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      The Use of Orbital Radiotherapy for Graves’ Ophthalmopathy: Quantitative Review of the Evidence

      meta-analysis
      , ,
      Ophthalmologica
      S. Karger AG
      Meta-analysis, Graves’ ophthalmopathy, Orbital radiotherapy, Glucocorticoids

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          Abstract

          Objective: To systematically evaluate the efficacy of orbital radiotherapy in the treatment of Graves’ ophthalmology. Methods: Pertinent studies were selected through an electronic search of Cochrane Library, Medline, Embase and Chinese Biomedical Database. Studies meeting selected criteria were reviewed systematically by meta-analysis. The treatment effect was measured as risk difference (RD) of treatment failure, and pooled estimates were computed according to a random effect model. Results: A total of 18 studies were included in this meta-analysis, 8 cohort and 10 randomized. Orbital radiotherapy alone was significantly more effective than a vehicle control [pooled RD = –0.26, 95% confidence interval (CI) = –0.41 to –0.10] and as effective as oral corticosteroids (pooled RD = –0.10, 95% CI = –0.20 to –0.00). The combination of orbital radiotherapy and oral corticosteroids was markedly more effective than other treatment modalities (pooled RD = –0.27, 95% CI = –0.36 to –0.17). Orbital radiotherapy combined with intravenous methylprednisolone was more efficacious than other treatment modalities (pooled RD = –0.18, 95% CI = –0.30 to –0.07). Conclusions: Orbital radiotherapy appears to be an effective treatment for Graves’ ophthalmology and seems to have an increased effect when given with systemic corticosteroids. Orbital radiotherapy combined with intravenous methylprednisolone seems to have the best documented efficacy.

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          Most cited references13

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          Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy.

          Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double-blind, prospective study. The CAS was determined by an opthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade. Responders (22) and non-responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non-responders. Twelve of 22 responders and three of 21 non-responders had a CAS > or = 4 (55% vs 14%; P or = 4 had a similar duration of Graves' ophthalmopathy as patients with a CAS < 4. The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.
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            A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy.

            Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.
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              Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study.

              The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation. In a double-blind randomised clinical trial, 30 patients with moderately severe Graves' orbitopathy had radiotherapy (20 Gy in ten fractions), and 30 were assigned sham-irradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables, such as eyelid aperture, proptosis, eye movements, subjective eye score, and clinical-activity score at 24 weeks. The qualitative treatment outcome was successful in 18 of 30 (60%) irradiated patients versus nine of 29 (31%) sham-irradiated patients at week 24 (relative risk [RR]=1.9 [95% CI 1.0-3.6], p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Quantitatively, elevation improved significantly in the radiotherapy group, whereas all other variables remained unchanged. The field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after sham-irradiation. Nevertheless, only 25% of the irradiated patients were spared from additional strabismus surgery. In these patients with moderately severe Graves' orbitopathy, radiotherapy should be used only to treat motility impairment.
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                978-3-8055-8455-5
                978-3-8055-8456-2
                0030-3755
                1423-0267
                2008
                December 2007
                19 December 2007
                : 222
                : 1
                : 27-31
                Affiliations
                Department of Ophthalmology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
                Article
                109275 Ophthalmologica 2008;222:27–31
                10.1159/000109275
                18097177
                7850125c-76b9-47c4-a7b1-98529b2c8912
                © 2007 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: 3, Tables: 1, References: 27, Pages: 5
                Categories
                Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Glucocorticoids,Orbital radiotherapy,Graves’ ophthalmopathy,Meta-analysis

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