{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:24:59Z","timestamp":1788272699884,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study evaluates the safety, tolerability, and efficacy of preservative-free Dorzolamide 2%-Timolol 0.5% (PF-DT), with a focus on improving the ocular microenvironment in a real-world transition setting. Materials and Methods: A prospective, multicenter, open-label study involving thirty patients with dry eye disease previously treated with BAK-DT was conducted. Participants were transitioned to PF-DT, and evaluated at weeks 4, 12, and 24. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included Break-Up Time (BUT), Schirmer test results, corneal staining, conjunctival hyperemia, intraocular pressure (IOP), and patient satisfaction. Results: Twenty-five patients completed the study. The OSDI improved from 21.5 to 12.5 (p &lt; 0.001), with 60.0% of patients showing improvement and 52.0% achieving complete symptom resolution. Among eyes with corneal staining, 78.4% demonstrated a reduction of at least one grade, and 50.0% of those with conjunctival redness showed similar improvement. By week 24, 78.0% exhibited no corneal staining, and 50.0% had no conjunctival redness. BUT increased from 5.0 to 7.0 (p &lt; 0.01), while IOP decreased by 1 mmHg (p &lt; 0.01). Satisfaction regarding comfort (\u226580%) and handling (\u226550%) was high, with 88.0% preferring PF-DT. Conclusions: Transitioning to PF-DT improved ocular surface health while maintaining IOP control, supporting the benefits of preservative-free formulations in restoring microenvironment homeostasis and enhancing tolerability and patient satisfaction.<\/jats:p>","DOI":"10.3390\/medicina62010184","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:39:37Z","timestamp":1768563577000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Real-World Transition to a Preservative-Free Fixed Combination of Dorzolamide\/Timolol: Impact on the Ocular Surface Microenvironment, Safety, Tolerability, and Efficacy"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-2916","authenticated-orcid":false,"given":"Ana","family":"Sanseau","sequence":"first","affiliation":[{"name":"Hospital J. M. Ramos Mej\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1221ADC, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4118-9957","authenticated-orcid":false,"given":"Arturo","family":"Burchakchi","sequence":"additional","affiliation":[{"name":"Hospital Italiano de Buenos Aires, Ciudad Aut\u00f3noma de Buenos Aires C1199ABB, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Cl\u00ednica de Ojos Dr. Nano, Buenos Aires B1636CSS, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Fontana","sequence":"additional","affiliation":[{"name":"Hospital Santa Luc\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1232AAC, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejo","family":"Peyret","sequence":"additional","affiliation":[{"name":"Hospital Durand, Ciudad Aut\u00f3noma de Buenos Aires C1405DCS, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2614-7708","authenticated-orcid":false,"given":"Giselle","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorios POEN S.A.U., Ciudad Aut\u00f3noma de Buenos Aires C1407BDR, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ail\u00edn","family":"Fantacone","sequence":"additional","affiliation":[{"name":"Laboratorios POEN S.A.U., Ciudad Aut\u00f3noma de Buenos Aires C1407BDR, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-9078","authenticated-orcid":false,"given":"Mar\u00eda Silvia","family":"Passerini","sequence":"additional","affiliation":[{"name":"Laboratorios POEN S.A.U., Ciudad Aut\u00f3noma de Buenos Aires C1407BDR, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier F.","family":"Casiraghi","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas, Ciudad Aut\u00f3noma de Buenos Aires C1120AAR, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jeyalatha, M.V., Qu, Y., He, X., Ou, S., Bu, J., Jia, C., Wang, J., and Wu, H. (2017). Dry Eye Management: Targeting the Ocular Surface Microenvironment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071398"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jtos.2023.08.009","article-title":"TFOS Lifestyle Report Executive Summary: A Lifestyle Epidemic\u2014Ocular Surface Disease","volume":"30","author":"Craig","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.jtos.2017.05.004","article-title":"TFOS DEWS II Iatrogenic Report","volume":"15","author":"Gomes","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1007\/s00417-010-1397-7","article-title":"Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide\/timolol fixed combination (COSOPTTM) in patients with elevated intraocular pressure in a randomized clinical trial","volume":"248","author":"Shedden","year":"2010","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5301\/ejo.5000220","article-title":"Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients","volume":"23","author":"Rossi","year":"2013","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1177\/112067210701700311","article-title":"Ocular symptoms and signs with preserved and preservative-free glaucoma medications","volume":"17","author":"Jaenen","year":"2007","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s00417-008-0881-9","article-title":"German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye","volume":"246","author":"Erb","year":"2008","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/IJG.0b013e31815c5f4f","article-title":"Prevalence of ocular surface disease in glaucoma patients","volume":"17","author":"Leung","year":"2008","journal-title":"J. Glaucoma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.jfo.2021.03.008","article-title":"Relationship between OSDI score and biomicroscopic ocular surface damages in glaucomatous patients treated with preserved antiglaucomatous eye drops","volume":"44","author":"Lajmi","year":"2021","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12325-020-01525-5","article-title":"Dorzolamide\/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future","volume":"38","author":"Konstas","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/jop.2018.0134","article-title":"Patient-reported nonadherence with glaucoma therapy","volume":"35","author":"Wolfram","year":"2019","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.2147\/PPA.S264926","article-title":"Improving adherence to topical medication in patients with glaucoma","volume":"15","author":"Tapply","year":"2021","journal-title":"Patient Prefer. Adherence"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5301\/ejo.5000181","article-title":"Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension","volume":"23","author":"Baudouin","year":"2013","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00061198-199504000-00012","article-title":"Topical Antiglaucomatous Therapy: Adverse Effects on the Conjunctiva and Implications for Filtration Surgery","volume":"4","author":"Broadway","year":"1995","journal-title":"J. Glaucoma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.preteyeres.2010.03.001","article-title":"Preservatives in eyedrops: The good, the bad and the ugly","volume":"29","author":"Baudouin","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15210","DOI":"10.1038\/s41598-020-72295-x","article-title":"Ocular surface inflammation induces de novo expression of substance P in the trigeminal primary afferents with large cell bodies","volume":"10","author":"Byun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1167\/tvst.13.10.31","article-title":"Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity","volume":"13","author":"Vereertbrugghen","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/ICO.0b013e31815cf651","article-title":"Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears","volume":"27","author":"Kahook","year":"2008","journal-title":"Cornea"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Brignole-Baudouin, F., Desbenoit, N., Hamm, G., Liang, H., Both, J.P., Brunelle, A., Fournier, I., Guerineau, V., Legouffe, R., and Stauber, J. (2012). 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, 7.","DOI":"10.1371\/journal.pone.0050180"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II Management and Therapy Report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_22","unstructured":"Yadgarov, B.Y.A., and Garg, R.A. (2016). Preservative-free alternatives. Glaucoma Today, 38\u201340. Available online: https:\/\/glaucomatoday.com\/articles\/2016-nov-dec\/preservative-free-alternatives."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/j.1755-3768.2008.01250.x","article-title":"Detrimental effect of preservatives in eyedrops: Implications for the treatment of glaucoma","volume":"86","author":"Baudouin","year":"2008","journal-title":"Acta Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1755-3768.2010.01907.x","article-title":"Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication","volume":"88","author":"Uusitalo","year":"2010","journal-title":"Acta Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"445","DOI":"10.2147\/OPTH.S91402","article-title":"Benefits of switching from latanoprost to preservative-free tafluprost eye drops: A meta-analysis of two phase IIIb clinical trials","volume":"10","author":"Uusitalo","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.2147\/OPTH.S382497","article-title":"Tolerability in Glaucoma Patients Switched from Preserved to Preservative-Free Prostaglandin-Timolol Combination: A Prospective Real-Life Study","volume":"16","author":"Pauk","year":"2022","journal-title":"Clin. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1177\/1120672118785280","article-title":"The RELIEF study: Tolerability and efficacy of preservative-free latanoprost in the treatment of glaucoma or ocular hypertension","volume":"29","author":"Pomorska","year":"2019","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s10792-025-03411-x","article-title":"Efficacy and safety of preservative\u2014free anti\u2014glaucomatous eye drops (dorzolamide\/timolol) in ocular hypertension and\/or glaucoma","volume":"45","author":"Lazreg","year":"2025","journal-title":"Int. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12982-024-00185-y","article-title":"Epidemiology of dry eye disease in Argentina","volume":"21","author":"Marini","year":"2024","journal-title":"Discov. Public Health"},{"key":"ref_30","first-page":"110","article-title":"Efficacy and Tolerability of a New Latanoprost 0.005% BAK-Free Nanoemulsion: A Nonrandomized Open-Label Trial","volume":"1","author":"Casiraghi","year":"2021","journal-title":"ReGEN Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.2147\/OPTH.S112711","article-title":"Efficacy and tolerability of benzalkonium chloride-free travoprost in glaucoma patients switched from benzalkonium chloride-preserved latanoprost or bimatoprost","volume":"10","author":"Hubatsch","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jtos.2024.08.001","article-title":"Preservatives and ocular surface disease: A review","volume":"34","author":"Kahook","year":"2024","journal-title":"Ocul. Surf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e000892","DOI":"10.1136\/bmjophth-2021-000892","article-title":"Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops","volume":"6","author":"Hedengran","year":"2021","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000517845","article-title":"Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro","volume":"6","author":"Hedengran","year":"2021","journal-title":"Biomed. Hub"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.clae.2015.01.016","article-title":"Goblet cell density association with tear function and ocular surface physiology","volume":"38","author":"Sapkota","year":"2015","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1097\/ICO.0b013e31823f8e7d","article-title":"Comparison of the long-term effects of various topical antiglaucoma medications on meibomian glands","volume":"31","author":"Arita","year":"2012","journal-title":"Cornea"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ajo.2008.10.019","article-title":"An In Vivo Confocal Microscopy Analysis of Effects of Topical Antiglaucoma Therapy With Preservative on Corneal Innervation and Morphology","volume":"147","author":"Martone","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_38","first-page":"40","article-title":"In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American ophthalmological society thesis)","volume":"110","author":"Baudouin","year":"2012","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2147\/OPTH.S229815","article-title":"Impact of ocular surface disease treatment in patients with glaucoma","volume":"14","author":"Boso","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/IJG.0b013e318264cd68","article-title":"Ocular surface disease exacerbated glaucoma: Optimizing the ocular surface improves intraocular pressure control","volume":"23","author":"Batra","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1097\/IJG.0000000000001041","article-title":"Influence of treating ocular surface disease on intraocular pressure in glaucoma patients intolerant to their topical treatments: A report of 10 cases","volume":"27","author":"Dubrulle","year":"2018","journal-title":"J. Glaucoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00176782","article-title":"Reliability of intraocular pressure measurement with the Goldmann applanation tonometer in epidemiological studies","volume":"232","author":"Dielemans","year":"1994","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/00132578-200307000-00008","article-title":"Factors for glaucoma progression and the effect of treatment","volume":"4","author":"Leske","year":"2003","journal-title":"Evid.-Based Eye Care"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e876","DOI":"10.1111\/aos.14410","article-title":"Preservative-free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008\u20132016","volume":"98","author":"Chamard","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1755-3768.2007.01155.x","article-title":"Self-application of single-use eyedrop containers in an elderly population: Comparisons with standard eyedrop bottle and with younger patients","volume":"86","author":"Dietlein","year":"2008","journal-title":"Acta Ophthalmol."},{"key":"ref_46","first-page":"10","article-title":"A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide","volume":"106","author":"Boyle","year":"1999","journal-title":"Ophthalmology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:35:36Z","timestamp":1768566936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["medicina62010184"],"URL":"https:\/\/doi.org\/10.3390\/medicina62010184","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}