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      Dietary Tocopherol Supplementation after Trabeculectomy and Phacotrabeculectomy: Double-Blind Randomized Placebo-Controlled Trial

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          Abstract

          Purpose: The vitamin E compound α-tocopherol inhibits fibroblast growth in vitro. To evaluate its potential benefit in preventing failure of glaucoma filtration surgery, we prospectively investigated the outcome of filtering surgery with postoperative dietary α-tocopherol supplementation. Patients and Methods: Thirty-nine patients (39 eyes) with primary open-angle glaucoma or pseudoexfoliative glaucoma were randomly assigned to two post-(phaco)-trabeculectomy treatment groups. Daily oral intake of 300 mg α-tocopheryl-acetate (absorbed as α-tocopherol in the intestine) for 2 months was compared to a placebo preparation in a double-blind trial. The follow-up time was 1 year. Success was defined as intraocular pressure (IOP) ≤18 mm Hg with no medication, no needling revision, and no subconjunctival injection. Results: In the tocopherol group, the relative risk for trabeculectomy failure decreased from 1.58 at 2 weeks (p = 0.95) to 1.0 at 1 year. Success rates (67–90%) and IOP reduction (mean 39 to 53%) were statistically comparable in the two groups. Considering postoperative complications, no relevant differences were found. Discussion: Trabeculectomy and phacotrabeculectomy outcome did not show any differences between α-tocopherol-supplemented patients and the placebo group.

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          Most cited references6

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          Basic science and clinical aspects of wound healing in glaucoma filtering surgery.

          Success of glaucoma filtration surgery is influenced by the wound healing response. Attention has been focused on pharmacological agents to control a process that leads to excessive scarring and eventual failure of glaucoma filtration surgery. Several agents, including 5-fluorouracil and mitomycin C, as well as other antiproliferative drugs will be discussed. Newer antifibrotic agents and novel drug delivery systems are under development in tissue culture and animal models in an effort to improve efficacy and safety. This article summarizes current treatment modalities and future prospects to prevent excessive wound healing and improve the success of glaucoma filtration surgery.
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            Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure produces good long term control of intraocular pressure without risk of sight threatening complications.

            To determine the long term outcome of systemic anti-inflammatory fibrosis suppression in cases of threatened trabeculectomy bleb failure in open angle glaucoma.
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              Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C.

              To evaluate the potential of the vitamin E compound alpha-tocotrienol as antifibrotic agent in vitro. Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms alpha-tocopherol, alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5 min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24 h. alpha-Tocopherol and alpha-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by alpha-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to alpha-tocopheryl succinate, 50 microM or repeatedly 20 microM of alpha-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400 microg/ml showed a stronger antiproliferative effect than alpha-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. Of the vitamin E forms tested, only alpha-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of alpha-tocotrienol.
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2009
                July 2009
                21 February 2009
                : 223
                : 4
                : 228-232
                Affiliations
                Departments of Ophthalmology, aUniversity of Bern, Inselspital, Bern, and bUniversity Hospital Basel, University of Basel, Basel, and cDepartment of Strabismus and Neuro-Ophthalmology, Kantonsspital St. Gallen, St. Gallen, Switzerland
                Article
                203367 Ophthalmologica 2009;223:226–230
                10.1159/000203367
                19246952
                292202bf-fb6d-4f68-a4d0-9375262b0ca7
                © 2009 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
                : 20 November 2008
                : 12 December 2008
                Page count
                Figures: 1, Tables: 2, References: 14, Pages: 5
                Categories
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Wound-healing,Glaucoma,Complications,Trabeculectomy,Failure,Surgery,Vitamin E

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