Intravitreal Ranibizumab or Aflibercept After Bevacizumab in Diabetic Macular Edema: Exploratory Retrospective Analysis

Bernardete Pessoa, Luísa Malheiro, Inês Carneiro, Sílvia Monteiro, João Coelho, Constança Coelho, João Figueira, Angelina Meireles, João Nuno Melo Beirão, Bernardete Pessoa, Luísa Malheiro, Inês Carneiro, Sílvia Monteiro, João Coelho, Constança Coelho, João Figueira, Angelina Meireles, João Nuno Melo Beirão

Abstract

Aim: To evaluate the efficacy of switching from bevacizumab to ranibizumab or aflibercept in eyes with diabetic macular edema (DME) unresponsive to bevacizumab.

Methods: Single-center retrospective comparative study of patients with DME unresponsive to intravitreal bevacizumab that was switched to ranibizumab or aflibercept. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were analysed prior to and 4 months after the switch. Ocular coherence tomography (OCT) biomarkers were also analysed.

Results: Fifty-six eyes from 40 patients were included in the study, 33 eyes switched to ranibizumab and 23 to aflibercept. A significant median CFT decrease was observed in both groups (p<0.001), with no between-group differences. BCVA gain was only significant in the ranibizumab group (p<0.001). None of the pre-baseline or baseline parameters were associated with the response to ranibizumab or aflibercept.

Conclusion: In persistent DME unresponsive to bevacizumab, both anatomical and functional improvements were observed with ranibizumab whereas aflibercept only showed an anatomical improvement. Clinicaltrials.gov NCT04018833.

Keywords: aflibercept; bevacizumab; diabetic macular edema; ranibizumab; refractory.

Conflict of interest statement

The authors have no conflicts of interest to declare for this work.

© 2021 Pessoa et al.

Figures

Figure 1
Figure 1
(A) Example of a central foveal image of an OCT 20x20º scan area (5.8 mm) acquisition where the existence of hard exudates (HE); hyperreflective foci (HRF) with small size (<30µm), with reflectivity similar to the nerve fiber layer and no back-shadowing; hard exudates (HE) with back-shadowing; and a vitreomacular adhesion with at least 1/3 of vitreomacular detachment from the macular area (VMA) can be observed. (B) Example of a central foveal image of an OCT 20x20º scan area acquisition with the presence of an epiretinal membrane without inner retinal distortion (ERMn); outer plexiform layer disruption (OPLd); disorganization of the retinal inner layers (DRIL); ellipsoid layer disruption (ELd); external limiting membrane disruption (ELMd); HE; and HRF.
Figure 2
Figure 2
Median central foveal thickness change between- and within- switch groups (ranibizumab or aflibercept) pre-bevacizumab, at the time of switch and 4 months after switch. *p

Figure 3

Best-corrected visual acuity change between-…

Figure 3

Best-corrected visual acuity change between- and within- switch groups (ranibizumab or aflibercept) pre-bevacizumab,…

Figure 3
Best-corrected visual acuity change between- and within- switch groups (ranibizumab or aflibercept) pre-bevacizumab, at the time of switch and 4 months after switch. *p
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References
    1. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–564. doi:10.2337/dc11-1909 - DOI - PMC - PubMed
    1. Summary of product characteristics ranibizumab. Approved by EMA. Last updated 2019 2007.
    1. Summary of product characteristics ranibizumab. Approved by FDA revised 2014 2006.
    1. Summary of product characteristics aflibercept. Approved by EMA. Last updated 2019 2012.
    1. Summary of product characteristics bevacizumab. Approved by EMA. Last updated 2018 2005.
Show all 26 references
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Figure 3
Figure 3
Best-corrected visual acuity change between- and within- switch groups (ranibizumab or aflibercept) pre-bevacizumab, at the time of switch and 4 months after switch. *p

References

    1. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–564. doi:10.2337/dc11-1909
    1. Summary of product characteristics ranibizumab. Approved by EMA. Last updated 2019 2007.
    1. Summary of product characteristics ranibizumab. Approved by FDA revised 2014 2006.
    1. Summary of product characteristics aflibercept. Approved by EMA. Last updated 2019 2012.
    1. Summary of product characteristics bevacizumab. Approved by EMA. Last updated 2018 2005.
    1. International Council of Ophthalmology. ICO guidelines for diabetic eye care; 2017. Available from: . Accessed January12, 2021.
    1. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185–222. doi:10.1159/000458539
    1. Hutton D, Newman-Casey PA, Tavag M, Zacks D, Stein J. Switching to less expensive blindness drug could save medicare part B $18 billion over a ten-year period. Health Aff (Millwood). 2014;33(6):931–939. doi:10.1377/hlthaff.2013.0832
    1. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123(6):1351–1359. doi:10.1016/j.ophtha.2016.02.022
    1. Binder S. Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol. 2012;96(1):1–2. doi:10.1136/bjophthalmol-2011-301236
    1. Katz G, Moisseiev E, Goldenberg D, et al. Ranibizumab for persistent diabetic macular edema after bevacizumab treatment. Eur J Ophthalmol. 2017;27(2):210–214. doi:10.5301/ejo.5000838
    1. Rahimy E, Shahlaee A, Khan MA, et al. Conversion to aflibercept after prior anti-VEGF therapy for persistent diabetic macular edema. Am J Ophthalmol. 2016;164(118):e112. doi:10.1016/j.ajo.2015.12.030
    1. Ashraf M, Souka AA, ElKayal H. Short-term effects of early switching to ranibizumab or aflibercept in diabetic macular edema cases with non-response to bevacizumab. Ophthalmic Surg Lasers Imaging Retina. 2017;48(3):230–236. doi:10.3928/23258160-20170301-06
    1. Bressler SB, Ayala AR, Bressler NM, et al. Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol. 2016;134(3):278–285. doi:10.1001/jamaophthalmol.2015.5346
    1. Ashraf M, Souka A, Adelman R. Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature. Br J Ophthalmol. 2016;100(12):1596–1604. doi:10.1136/bjophthalmol-2016-308388
    1. Maheshwary AS, Oster SF, Yuson RM, Cheng L, Mojana F, Freeman WR. The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema. Am J Ophthalmol. 2010;150(1):63–67 e61. doi:10.1016/j.ajo.2010.01.039
    1. Reznicek L, Cserhati S, Seidensticker F, et al. Functional and morphological changes in diabetic macular edema over the course of anti-vascular endothelial growth factor treatment. Acta Ophthalmol. 2013;91(7):e529–536. doi:10.1111/aos.12153
    1. Sun JK, Radwan SH, Soliman AZ, et al. Neural retinal disorganization as a robust marker of visual acuity in current and resolved diabetic macular edema. Diabetes. 2015;64(7):2560–2570. doi:10.2337/db14-0782
    1. Vujosevic S, Torresin T, Berton M, Bini S, Convento E, Midena E. Diabetic macular edema with and without subfoveal neuroretinal detachment: two different morphologic and functional entities. Am J Ophthalmol. 2017;181:149–155. doi:10.1016/j.ajo.2017.06.026
    1. Karaca EE, Kepez Yldz B, Cubuk MO, Ozdek S. Epiretinal membranes in neovascular age-related macular degeneration: effect on outcomes of anti-vascular endothelial growth factor therapy. Retina. 2015;35(8):1540–1546. doi:10.1097/IAE.0000000000000531
    1. Pessoa B, Coelho J, Coelho C, et al. Enzymatic vitreolysis for the treatment of tractional diabetic macular edema. Ther Adv Ophthalmol. 2019;11:1–10.
    1. Trevino A, Martinez MR, Ophir A. Chronic macular edema associated with extrafoveal vitreoretinal traction. Int J Ophthalmol. 2010;3(4):321–325. doi:10.3980/j.issn.2222-3959.2010.04.10
    1. Das R, Spence G, Hogg RE, Stevenson M, Chakravarthy U. Disorganization of inner retina and outer retinal morphology in diabetic macular edema. JAMA Ophthalmol. 2018;136(2):202–208. doi:10.1001/jamaophthalmol.2017.6256
    1. Sun JK, Lin MM, Lammer J, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132(11):1309–1316. doi:10.1001/jamaophthalmol.2014.2350
    1. Massin P, Bandello F, Garweg JG, et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care. 2010;33(11):2399–2405. doi:10.2337/dc10-0493
    1. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol i data. Am J Ophthalmol. 2016;172:72–79. doi:10.1016/j.ajo.2016.09.012

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