Prognostische Faktoren beim chronisch-diabetischen Makulaödem nach intravitrealer Therapie

Zusammenfassung

Hintergrund: Seit wenigen Jahren wird zunehmend Bevacizumab und Triamcinolonazetat (TA) zur Behandlung des diabetischen Makulaödems intravitreal eingesetzt. Es ist jedoch ungeklärt, welche Patienten davon profitieren. In dieser Studie untersuchen wir Faktoren, die das Visuslangzeitergebnis nach intravitrealen Injektionen bei DMÖ beeinflussen. Methoden: Es wurden 50 Augen (37 Patienten) analysiert, die bei diabetischem Makulaödem mit intravitrealem Bevacizumab, Triamcinolon oder beidem behandelt wurden und eine Mindest-Nachbeobachtungszeit von 6 Monaten hatten. Ausgewertet wurden klinische, angiografische und OCT-Befunde. Ergebnisse: Nach einer mittleren Beobachtungszeit von 14,6 ± 6 Monaten stieg der Visus bei 22 Augen signifikant an und fiel bei 28 Augen ab. Das Vorliegen eines, im OCT sichtbaren zystoiden Makulaödems korrelierte mit einem ungünstigen Visuslangzeitergebnis (p < 0,001), wohingegen ein frühes Ansprechen (nach 5 Wochen) auf die Therapie mit einer Visusverbesserung (p = 0,016) verbunden war. Die initiale zentrale Makuladicke im OCT, die Art des Wirkstoffs bei Monotherapie, Alter und Geschlecht hatten keinen Einfluss auf das Visuslangzeitergebnis. Schlussfolgerung: Bei initialem zystoidem diabetischem Makulaödem ist die Visusprognose ungünstig. Eine intravitreale Behandlung sollte vor Entwicklung eines zystoiden Makulaödems begonnen werden, da dann ein Ansprechen auf die Therapie schon bei einer niedrigen Zahl von Injektionen wahrscheinlich ist. Ein frühes Ansprechen auf die Therapie ist ein guter Vorhersageparameter für einen guten Endvisus.

Abstract

Background: In recent years, intravitreal bevacizumab and triamcinolone acetonide (TA) have been widely used to treat diabetic macular oedema (DMO). However, the indication criteria are not clear. The purpose of this study was to evaluate factors which are decisive for long-term visual outcome after intravitreal drug treatment for eyes with DMO. Materials and Methods: Fifty eyes (37 patients) treated with intravitreal bevacizumab, TA, or sequentially with both for DMO with a minimum follow-up period of 6 months were analysed retrospectively. The eyes with an increase of best-corrected visual acuity (BCVA) at the last visit were classified as gainers, and eyes with stable or decreased BCVA as non-gainers. Clinical and imaging findings were evaluated. Results: BCVA significantly increased in 22 eyes and decreased in 28 eyes after a mean follow-up period of 14.6 ± 6 months after initial intravitreal intervention. Unfavourable for the long-term visual outcome was the presence of cystoid macular oedema (CMO, p < 0.001), whereas an early response at 5 weeks into therapy indicated a positive outcome (p = 0.016). The initial central macular thickness measured by OCT, the type of agent used in monotherapy, age and gender were without influence on long-term visual acuity. Conclusions: An initial CMO is unfavourable for the prognosis of long-term visual outcome of DMO. Hence, benefit from intravitreal treatment with bevacizumab and/or TA is more likely in the early stages of chronic DMO before CMO has evolved. In eyes without CMO even a low number of injections is beneficial. An early response following intravitreal bevacizumab or TA is a predictor of long-term benefit.

Bevacizumab - Triamcinolonazetat - zystoides Makulaödem - diabetisches Makulaödem - Prognose

bevacizumab - triamcinolone acetate - cystoid macular oedema - diabetic macular oedema - prognosis

Literatur

• 1 Klein R, Klein B E, Moss S E et al. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema.  Ophthalmology. 1984;  91 1464-1474
• 2 Sander B, Hamann P, Larsen M. A 5-year follow-up of photocoagulation in diabetic macular edema: the prognostic value of vascular leakage for visual loss.  Graefes Arch Clin Exp Ophthalmol. 2008;  246 1535-1539
• 3 Beck R W, Edwards A R, Aiello L P et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema.  Arch Ophthalmol. 2009;  127 245-251
• 4 Cantrill H L. The diabetic retinopathy study and the early treatment diabetic retinopathy study.  Int Ophthalmol Clin. 1984;  24 13-29
• 5 Lovestam-Adrian M, Agardh E. Photocoagulation of diabetic macular oedema – complications and visual outcome.  Acta Ophthalmol Scand. 2000;  78 667-671
• 6 Williams B, Gallacher B, Patel H et al. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro.  Diabetes. 1997;  46 1497-1503
• 7 Lam D S, Lai T Y, Lee V Y et al. Efficacy of 1.25 MG versus 2.5 MG intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial.  Retina. 2009;  29 292-299
• 8 Gillies M C, Sutter F K, Simpson J M et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial.  Ophthalmology. 2006;  113 1533-1538
• 9 Paccola L, Costa R A, Folgosa M S et al. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study).  Br J Ophthalmol. 2008;  92 76-80
• 10 Shimura M, Nakazawa T, Yasuda K et al. Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema.  Am J Ophthalmol. 2008;  145 854-861
• 11 Soheilian M, Ramezani A, Obudi A et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.  Ophthalmology. 2009;  116 1142-1150
• 12 Arevalo J F, Sanchez J G, Fromow-Guerra J et al. Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up.  Graefes Arch Clin Exp Ophthalmol. 2009;  247 735-743
• 13 Kook D, Wolf A, Kreutzer T et al. Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema.  Retina. 2008;  28 1053-1060
• 14 Soliman W, Sander B, Jorgensen T M. Enhanced optical coherence patterns of diabetic macular oedema and their correlation with the pathophysiology.  Acta Ophthalmol Scand. 2007;  85 613-617
• 15 Kang S W, Park C Y, Ham D I. The correlation between fluorescein angiographic and optical coherence tomographic features in clinically significant diabetic macular edema.  Am J Ophthalmol. 2004;  137 313-322
• 16 Jaissle G B, Szurman P, Bartz-Schmidt K U. Recommendation for the implementation of intravitreal injections – statement of the German Retina Society, the German Society of Ophthalmology (DOG) and the German Professional Association of Ophthalmologists (BVA).  Klin Monatsbl Augenheilkd. 2005;  222 390-395
• 17 Yanoff M, Fine B S, Brucker A J et al. Pathology of human cystoid macular edema.  Surv Ophthalmol. 1984;  28 Suppl 505-511
• 18 Bringmann A, Reichenbach A, Wiedemann P. Pathomechanisms of cystoid macular edema.  Ophthalmic Res. 2004;  36 241-249
• 19 Lardenoye C W, Probst K, DeLint P J et al. Photoreceptor function in eyes with macular edema.  Invest Ophthalmol Vis Sci. 2000;  41 4048-4053
• 20 Coscas G, Gaudric A. Natural course of nonaphakic cystoid macular edema.  Surv Ophthalmol. 1984;  28 Suppl 471-484
• 21 Audren F, Erginay A, Haouchine B et al. Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial.  Acta Ophthalmol Scand. 2006;  84 624-630
• 22 Soliman W, Sander B, Soliman K A et al. The predictive value of optical coherence tomography after grid laser photocoagulation for diffuse diabetic macular oedema.  Acta Ophthalmol. 2008;  86 284-291
• 23 Brasil O F, Smith S D, Galor A et al. Predictive factors for short-term visual outcome after intravitreal triamcinolone acetonide injection for diabetic macular oedema: an optical coherence tomography study.  Br J Ophthalmol. 2007;  91 761-765
• 24 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
• 25 Kim J E, Pollack J S, Miller D G et al. ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema.  Retina. 2008;  28 735-740
• 26 Pournaras J A, Erginay A, Lazrak Z et al. Spectral domain optical coherence tomography in diabetic macular edema.  Ophthalmic Surg Lasers Imaging. 2009;  40 548-553
• 27 Rosenfeld P J, Moshfeghi A A, Puliafito C A. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.  Ophthalmic Surg Lasers Imaging. 2005;  36 331-335