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      Comparison of the Effects of Preserved and Unpreserved Formulations of Timolol on the Ocular Surface of Albino Rabbits

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          Abstract

          Thirty-six albino rabbits, randomly divided into six groups, were used to study their ocular tolerance to (a) 0.25 and 0.50% Timoptol<sup>®</sup> preserved with 0.01% benzalkonium chloride, (b) 0.25 and 0.50% Timoptol-LP<sup>®</sup>, a gel-forming solution preserved with 0.012% benzododecinium bromide, and (c) 0.25 and 0.50% Timabak<sup>®</sup> unpreserved in the ABAK<sup>®</sup> eyedrops dispenser. All eyedrops were applied in the right eye for 60 days. A clinical follow-up with slitlamp examination and break-up time evaluation was performed for 2 months. At the end of the experimentation, the animals were sacrificed and their eyes enucleated for histological analyses of the conjunctiva and cornea. There was no significant difference in the clinical examination between each group, except for the break-up time evaluation between Timoptol and Timabak at each concentration which was better with the unpreserved timolol. Histological results showed a significant difference in the corneal stroma edema between preserved and unpreserved timolol. This study confirms that using unpreserved timolol may be beneficial for the long-term treatment of glaucomatous patients as it increases tear film stability and decreases epithelial permeability and stromal aggression of the cornea.

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          Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies.

          To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol. Experimental animal and human tissue study. Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month. Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study. Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied. Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups. These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.
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            Author and article information

            Journal
            ORE
            Ophthalmic Res
            10.1159/issn.0030-3747
            Ophthalmic Research
            S. Karger AG
            0030-3747
            1423-0259
            2000
            February 2000
            04 February 2000
            : 32
            : 1
            : 3-8
            Affiliations
            aDepartment of Ophthalmology, Ambroise Paré Hospital, APHP, and bToxicology Laboratory, University of Paris-V René Descartes, and cDepartment of Cellular Pharmacotoxicology, XV–XX Hospital, Paris, dDepartment of Ophthalmology, University of Nice, and eIris Pharma, La Gaude, France
            Article
            55579 Ophthalmic Res 2000;32:3–8
            10.1159/000055579
            10657748
            e62ae479-cead-47f6-8019-c73e4e387b3a
            © 2000 S. Karger AG, Basel

            Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

            History
            Page count
            Figures: 6, Tables: 3, References: 19, Pages: 6
            Categories
            Original Paper

            Vision sciences,Ophthalmology & Optometry,Pathology
            Benzalkonium,Cornea,Glaucoma,Toxicity,Preservative,Conjunctiva

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