Ophthalmologica
Current Treatment Approaches in Diabetic Macular EdemaMeyer C.H.Department of Ophthalmology, Philipps University, Marburg, Germany
|
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Article / Publication Details
Published online: March 26, 2007
Issue release date: March 2007
Number of Print Pages: 14
Number of Figures: 13
Number of Tables: 1
ISSN: 0030-3755 (Print)
eISSN: 1423-0267 (Online)
For additional information: https://www.karger.com/OPH
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.
© 2007 S. Karger AG, Basel
Related Articles:
References
- Klein R, Klein BEK, Moss SE, Davis MD, Demets DL: The Wisconsin epidemiologic study of diabetic retinopathy. Ophthalmology 1984;91:1464–1474.
- Hörle S, Gruner F, Kroll P: Epidemiologie diabetischer Erblindung: eine Übersicht. Klin Monatsbl Augenheilkd 2002;219:777–784.
-
Fauser S, Krohne TU, Kirchhof B, Joussen AM: Diabetic maculopathy – classification and therapy. Klin Monatsbl Augenheilkd 2003;220:526–531.
External Resources
-
Graefe von A: Über die mit Diabetes mellitus vorkommenden Sehstörungen. Dies Arch IV 1858;2:230–234.
- Hesse L, Grusser M, Hoffstadt K, Jorgens V, Hartmann P, Kroll P: Population-based study of diabetic retinopathy in Wolfsburg. Ophthalmologe 2001;98:1065–1068.
- Bresnick GH: Diabetic maculopathy: a critical review highlighting diffuse macular edema. Ophthalmology 1983;90:1301–1317.
- Ferris FL, Patz A: Macular edema: a complication of diabetic retinopathy. Surv Ophthalmol 1984;28(suppl):452–461.
- Perkovich BT, Meyers SM: Systemic factors affecting diabetic macular edema. Am J Ophthalmol 1988;105:211–212.
- Klein R, Moss SE, Klein BEK, et al.: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XI. The incidence of macular edema. Ophthalmology 1989;96:1501–1510.
- Meyer CH, Kroll P, Hammes HP: Führt Insulin glargin (Lantus) zu einer Progression der diabetischen Retinopathie? Klin Monatsbl Augenheilkd 2005;222:353–354.
-
Diabetic Retinopathy Study Research Group: A modification of the Airlie House classification of diabetic retinopathy. Report 7. Invest Ophthalmol Vis Sci 1981;21:210–226.
- Hesse L, Kroll P: What is the ophthalmologic recommendation for managing diabetes with reference to diabetic retinopathy. Internist (Berl) 1993;34:477.
- Kroll P, Meyer-Rüsenberg HW, Busse H: Recommendation for staging of proliferative diabetic retinopathy. Fortschr Ophthalmol 1987;84:360–363.
- Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema. ETDRS report No 4. Int Ophthalmol Clin 1987;27:254–264.
- Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT; Global Diabetic Retinopathy Project Group: Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110:1677–1682.
- Early Treatment Diabetic Retinopathy Study Research Group: Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report No 1. Arch Ophthalmol 1985;103:1796–1806.
- Ulbig MW, McHugh JDA, Hamilton AMP: Focal diode laser treatment for diabetic macular edema. Br J Ophthalmol 1995;79:318–321.
- Blankenship GW: Diabetic macular edema and argon laser photocoagulation: a prospective randomized study. Ophthalmology 1979;86:69–78.
- Lee CM, Olk RJ: Modified grid laser photocoagulation for diffuse diabetic macular edema: long-term visual results. Ophthalmology 1991;98:1594–1602.
- McDonald HR, Schatz H: Macular edema following panretinal photocoagulation. Retina 1985;5:5–10.
- Olk RJ: Modified grid argon (blue-green) laser photocoagulation for diffuse diabetic macular edema. Ophthalmology 1986;93:938–950.
-
Tachi N, Ogino N: Long-term follow up of grid photocoagulation for diffuse macular edema associated with diabetic retinopathy. Folia Ophthalmol Jpn 1996;47:1252–1256.
- McDonald HR, Schatz H: Grid photocoagulation of diffuse macular edema. Retina 1985;5:65–72.
- McNaught El, Foulds WS, Allan D: Grid photocoagulation improves reading ability in diffuse macular edema. Eye 1988;2:288–296.
- Stefansson E, Landers MB: How does vitrectomy affect diabetic macular edema? Am J Ophthalmol 2006;141:984.
- Stefansson E: The therapeutic effects of retinal laser treatment and vitrectomy: a theory based on oxygen and vascular physiology. Acta Ophthalmol Scand 2001;79:435–440.
- Grewing R, Mester U: Early vitrectomy for progressive diabetic proliferations covering the macula. Br J Ophthalmol 1994;78:433–436.
- Nasrallah FP, Jalkh AE, VanCoppenrolle F, et al: The role of the vitreous in diabetic macular edema. Ophthalmology 1988;95:1335–1339.
- Hikichi T, Fujio N, Akiba Y, Takahashi M, Yoshida A: Association between the short-term natural history of diabetic macular edema and the vitreomacular relationship in type II diabetes mellitus. Ophthalmology 1997;104:473–478.
- Sebag J, Buckingham B, Charles MA, Reiser K: Biochemical abnormalities of vitreous in humans with proliferative diabetic retinopathy. Arch Ophthalmol 1992;110:1472–476.
- Sebag J, Nie S, Reiser K, et al: Raman spectroscopy of human vitreous in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 1994;35:2976–2980.
-
Sebag J, Balazs EA: Pathogenesis of CME: anatomic consideration of vitreoretinal adhesions. Surv Ophthalmol 1984;29(suppl): 493–498.
External Resources
- Walton KA, Meyer CH, Harkrider CJ, Cox TA, Toth CA. Age-related changes in vitreous mobility as measured by video B scan ultrasound. Exp Eye Res 2002;74:173–180.
- Lewis H, Abrams GW, Blumenkranz MS, Campo RV: Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992;99:753–759.
- Harbour JW, Smiddy WE, Flynn HW Jr, Rubsamen PE: Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. Am J Ophthalmol 1996;121:405–413.
- Pendergast SD: Vitrectomy for diabetic macular edema associated with a taut premacular posterior hyaloid. Curr Opin Ophthalmol 1998;9:71–75.
- Pendergast SD, Hassan TS, Williams GA et al: Vitrectomy for diffuse diabetic macular edema associated with a taut premacular posterior hyaloid. Am J Ophthalmol 2000;130:178–186.
- Lewis H: The role of vitrectomy in the treatment of diabetic macular edema. Am J Ophthalmol 2001;131:123–125.
- Kaiser PK, Riemann CD, Sears JE, Lewis H: Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction. Am J Ophthalmol 2001;131:44–49.
- La Heij EC, Hebdrikse F, Kessels AGH, Derhaag PJFM: Vitrectomy results in diabetic macular oedema without evident vitreomacular traction. Graefes Arch Clin Exp Ophthalmol 2001;239:264–270.
- Tachi N, Ogino N: Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol 1996;122:258–260.
- Ikeda T, Sato K, Katano T, Hayashi Y: Improved visual acuity following pars plana vitrectomy for diabetic cystoid macular edema and detached posterior hyaloid. Retina 2000;20:220–222.
- Kumagai K, Ogino N, Furukawa M, et al: Internal limiting membrane peeling in vitreous surgery for diabetic macular edema. Nippon Ganka Gakkai Zasshi 2002;106:590–594.
- Yamamoto T, Naoko A, Takeuchi S: Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol 2001;132:369–377.
- Otani T, Kishi S: A controlled study of vitrectomy for diabetic macular edema. Am J Ophthalmol 2002;134:214–219.
-
Hörle S, Poestgens H, Schmidt J, Kroll P: Effect of pars plana vitrectomy for proliferative diabetic vitreoretinopathy on preexisting diabetic maculopathy. Graefe’s Arch Clin Exp Ophthalmol 2002;240:197–201.
- Yamamoto T, Hitani K, Sato Y, Yamashita H, Takeuchi S: Vitrectomy for diabetic macular edema with and without internal limiting membrane removal. Ophthalmologica 2005;219:206–213.
- Yamamoto T, Hitani K, Tsukahara I, et al: Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol 2003;135:14–19.
- Stolba U, Binder S, Gruber D, Krebs I, Aggermann T, Neumaier B: Vitrectomy for persistent diffuse diabetic macular edema. Am J Ophthalmol 2005;140:295–301.
- Lai WW, Mohamed S, Lam DS: Improvement of visual acuity in eyes with diabetic macular edema after treatment with pars plana vitrectomy. Ophthalmologica 2005;219:189.
- Jahn CE, Topfner von Schutz K, Richter J, Boller J, Kron M: Improvement of visual acuity in eyes with diabetic macular edema after treatment with pars plana vitrectomy. Ophthalmologica 2004;218:378–384.
- Dillinger P, Mester U: Vitrectomy with removal of the internal limiting membrane in chronic diabetic macular oedema. Graefes Arch Clin Exp Ophthalmol 2004;242:630–637.
- Hesse L, Bodanowitz S, Hühnermann M, Kroll P: Prediction of visual acuity after early vitrectomy in diabetics. Ger J Ophthalmol 1996;5:257–256.
-
Meyer CH, Zaki NV, Mennel S, Hörle S, Schmidt JC, Kroll P: Verlauf der diabetischen Retinopathie bei einem Zwillingspaar 5 Jahre nach Pankreas-Transplantation. Spektrum Augenheilkd 2005;19:183–187.
External Resources
- Jumper MJ, Embabi SN, Toth CA, McCuen BW, Hatchell DL: Electron immunocytochemical analysis of posterior hyaloid associated with diabetic macular edema. Retina 2000;20:63–68.
- Giovannini A, Amato G, Mariotti C, Scassellati-Sforzolini B: Optical coherence tomography findings in diabetic macular edema before and after vitrectomy. Ophthalmic Surg Lasers 2000;31:187–191.
- Grigorian R, Bhagat N, Lanzetta P, Tutela A, Zarbin M: Pars plana vitrectomy for refractory diabetic macular edema. Semin Ophthalmol 2003;18:116–120.
- Gandorfer A, Messmer EM, Ulbig MW, Kampik A: Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane. Retina 2000;20:126–133.
- Gandorfer A, Kampik A: Surgical removal of the internal limiting membrane in diabetic cystoid macular edema. Retina 2006;26:485–4856.
- Kishi S, Shimizu K: Posterior vitreous precortical pocket. Arch Ophthalmol 1990;108:979–982.
- Stefaniotou M, Aspiotis M, Kalogeropoulos C, et al: Vitrectomy results for diffuse diabetic macular edema with and without inner limiting membrane removal. Eur J Ophthalmol 2004;14:137–143.
- Patel JI, Hykin PG, Schadt M, Luong V, Fitzke F, Gregor ZJ: Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema. Retina 2006;26:5–13.
- Kralinger MT, Pedri M, Kralinger F, Troger J, Kieselbach GF: Long-term outcome after vitrectomy for diabetic macular edema. Ophthalmologica 2006;220:147–152.
- Lam RF, Lai WW, Chan WM, Liu DT, Lam DS: Vitrectomy for diabetic macular edema with and without internal limiting membrane removal. Ophthalmologica 2006;220:206.
- Meyer CH, Mennel S, Rodrigues EB: Retinal striae after surgical and spontaneous ILM-peeling. Am J Ophthalmol 2005;139:396.
- Rodrigues EB, Meyer CH, Farah ME, Kroll P: Intravitreal staining of the internal limiting membrane using indocyanine green in the treatment of macular holes. Ophthalmologica 2005;219:251–262.
- Rodrigues EB, Meyer CH, Schmidt JC, Kroll P: Surgical management of epiretinal membrane with indocyanine-green-assisted peeling. Ophthalmologica 2004;218:73–74.
- Schmidt JC, Rodrigues EB, Meyer CH, Hörle S, Kroll P: A modified technique to stain the internal limiting membrane with indocyanine green. Ophthalmologica 2004;218:176–179.
- Meyer CH, Rodrigues EB, Kroll P: Reduced concentration and incubation of intravitreal indocyanine green can improve the functional outcome in macular hole surgery. Am J Ophthalmol 2004;137:386.
- Shah SP, Laidlaw DA: Vitrectomy for diabetic macular edema. Am J Ophthalmol 2006;141:225.
- Joussen AM, Llacer H, Mazciewicz J, Kirchhof B: Surgical treatment of diabetic retinopathy and maculopathy. Ophthalmologe 2004;101:1171–1180.
- Stefansson E, Landers MB, Wolbarsht ML: Increased retinal oxygen supply following panretinal photocoagulation and vitrectomy and lensectomy. Trans Am Ophthalmol Soc 1981;79:307–334.
- Hesse L, Kroll P: Enzymatically induced posterior vitreous detachment in proliferative diabetic vitreoretinopathy. Klin Monatsbl Augenheilkd 1999;214:84–89.
- Hesse L, Nebeling B, Schroeder B, Heller G, Kroll P: Induction of posterior vitreous detachment in rabbits by intravitreal injection of tissue plasminogen activator following cryopexy. Exp Eye Res 2000;70:31–39.
- Azzolini C, D’Angelo A, Maestranzi G, Codenotti M, Della Valle P, Prati M, Brancato R: Intrasurgical plasmin enzyme in diabetic macular edema. Am J Ophthalmol 2004;138:560–566.
- Machemer R, Sugita G, Tano Y: Treatment of intraocular proliferations with intravitreal steroids. Trans Am Ophthalmol Soc 1979;77:171–180.
- Tano Y, Sugita G, Abrams G, Machemer R: Inhibition of intraocular proliferation with intravitreal corticosteroid. Am J Ophthalmol 1980;89:131–136.
- Tano Y, Chandler D, Machemer R: Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 1980;90:810–816.
- McCuen BW II, Bessler M, Tano Y, et al: The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol 1981;91:785–788.
- Hida T, Chandler D, Arena JE, Machemer R: Experimental and clinical observations of the intraocular toxicity of commercial corticosteroid preparations. Am J Ophthalmol 1986;101:190–195.
- Wilson CA, Berkoviz BA, Sato Y, et al: Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation. Arch Ophthalmol 1992;110:1155–1159.
- Fischer S, Renz D, Schaper W, Karliczek GF: In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor. Eur J Pharmacol 2001;411:231–243.
- Folkman J, Ingber DE: Angiostatic steroids: method of discovery and mechanism of action. Ann Surg 1987;206:374–383.
- Penfold PL, Wen L, Madigan MC, Gillies MC, King NJ, Provis JM: Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol 2000;121:458–465.
- Penfold PL, Wong JG, Gyory J, Billson FA: Effects of triamcinolone acetonide on microglial morphology and quantitative expression of MHC-II in exudative age-related macular degeneration. Clin Experiment Ophthalmol 2001;29:188–192.
- Bhattacherjee P, Williams RN, Eakins KE: A comparison of the ocular anti-inflammatory activity of steroidal and nonsteroidal compounds in the rat. Invest Ophthalmol Vis Sci 1983;24:1143–1146.
- Umland SP, Nahrebne DK, Razac S, Beavis A, Pennline KJ, Egan RW, Billah MM: The inhibitory effects of topically active glucocorticoids on IL-4, IL-5, and interferon gamma production by cultured primary CD4+ T cells. J Allergy Clin Immunol 1997;100:511–519.
- Nauck M, Karakiulakis G, Perruchoud AP, Papakonstantinou E, Roth M: Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 1998;341:309–315.
- Martidis A, Duker JS, Greenberg PB et al: Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920–927.
- Avitabile T, Longo A, Reibaldi A: Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema. Am J Ophthalmol 2005;140:695–702.
- Er H, Yilmaz H: Intravitreal cortisone injection for refractory diffuse diabetic macular edema. Ophthalmologica 2005;219:394–400.
- Patelli F, Fasolino G, Radice P, Russo S, Zumbo G, Di Tizio FM, Frisone G, Marchi S: Time course of changes in retinal thickness and visual acuity after intravitreal triamcinolone acetonide for diffuse diabetic macular edema with and without previous macular laser treatment. Retina 2005;25:840–845.
-
Itakura H, Akiyama H, Hagimura N, Doi H, Tanaka T, Kishi S, Kurabayashi M: Triamcinolone acetonide suppresses interleukin-1 beta-mediated increase in vascular endothelial growth factor expression in cultured rat Müller cells. Graefes Arch Clin Exp Ophthalmol 2005;28:1–6.
- Avci R, Kaderli B: Intravitreal triamcinolone injection for chronic diabetic macular oedema with severe hard exudates. Graefes Arch Clin Exp Ophthalmol 2006;244:28–35.
- Spandau UH, Derse M, Schmitz-Valckenberg P, Papoulis C, Jonas JB: Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema. Br J Ophthalmol 2005;89:999–1003.
- Bakri SJ, Kaiser PK: Posterior subtenon triamcinolone acetonide for refractory diabetic macular edema. Am J Ophthalmol 2005;139:290–294.
- Fluocinolone acetonide ophthalmic–Bausch & Lomb: fluocinolone acetonide Envision TD implant. Drugs R D 2005;6:116–119.
- Lim LL, Smith JR, Rosenbaum JT: Retisert (Bausch & Lomb/Control Delivery Systems). Curr Opin Investig Drugs 2005;6:1159–1167.
- Jaffe GJ, Ben-Nun J, Guo H, Dunn JP, Ashton P: Fluocinolone acetonide sustained drug delivery device to treat severe uveitis. Ophthalmology 2000;107:2024–2033.
- Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D’Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD; Macugen Diabetic Retinopathy Study Group: A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 2005;112:1747–1757.
- Krzystolik MG, Filippopoulos T, Ducharme JF, Loewenstein JI: Pegaptanib as an adjunctive treatment for complicated neovascular diabetic retinopathy. Arch Ophthalmol 2006;124:920–921.
- Adamis AP, Altaweel M, Bressler NM, Cunningham ET Jr, Davis MD, Goldbaum M, Gonzales C, Guyer DR, Barrett K, Patel M; Macugen Diabetic Retinopathy Study Group: Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 2006;113:23–28.
- Jaissle GB, Ziemssen F, Petermeier K, Szurman P, Ladewig M, Gelisken F, Volker M, Holz FG, Bartz-Schmidt KU: Bevacizumab for treatment of macular edema secondary to retinal vein occlusion. Ophthalmologe 2006;103:471–475.
- Ladewig MS, Ziemssen F, Jaissle G, Helb HM, Scholl HP, Eter N, Bartz-Schmidt KU, Holz FG: Intravitreal bevacizumab for neovascular age-related macular degeneration. Ophthalmologe 2006;103:463–470.
-
Aiello LP: The potential role of PKC beta in diabetic retinopathy and macular edema. Surv Ophthalmol 2002;47(suppl 2)S263–S269.
External Resources
Article / Publication Details
Published online: March 26, 2007
Issue release date: March 2007
Number of Print Pages: 14
Number of Figures: 13
Number of Tables: 1
ISSN: 0030-3755 (Print)
eISSN: 1423-0267 (Online)
For additional information: https://www.karger.com/OPH
Copyright / Drug Dosage / Disclaimer
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.
