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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-04-2020 | Edema | Medical Ophthalmology

Simultaneous intravitreal dexamethasone and aflibercept for refractory macular edema secondary to retinal vein occlusion

Authors: Chiara Giuffrè, Maria Vittoria Cicinelli, Alessandro Marchese, Michele Coppola, Maurizio Battaglia Parodi, Francesco Bandello

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 4/2020

Abstract

Purpose

To assess the functional and anatomical outcomes of concurrent administration of aflibercept injection and dexamethasone (DEX) implant in patients with macular edema (ME) secondary to retinal vein occlusion (RVO), refractory to each of the two drugs previously administered as monotherapy. Secondary outcomes included the number of retreatments required in a 12-month follow-up and safety.

Methods

This is a prospective, interventional case series of consecutive patients with refractory ME secondary to RVO, followed over a year. One injection of aflibercept was followed by a DEX implant on the same day; retreatment was driven by the persistence of ME on SD-OCT at least 4 months after the previous combined therapy. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were collected at 1 month and then every 2 months until the end of follow-up.

Results

Thirty eyes of 30 Caucasian patients were enrolled; mean duration of RVO before the first combined treatment was 25 ± 5 months (range 11 ± 30). Baseline BCVA was 0.73 ± 0.5 LogMAR, with no significant changes at 12 months (0.77 ± 0.51 μm, p = 0.2). Baseline CRT was 578.3 ± 161 μm, reducing to 352.5 ± 81 μm at 12 months (p = 0.003). Thirteen eyes (43.3%) required a second treatment. Twenty eyes (66.6%) showed no ME at the end of follow-up. One patient (3.3%) required topical IOP-lowering therapy during the study.

Conclusion

In eyes with ME secondary to RVO unresponsive to either aflibercept or DEX administered singularly, a combination therapy with simultaneous administration of aflibercept and DEX was effective in resolving ME, despite the absence of visual improvement. Earlier combined treatment in the course of the disease might lead to better functional outcomes.

Cugati S, Wang JJ, Rochtchina E, Mitchell P (2006) Ten-year incidence of retinal emboli in an older population. Stroke 37:908–910CrossRef

Ascaso FJ, Huerva V, Grzybowski A (2014) The role of inflammation in the pathogenesis of macular edema secondary to retinal vascular diseases. Mediat Inflamm 2014:432685CrossRef

Campochiaro PA, Sophie R, Pearlman J, Brown DM, Boyer DS, Heier JS et al (2014) Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology 121:209–219CrossRef

Tadayoni R, Waldstein SM, Boscia F, Gerding H, Gekkieva M, Barnes E et al (2017) Sustained benefits of ranibizumab with or without laser in branch retinal vein occlusion: 24-month results of the BRIGHTER study. Ophthalmology 124:1778–1787CrossRef

Lotfy A, Solaiman KAM, Abdelrahman A, Samir A (2017) Efficacy and frequency of intravitreal aflibercept versus bevacizumab for macular edema secondary to central retinal vein occlusion. Retina 38:1795–1800CrossRef

Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J et al (2010) Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 117:1134–46 e3CrossRef

Yoon YH, Kim JW, Lee JY, Kim IT, Kang SW, Yu HG et al (2018) Dexamethasone intravitreal implant for early treatment and retreatment of macular edema related to branch retinal vein occlusion: the multicenter COBALT study. Ophthalmologica 240:81–89CrossRef

Pielen A, Buhler AD, Heinzelmann SU, Bohringer D, Ness T, Junker B (2017) Switch of intravitreal therapy for macular edema secondary to retinal vein occlusion from anti-VEGF to dexamethasone implant and vice versa. J Ophthalmol 2017:5831682CrossRef

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Awh CC et al (2017) Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial. JAMA 317:2072–2087CrossRef

10.

Hoerauf H, Feltgen N, Weiss C, Paulus EM, Schmitz-Valckenberg PA et al (2016) Clinical efficacy and safety of ranibizumab versus dexamethasone for central retinal vein occlusion (COMRADE C): a European label study. Am J Ophthalmol 169:258–267CrossRef

11.

Battaglia Parodi M, Iacono P, De Benedetto U, Cascavilla M, Bandello F (2012) Rebound effect after intravitreal dexamethasone implant for the treatment of macular edema secondary to central retinal vein occlusion. J Ocul Pharmacol Ther 28:566–568CrossRef

12.

Karia N (2010) Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol 4:809–816CrossRef

13.

Esmaili DD, Boyer DS (2018) Recent advances in understanding and managing retinal vein occlusions. F1000Res 7:467CrossRef

14.

Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J et al (2011) Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 118:2453–2460CrossRef

15.

Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ et al (2012) Vascular endothelial growth factor trap-eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology 119:1024–1032CrossRef

16.

Heier JS, Clark WL, Boyer DS, Brown DM, Vitti R, Berliner AJ et al (2014) Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology 121:1414–20 e1CrossRef

17.

Holz FG, Roider J, Ogura Y, Korobelnik JF, Simader C, Groetzbach G et al (2013) VEGF trap-eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol 97:278–284CrossRef

18.

Clark WL, Boyer DS, Heier JS, Brown DM, Haller JA, Vitti R et al (2016) Intravitreal aflibercept for macular edema following branch retinal vein occlusion: 52-week results of the VIBRANT study. Ophthalmology 123:330–336CrossRef

19.

Pulido JS, Flaxel CJ, Adelman RA, Hyman L, Folk JC, Olsen TW (2016) Retinal vein occlusions preferred practice pattern ((R)) guidelines. Ophthalmology 123:P182–P208CrossRef

20.

Jumper JM, Dugel PU, Chen S, Blinder KJ, Walt JG (2018) Anti-VEGF treatment of macular edema associated with retinal vein occlusion: patterns of use and effectiveness in clinical practice (ECHO study report 2). Clin Ophthalmol 12:621–629CrossRef

21.

Binder S (2012) Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol 96:1–2CrossRef

22.

Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y et al (2009) Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One 4:e8158CrossRef

23.

Funk M, Kriechbaum K, Prager F, Benesch T, Georgopoulos M, Zlabinger GJ et al (2009) Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Invest Ophthalmol Vis Sci 50:1025–1032CrossRef

24.

Noma H, Funatsu H, Mimura T, Harino S, Hori S (2009) Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology 116:87–93CrossRef

25.

Chhablani J, Narayanan R, Mathai A, Tyagi M (2016) Combination of peripheral laser photocoagulation with intravitreal bevacizumab in naive eyes with macular edema secondary to CRVO: prospective randomized study. Eye (Lond) 30:1025–1027CrossRef

26.

Terashima H, Hasebe H, Okamoto F, Matsuoka N, Sato Y, Fukuchi T (2019) Combination therapy of intravitreal ranibizumab and subthreshold micropulse photocoagulation for macular edema secondary to branch retinal vein occlusion: 6-month result. Retina 39:1377–1384CrossRef

27.

Shimura M, Yasuda K, Nakazawa T, Takeshita T, Shiono T, Sakamoto T (2010) Combination therapy for retinal vein occlusion. Ophthalmology 117(1858):58 e1–58 e3

28.

Iu LP, Zhao P, Yeung IY, Fung NS, Lee JW, Wong RL et al (2015) Sequential therapy with ranibizumab and dexamethasone intravitreal implant is better than dexamethasone monotherapy for macular oedema due to retinal vein occlusion. Br J Ophthalmol 99:210–214CrossRef

29.

Singer MA, Bell DJ, Woods P, Pollard J, Boord T, Herro A et al (2012) Effect of combination therapy with bevacizumab and dexamethasone intravitreal implant in patients with retinal vein occlusion. Retina 32:1289–1294CrossRef

30.

Lip PL, Cikatricis P, Sarmad A, Damato EM, Chavan R, Mitra A et al (2018) Efficacy and timing of adjunctive therapy in the anti-VEGF treatment regimen for macular oedema in retinal vein occlusion: 12-month real-world result. Eye (Lond) 32:537–545CrossRef

31.

Singer MA, Jansen ME, Tyler L, Woods P, Ansari F, Jain U et al (2017) Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series. Clin Ophthalmol 11:31–38CrossRef

32.

Busch C, Rehak M, Sarvariya C, Zur D, Iglicki M, Lima LH et al (2019) Long-term visual outcome and its predictors in macular oedema secondary to retinal vein occlusion treated with dexamethasone implant. Br J Ophthalmol 103:463–468CrossRef

33.

Blanc J, Deschasse C, Kodjikian L, Dot C, Bron AM, Creuzot-Garcher C (2018) Safety and long-term efficacy of repeated dexamethasone intravitreal implants for the treatment of cystoid macular edema secondary to retinal vein occlusion with or without a switch to anti-VEGF agents: a 3-year experience. Graefes Arch Clin Exp Ophthalmol 256:1441–1448CrossRef

34.

Deak GG, Schmidt-Erfurth UM, Jampol LM (2018) Correlation of central retinal thickness and visual acuity in diabetic macular edema. JAMA Ophthalmol 136:1215–1216CrossRef

35.

Danis RP, Sadda S, Jiao J, Li XY, Whitcup SM (2016) Relationship between retinal thickness and visual acuity in eyes with retinal vein occlusion treated with dexamethasone implant. Retina 36:1170–1176CrossRef

36.

Battaglia Parodi M, Iacono P, Scaramuzzi M, Bandello F (2017) Outer retinal layer changes after dexamethasone implant for central retinal vein occlusion. Retina 37:1888–1895CrossRef

Title: Simultaneous intravitreal dexamethasone and aflibercept for refractory macular edema secondary to retinal vein occlusion
Authors: Chiara Giuffrè
Maria Vittoria Cicinelli
Alessandro Marchese
Michele Coppola
Maurizio Battaglia Parodi
Francesco Bandello
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keywords: Edema
Aflibercept
Dexamethasone
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 4/2020
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-019-04577-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Simultaneous intravitreal dexamethasone and aflibercept for refractory macular edema secondary to retinal vein occlusion

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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