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      Current Treatment Approaches in Diabetic Macular Edema

      review-article
      Ophthalmologica
      S. Karger AG
      Diabetic macular edema, Laser photocoagulation, Pars plana vitrectomy, Intravitreal injection

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          Abstract

          Purpose: To review current treatment approaches in diabetic macular edema (DME). Methods: The underlying pathopathology, classifications and diagnostic examination techniques including fluorescein angiography, optical coherence tomography and stereoscopic biomicroscopy. Treatment modalities with focal or grid argon laser photocoagulation, pars plana vitrectomy with and without peeling of the inner limiting membrane (ILM), as well as intravitreal injections using triamcinolone acetonide or novel vascular endothelial growth factor (VEGF) inhibitors are described. Results: DME results from a series of biochemical and cellular changes, causing progressive leakage and exudation. Focal and grid photocoagulation remains the standard care for diabetic maculopathy. However, the availability of new agents raises the possibility of improvements if significant benefits can be validated in randomized clinical trials. Posterior vitreous attachments play a critical role through several mechanical or physiological mechanisms. Vitrectomy without ILM removal seems to be effective in reducing the retinal thickness and improving visual acuity. Conclusion: A proper evaluation of the vitreous and retina is fundamental to select the most appropriate treatment approach in DME. While small microaneurysms with focal DME may be treated by conventional focal photocoagulation, diffuse DME which do not respond to grid photocoagulation may benefit from intravitreal injections using triamcinolone acetonide or novel VEGF inhibitors. Eyes with DME and additional vitreous traction may benefit from pars plana vitrectomy without ILM peeling. A combination of laser, pharmacological and surgical treatment modalities may be necessary to maintain central vision in eyes with DME.

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          Most cited references64

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          A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema.

          To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME). Randomized, double-masked, multicenter, dose-ranging, controlled trial. Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks. Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36. Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36. One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss. In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.
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            Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells.

            The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.
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              Macular edema. A complication of diabetic retinopathy.

              Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                978-3-8055-8262-9
                978-3-318-01449-5
                0030-3755
                1423-0267
                2007
                March 2007
                26 March 2007
                : 221
                : 2
                : 118-131
                Affiliations
                Department of Ophthalmology, Philipps University, Marburg, Germany
                Article
                98257 Ophthalmologica 2007;221:118–131
                10.1159/000098257
                17380066
                c554ffaa-07a8-471b-8606-37c0dd554538
                © 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: 13, Tables: 1, References: 105, Pages: 14
                Categories
                Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Intravitreal injection,Diabetic macular edema,Pars plana vitrectomy,Laser photocoagulation

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