{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:41:57Z","timestamp":1772152917395,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"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: A prospective, randomized clinical trial was conducted to evaluate the concentration of ofloxacin in the aqueous humour (AqH) of patients suffering from dry eye disease (DED) after topical instillation. Materials and Methods: Ninety-one (91) cataract patients scheduled for phacoemulsification were categorized into three groups according to DED severity. Group I (n = 17) was comprised of subjects without DED, patients in group II (n = 37) were evaluated as having non-severe DED, while group III (n = 37) consisted of patients suffering from severe DED. Preoperatively, patients received 4 drops of 0.3% of ofloxacin at 15 min intervals. One hour after the last instillation, aqueous samples were collected intraoperatively. Results: The median AqH concentration of ofloxacin in group I was 199.9 ng\/mL (range 92.2\u2013442.8 ng\/mL), while in group II it was 530.5 ng\/mL (range 283.7\u20131004.9 ng\/mL), and 719.2 ng\/mL (range 358.0\u20131512.4 ng\/mL) in Group III, p &lt; 0.001 (Kruskal-Wallis tests). Pairwise tests (two-tailed with Bonferroni corrections) between groups resulted in a p-value of 0.001 when group II was compared to group I and group III was compared to group I, and a p-value of 0.020 when group II was compared to group III. The severity of DED, across groups I, II, and III, and the levels of ofloxacin revealed a strong positive correlation (r = 0.639, p &lt; 0.001). Conclusions: Ofloxacin concentration in the AqH after topical drop instillation may be affected by the degree of ocular surface inflammation in patients suffering from DED.<\/jats:p>","DOI":"10.3390\/medicina58081031","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T21:01:24Z","timestamp":1659387684000},"page":"1031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aqueous Humour Ofloxacin Concentration after Topical Instillation in Patients with Dry Eye Disease"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6648-8921","authenticated-orcid":false,"given":"Konstantinos","family":"Kagkelaris","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Patras, 26504 Patras, Greece"},{"name":"Pharmacology Laboratory, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A.","family":"El Mubarak","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacokinetics, Department of Pharmacy, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Plotas","sequence":"additional","affiliation":[{"name":"Lab Primary Health Care, School of Health Rehabilitation Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitris","family":"Panaretos","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George D.","family":"Panayiotakopoulos","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory B.","family":"Sivolapenko","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacokinetics, Department of Pharmacy, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5646-1370","authenticated-orcid":false,"given":"Constantinos D.","family":"Georgakopoulos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jtos.2017.05.005","article-title":"TFOS DEWS II Introduction","volume":"15","author":"Nelson","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/cxo.12849","article-title":"Molecular Evidence for the Role of Inflammation in Dry Eye Disease","volume":"102","author":"Ganesalingam","year":"2019","journal-title":"Clin. Exp. Optom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/jop.2019.0060","article-title":"The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options","volume":"36","author":"Periman","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tsubota, K., Pflugfelder, S.C., Liu, Z., Baudouin, C., Kim, H.M., Messmer, E.M., Kruse, F., Liang, L., Carreno-Galeano, J.T., and Rolando, M. (2020). Defining Dry Eye from a Clinical Perspective. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239271"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108294","DOI":"10.1016\/j.exer.2020.108294","article-title":"Inflammatory Basis for Dry Eye Disease Flares","volume":"201","author":"Perez","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jtos.2021.04.002","article-title":"Altered Ocular Surface Immune Cell Profile in Patients with Dry Eye Disease","volume":"21","author":"Nair","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ophtha.2018.10.023","article-title":"Dry Eye Syndrome Preferred Practice Pattern\u00ae","volume":"126","author":"Akpek","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1548","DOI":"10.1002\/wnan.1548","article-title":"Fundamentals, Challenges, and Nanomedicine-based Solutions for Ocular Diseases","volume":"11","author":"Srinivasarao","year":"2019","journal-title":"WIREs Nanomed. Nanobiotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0168-3659(90)90122-A","article-title":"Mechanisms and Facilitation of Corneal Drug Penetration","volume":"11","author":"Lee","year":"1990","journal-title":"J. Control. Release"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101389","DOI":"10.1016\/j.jddst.2019.101389","article-title":"Target Strategies for Drug Delivery Bypassing Ocular Barriers","volume":"55","author":"Suri","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1124\/jpet.119.256933","article-title":"Ocular Drug Delivery: Present Innovations and Future Challenges","volume":"370","author":"Gote","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s13346-016-0339-2","article-title":"A Comprehensive Insight on Ocular Pharmacokinetics","volume":"6","author":"Agrahari","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1128\/AAC.29.1.163","article-title":"Synthesis and Antibacterial Activities of Optically Active Ofloxacin","volume":"29","author":"Hayakawa","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","first-page":"CD006364","article-title":"Perioperative Antibiotics for Prevention of Acute Endophthalmitis after Cataract Surgery","volume":"2","author":"Gower","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","unstructured":"(2021, December 15). PubChem Compound Summary for CID 4583, Ofloxacin, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Ofloxacin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1001\/archopht.1981.03930010303017","article-title":"Normal Human Tear PH by Direct Measurement","volume":"99","author":"Abelson","year":"1981","journal-title":"Arch. Ophthalmol. (Chic. IL. 1960)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4137\/PMC.S14459","article-title":"Antibiotics and Bacterial Resistance in the 21st Century","volume":"6","author":"Fair","year":"2014","journal-title":"Perspect. Medicin. Chem."},{"key":"ref_18","first-page":"1","article-title":"An Eye for Azithromycin: Review of the Literature","volume":"10","author":"Kagkelaris","year":"2018","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/00055735-200408000-00007","article-title":"Fourth-Generation Fluoroquinolones: New Topical Agents in the War on Ocular Bacterial Infections","volume":"15","author":"Mah","year":"2004","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tyagi, R.K., Garg, N., Shukla, R., and Bisen, P.S. (2020). Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery into the Posterior Segment of the Eyeball. Role of Novel Drug Delivery Vehicles in Nanobiomedicine, IntechOpen. [1st ed.].","DOI":"10.5772\/intechopen.77468"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1136\/bjophthalmol-2013-304619","article-title":"Diagnosing the Severity of Dry Eye: A Clear and Practical Algorithm","volume":"98","author":"Baudouin","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jcrs.2019.03.023","article-title":"An Algorithm for the Preoperative Diagnosis and Treatment of Ocular Surface Disorders","volume":"45","author":"Starr","year":"2019","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_23","first-page":"435","article-title":"Quantification of Ofloxacin in Human Aqueous Humour of the Eye by LC-MS\/MS","volume":"13","author":"Kagkelaris","year":"2022","journal-title":"J. Anal. Bioanal. Tech."},{"key":"ref_24","unstructured":"(2021, December 15). EMEA Guideline on Bioanalytical Method Validation. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf."},{"key":"ref_25","unstructured":"(2021, December 15). FDA & CDER Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Contains Nonbinding Recommendations, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioanalytical-method-validation-guidance-industry."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II Epidemiology Report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1056\/NEJMra1407936","article-title":"Dry Eye","volume":"378","author":"Clayton","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2147\/OPTH.S188314","article-title":"Dry Eye Disease Ranking among Common Reasons for Seeking Eye Care in a Large US Claims Database","volume":"13","author":"Bradley","year":"2019","journal-title":"Clin. Ophthalmol."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00055735-199604000-00014","article-title":"Side Effects of Antiglaucomatous Drugs on the Ocular Surface","volume":"7","author":"Baudouin","year":"1996","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/00003226-199601000-00013","article-title":"The Kinetics of Anterior Chamber Ofloxacin Penetration","volume":"15","author":"Bouchard","year":"1996","journal-title":"Cornea"},{"key":"ref_32","first-page":"123","article-title":"Factors Affecting Corneal Penetration of Drugs","volume":"12","author":"Sadiq","year":"2016","journal-title":"Al-Shifa J. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1517\/17425247.5.5.567","article-title":"Ocular Novel Drug Delivery: Impacts of Membranes and Barriers","volume":"5","author":"Barar","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1248\/cpb.58.1301","article-title":"Effects of Pathological Conditions on Ocular Pharmacokinetics of Antimicrobial Drugs","volume":"58","author":"Ueda","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1128\/AAC.39.2.549","article-title":"Effect of Inflammation on Intraocular Penetration of Intravenous Ofloxacin in Albino Rabbits","volume":"39","author":"Gatti","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1076\/ceyr.19.6.461.5277","article-title":"The Effect of Long-Term Use and Inflammation on the Ocular Penetration of Topical Ofloxacin","volume":"19","author":"Kortunay","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0378-5173(00)00482-8","article-title":"Penetration of Topical and Oral Ofloxacin into the Aqueous and Vitreous Humor of Inflamed Rabbit Eyes","volume":"204","author":"Kurt","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0181-5512(07)89584-2","article-title":"The Vicious Circle in Dry Eye Syndrome: A Mechanistic Approach","volume":"30","author":"Baudouin","year":"2007","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.survophthal.2021.03.007","article-title":"Corneal Lymphangiogenesis as a Potential Target in Dry Eye Disease-a Systematic Review","volume":"66","author":"Chennakesavalu","year":"2021","journal-title":"Surv. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry Eye Disease and Oxidative Stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/aos.13436","article-title":"Clinical Impact of Inflammation in Dry Eye Disease: Proceedings of the ODISSEY Group Meeting","volume":"96","author":"Baudouin","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/archophthalmol.2011.364","article-title":"Dry Eye Disease: An Immune-Mediated Ocular Surface Disorder","volume":"130","author":"Stevenson","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0002-9394(02)01334-X","article-title":"Fourth Generation Fluoroquinolones: New Weapons in the Arsenal of Ophthalmic Antibiotics","volume":"133","author":"Mather","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1097\/IAE.0b013e3180323f96","article-title":"Endophthalmitis: A Review of Current Evaluation and Management","volume":"27","author":"Lemley","year":"2007","journal-title":"Retina"},{"key":"ref_45","first-page":"27","article-title":"A UPLC-MS Method for the Determination of Ofloxacin Concentrations in Aqueous Humor","volume":"9","author":"Plotas","year":"2014","journal-title":"Anal. Chem. Insights"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/00006982-199806000-00005","article-title":"Penetration of Ofloxacin in Human Aqueous and Vitreous Humors Following Oral and Topical Administration","volume":"18","author":"Cekic","year":"1998","journal-title":"Retina"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/1031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:53Z","timestamp":1760140853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/1031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,1]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["medicina58081031"],"URL":"https:\/\/doi.org\/10.3390\/medicina58081031","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,1]]}}}