедрой офтальмологии,

443068, Самара, ул. Ново-Садовая, 158

Med.Sc.D., Head of Department, Ophthalmology Department,

158 Novo-Sadovaya str., Samara, 443068

КарловаЕ. В.KarlovaE. V.

к.м.н., заведующая глаукомным отделением,

443068, Самара, ул. Ново-Садовая, 158

Ph.D., Head of Department, Glaucoma Department,

158 Novo-Sadovaya str., Samara, 443068

ПетровС. Ю.PetrovS. Yu.

к.м.н., ведущий научный сотрудник,

119021,  Москва, ул. Россолимо, 11А

Ph.D., Leading Research Associate,

11A Rossolimo st., Moscow, 119021

ФГБОУ ВО «Самарский государственный медицинский университет» МЗ РФРоссияSamara State Medical UniversityRussian FederationФГБНУ «Научно-исследовательский институт глазных болезней»РоссияScientific Research Institute of Eye DiseasesRussian FederationГБУЗ «Самарская областная клиническая офтальмологическая больница им. Т.И. Ерошевского»РоссияEroshevskiy Eye HospitalRussian Federation20173008201716292100Copyright © Германова В.Н., Волжанин А.В., Золотарев А.В., Карлова Е.В., Петров С.Ю., 20172017Германова В.Н., Волжанин А.В., Золотарев А.В., Карлова Е.В., Петров С.Ю.Germanova V.N., Volzhanin A.V., Zolotarev A.V., Karlova E.V., Petrov S.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.glaucomajournal.ru/jour/article/view/155

Основной причиной неэффективности хирургического лечения глаукомы является послеоперационное рубцевание. Для его профилактики в разное время было предложено использование различных дренажей и имплантов, интра- или послеоперационное использо- вание лекарственных веществ. Наибольшее распространение получило применение Митомицина-С и 5-фторурацила. Данные вещества значительно повышают эффективность хирургических вмешательств при глаукоме, однако их использование во время гипотензивных вмешательств зачастую приводит к осложнениям. В настоящее время проводятся исследования по поиску более безопасной, но в то же время достаточно эффективной замены вышеназванным препаратам в хирур- гическом лечении глаукомы для профилактики послеоперационного рубцевания. Рядом зарубежных авторов в качестве альтернативы было предложено использование циклоспорина А. Данный препарат избирательно действует на Т-лимфоциты, ингибируя синтез интерлейкина-2 – одного из ключевых медиаторов воспаления, запускающих каскад реакций, приводящих в итоге к избыточной пролиферации фибробластов. В обзоре представлены патофизиологические аспекты рубцевания после гипотензивных вмешательств и методы борьбы с ним. Рассмотрен механизм действия циклоспорина А, представлены результаты исследований эффективности данного препарата, а также безопасности его применения при хирургическом лечении глаукомы.

Postoperative scarring is one of the main reasons of glaucoma surgery failure. At different times it has been proposed to use various drainage implants, intra- or postoperative medications in order to prevent scarring. Mitomycin-C and 5-fluorouracil are widely used today for this purpose. These medications are effective in glaucoma surgery but often lead to severe complications. Nowadays investigations are being carried out in order to find a safer but not less effective substitution to them. Some foreign authors have proposed to use Cyclosporine-A (CsA) as an alternative. CsA selectively affects T-cells causing Interleukin-2 (IL-2) synthesis inhibition. IL-2 is one of the key inflammatory mediators triggering inflammatory cascade leading to fibroblast proliferation. The review deals with pathological bases of scarring after glaucoma surgery as well as possible methods of its modulation, provides results of investigations of CsA effectiveness and safety in glaucoma surgery.

хирургия глаукомыциклоспорин Арубцеваниецитокиныфибробластыинтерлейкин-2Т-лимфоцитывоспалениеglaucoma surgeryCyclosporine-AscarringcytokinesfibroblastsInterleukin-2T-cellsinflammationReferencesTham 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.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.Астахов Ю.С., Егоров Е.А., Астахов С.Ю., Брезель Ю.А. Хирургическое лечение «рефрактерной» глаукомы. Клиническая офтальмология 2006; 7(1):25-27. [Astakhov Yu.S., Egorov E.A., Astakhov S.Yu., Brezel’ Yu.A. Surgical treatment of refractory glaucoma. Clinical ophthalmology 2006; 7(1):25-27. (In Russ.)].Астахов Ю.С., Егоров Е.А., Астахов С.Ю., Брезель Ю.А. Хирургическое лечение «рефрактерной» глаукомы. Клиническая офтальмология 2006; 7(1):25-27. [Astakhov Yu.S., Egorov E.A., Astakhov S.Yu., Brezel’ Yu.A. Surgical treatment of refractory glaucoma. Clinical ophthalmology 2006; 7(1):25-27. (In Russ.)].Terminology and Guidelines for Glaucoma. 4th ed. Italy, 2014; European Glaucoma Society.Terminology and Guidelines for Glaucoma. 4th ed. Italy, 2014; European Glaucoma Society.Cvenkel B., Kopitar A.N., Ihan A. Inflammatory molecules in aqueous humour and on ocular surface and glaucoma surgery outcome. Mediators of inflammation 2010; 939602. doi:10.1155/2010/939602.Cvenkel B., Kopitar A.N., Ihan A. Inflammatory molecules in aqueous humour and on ocular surface and glaucoma surgery outcome. Mediators of inflammation 2010; 939602. doi:10.1155/2010/939602.Глаукома. Национальное руководство. Под ред. Е.А. Егорова. М., ГЭОТАР-Медиа, 2014: 824 c. [Glaukoma. Natsional’noe rukovodstvo [Glaucoma. National guidance]. Ed. by Egorov E.A. М.: GEOTAR-media; 2013; 824 p. (In Russ.)].Глаукома. Национальное руководство. Под ред. Е.А. Егорова. М., ГЭОТАР-Медиа, 2014: 824 c. [Glaukoma. Natsional’noe rukovodstvo [Glaucoma. National guidance]. Ed. by Egorov E.A. М.: GEOTAR-media; 2013; 824 p. (In Russ.)].Бабушкин А.Э. Повторные антиглаукоматозные фистулизирующие операции (обзор литературы). Вестник офтальмологии 1990; 2:74-78. [Babushkin A.E. Repeated anti-glaucoma filtering surgery (literature review). Vestn Oftalmol 1990; 2:74-78. (In Russ.)].Бабушкин А.Э. Повторные антиглаукоматозные фистулизирующие операции (обзор литературы). Вестник офтальмологии 1990; 2:74-78. [Babushkin A.E. Repeated anti-glaucoma filtering surgery (literature review). Vestn Oftalmol 1990; 2:74-78. (In Russ.)].Шмырева В.Ф., Петров С.Ю., Макарова А.С. Причины снижения отдаленной гипотензивной эффективности антиглаукоматозных операций и возможности ее повышения. Глаукома 2010; 9(2):43-49. [Shmyreva V.F., Petrov S.Yu., Makarova A.S. Causes of glaucoma surgery efficacy decrease in the late postoperative period and the methods of its enhancement. Glaukoma 2010; 2(9):43 49. (In Russ.)].Шмырева В.Ф., Петров С.Ю., Макарова А.С. Причины снижения отдаленной гипотензивной эффективности антиглаукоматозных операций и возможности ее повышения. Глаукома 2010; 9(2):43-49. [Shmyreva V.F., Petrov S.Yu., Makarova A.S. Causes of glaucoma surgery efficacy decrease in the late postoperative period and the methods of its enhancement. Glaukoma 2010; 2(9):43 49. (In Russ.)].Лебедев О.И., Яворский А.Е., Столяров Г.М., Молчанова Е.В., Ковалевский В.В. Профилактика избыточного рубцевания при непроникающей глубокой склерэктомии. Национальный журнал глаукома 2011; 10(1)32-36. [Lebedev O.I., Yavorskiy A.V., Stolyarov G.M., Molchanova E.V., Kovalevskiy V.V. Prevention of excessive scarring in non-penetrating deep sclerectomy. Natsional’nyi zhurnal glaukoma 2011; 10(1):32-36. (In Russ.)].Лебедев О.И., Яворский А.Е., Столяров Г.М., Молчанова Е.В., Ковалевский В.В. Профилактика избыточного рубцевания при непроникающей глубокой склерэктомии. Национальный журнал глаукома 2011; 10(1)32-36. [Lebedev O.I., Yavorskiy A.V., Stolyarov G.M., Molchanova E.V., Kovalevskiy V.V. Prevention of excessive scarring in non-penetrating deep sclerectomy. Natsional’nyi zhurnal glaukoma 2011; 10(1):32-36. (In Russ.)].Peng T. Khaw, Jones E., Mireskandari K., Dahlmann A., Cambrey A. Modulating wound healing after glaucoma surgery. Glaucoma today July/August 2004; 12-19.Peng T. Khaw, Jones E., Mireskandari K., Dahlmann A., Cambrey A. Modulating wound healing after glaucoma surgery. Glaucoma today July/August 2004; 12-19.Yamanaka O., Kitano-Izutani A., Tomoyose K., Reinach P. Pathobiology of wound healing after glaucoma filtration surgery. BMC Ophthalmology 2015; 15 (suppl. 1): 19-27.Yamanaka O., Kitano-Izutani A., Tomoyose K., Reinach P. Pathobiology of wound healing after glaucoma filtration surgery. BMC Ophthalmology 2015; 15 (suppl. 1): 19-27.Van Bergen T., Van de Velde S., Van de Walle E., Moons L., Stalmans I. Improving patient outcomes following glaucoma surgery: state of the art and future perspectives. Clinical Ophthalmology 2014; 8:857-867.Van Bergen T., Van de Velde S., Van de Walle E., Moons L., Stalmans I. Improving patient outcomes following glaucoma surgery: state of the art and future perspectives. Clinical Ophthalmology 2014; 8:857-867.Зайчик А.Ш., Чурилов Л.П. Патофизиология. Том 1. Общая патофизиология с основами иммунопатологии. СПб: ЭЛБИ-СПб., 2008; 656 c. [Zaichik A.Sh., Churilov L.P. Patofiziologiya. Tom 1. Obshchaya patofiziologiya s osnovami immunopatologii [Pathophysiology. Vol. 1. General pathophysiology with the course of immunopathology]. St. Petersburg: ELBI-SpB Publ., 2008; 656 p. (In Russ.)].Зайчик А.Ш., Чурилов Л.П. Патофизиология. Том 1. Общая патофизиология с основами иммунопатологии. СПб: ЭЛБИ-СПб., 2008; 656 c. [Zaichik A.Sh., Churilov L.P. Patofiziologiya. Tom 1. Obshchaya patofiziologiya s osnovami immunopatologii [Pathophysiology. Vol. 1. General pathophysiology with the course of immunopathology]. St. Petersburg: ELBI-SpB Publ., 2008; 656 p. (In Russ.)].Молекулярные механизмы воспаления: учебное пособие. Под ред. В.А. Черешнева. Екатеринбург: УрО РАН, 2010; 262 с. [Molekulyarnye mekhanizmy vospaleniya: uchebnoe posobie [The molecular mechanisms of inflammation: A Textbook]. Edited by V.A. Chereshnev. Yekaterinburg: Ural Branch of RAS, 2010; 261 p. (In Russ.)].Молекулярные механизмы воспаления: учебное пособие. Под ред. В.А. Черешнева. Екатеринбург: УрО РАН, 2010; 262 с. [Molekulyarnye mekhanizmy vospaleniya: uchebnoe posobie [The molecular mechanisms of inflammation: A Textbook]. Edited by V.A. Chereshnev. Yekaterinburg: Ural Branch of RAS, 2010; 261 p. (In Russ.)].Kumar V., Abul K. Abbas, Fausto N., Aster J. Robbins and Cotran Pathologic Basis of Disease, 9th Edition. 2014. Elsevier Saunders, Italy; 1408 p.Kumar V., Abul K. Abbas, Fausto N., Aster J. Robbins and Cotran Pathologic Basis of Disease, 9th Edition. 2014. Elsevier Saunders, Italy; 1408 p.Khaw P.T., Occleston N.L., Schultz G., Grierson I., Sherwood M.B., Larkin G. Activation and suppression of fibroblast function. Eye (Lond) 1994; 8(Pt 2):188-195.Khaw P.T., Occleston N.L., Schultz G., Grierson I., Sherwood M.B., Larkin G. Activation and suppression of fibroblast function. Eye (Lond) 1994; 8(Pt 2):188-195.Lei D., Dong C., Wu W.K., Dong A., Li T., Chan M.T., Zhou X., Yuan H. Lentiviral delivery of small hairpin RNA targeting connective tissue growth factor blocks profibrotic signaling in tenon’s capsule fibroblasts. Invest Ophthalmol Vis Sci 2016; 57(13): 5171-5180. doi: 10.1167/iovs.16-19480.Lei D., Dong C., Wu W.K., Dong A., Li T., Chan M.T., Zhou X., Yuan H. Lentiviral delivery of small hairpin RNA targeting connective tissue growth factor blocks profibrotic signaling in tenon’s capsule fibroblasts. Invest Ophthalmol Vis Sci 2016; 57(13): 5171-5180. doi: 10.1167/iovs.16-19480.Liu Y., Liu Y., Xu D., Li J. Latanoprost-induced cytokine and chemokine release from human tenon’s capsule fibroblasts: role of MAPK and NF- B signaling pathways. J Glaucoma 2015; 24(9):635-641. doi: 10.1097/IJG.0000000000000140.Liu Y., Liu Y., Xu D., Li J. Latanoprost-induced cytokine and chemokine release from human tenon’s capsule fibroblasts: role of MAPK and NF- B signaling pathways. J Glaucoma 2015; 24(9):635-641. doi: 10.1097/IJG.0000000000000140.Cunliffe I.A., Richardson P.S., Rees R.C., Rennie I.G. Effect of TNF, IL-1, and IL-6 on the proliferation of human Tenon’s capsule fibroblasts in tissue culture. Br J Ophthalmol 1995; 79(6):590–595.Cunliffe I.A., Richardson P.S., Rees R.C., Rennie I.G. Effect of TNF, IL-1, and IL-6 on the proliferation of human Tenon’s capsule fibroblasts in tissue culture. Br J Ophthalmol 1995; 79(6):590–595.Daniels J.T., Schultz G.S., Blalock T.D., Garrett Q., Grotendorst G.R., Dean N.M, Khaw P.T. Mediation of transforming growth factorbeta(1)-stimulated matrix contraction by fibroblasts: a role for connective tissue growth factor in contractile scarring. Am J Pathol 2003; 163(5):2043-2052.Daniels J.T., Schultz G.S., Blalock T.D., Garrett Q., Grotendorst G.R., Dean N.M, Khaw P.T. Mediation of transforming growth factorbeta(1)-stimulated matrix contraction by fibroblasts: a role for connective tissue growth factor in contractile scarring. Am J Pathol 2003; 163(5):2043-2052.Occleston N.L., Alexander R.A., Mazure A., Larkin G., Khaw P.T. Effects of single exposures to antiproliferative agents on ocular fibroblast-mediated collagen contraction. Invest Ophthalmol Vis Sci 1994; 35(10):3681-3690.Occleston N.L., Alexander R.A., Mazure A., Larkin G., Khaw P.T. Effects of single exposures to antiproliferative agents on ocular fibroblast-mediated collagen contraction. Invest Ophthalmol Vis Sci 1994; 35(10):3681-3690.Chang L., Crowston J.G., Cordeiro M.F., Akbar A.N., Khaw P.T. The role of the immune system in conjunctival wound healing after glaucoma surgery. Surv Ophthalmol 2000; 45(1):49-68.Chang L., Crowston J.G., Cordeiro M.F., Akbar A.N., Khaw P.T. The role of the immune system in conjunctival wound healing after glaucoma surgery. Surv Ophthalmol 2000; 45(1):49-68.Masoumpour M.B., Nowroozzadeh M.H., Razeghinejad M.R. Current and future techniques in wound healing modulation after glaucoma filtering surgeries. Open Ophthalmol J 2016; (10): 68-85. doi: 10.2174/1874364101610010068.Masoumpour M.B., Nowroozzadeh M.H., Razeghinejad M.R. Current and future techniques in wound healing modulation after glaucoma filtering surgeries. Open Ophthalmol J 2016; (10): 68-85. doi: 10.2174/1874364101610010068.Vijaya L., Manish P., Ronnie G., Shantha B. Management of complications in glaucoma surgery. Indian J Ophthalmol 2011; 59(Suppl1): S131–S140. doi: 10.4103/0301-4738.73689.Vijaya L., Manish P., Ronnie G., Shantha B. Management of complications in glaucoma surgery. Indian J Ophthalmol 2011; 59(Suppl1): S131–S140. doi: 10.4103/0301-4738.73689.Lockwood A., Brocchini S., Khaw P.T. New developments in the pharmacological modulation of wound healing after glaucoma filtration surgery. Curr Opin Pharmacol 2013; 13(1):65-71. doi: 10.1016/j.coph.2012.10.008.Lockwood A., Brocchini S., Khaw P.T. New developments in the pharmacological modulation of wound healing after glaucoma filtration surgery. Curr Opin Pharmacol 2013; 13(1):65-71. doi: 10.1016/j.coph.2012.10.008.Fan Gaskin J.C., Nguyen D.Q., Soon Ang G., O’Connor J., Crowston J.G. Wound healing modulation in glaucoma filtration surgery — conventional practices and new perspectives: the role of antifibrotic agents (Part I). J Curr Glaucoma Pract 2014; 8(2):37-45. doi: 10.5005/jp-journals-10008-1159.Fan Gaskin J.C., Nguyen D.Q., Soon Ang G., O’Connor J., Crowston J.G. Wound healing modulation in glaucoma filtration surgery — conventional practices and new perspectives: the role of antifibrotic agents (Part I). J Curr Glaucoma Pract 2014; 8(2):37-45. doi: 10.5005/jp-journals-10008-1159.Fan Gaskin J.C., Nguyen D.Q., Soon Ang G., O’Connor J., Crowston J.G. Wound healing modulation in glaucoma filtration surgery — conventional practices and new perspectives: antivascular endothelial growth factor and novel agents (Part II). J Curr Glaucoma Pract 2014; 8(2):46-53. doi: 10.5005/jp-journals-10008-1160. Epub 2014 Jun 12.Fan Gaskin J.C., Nguyen D.Q., Soon Ang G., O’Connor J., Crowston J.G. Wound healing modulation in glaucoma filtration surgery — conventional practices and new perspectives: antivascular endothelial growth factor and novel agents (Part II). J Curr Glaucoma Pract 2014; 8(2):46-53. doi: 10.5005/jp-journals-10008-1160. Epub 2014 Jun 12.Khaw P.T. Advances in glaucoma surgery: evolution of antimetabolite adjunctive therapy. J Glaucoma 2001; 10(5 Suppl 1):S81-4.Khaw P.T. Advances in glaucoma surgery: evolution of antimetabolite adjunctive therapy. J Glaucoma 2001; 10(5 Suppl 1):S81-4.Khaw P.T. Antiproliferative agents and the prevention of scarring after surgery: friend or foe? Br J Ophthalmol 1995; 79(7):627.Khaw P.T. Antiproliferative agents and the prevention of scarring after surgery: friend or foe? Br J Ophthalmol 1995; 79(7):627.Daniels J.T., Occleston N.L., Crowston J.G., Khaw P.T. Effects of antimetabolite induced cellular growth arrest on fibroblast-fibroblast interactions. Exp Eye Res 1999; 69(1):117-127.Daniels J.T., Occleston N.L., Crowston J.G., Khaw P.T. Effects of antimetabolite induced cellular growth arrest on fibroblast-fibroblast interactions. Exp Eye Res 1999; 69(1):117-127.Khaw P.T., Sherwood M.B., MacKay S.L., Rossi M.J., Schultz G. Five-minute treatments with fluoruracil, floxuridine, and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch Ophthalmol 1992; 110(8): 1150-1154.Khaw P.T., Sherwood M.B., MacKay S.L., Rossi M.J., Schultz G. Five-minute treatments with fluoruracil, floxuridine, and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch Ophthalmol 1992; 110(8): 1150-1154.Van Bergen T., Jonckx B., Moons L., Feyen J.H., Stalmans I. The Combination of PlGF inhibition and MMC as a novel anti-scarring strategy for glaucoma filtration surgery. Invest Ophthalmol Vis Sci 2016; 57(10):4347-55. doi: 10.1167/iovs.16-19725.Van Bergen T., Jonckx B., Moons L., Feyen J.H., Stalmans I. The Combination of PlGF inhibition and MMC as a novel anti-scarring strategy for glaucoma filtration surgery. Invest Ophthalmol Vis Sci 2016; 57(10):4347-55. doi: 10.1167/iovs.16-19725.Cheng J.W., Cheng S.W., Wei R.L., Lu G.C. Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery. Cochrane Database Syst Rev 2016; (1):CD009782. doi: 10.1002/14651858.CD009782.pub2.Cheng J.W., Cheng S.W., Wei R.L., Lu G.C. Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery. Cochrane Database Syst Rev 2016; (1):CD009782. doi: 10.1002/14651858.CD009782.pub2.Cordeiro M.F. Beyond Mitomycin: TGF-beta and wound healing. Prog Retin Eye Res 2002; 21(1):75-89.Cordeiro M.F. Beyond Mitomycin: TGF-beta and wound healing. Prog Retin Eye Res 2002; 21(1):75-89.Amoozgar B., Lin S.C., Han Y., Kuo J. A role for antimetabolites in glaucoma tube surgery: current evidence and future directions. Curr Opin Ophthalmol 2016; 27(2):164-169. doi: 10.1097/ICU.0000000000000244.Amoozgar B., Lin S.C., Han Y., Kuo J. A role for antimetabolites in glaucoma tube surgery: current evidence and future directions. Curr Opin Ophthalmol 2016; 27(2):164-169. doi: 10.1097/ICU.0000000000000244.Cabourne E., Clarke J.C., Schlottmann P.G., Evans J.R. Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery. Cochrane Database Syst Rev 2015; (11):CD006259. doi: 10.1002/14651858.CD006259.pub2.Cabourne E., Clarke J.C., Schlottmann P.G., Evans J.R. Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery. Cochrane Database Syst Rev 2015; (11):CD006259. doi: 10.1002/14651858.CD006259.pub2.Tatlipinar S., Akpek E.K. Topical cyclosporine in the treatment of ocular surface disorders. Br J Ophthalmol 2005; 89(10):1363-1367.Tatlipinar S., Akpek E.K. Topical cyclosporine in the treatment of ocular surface disorders. Br J Ophthalmol 2005; 89(10):1363-1367.Faulds D., Goa K.L., Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 1993; 45(6):953-1040.Faulds D., Goa K.L., Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 1993; 45(6):953-1040.Tatlipinar S., Akpek E.K. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol 2005; 89:1363-1367. doi:10.1136/bjo.2005.070888.Tatlipinar S., Akpek E.K. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol 2005; 89:1363-1367. doi:10.1136/bjo.2005.070888.Crabtree G.R. Calcium, calcineurin, and the control of transcription. J Biol Chem 2001; 276(4):2313-2316. Epub 2000 Nov 28.Crabtree G.R. Calcium, calcineurin, and the control of transcription. J Biol Chem 2001; 276(4):2313-2316. Epub 2000 Nov 28.Matsuda S., Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology 2000; 47(2-3):119-125.Matsuda S., Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology 2000; 47(2-3):119-125.Hogan P.G., Chen L., Nardone J., Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 2003; 17(18): 2205-2232.Hogan P.G., Chen L., Nardone J., Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 2003; 17(18): 2205-2232.Wang Ping , Heitman J. The cyclophilins. Genome Biol 2005; 6(7):226.Wang Ping , Heitman J. The cyclophilins. Genome Biol 2005; 6(7):226.Rusnak F., Mertz P. Calcineurin: form and function. Physiol Rev 2000; 80(4):1483-1521.Rusnak F., Mertz P. Calcineurin: form and function. Physiol Rev 2000; 80(4):1483-1521.Fakhraie G., Lopes J.F., Spaeth G.L., Almodin J., Ichhpujani P., Moster M.R. Effects of postoperative cyclosporine ophthalmic emulsion 0.05% (Restasis) following glaucoma surgery. Clin Exper Ophthalmol 12/2009; 37(9):842-848.Fakhraie G., Lopes J.F., Spaeth G.L., Almodin J., Ichhpujani P., Moster M.R. Effects of postoperative cyclosporine ophthalmic emulsion 0.05% (Restasis) following glaucoma surgery. Clin Exper Ophthalmol 12/2009; 37(9):842-848.Lattanzio F.A. Jr., Crouch E.R. Jr., Mitrev P.V., Williams P.B., Allen R.C. Cyclosporin as an adjunct to glaucoma filtration surgery. J Glaucoma 2005; 14(6).Lattanzio F.A. Jr., Crouch E.R. Jr., Mitrev P.V., Williams P.B., Allen R.C. Cyclosporin as an adjunct to glaucoma filtration surgery. J Glaucoma 2005; 14(6).Park K.H., Kim D.M., Youn D.H. Topical cyclosporine and glaucoma drainage implant surgery in rabbits. Ophthalmic Surg Lasers 1996; 27(6):452-458.Park K.H., Kim D.M., Youn D.H. Topical cyclosporine and glaucoma drainage implant surgery in rabbits. Ophthalmic Surg Lasers 1996; 27(6):452-458.Tura li M.E., G nd z K., Aktan G., Sencer H. Topical cyclosporine as a possible new antimetabolite in trabeculectomy. Ophthalmic Surg Lasers 1996; 27(6):438-444.Tura li M.E., G nd z K., Aktan G., Sencer H. Topical cyclosporine as a possible new antimetabolite in trabeculectomy. Ophthalmic Surg Lasers 1996; 27(6):438-444.Hondur A., Onol M. Nonpenetrating glaucoma surgery: Metaanalysis of Recent Results. J Glaucoma 2008; 17(2):139-146.Hondur A., Onol M. Nonpenetrating glaucoma surgery: Metaanalysis of Recent Results. J Glaucoma 2008; 17(2):139-146.Анисимова С.Ю., Анисимов С.И., Рогачева И.В., Панасюк А.Ф., Ларионов Е.В. Новый нерассасываемый коллагеновый дренаж для повышения эффективности непроникающей глубокой склерлимбэктомии. Глаукома 2003; 1:19-24. [Anisimova S.Yu., Anisimov S.I., Rogachoyva I.V., Panasuk A.F., Laryonov E.V. New non-absorbed collagen implant increases the efficacy of the non-penetrating deep sclerlimbectomy. Glaucoma 2003; 1:19-24. (In Russ.)].Анисимова С.Ю., Анисимов С.И., Рогачева И.В., Панасюк А.Ф., Ларионов Е.В. Новый нерассасываемый коллагеновый дренаж для повышения эффективности непроникающей глубокой склерлимбэктомии. Глаукома 2003; 1:19-24. [Anisimova S.Yu., Anisimov S.I., Rogachoyva I.V., Panasuk A.F., Laryonov E.V. New non-absorbed collagen implant increases the efficacy of the non-penetrating deep sclerlimbectomy. Glaucoma 2003; 1:19-24. (In Russ.)].Анисимова С.Ю., Анисимов С.И., Рогачева И.В. Отдаленные результаты хирургического лечения рефрактерной глаукомы с использованием стойкого к биодеструкции коллагенового дренажа. Глаукома 2011; (2):28-33. [Anisimova S.Yu., Anisimov S.I., Rogacheva I.V. Long-term results of surgical treatment of refractory glaucoma with biodestruction resistent collagen antiglaucomatous drainage. Glaucoma 2011; 2:28-33. (In Russ.)].Анисимова С.Ю., Анисимов С.И., Рогачева И.В. Отдаленные результаты хирургического лечения рефрактерной глаукомы с использованием стойкого к биодеструкции коллагенового дренажа. Глаукома 2011; (2):28-33. [Anisimova S.Yu., Anisimov S.I., Rogacheva I.V. Long-term results of surgical treatment of refractory glaucoma with biodestruction resistent collagen antiglaucomatous drainage. Glaucoma 2011; 2:28-33. (In Russ.)].Thomson A.W., Whiting P.H., Simpson J.G. Cyclosporine: immunology, toxicity and pharmacology in experimental animals. Agents Actions 1984; 15(3-4):306-327.Thomson A.W., Whiting P.H., Simpson J.G. Cyclosporine: immunology, toxicity and pharmacology in experimental animals. Agents Actions 1984; 15(3-4):306-327.Vernillet L., Lundh R.L., Acezat-Mispelter F., Goizel C., Humbert H., Pouliquen Y. Ocular distribution of cyclosporin A (Sandimmun) following systemic and topical administration to rabbits. Eur J Drug Metab Pharmacokinet 1991; 3:150-158.Vernillet L., Lundh R.L., Acezat-Mispelter F., Goizel C., Humbert H., Pouliquen Y. Ocular distribution of cyclosporin A (Sandimmun) following systemic and topical administration to rabbits. Eur J Drug Metab Pharmacokinet 1991; 3:150-158.Kuwano M., Ibuki H., Morikawa N., Ota A., Kawashima Y. Cyclosporine A formulation affects its ocular distribution in rabbits. Pharm Res 2002; 19(1):108-111.Kuwano M., Ibuki H., Morikawa N., Ota A., Kawashima Y. Cyclosporine A formulation affects its ocular distribution in rabbits. Pharm Res 2002; 19(1):108-111.Theng J., Zhou L., Tan D., La K.W. Distribution of cyclosporin A in the cornea after topical or oral administration. J Ocul Pharmacol Ther 2002; 18(1):83-88.Theng J., Zhou L., Tan D., La K.W. Distribution of cyclosporin A in the cornea after topical or oral administration. J Ocul Pharmacol Ther 2002; 18(1):83-88.P rez-Rico C., Germain F., Castro-Rebollo M., Moreno-Salgueiro A., Teus M. . Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease. Int J Ophthalmol 2013; 6(4):471-474. doi: 10.3980/j.issn.2222-3959.2013.04.12.P rez-Rico C., Germain F., Castro-Rebollo M., Moreno-Salgueiro A., Teus M. . Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease. Int J Ophthalmol 2013; 6(4):471-474. doi: 10.3980/j.issn.2222-3959.2013.04.12.Garweg J.G., Wegmann-Burns M., Goldblum D. Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines. Graefes Arch Clin Exp Ophthalmol 2006; 244(3): 382-389. Epub 2005 Aug 10.Garweg J.G., Wegmann-Burns M., Goldblum D. Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines. Graefes Arch Clin Exp Ophthalmol 2006; 244(3): 382-389. Epub 2005 Aug 10.BenEzra D., Maftzir G., de Courten C., Timonen P. Ocular penetration of cyclosporin A. III: The human eye. Br J Ophthalmol 1990; 74(6):350-352.BenEzra D., Maftzir G., de Courten C., Timonen P. Ocular penetration of cyclosporin A. III: The human eye. Br J Ophthalmol 1990; 74(6):350-352.Tang-Liu D.D., Acheampong A. Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye. Clin Pharmacokinet 2005; 44(3):247-261.Tang-Liu D.D., Acheampong A. Ocular pharmacokinetics and safety of ciclosporin, a novel topical treatment for dry eye. Clin Pharmacokinet 2005; 44(3):247-261.

The authors declare that there are no conflicts of interest present.