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      Experimental Posterior Perforating Ocular Injury in Rabbit Eyes: Effects of Radiotherapy with or without Intravitreal Cyclosporin on Vitreous Proliferation


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          Double perforating ocular injuries were made in 30 rabbits and the effects of radiotherapy (RT) alone or in combination with cyclosporin (CS) on vitreous proliferation investigated. Thirteen rabbits in group 1 received RT alone (600 cGy), and 13 rabbits in group 2 received RT combined with 100 µg of intravitreal CS. No treatment was given to 4 rabbits in the control group (group 3). All animals were ophthalmologically examined on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings scored; they were sacrificed on the 28th day, and histopathological scoring was made. The median histopathological score of the RT group (4.0; range: 0–8) was significantly higher than that of the CS + RT group (1.0; range: 0–5; p = 0.018). We conclude that intravitreal CS may be used as an adjunctive agent to RT to inhibit intraocular proliferation following penetrating ocular injury in rabbits.

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          Most cited references12

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          Distribution of cyclosporin in organ transplant recipients.

          Cyclosporin is an immunosuppressive agent with a narrow therapeutic index. The total concentration of cyclosporin in blood is usually monitored to guide dosage adjustment and to compensate for substantial interindividual and intraindividual variability in cyclosporin pharmacokinetics. Cyclosporin is a highly lipophilic molecule and widely distributes into blood, plasma and tissue components. It mainly accumulates in fat-rich organs, including adipose tissue and liver. In blood, it binds to erythrocytes in a saturable fashion that is dependent on haematocrit, temperature and the concentration of plasma proteins. In plasma, it binds primarily to lipoproteins, including high-density, low-density and very-low-density lipoprotein, and, to a lesser extent, albumin. The unbound fraction of cyclosporin in plasma (CsA(fu)) expressed as a percentage is approximately 2%. It has been shown that both the pharmacokinetic and pharmacodynamic properties of cyclosporin are related to its binding characteristics in plasma. Furthermore, there is some evidence to indicate that the unbound concentration of cyclosporin (CsA(U)) has a closer association with both kidney and heart allograft rejection than the total (bound + unbound) concentration. However, the measurement of CsA(fu) is inherently complex and cannot easily be performed in a clinical setting. Mathematical models that calculate CsA(fu), and hence CsA(U), from the concentration of plasma lipoproteins may be a more practical option, and should provide a more accurate correlate of effectiveness and toxicity of this drug in transplant recipients than do conventional monitoring procedures. In conclusion, the distribution characteristics of cyclosporin in blood, plasma and various tissues are clinically important. Further investigations are needed to verify whether determination of CsA(U) improves the clinical management of transplant recipients.
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            Liposome-bound cyclosporine: retinal toxicity after intravitreal injection.

            The retinal toxicity of intraocular liposome-bound cyclosporine was studied in albino rabbits by means of electrophysiology and histopathology. During a followup period of one month, no histopathological or electroretinographic changes were noted using concentrations of 100, 200 and 500 micrograms injected intravitreally.
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              Experimental posterior penetrating eye injury in the rabbit. II. Histology of wound, vitreous, and retina.

              The histological findings of the wound, the vitreous, and the retina in the rabbit eye with experimental posterior penetrating injury are described. Wound healing had just begun at 3 days after injury and was well established by 9 to 12 days. It involved proliferation of cells from the episclera and from the choroid. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had begen at 6 days after injury and seemed to be derived from the choroid, the nonpigmented ciliary epithelium and, posteriorly, from the optic nervehead. During the development of retinal detachment the configuration of the peripheral and posterior retina, together with the orientation of vitreous strands, suggested the presence of vitreous traction. We postulate that the presence of contractile fibroblasts (myofibroblasts) in the vitreous may provide the mechanism for vitreous traction. The retinal detachments were also characterised by epiretinal and subretinal membranes, but these were not prominent. The end-stage appearance of a soft, shrunken eye with cyclitic membrane formation and retinal detachment resembles the outcome in many human eyes after severe penetrating injuries.

                Author and article information

                S. Karger AG
                December 2005
                21 December 2005
                : 220
                : 1
                : 6-11
                Departments of aOphthalmology, bRadiation Oncology, cPathology, dBiochemistry and eAnesthesiology, Erciyes University Faculty of Medicine, Kayseri, Turkey
                89268 Ophthalmologica 2006;220:6–11
                © 2006 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.

                : 21 September 2004
                Page count
                Figures: 3, Tables: 2, References: 21, Pages: 6
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Radiotherapy,Cyclosporin,Eye injuries, rabbits,Proliferative vitreoretinopathy


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