A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients with Treatment Resistant Neovascular Age-Related Macular Degeneration following Switching to Treatment with Aflibercept

Seguin-Greenstein, Sophie; Lightman, Sue; Tomkins-Netzer, Oren

doi:10.1155/2016/4095852

Cited by 43 publications

(37 citation statements)

References 36 publications

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“…This meta-analysis validates the effectiveness of aflibercept in improving morphology in patients with AMD refractory to ranibizumab and bevacizumab 67,68. This may be because aflibercept binds VEGF-A, VEGF-B, and PlGF, while other anti-VEGFs only bind with VEGF-A.…”

Section: Discussionsupporting

confidence: 65%

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Spooner

Hong

Wijeyakumar

et al. 2017

OPTH

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PurposeTo systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD).DesignSystematic review and meta-analysis.MethodsMedline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs).ResultsOf 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI −0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI −0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (−61.90 µm, 95% CI −77.10 to −46.80, P<0.001 and −50.00 µm, 95% CI −63.20 to −36.80, P<0.001 at 6 and 12 months, respectively).ConclusionPooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.

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Section: Discussionsupporting

confidence: 65%

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Spooner

Hong

Wijeyakumar

et al. 2017

OPTH

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“…Our results are in accordance with studies investigating both the outcome after switching from ranibizumab and/or bevacizumab to aflibercept [3, 8–14, 18] and after switching from bevacizumab to ranibizumab [5, 15, 16]. Fassnacht-Riederle et al only found minimal functional improvement when switching to aflibercept after initial treatment with ranibizumab and/or bevacizumab: Visual acuity increased about 1.8 letters in ETDRS visual acuity score but did not reach statistical significance [3].…”

Section: Discussionsupporting

confidence: 92%

Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD

et al. 2017

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BackgroundTo evaluate changes in central macular thickness (CMT) and visual outcome in patients with neovascular age-related macular degeneration (AMD) treated initially with bevacizumab and subsequently switched to either aflibercept or ranibizumab.MethodsObservational clinical study was performed. We measured the structural outcome (CMT on SD-OCT; μm) and the visual outcome (best corrected visual acuity (BCVA); logMAR), as follows: before treatment (at baseline), following bevacizumab treatment (switch follow-up) and after switching from bevacizumab to aflibercept- or ranibizumab treatment (final follow-up, AG/, RG).ResultsFrom a total of 96 eyes treated with intravitreal injections of bevacizumab (10.5 ± 7.6 (mean ± SD)), 58 eyes switched to aflibercept (6.5 ± 3.9; AG) and 38 eyes switched to ranibizumab (7.1 ± 5.3; RG) (≥ 3 injections, each). In addition, these eyes were compared to 37 eyes under bevacizumab monotherapy.Primary outcome: In the AG, the CMT decreased slightly from 430 ± 220 μm at baseline to 419 ± 212 μm at switch follow-up (p = 0.86), but decreased significantly to 318 ± 159 μm at final follow-up, AG (p < 0.0001). In the ranibizumab group (RG), the CMT increased from 396 ± 174 μm at baseline to 499 ± 333 μm at switch follow-up (p = 0.012), but decreased significantly to 394 ± 202 μm at final follow-up, RG (p = 0.007).Secondary outcome: In the AG, the mean BCVA worsened from logMAR 0.57 ± 0.33 at baseline to 0.63 ± 0.30 at switch follow-up and improved slightly to 0.53 ± 0.71 at final follow-up, AG (p = 0.46). In the RG, mean BCVA worsened from 0.57 ± 0.28 at baseline to 0.64 ± 0.31 at switch follow-up and improved slightly to 0.60 ± 0.36 at final follow-up, RG (p = 0.64).ConclusionSwitching from bevacizumab to either aflibercept, or ranibizumab, has a strong anatomical effect in eyes with neovascular AMD. Nevertheless, even if the switch to aflibercept shows a minimal functional benefit over that to ranibizumab, visual prognosis remains limited.

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“…patients who are refractory to ranibizumab (Seguin‐Greenstein et al. ). Hence, a more inclusive systematic review of up‐to‐date knowledge is needed to study the efficacy of aflibercept.…”

Section: Introductionmentioning

confidence: 99%

One year effectiveness study of intravitreal aflibercept in neovascular age‐related macular degeneration: a meta‐analysis

Guo

Cheng

Etminan

et al. 2018

Acta Ophthalmologica

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The current body of evidence on the efficacy and safety of aflibercept for age-related macular degeneration (AMD) is steadily growing as large clinical trials and observational studies are continually completed. Our aim was to analyse 1-year visual acuity (VA) outcomes in response to aflibercept therapy and identify factors affecting treatment response using evidence generated from a pooled analysis of current studies. A literature review of multiple electronic databases (EMBASE, MEDLINE, MedMEME) revealed 12 studies meeting inclusion and exclusion criteria for statistical analysis. Treatment posology, baseline patient characteristics, study type, sample size and 12-month change in VA were pooled in a meta-analysis with VA change as the main outcome. Data were then stratified by study design and posology in subgroup analyses. A meta-regression was conducted to regress 12-month VA change against posology, baseline VA and age. Users of aflibercept experienced an overall increase of 7.37 letters (95% confidence interval: 6.27-8.48, p heterogeneity: <0.001) in VA at 12 months of follow-up. In subgroup analyses, mean VA change was higher for randomized control trials and cohorts following regular posology (>7 injections/year) compared to observational studies and irregular posology. The meta-regression showed larger VA gains with regular posology compared to an irregular posology, and decreased effect size as age increased. This meta-analysis strongly suggests improved VA outcomes at 12 months in patients with wet AMD for 2.0 mg aflibercept, comparable to but slightly lower than landmark trials. Increased injection frequency and younger age demonstrates a trend with improved outcomes.

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A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients with Treatment Resistant Neovascular Age-Related Macular Degeneration following Switching to Treatment with Aflibercept

Cited by 43 publications

References 36 publications

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD

One year effectiveness study of intravitreal aflibercept in neovascular age‐related macular degeneration: a meta‐analysis

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