title: 24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.
abstract: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD).
  
  
  
  Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period.
  
  
  
  Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001).
  
  
  
  In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy.
  
  
  
  ClinicalTrials.gov (NCT02802137).
  
  
  
  Santen.
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece. konstas@med.auth.gr.|3rd University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece. konstas@med.auth.gr.
authors.forename: Anastasios-Georgios
authors.initials: AG
authors.lastname: Konstas
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.|3rd University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstadinos G
authors.initials: KG
authors.lastname: Boboridis
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Paraskevas
authors.initials: P
authors.lastname: Kapis
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Marinopoulos
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Irini C
authors.initials: IC
authors.lastname: Voudouragkaki
authors.affiliation: 1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Panayiotou
authors.affiliation: 3rd University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Mikropoulos
authors.affiliation: Department of Hygiene, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Pagkalidou
authors.affiliation: Department of Hygiene, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Anna-Bettina
authors.initials: AB
authors.lastname: Haidich
authors.affiliation: Department of Ophthalmology, University of Ioannina, Ioannina, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Katsanos
authors.affiliation: Department of Medical and Surgical Specialties, Section of Ophthalmology, University of Brescia, Brescia, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Quaranta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D011310:Preservatives, Pharmaceutical; D011446:Prospective Studies; D011460:Prostaglandins F / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014065:Tonometry, Ocular; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011310:Preservatives, Pharmaceutical; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; D013449:Sulfonamides; D013876:Thiophenes; C479140:dorzolamide-timolol combination; C485333:tafluprost; D000077338:Latanoprost; D013999:Timolol
keywords: 24-h efficacy; BAK; Dorzolamide/timolol fixed combination; Latanoprost; OSD; Preservative-free tafluprost