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01-08-2018 | Original Article

Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema

Authors: Catharina Busch, Dinah Zur, Samantha Fraser-Bell, Inês Laíns, Ana Rita Santos, Marco Lupidi, Carlo Cagini, Pierre-Henry Gabrielle, Aude Couturier, Valérie Mané-Tauty, Ermete Giancipoli, Giuseppe D’Amico Ricci, Zafer Cebeci, Patricio J. Rodríguez-Valdés, Voraporn Chaikitmongkol, Atchara Amphornphruet, Isaac Hindi, Kushal Agrawal, Jay Chhablani, Anat Loewenstein, Matias Iglicki, Matus Rehak, For the International Retina Group

Published in: Acta Diabetologica | Issue 8/2018

Abstract

Aims

To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting.

Methods

To be included in this retrospective multicenter, case–control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group.

Results

A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was − 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and − 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19–11.61, P = 0.024) at month 12.

Conclusions

In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.

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Arroba AI, Valverde AM (2017) Modulation of microglia in the retina: new insights into diabetic retinopathy. Acta Diabetol 54(6):527–533. https://doi.org/10.1007/s00592-017-0984-z CrossRefPubMed

Yau JW, Rogers SL, Kawasaki R et al (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35(3):556–564. https://doi.org/10.2337/dc11-1909 CrossRefPubMedPubMedCentral

Nguyen QD, Shah SM, Heier JS et al (2009) Primary end point (six months) results of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology 116(11):2175–2181. https://doi.org/10.1016/j.ophtha.2009.04.023 CrossRefPubMed

Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR et al (2015) Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372(13):1193–1203. https://doi.org/10.1056/NEJMoa1414264 CrossRef

Gillies MC, Lim LL, Campain A et al (2014) A randomized clinical trial of intravitreal bevacizumab versus intravitreal dexamethasone for diabetic macular edema: the BEVORDEX study. Ophthalmology 121(12):2473–2481. https://doi.org/10.1016/j.ophtha.2014.07.002 CrossRefPubMed

Boyer DS, Yoon YH, Belfort R Jr et al (2014) Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121(10):1904–1914. https://doi.org/10.1016/j.ophtha.2014.04.024 CrossRefPubMed

Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G (2017) Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol 101(12):1689–1693. https://doi.org/10.1136/bjophthalmol-2017-310242 CrossRefPubMed

Pacella F, Romano MR, Turchetti P et al (2016) An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy. Int J Ophthalmol 9(10):1427–1432. https://doi.org/10.18240/ijo.2016.10.10 PubMedPubMedCentralCrossRef

Fraser-Bell S, Lim LL, Campain A et al (2016) Bevacizumab or dexamethasone implants for DME: 2-year results (the BEVORDEX study). Ophthalmology 123(6):1399–1401. https://doi.org/10.1016/j.ophtha.2015.12.012 CrossRefPubMed

10.

Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122(7):1375–1394. https://doi.org/10.1016/j.ophtha.2015.03.024 CrossRefPubMed

11.

Hussain RM, Ciulla TA (2016) Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy. Expert Opin Biol Ther 16(3):365–374. https://doi.org/10.1517/14712598.2016.1131265 CrossRefPubMed

12.

Schmidt-Erfurth U, Garcia-Arumi J, Bandello F et al (2017) Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica 237(4):185–222. https://doi.org/10.1159/000458539 CrossRefPubMed

13.

Gonzalez VH, Campbell J, Holekamp NM et al (2016) Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol 172:72–79. https://doi.org/10.1016/j.ajo.2016.09.01 CrossRefPubMed

14.

Mehta H, Fraser-Bell S, Nguyen V, Lim LL, Gillies MC (2017) Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2017-310737 CrossRefPubMed

15.

Chalam KV, Bressler SB, Edwards AR et al (2012) Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography. Investig Ophthalmol Vis Sci 53(13):8154–8161. https://doi.org/10.1167/iovs.12-10290 CrossRef

16.

Giani A, Cigada M, Choudhry N et al (2010) Reproducibility of retinal thickness measurements on normal and pathologic eyes by different optical coherence tomography instruments. Am J Ophthalmol 150(6):815–824. https://doi.org/10.1016/j.ajo.2010.06.02 CrossRefPubMed

17.

Hajian-Tilaki K (2013) Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Casp J Intern Med 4(2):627–635

18.

Dutra Medeiros M, Postorino M, Navarro R, Garcia-Arumi J, Mateo C, Corcostegui B (2014) Dexamethasone intravitreal implant for treatment of patients with persistent diabetic macular edema. Ophthalmologica 231(3):141–146. https://doi.org/10.1159/000356413 CrossRefPubMed

19.

Maturi RK, Bleau L, Saunders J, Mubasher M, Stewart MW (2015) A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the efficacy of the dexamethasone-delayed delivery system as an adjunct to bevacizumab compared with continued bevacizumab monotherapy. Retina 35(8):1604–1614. https://doi.org/10.1097/IAE.0000000000000533 CrossRefPubMed

20.

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):29–38. https://doi.org/10.1001/jamaophthalmol.2017.4914 CrossRefPubMed

21.

Shah SU, Harless A, Bleau L, Maturi RK (2016) Prospective randomized subject-masked study of intravitreal bevacizumab monotherapy versus dexamethasone implant monotherapy in the treatment of persistent diabetic macular edema. Retina 36(10):1986–1996. https://doi.org/10.1097/IAE.0000000000001038 CrossRefPubMed

22.

Chatziralli I, Theodossiadis P, Parikakis E et al (2017) Dexamethasone intravitreal implant in diabetic macular edema: real-life data from a prospective study and predictive factors for visual outcome. Diabetes Ther 8(6):1393–1404. https://doi.org/10.1007/s13300-017-0332-x CrossRefPubMedPubMedCentral

23.

Chatziralli I, Santarelli M, Patrao N et al (2017) Identification of time point to best define ‘sub-optimal response’ following intravitreal ranibizumab therapy for diabetic macular edema based on real-life data. Eye 31(11):1594–1599. https://doi.org/10.1038/eye.2017.111 CrossRefPubMed

24.

Zur D, Iglicki M, Busch C et al (2017) Optical coherence tomography biomarkers as functional outcome predictors in diabetic macular edema treated with dexamethasone implant. Ophthalmology. https://doi.org/10.1016/j.ophtha.2017.08.031 PubMedCrossRef

25.

Iglicki M, Zur D, Busch C, Okada M, Loewenstein A (2018) Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the ‘DR-Pro-DEX Study’. Acta Diabetol. https://doi.org/10.1007/s00592-018-1117-z CrossRefPubMed

26.

Iglicki M, Busch C, Zur D, et al. (2018) Dexamethasone implant for diabetic macular edeme in naive compared with refactory eyes: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study. https://doi.org/10.1097/IAE.0000000000002196

Title: Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema
Authors: Catharina Busch
Dinah Zur
Samantha Fraser-Bell
Inês Laíns
Ana Rita Santos
Marco Lupidi
Carlo Cagini
Pierre-Henry Gabrielle
Aude Couturier
Valérie Mané-Tauty
Ermete Giancipoli
Giuseppe D’Amico Ricci
Zafer Cebeci
Patricio J. Rodríguez-Valdés
Voraporn Chaikitmongkol
Atchara Amphornphruet
Isaac Hindi
Kushal Agrawal
Jay Chhablani
Anat Loewenstein
Matias Iglicki
Matus Rehak
For the International Retina Group
Publication date: 01-08-2018
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 8/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-1151-x

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