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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 3/2020

01.03.2020 | Retinal Disorders

Bevacizumab versus triamcinolone for persistent diabetic macular edema: a randomized clinical trial

verfasst von: Murilo W. Rodrigues, José A. Cardillo, André Messias, Rubens C. Siqueira, Ingrid U. Scott, Rodrigo Jorge

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 3/2020

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Abstract

Purpose

To evaluate 24-week visual acuity and anatomic outcomes of two “pro re nata” (prn) treatment strategies (intravitreal bevacizumab [IVB] prn versus intravitreal triamcinolone acetonide [IVT] prn) in patients with persistent diabetic macular edema (pDME) after 24 weeks of prn-IVB.

Methods

One hundred eyes with center-involving DME were enrolled and treated with prn-IVB for 24 weeks; at week 24, eyes with pDME (central subfield thickness [CST] on spectral domain optical coherence tomography > 300 μm) were randomized to IVB monthly prn (group I; prn-IVB) or IVT every 3 months prn (group II; prn-IVT) and eyes in which the CST was ≤ 300 μm were assigned to continue prn-IVB (group III).

Results

Seventy-four eyes completed a 48-week study period. At week 24, 65 (79.3%) eyes still had DME with CST > 300 μm and, therefore, were randomized to prn-IVB (group I, n = 33) or prn-IVT (group II, n = 32); the remaining 17 (20.7%) eyes had CST ≤ 300 μm and were assigned to continued treatment with prn-IVB (group III). At baseline, mean CST (μm) ± standard error of the mean (SEM) was 447.2 ± 24.4, 478.0 ± 19.7, and 386.0 ± 21.0 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no significant difference in mean CST between groups I and II (369.9 ± 23.3 and 426.0 ± 26.1, respectively; p = 0.9995). A significant reduction in mean CST, compared with baseline, was noted at weeks 28 (p = 0.0002) and 44 (p = 0.0002) in group II. Group I did not show a significant reduction in mean CST compared with baseline at any study visit. There were no significant differences in mean CST between groups I and II at any study visit. At baseline, mean ± SEM best-corrected visual acuity (BCVA) (logMAR) was 0.50 ± 0.00, 0.60 ± 0.10, and 0.50 ± 0.10 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no statistically significant difference in mean BCVA between groups I and II (0.50 ± 0.10 and 0.80 ± 0.10, respectively; p = 0.4473). There was no significant improvement in mean BCVA, as compared with baseline, at any study follow-up visit in any of the groups. Group II demonstrated significantly lower BCVA after 24 weeks of IVT (at week 48) compared with baseline (p = 0.0435). There was no significant difference in mean BCVA between groups I and II at any time-point.

Conclusion

In eyes with pDME after 24 weeks of treatment with prn-IVB, there was no difference between continued treatment with prn-IVB versus a treatment switch to prn-IVT with respect to mean BCVA or mean CST at week 48. However, BCVA was stable in the prn-IVB group, while prn-IVT was associated with BCVA reduction from baseline and a higher risk of IOP elevation.
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Literatur
2.
Zurück zum Zitat Yau JW, Rogers SL, Kawasaki R et al (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35(3):556–564CrossRef Yau JW, Rogers SL, Kawasaki R et al (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35(3):556–564CrossRef
3.
Zurück zum Zitat Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122(7):1375–1394CrossRef Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122(7):1375–1394CrossRef
4.
Zurück zum Zitat Elman MJ, Aiello LP, Beck RW et al (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117(6):1064–1077.e35CrossRef Elman MJ, Aiello LP, Beck RW et al (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117(6):1064–1077.e35CrossRef
5.
Zurück zum Zitat Wells JA, Glassman AR, Ayala AR et al (2015) Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372(13):1193–1203CrossRef Wells JA, Glassman AR, Ayala AR et al (2015) Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372(13):1193–1203CrossRef
6.
Zurück zum Zitat Channa R, Sophie R, Khwaja AA et al (2013) Factors affecting visual outcomes in patients with diabetic macular edema treated with ranibizumab. Eye (Lond) 28(3):269–278CrossRef Channa R, Sophie R, Khwaja AA et al (2013) Factors affecting visual outcomes in patients with diabetic macular edema treated with ranibizumab. Eye (Lond) 28(3):269–278CrossRef
7.
Zurück zum Zitat Brown DM, Nguyen QD, Marcus DM et al (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120(10):2013–2022CrossRef Brown DM, Nguyen QD, Marcus DM et al (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120(10):2013–2022CrossRef
8.
Zurück zum Zitat Elman MJ, Bressler NM, Qin H et al (2011) Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 118(4):609–614CrossRef Elman MJ, Bressler NM, Qin H et al (2011) Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 118(4):609–614CrossRef
9.
Zurück zum Zitat Bressler SB, Ayala AR, Bressler NM et al (2016) Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol 134(3):278–285CrossRef Bressler SB, Ayala AR, Bressler NM et al (2016) Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol 134(3):278–285CrossRef
10.
Zurück zum Zitat Nauck M, Karakiulakis G, Perruchoud AP et al (1998) Corticosteriods inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 341(2–3):309–315CrossRef Nauck M, Karakiulakis G, Perruchoud AP et al (1998) Corticosteriods inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 341(2–3):309–315CrossRef
11.
Zurück zum Zitat Nauck M, Roth M, Tamm M et al (1997) Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. Am J Respir Cell Mol Biol 16(4):398–406CrossRef Nauck M, Roth M, Tamm M et al (1997) Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. Am J Respir Cell Mol Biol 16(4):398–406CrossRef
12.
Zurück zum Zitat Mason JO 3rd, White MF, Feist RM et al (2008) Incidence of acute onset endophthalmitis following intravitreal bevacizumab injection. Retina 28(4):564–567CrossRef Mason JO 3rd, White MF, Feist RM et al (2008) Incidence of acute onset endophthalmitis following intravitreal bevacizumab injection. Retina 28(4):564–567CrossRef
13.
Zurück zum Zitat Aiello LP, Brucker AJ, Chang S, et al.(2004) Evolving guidelines for intravitreal injections. Retina; 24(5 Suppl):S3–19CrossRef Aiello LP, Brucker AJ, Chang S, et al.(2004) Evolving guidelines for intravitreal injections. Retina; 24(5 Suppl):S3–19CrossRef
14.
Zurück zum Zitat Hauser D, Bukelman A, Pokroy R et al (2008) Intravitreal triamcinolone for diabetic macular edema: comparison of 1, 2, and 4 mg. Retina 28(6):825–830CrossRef Hauser D, Bukelman A, Pokroy R et al (2008) Intravitreal triamcinolone for diabetic macular edema: comparison of 1, 2, and 4 mg. Retina 28(6):825–830CrossRef
15.
Zurück zum Zitat Michaelides M, Kaines A, Hamilton RD et al (2010) A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 117(6):1078–1086CrossRef Michaelides M, Kaines A, Hamilton RD et al (2010) A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 117(6):1078–1086CrossRef
16.
Zurück zum Zitat Elman MJ, Qin H, Aiello LP et al (2012) Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment. Diabetic Retinopathy Clinical Research Network* Writing Committee: Ophthalmology 119(11):2312–2318 Elman MJ, Qin H, Aiello LP et al (2012) Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment. Diabetic Retinopathy Clinical Research Network* Writing Committee: Ophthalmology 119(11):2312–2318
17.
Zurück zum Zitat Aiello LP, Beck RW, Bressler NM, et al.(2011) Rationale for the diabetic retinopathy clinical research network protocol for center-involved diabetic macular edema. diabetic retinopathy clinical research network. Writing Committee: Ophthalmology; 118(12):e5–14 Aiello LP, Beck RW, Bressler NM, et al.(2011) Rationale for the diabetic retinopathy clinical research network protocol for center-involved diabetic macular edema. diabetic retinopathy clinical research network. Writing Committee: Ophthalmology; 118(12):e5–14
18.
Zurück zum Zitat Willmann G, Nepomuceno AB, Messias K et al (2017) Foveal thickness reduction after anti-VEGF treatment in chronic diabetic macular edema. Int J Ophthalmol 10(5):760–764PubMedPubMedCentral Willmann G, Nepomuceno AB, Messias K et al (2017) Foveal thickness reduction after anti-VEGF treatment in chronic diabetic macular edema. Int J Ophthalmol 10(5):760–764PubMedPubMedCentral
19.
Zurück zum Zitat Wang MZ, Feng K, Lu Y et al (2016) Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion. Int J Ophthalmol 9(1):86–92PubMedPubMedCentral Wang MZ, Feng K, Lu Y et al (2016) Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion. Int J Ophthalmol 9(1):86–92PubMedPubMedCentral
20.
Zurück zum Zitat Paccola L, Costa RA, Folgosa MS et al (2008) Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular edema (IBEME study). Br J Ophthalmol 92(1):76–80CrossRef Paccola L, Costa RA, Folgosa MS et al (2008) Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular edema (IBEME study). Br J Ophthalmol 92(1):76–80CrossRef
21.
Zurück zum Zitat Lee J, Moon BG, Cho AR et al (2016) Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology 123(11):2368–2375CrossRef Lee J, Moon BG, Cho AR et al (2016) Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology 123(11):2368–2375CrossRef
22.
Zurück zum Zitat Bressler SB, Odia I et al (2019) Factors associated with visual acuity and central subfield thickness changes when treating diabetic macular edema with anti-vascular endothelial growth factor therapy: an exploratory analysis of the protocol t randomized clinical trial. JAMA Ophthalmology 137(4):382–389CrossRef Bressler SB, Odia I et al (2019) Factors associated with visual acuity and central subfield thickness changes when treating diabetic macular edema with anti-vascular endothelial growth factor therapy: an exploratory analysis of the protocol t randomized clinical trial. JAMA Ophthalmology 137(4):382–389CrossRef
23.
Zurück zum Zitat Kreutzer TC, Al Saeidi R, Kook D, et al.(2010) Comparison of intravitreal bevacizumab versus triamcinolone for the treatment of diffuse diabetic macular edema. Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany. Ophthalmologica; 224(4):258–264 Kreutzer TC, Al Saeidi R, Kook D, et al.(2010) Comparison of intravitreal bevacizumab versus triamcinolone for the treatment of diffuse diabetic macular edema. Department of Ophthalmology, Ludwig-Maximilians University, Munich, Germany. Ophthalmologica; 224(4):258–264
24.
Zurück zum Zitat Penha FM, Maia M, Cardillo JA, Arevalo JF, Wu L, Rodriguez FJ, Berrocal MH, Farah ME, The Pan-American Collaborative Retina Study Group (PACORES) (2012) Comparison of a single intravitreal injection of bevacizumab versus triamcinolone acetonide as primary treatment for diffuse diabetic macular oedema. Acta Ophthalmol 90(2):e160–e161CrossRef Penha FM, Maia M, Cardillo JA, Arevalo JF, Wu L, Rodriguez FJ, Berrocal MH, Farah ME, The Pan-American Collaborative Retina Study Group (PACORES) (2012) Comparison of a single intravitreal injection of bevacizumab versus triamcinolone acetonide as primary treatment for diffuse diabetic macular oedema. Acta Ophthalmol 90(2):e160–e161CrossRef
25.
Zurück zum Zitat Neto HO, Regatieri CV, Nobrega MJ et al (2017) Multicenter, randomized clinical trial to assess the effectiveness of Intravitreal injections of bevacizumab, triamcinolone, or their combination in the treatment of diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 48(9):734–740CrossRef Neto HO, Regatieri CV, Nobrega MJ et al (2017) Multicenter, randomized clinical trial to assess the effectiveness of Intravitreal injections of bevacizumab, triamcinolone, or their combination in the treatment of diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 48(9):734–740CrossRef
26.
Zurück zum Zitat Otani T, Yamaguchi Y, Kishi S (2010) Correlation between visual acuity and foveal microstructural changes in diabetic macular edema. Retina 30(5):774–780CrossRef Otani T, Yamaguchi Y, Kishi S (2010) Correlation between visual acuity and foveal microstructural changes in diabetic macular edema. Retina 30(5):774–780CrossRef
27.
Zurück zum Zitat Alasil T, Keane PA, Updike JF et al (2010) Relationship between optical coherence tomography retinal parameters and visual acuity in diabetic macular edema. Ophthalmology 117(12):2379–2386CrossRef Alasil T, Keane PA, Updike JF et al (2010) Relationship between optical coherence tomography retinal parameters and visual acuity in diabetic macular edema. Ophthalmology 117(12):2379–2386CrossRef
28.
Zurück zum Zitat Das R, Spence G, Hogg RE et al (2018) Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol 136(2):202–208CrossRef Das R, Spence G, Hogg RE et al (2018) Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol 136(2):202–208CrossRef
29.
Zurück zum Zitat Liu S, Wang D, Chen F et al (2019) Hyperreflective foci in OCT image as a biomarker of poor prognosis in diabetic macular edemapatients treating with Conbercept in China. BMC Ophthalmol 19(1):157CrossRef Liu S, Wang D, Chen F et al (2019) Hyperreflective foci in OCT image as a biomarker of poor prognosis in diabetic macular edemapatients treating with Conbercept in China. BMC Ophthalmol 19(1):157CrossRef
30.
Zurück zum Zitat Jonas JB, Degenring RF, Kreissig I et al (2005) Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology 112(4):593–598CrossRef Jonas JB, Degenring RF, Kreissig I et al (2005) Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology 112(4):593–598CrossRef
31.
Zurück zum Zitat Puliafito CA, Cousins SW, Bacharach J et al (2016) Forming a consensus: data and guidance for physicians treating diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 47(4):S4–S15PubMed Puliafito CA, Cousins SW, Bacharach J et al (2016) Forming a consensus: data and guidance for physicians treating diabetic macular edema. Ophthalmic Surg Lasers Imaging Retina 47(4):S4–S15PubMed
32.
Zurück zum Zitat Maturi RK, Glassman AR, Liu D et al (2018) Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR network phase 2 randomized clinical trial. JAMA Ophthalmol 136(1):29–38CrossRef Maturi RK, Glassman AR, Liu D et al (2018) Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR network phase 2 randomized clinical trial. JAMA Ophthalmol 136(1):29–38CrossRef
33.
Zurück zum Zitat Lang GE, Berta A, Eldem BM, Simader C, Sharp D, Holz FG, Sutter F, Gerstner O, Mitchell P, RESTORE Extension Study Group (2013) Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study. Ophthalmology. 120(10):2004–2012CrossRef Lang GE, Berta A, Eldem BM, Simader C, Sharp D, Holz FG, Sutter F, Gerstner O, Mitchell P, RESTORE Extension Study Group (2013) Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study. Ophthalmology. 120(10):2004–2012CrossRef
34.
Zurück zum Zitat CATT Research Group, Martin DF, Maguire MG, Ying GS et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364(20):1897–1908CrossRef CATT Research Group, Martin DF, Maguire MG, Ying GS et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364(20):1897–1908CrossRef
35.
Zurück zum Zitat Elman MJ, Ayala A, Bressler NM et al (2015) Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology 122(2):375–381CrossRef Elman MJ, Ayala A, Bressler NM et al (2015) Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology 122(2):375–381CrossRef
36.
Zurück zum Zitat Michalska-Małecka K, Kabiesz A, Kimsa MW et al (2016) Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration. Clin Interv Aging 11:357–365CrossRef Michalska-Małecka K, Kabiesz A, Kimsa MW et al (2016) Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration. Clin Interv Aging 11:357–365CrossRef
37.
Zurück zum Zitat Matsuyama K, Ogata N, Matsuoka M et al (2011) Effects of intravitreally injected bevacizumab on vascular endothelial growth factor in fellow eyes. J Ocul Pharmacol Ther 27(4):379–383CrossRef Matsuyama K, Ogata N, Matsuoka M et al (2011) Effects of intravitreally injected bevacizumab on vascular endothelial growth factor in fellow eyes. J Ocul Pharmacol Ther 27(4):379–383CrossRef
Metadaten
Titel
Bevacizumab versus triamcinolone for persistent diabetic macular edema: a randomized clinical trial
verfasst von
Murilo W. Rodrigues
José A. Cardillo
André Messias
Rubens C. Siqueira
Ingrid U. Scott
Rodrigo Jorge
Publikationsdatum
01.03.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 3/2020
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-019-04564-z

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