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      Changes in Ocular Surface Characteristics after Switching from Benzalkonium Chloride-Preserved Latanoprost to Preservative-Free Tafluprost or Benzalkonium Chloride-Preserved Tafluprost

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          Abstract

          Purpose

          The aim of the present study was to examine the effects of switching from Latanoprost ophthalmic solution containing a preservative to preservative-free Tafluprost ophthalmic solution or Tafluprost containing a preservative on ocular surfaces.

          Materials and Methods

          Forty patients (40 eyes) with glaucoma (mean age: 62.0 ± 10.9 years) using Latanoprost with preservative for six months or longer were assigned either to a Tafluprost-containing-preservative group (20 eyes) or preservative-free-Tafluprost group (20 eyes). The intraocular pressure, corneal epithelial barrier function (fluorescein uptake concentration with fluorophotometer FL-500), superficial punctate keratopathy (AD classification), and tear film breakup time (TBUT) were assessed before switching and at 12 weeks after switching.

          Results

          No significant differences in intraocular pressure were noted after switching in either group. Corneal epithelial barrier function was improved significantly after switching in both the Tafluprost-containing-preservative and the preservative-free-Tafluprost groups. There were no significant differences in AD scores after switching in the Tafluprost-containing-preservative group, but significant improvements were noted in the preservative-free-Tafluprost group. No significant differences in TBUT were noted in the Tafluprost-containing-preservative or preservative-free-Tafluprost groups after switching.

          Conclusion

          After switching from preservative Latanoprost to Tafluprost containing-preservative or preservative-free Tafluprost, corneal epithelial barrier function was improved while the intraocular pressure reduction was retained.

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          Most cited references33

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          Preservatives in eyedrops: the good, the bad and the ugly.

          Christophe Baudouin, Antoine Labbe, Hong Liang … (2010)
          There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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            A novel grading method for superficial punctate keratopathy magnitude and its correlation with corneal epithelial permeability.

            Kazunori Miyata, Mitsuru Sawa, Shiro Amano … (2003)
            To propose a novel grading method for superficial punctate keratopathy (SPK) magnitude and to examine the quantitativeness of the method. In 351 eyes diagnosed as having dry eye syndrome, SPK was graded as follows. After fluorescein staining, the total sum of the area of SPK was graded from A0 through A3, and the density was graded from D0 through D3. The grading was represented as the combination of the area and density grades. The correlation between the SPK grade and the corneal epithelial permeability to fluorescence, measured using an anterior fluorophotometer, was analyzed in the 351 eyes. The correlation between the fluorescein concentration in the cornea and the sum of the area and density grades. The higher the density and area grades, the higher the fluorescein concentration, except for A3D2. There was a clear exponential correlation between the sum of the area and density grades and the fluorescein concentration in the cornea, measured using an anterior fluorophotometer. The regression curve was y = 61.2e(0.59x), where y is the fluorescein concentration (nanograms per milliliter), and x is the sum of the area and density grades (P<.001). The SPK grade is positively correlated with the corneal epithelial permeability to fluorescence, measured using an anterior fluorophotometer. Our results indicate that this grading method can be clinically useful.
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              Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication.

              P Puska, Auli Ropo, Elina Palmgren … (2010)
              The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment. A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Ophthalmol
                Journal ID (iso-abbrev): J Ophthalmol
                Journal ID (publisher-id): JOPH
                Title: Journal of Ophthalmology
                Publisher: Hindawi
                ISSN (Print): 2090-004X
                ISSN (Electronic): 2090-0058
                Publication date (Print): 2017
                Publication date (Electronic): 2 August 2017
                Volume: 2017
                Electronic Location Identifier: 3540749
                Affiliations
                Department of Ophthalmology, St Marianna University School of Medicine, Kanagawa, Japan
                Author notes

                Academic Editor: Usha P. Andley

                Author information
                http://orcid.org/0000-0002-5268-4534
                Article
                DOI: 10.1155/2017/3540749
                PMC ID: 5558672
                SO-VID: ca74898e-028c-429b-ab4d-fa3467f1d7ba
                Copyright © Copyright © 2017 Naoto Tokuda et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 3 May 2017
                Date accepted : 16 July 2017
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Ophthalmology & Optometry
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry

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