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

Anastasios-Georgios Konstas, Konstadinos G Boboridis, Paraskevas Kapis, Konstantinos Marinopoulos, Irini C Voudouragkaki, Dimitrios Panayiotou, Dimitrios G Mikropoulos, Eirini Pagkalidou, Anna-Bettina Haidich, Andreas Katsanos, Luciano Quaranta, Anastasios-Georgios Konstas, Konstadinos G Boboridis, Paraskevas Kapis, Konstantinos Marinopoulos, Irini C Voudouragkaki, Dimitrios Panayiotou, Dimitrios G Mikropoulos, Eirini Pagkalidou, Anna-Bettina Haidich, Andreas Katsanos, Luciano Quaranta

Abstract

Introduction: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov (NCT02802137).

Funding: Santen.

Keywords: 24-h efficacy; BAK; Dorzolamide/timolol fixed combination; Latanoprost; OSD; Preservative-free tafluprost.

Figures

Fig. 1
Fig. 1
Flowchart of the study. BAK benzalkonium chloride, DTFC dorzolamide/timolol fixed combination, OSE ocular surface evaluation
Fig. 2
Fig. 2
24-h IOP control with BAK-preserved latanoprost (red), preservative-free tafluprost (green), and combined PF triple therapy (tafluprost and dorzolamide/timolol fixed combination) (yellow)
Fig. 3
Fig. 3
Daytime (orange) and nighttime (blue) efficacy of the study medications

References

    1. European Glaucoma Society . Terminology and guidelines for glaucoma. 4. Savona: PubliComm; 2014.
    1. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385:1295–1304. doi: 10.1016/S0140-6736(14)62111-5.
    1. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–713. doi: 10.1001/archopht.120.6.701.
    1. Olthoff CM, Schouten JS, van de Borne BW, Webers CA. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005;112:953–961. doi: 10.1016/j.ophtha.2004.12.035.
    1. Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26:233–236.
    1. Baudouin C, Renard JP, Nordmann JP, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol. 2013;23:47–54. doi: 10.5301/ejo.5000181.
    1. Batra R, Tailor R, Mohamed S. Ocular surface disease exacerbated glaucoma: optimizing the ocular surface improves intraocular pressure control. J Glaucoma. 2014;23:56–60. doi: 10.1097/IJG.0b013e318264cd68.
    1. Quaranta L, Biagioli E, Riva I, et al. Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: a systematic review and meta-analysis. J Ocul Pharmacol Ther. 2013;29:382–389. doi: 10.1089/jop.2012.0186.
    1. Konstas AGP, Quaranta L, Katsanos A, Voudouragkaki IC, Dutton GN. Fixed combination therapies in glaucoma. In: Shaarawy TM, Sherwood MB, Hitchings RA, Crowston JG, editors. Glaucoma. 2nd ed. Amsterdam: Elsevier; 2015. pp. 583–592.
    1. Baudouin C, Labbe A, Liang H, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–334. doi: 10.1016/j.preteyeres.2010.03.001.
    1. Freeman PD, Kahook MY. Preservatives in topical ophthalmic medications: historical and clinical perspectives. Expert Rev Ophthalmol. 2009;4:59–64. doi: 10.1586/17469899.4.1.59.
    1. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29:618–621. doi: 10.1097/ICO.0b013e3181c325b2.
    1. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17:350–355. doi: 10.1097/IJG.0b013e31815c5f4f.
    1. Ramli N, Supramaniam G, Samsudin A, Juana A, Zahari M, Choo MM. Ocular surface disease in glaucoma: effect of polypharmacy and preservatives. Optom Vis Sci. 2015;92:e222–e226. doi: 10.1097/OPX.0000000000000542.
    1. Cvenkel B, Štunf Š, Srebotnik Kirbiš I, Strojan Fležar M. Symptoms and signs of ocular surface disease related to topical medication in patients with glaucoma. Clin Ophthalmol. 2015;9:625–631. doi: 10.2147/OPTH.S81247.
    1. Lee SY, Wong TT, Chua J, Boo C, Soh YF, Tong L. Effect of chronic anti-glaucoma medications and trabeculectomy on tear osmolarity. Eye (Lond) 2013;27:1142–1150. doi: 10.1038/eye.2013.144.
    1. Schiffman RM, Walt JG, Jacobsen G, et al. Utility assessment among patients with dry eye disease. Ophthalmology. 2003;110:1412–1419. doi: 10.1016/S0161-6420(03)00462-7.
    1. Zimmerman TJ, Hahn SR, Gelb L, et al. The impact of ocular adverse effects in patients treated with topical prostaglandin analogs: changes in prescription patterns and patient persistence. J Ocular Pharmacol Ther. 2009;25:145–152. doi: 10.1089/jop.2008.0072.
    1. Boimer C, Birt CM. Preservative exposure and surgical outcomes in glaucoma patients: the PESO study. J Glaucoma. 2013;22:730–735. doi: 10.1097/IJG.0b013e31825af67d.
    1. Broadway D, Hitchings R, Grierson I. Topical antiglaucomatous therapy: adverse effects on the conjunctiva and implications for filtration surgery. J Glaucoma. 1995;4:136. doi: 10.1097/00061198-199504000-00012.
    1. Broadway DC, Chang LP. Trabeculectomy, risk factors for failure and the preoperative state of the conjunctiva. J Glaucoma. 2001;10:237–249. doi: 10.1097/00061198-200106000-00017.
    1. Ammar DA, Kahook MY. Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells. Mol Vis. 2011;17:1806–1813.
    1. IMS Health MIDAS, MAT Q1/2016 data.
    1. Pfizer Labs. Xalatan® package insert. Available at: . Accessed 21 Sept 2016.
    1. Heijl A, Patella VM, Bengtsson B. The field analyzer primer: effective perimetry. 4. Dublin: Carl Zeiss Meditec; 2012.
    1. The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf 2007;5:75–2.
    1. Schaumberg DA, Nichols JJ, Papas EB, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011;52:1994–2005. doi: 10.1167/iovs.10-6997e.
    1. van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Arch Ophthalmol. 1969;82:10–14. doi: 10.1001/archopht.1969.00990020012003.
    1. Konstas AG, Holló G, Mikropoulos D, et al. Twenty-four-hour intraocular pressure control with bimatoprost and the bimatoprost/timolol fixed combination administered in the morning, or evening in exfoliative glaucoma. Br J Ophthalmol. 2010;94:209–213. doi: 10.1136/bjo.2008.155317.
    1. Konstas AG, Quaranta L, Katsanos A, et al. Twenty-four hour efficacy with preservative free tafluprost compared with latanoprost in patients with primary open angle glaucoma or ocular hypertension. Br J Ophthalmol. 2013;97:1510–1515. doi: 10.1136/bjophthalmol-2012-303026.
    1. Konstas AG, Quaranta L, Bozkurt B, et al. 24-h efficacy of glaucoma treatment options. Adv Ther. 2016;33:481–517. doi: 10.1007/s12325-016-0302-0.
    1. Quaranta L, Katsanos A, Russo A, et al. 24-hour intraocular pressure and ocular perfusion pressure in glaucoma. Surv Ophthalmol. 2013;58:26–41. doi: 10.1016/j.survophthal.2012.05.003.
    1. Konstas AG, Voudouragkaki IC, Boboridis KG, et al. 24-hour efficacy of travoprost/timolol BAK-free versus latanoprost/timolol fixed combinations in patients insufficiently controlled with latanoprost. Adv Ther. 2014;31:592–603. doi: 10.1007/s12325-014-0125-9.
    1. Research in dry eye: report of the research subcommittee of the international dry eye workshop (2007). Ocul Surf 2007;5:179–3.
    1. Konstas AG, Katsanos A, Quaranta L, et al. Twenty-four hour efficacy of glaucoma medications. Prog Brain Res. 2015;221:297–318. doi: 10.1016/bs.pbr.2015.06.010.
    1. Konstas AG, Mantziris DA, Cate EA, Stewart WC. Effect of timolol on the diurnal intraocular pressure in exfoliation and primary open-angle glaucoma. Arch Ophthalmol. 1997;115:975–979. doi: 10.1001/archopht.1997.01100160145002.
    1. Bergeå B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology. 1999;106:997–1004. doi: 10.1016/S0161-6420(99)00523-0.
    1. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134–142. doi: 10.1097/00061198-200004000-00002.
    1. Hughes E, Spry P, Diamond J. 24-hour monitoring of intraocular pressure in glaucoma management: a retrospective review. J Glaucoma. 2003;12:232–236. doi: 10.1097/00061198-200306000-00009.
    1. Barkana Y, Anis S, Liebmann J, et al. Clinical utility of intraocular pressure monitoring outside of normal office hours in patients with glaucoma. Arch Ophthalmol. 2006;124:793–797. doi: 10.1001/archopht.124.6.793.
    1. Konstas AG, Quaranta L, Mikropoulos DG, et al. Peak intraocular pressure and glaucomatous progression in primary open-angle glaucoma. J Ocul Pharmacol Ther. 2012;28:26–32. doi: 10.1089/jop.2011.0081.
    1. Konstas AG, Holló G, Mikropoulos D, et al. Second-line therapy with dorzolamide/timolol or latanoprost/timolol fixed combination versus adding dorzolamide/timolol fixed combination to latanoprost monotherapy. Br J Ophthalmol. 2008;92:1498–1502. doi: 10.1136/bjo.2008.145219.
    1. Lanza NL, Valenzuela F, Perez VL, Galor A. The matrix metalloproteinase 9 point-of-care test in dry eye. Ocul Surf. 2016;14:189–195. doi: 10.1016/j.jtos.2015.10.004.
    1. López-Miguel A, Gutiérrez-Gutiérrez S, García-Vázquez C, Enríquez-de-Salamanca A. RNA collection from human conjunctival epithelial cells obtained with a new device for impression cytology. Cornea (Epub Aug 17, 2016).
    1. Tian L, Qu JH, Zhang XY, Sun XG. Repeatability and reproducibility of noninvasive Keratograph 5 M measurements in patients with dry eye disease. J Ophthalmol. 2016;2016:8013621. doi: 10.1155/2016/8013621.
    1. Martone G, Frezzotti P, Tosi GM, et al. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol. 2009;147:725–35, e1. doi: 10.1016/j.ajo.2008.10.019.

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