{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:25:56Z","timestamp":1792661156835,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T00:00:00Z","timestamp":1378857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To evaluate the effects at 1\u00a0year of preservative\u2010free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty patients with primary open\u2010angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age\u2010matched controls. Clinical tests (<jats:styled-content style=\"fixed-case\">IOP<\/jats:styled-content>, Schirmer I test, and lacrimal film break\u2010up time <jats:styled-content style=\"fixed-case\">BUT<\/jats:styled-content>) and <jats:italic>in vivo<\/jats:italic> conjunctival confocal microscopy (<jats:styled-content style=\"fixed-case\">IVCM<\/jats:styled-content>) were performed in all patients at baseline and after 12\u00a0months. <jats:styled-content style=\"fixed-case\">IVCM<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HRT II R<\/jats:styled-content>ostock <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ornea <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>odule; <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>eidelberg <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>ngineering <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>mb<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> H<\/jats:styled-content>eidelberg, <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ermany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main <jats:styled-content style=\"fixed-case\">IVCM<\/jats:styled-content> outcomes were goblet cell density and epithelial regularity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IVCM<\/jats:styled-content> and clinical parameters were similar in the three groups at baseline. After 12\u00a0months, intra\u2010epithelial goblet cell density was significantly lower in the preserved (48.25\u00a0\u00b1\u00a07.70) than in the preservative\u2010free beta\u2010blocker group (86.83\u00a0\u00b1\u00a022.17, p\u00a0&lt;\u00a00.001) and controls (88.9\u00a0\u00b1\u00a018.33, p\u00a0&lt;\u00a00.001). The epithelial layer was significantly more regular in the preserved beta\u2010blocker medication group than in the preservative\u2010free beta\u2010blocker group (p\u00a0&lt;\u00a00.001) and the control group (p\u00a0&lt;\u00a00.001). A significant reduction in both <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>chirmer I and <jats:styled-content style=\"fixed-case\">BUT<\/jats:styled-content> was found in the group of preserved timolol (respectively, 11.3\u00a0\u00b1\u00a02.97 and 8.12\u00a0\u00b1\u00a00.99) compared with preservative\u2010free timolol (16.8\u00a0\u00b1\u00a01.83 and 11.27\u00a0\u00b1\u00a01.27, p\u00a0&lt;\u00a00.001) and controls (17.8\u00a0\u00b1\u00a01.87 and 12.10\u00a0\u00b1\u00a01.28, p\u00a0&lt;\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on our <jats:styled-content style=\"fixed-case\">IVCM<\/jats:styled-content> data, preservative\u2010free beta\u2010blocker gel induces less changes at ocular surface than preserved beta\u2010blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.12261","type":"journal-article","created":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T12:40:08Z","timestamp":1378903208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["<i>In vivo<\/i> confocal microscopy of conjunctiva in preservative\u2010free timolol 0.1% gel formulation therapy for glaucoma"],"prefix":"10.1111","volume":"92","author":[{"given":"Paolo","family":"Frezzotti","sequence":"first","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fogagnolo","sequence":"additional","affiliation":[{"name":"Eye Clinic San Paolo Hospital Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gentiana","family":"Haka","sequence":"additional","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Motolese","sequence":"additional","affiliation":[{"name":"University of Genova Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iester","sequence":"additional","affiliation":[{"name":"University of Genova Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone A.","family":"Bagaglia","sequence":"additional","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mittica","sequence":"additional","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Menicacci","sequence":"additional","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Eye Clinic San Paolo Hospital Universit\u00e0 degli Studi di Milano Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Motolese","sequence":"additional","affiliation":[{"name":"Department of Surgery Ophthalmology Unit University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-9071.2000.00237.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.all.0000183112.86181.9e"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)90116-1"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.01.036"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2010.03.001"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e3181ca7c7a"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1994.01090230060021"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/112067210801800314"},{"key":"e_1_2_5_10_1","first-page":"851","article-title":"Hyperosmolarity potentiates toxic effects of benzalkonium chloride on conjunctival epithelial cells in vitro","volume":"18","author":"Clouzeau C","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_5_11_1","first-page":"619","article-title":"Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells","volume":"40","author":"De Saint Jean M","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_12_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1076\/0271-3683(200002)2021-DFT085","article-title":"Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells","volume":"20","author":"De Saint Jean M","year":"2000","journal-title":"Curr Eye Res"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.43"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1989.tb01883.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2006.07.006"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2012.05.001"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2008.0140"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.579901"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.44"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(92)31847-0"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2009.161059"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-200312000-00007"},{"key":"e_1_2_5_23_1","first-page":"3442","article-title":"Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry","volume":"33","author":"Kuppens EV","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3886"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033913"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2004.08.028"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32830e6b04"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2008.10.019"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2005.11.053"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2011.11.003"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000224648.74095.90"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2012.02481.x"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.131722"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1983.01040020871007"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000116526.57227.82"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v11.i34.30"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10766"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000055579"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.86.4.418"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1067"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.84.11.1250"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1159\/000417219"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2010.01907.x"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(80)35215-9"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2005.01.042"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2722"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.80.7.583"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.155820"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2008.0072"}],"container-title":["Acta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Faos.12261","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.12261","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:16:31Z","timestamp":1695550591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aos.12261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,11]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/aos.12261"],"URL":"https:\/\/doi.org\/10.1111\/aos.12261","archive":["Portico"],"relation":{},"ISSN":["1755-375X","1755-3768"],"issn-type":[{"value":"1755-375X","type":"print"},{"value":"1755-3768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,11]]},"assertion":[{"value":"2012-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}