{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:45:23Z","timestamp":1784357123734,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To investigate the effect of fixed combination versus concomitant unfixed topical glaucoma treatment on patients\u2019 adherence and ocular surface health. Patients and Methods: This is a 6-month, prospective, parallel-group, observational study in patients with ocular hypertension (OHT), primary open-angle glaucoma (POAG), or exfoliation glaucoma (XFG). A total of 142 patients with similar baseline characteristics were enrolled in this study. Seventy-one patients received a Latanoprost 0.005%\/Timolol 0.5% fixed combination in the evening, whereas seventy-one patients received the unfixed treatment with Latanoprost 0.005% in the evening and Timolol 0.5% twice daily. The primary outcome was the adherence rate at baseline, and at the 3- and 6-month follow-up visits. The secondary outcomes included the signs of ocular surface disease (OSD) and intraocular pressure (IOP). Results: The adherence of patients treated with the fixed combination was higher than the unfixed treatment at the 3-month (78.0% vs. 63.0%, p &lt; 0.001) and at the 6-month visits (73.0% vs. 58.5%, p &lt; 0.01). The Break-up Time, Schirmer test, and Van Bijsterveld score were worse in the unfixed group at baseline and all subsequent examinations (p &lt; 0.05 for all comparisons). There were no differences in the mean IOP between groups at baseline, 1-, and 3-month visits. IOP appears higher in the unfixed group at 6 months (16.7 vs. 15.0 mmHg, p &lt; 0.01). Conclusion: The patients with ocular hypertension and primary open-angle glaucoma treated with a fixed combination are significantly more adherent and show a healthier ocular surface than those treated with an unfixed combination. The study provides significant evidence of the benefits of fixed combination treatment.<\/jats:p>","DOI":"10.3390\/jcm12093137","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T02:18:34Z","timestamp":1682561914000},"page":"3137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fixed versus Unfixed Combination of Topical Latanoprost\/Timolol for Glaucoma: An Observational Study Investigating the Level of Adherence and Ocular Surface Health"],"prefix":"10.3390","volume":"12","author":[{"given":"Victoria","family":"Toumanidou","sequence":"first","affiliation":[{"name":"2nd Department of Ophthalmology, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-050X","authenticated-orcid":false,"given":"Asterios","family":"Diafas","sequence":"additional","affiliation":[{"name":"2nd Department of Ophthalmology, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Georgiadis","sequence":"additional","affiliation":[{"name":"1st Department of Ophthalmology, Ahepa Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Tsinopoulos","sequence":"additional","affiliation":[{"name":"2nd Department of Ophthalmology, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4103\/0253-7613.108279","article-title":"Drug use in primary open angle glaucoma: A prospective study at a tertiary care teaching hospital","volume":"45","author":"Yadav","year":"2013","journal-title":"Indian J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/S0161-6420(01)00873-9","article-title":"Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery","volume":"108","author":"Lichter","year":"2001","journal-title":"Ophthalmology"},{"key":"ref_3","first-page":"95","article-title":"Costs of treating primary open-angle glaucoma and ocular hypertension: A retrospective observational two-year chart review of newly diagnosed patients in Sweden and the United States","volume":"7","author":"Gerdtham","year":"1998","journal-title":"J. Glaucoma."},{"key":"ref_4","unstructured":"Shaarawy, T., Hitchings, R., Sherwood, M., and Crowston, J. (2009). Glaucoma, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1136\/bjo.2008.139329","article-title":"Efficacy of antiglaucoma fixed combination therapy vs unfixed components in reducing intraocular pressure: A systematic review","volume":"92","author":"Cox","year":"2008","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ophtha.2005.10.034","article-title":"Patient-reported behavior and problems in using glaucoma medications","volume":"113","author":"Sleath","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_7","first-page":"1","article-title":"Considerations in glaucoma therapy: Fixed combinations vs their component medications","volume":"4","author":"Higginbotham","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1517\/14656561003667540","article-title":"Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma","volume":"11","author":"Razeghinejad","year":"2010","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.survophthal.2008.08.011","article-title":"A review of additivity to prostaglandin analogs: Fixed and unfixed combinations","volume":"53","author":"Tabet","year":"2008","journal-title":"Surv. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/00055735-200404000-00013","article-title":"Fixed combinations of topical glaucoma medications","volume":"15","author":"Fechtner","year":"2004","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/eye.2000.197","article-title":"Compliance and Viewpoint of Glaucoma Patients in Greece","volume":"14","author":"Konstas","year":"2000","journal-title":"Eye"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0002-9394(14)74225-4","article-title":"Compliance with topical timolol treatment","volume":"103","author":"Kass","year":"1987","journal-title":"Am. J. Ophthalmol."},{"key":"ref_13","first-page":"1","article-title":"Medication behaviour. A study of outpatients treated with pilocarpine eye drops for primary open angle glaucoma","volume":"58","author":"Norell","year":"1980","journal-title":"Acta Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/S0149-2918(99)80026-5","article-title":"Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice","volume":"21","author":"Farmer","year":"1999","journal-title":"Clin. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0738-3991(78)80033-0","article-title":"Patient compliance with antihypertensive regimens","volume":"1","author":"Sackett","year":"1978","journal-title":"Patient Couns. Health Educ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.ophtha.2004.12.026","article-title":"Does Adjunctive Glaucoma Therapy Affect Adherence to the Initial Primary Therapy?","volume":"112","author":"Robin","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop","volume":"5","author":"Lemp","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1001\/archinte.159.12.1359","article-title":"Dry eye and dry mouth in the elderly: A population-based assessment","volume":"159","author":"Schein","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/01.ico.0000220776.93852.d9","article-title":"Incidence and prevalence of glaucoma in severe ocular surface disease","volume":"25","author":"Tsai","year":"2006","journal-title":"Cornea"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2147\/OPTH.S30717","article-title":"Efficacy and safety of travoprost 0.004%\/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy","volume":"6","author":"Costa","year":"2012","journal-title":"Clin. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2147\/PPA.S23780","article-title":"Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: A systematic review","volume":"5","author":"Reardon","year":"2011","journal-title":"Patient Prefer. Adherence"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/0301-4738.73693","article-title":"Compliance and adherence in glaucoma management","volume":"59","author":"Robin","year":"2011","journal-title":"Indian J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.ophtha.2004.12.035","article-title":"Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension","volume":"112","author":"Olthoff","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/01.icu.0000156139.05323.26","article-title":"Compliance and persistency in glaucoma follow-up treatment","volume":"16","author":"Schwartz","year":"2005","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.survophthal.2008.08.002","article-title":"Adherence and persistence with glaucoma therapy","volume":"53","author":"Schwartz","year":"2008","journal-title":"Surv. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1089\/jop.2011.0057","article-title":"Ocular Hypotensive Effects and Safety over 3 Months of Switching from an Unfixed Combination to Latanoprost 0.005%\/Timolol Maleate 0.5% Fixed Combination","volume":"27","author":"Inoue","year":"2011","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2147\/PPA.S47785","article-title":"A study to assess the feasibility of undertaking a randomized controlled trial of adherence with eye drops in glaucoma patients","volume":"7","author":"Richardson","year":"2013","journal-title":"Patient Prefer. Adherence"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/S0149-2918(01)80109-0","article-title":"A systematic review of the associations between dose regimens and medication compliance","volume":"23","author":"Claxton","year":"2001","journal-title":"Clin. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2147\/OPTH.S29062","article-title":"Ocular hypotensive effect and safety of travoprost 0.004%\/timolol maleate 0.5% fixed combination after change of treatment regimen from \u03b2-blockers and prostaglandin analogs","volume":"6","author":"Inoue","year":"2012","journal-title":"Clin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.ophtha.2011.05.013","article-title":"The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity","volume":"118","author":"Sleath","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3109\/02713683.2011.562340","article-title":"Review Ocular surface disease in patients with ocular hypertension and glaucoma","volume":"36","author":"Stewart","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_33","first-page":"350","article-title":"Review Management of dry eye disease","volume":"146","author":"Lemp","year":"2008","journal-title":"Am. J. Manag. Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/15569520902995834","article-title":"Ocular preservatives: Associated risks and newer options","volume":"28","author":"Kaur","year":"2009","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/BF02853166","article-title":"Effects of common ophthalmic preservatives on ocular health","volume":"18","author":"Noecker","year":"2001","journal-title":"Adv. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/ICU.0b013e328089f1c8","article-title":"The effect of drop vehicle on the efficacy and side effects of topical glaucoma therapy: A review","volume":"18","author":"Yee","year":"2007","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2165\/11588830-000000000-00000","article-title":"Effects of common topical antiglaucoma medications on the ocular surface, eyelids and periorbital tissue","volume":"28","author":"Servat","year":"2011","journal-title":"Drugs Aging"},{"key":"ref_38","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_39","first-page":"714","article-title":"Short-term effect of topical brinzolamide-timolol fixed combination on ocular surface of glaucoma patients","volume":"5","author":"Firat","year":"2012","journal-title":"Int. J. Ophthalmol."},{"key":"ref_40","first-page":"230","article-title":"The influence of ocular surface diseases in the management of glaucoma","volume":"34","author":"Brasnu","year":"2011","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1517\/14656566.2011.589384","article-title":"From dorzolamide 2%\/timolol 0.5% to brinzolamide 1%\/timolol 0.5% fixed combination: A 6-month, multicenter, open-label tolerability switch study","volume":"12","author":"Rossi","year":"2011","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s40123-018-0150-x","article-title":"Brinzolamide\/Brimonidine Fixed Combination: Simplifying Glaucoma Treatment Regimens","volume":"7","author":"Moosavi","year":"2018","journal-title":"Ophthalmol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s10384-011-0078-3","article-title":"Effects of antiglaucoma drugs on the ocular surface in rabbits: A fixed-combination drug versus two concomitant drugs","volume":"55","author":"Cho","year":"2011","journal-title":"JPN J. Ophthalmol."},{"key":"ref_44","first-page":"750","article-title":"Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy","volume":"9","author":"Liu","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1185\/03007995.2015.1039504","article-title":"Efficacy and tolerability of prostaglandin\u2013timolol fixed combinations: An updated systematic review and meta-analysis","volume":"31","author":"Lou","year":"2015","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cheng, J.-W., Cheng, S.-W., Gao, L.-D., Lu, G.-C., and Wei, R.-L. (2012). Intraocular Pressure-Lowering Effects of Commonly Used Fixed-Combination Drugs with Timolol: A Systematic Review and Meta-Analysis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045079"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1089\/jop.2004.20.375","article-title":"Intraocular pressure and safety in glaucoma patients switching to latanoprost\/timolol maleate fixed combination from mono- and adjunctive therapies","volume":"20","author":"Konstas","year":"2004","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_48","first-page":"879","article-title":"Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension: A systematic review and meta-analysis","volume":"7","author":"Xing","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/bjo.2003.018234","article-title":"A 12 week study comparing the fixed combination of latanoprost and timolol with the concomitant use of the individual components in patients with open angle glaucoma and ocular hypertension","volume":"88","author":"Diestelhorst","year":"2004","journal-title":"Br. J. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:23:46Z","timestamp":1760124226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12093137"],"URL":"https:\/\/doi.org\/10.3390\/jcm12093137","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,26]]}}}