Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration

Cheng, Skye Hongiun; Leng, Theodore

doi:10.3928/23258160-20160419-09

Cited by 3 publications

(3 citation statements)

References 51 publications

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“…The chronic nature of nAMD in these patients may progress to atrophic changes12,53,54 and subsequent photoreceptor and RPE damage55 leading to a possible pharmacological ceiling effect. The CATT trials showed an increase in GA with monthly ranibizumab injections;55 thus, it has been suggested aflibercept’s higher binding affinity for VEGF may aggravate preexisting GA in switching patients 56…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…We have shown the outcome of anti-VEGF (in context to number of injections given during the disease course) associated with both environmental (alcohol consumption and cataract history) and genetic factors (genetic variants of B3GALTL and LIPC). Poor response of Aflibercept has also been observed with higher BMI and geographic atrophy AMD patients 19 . Aqueous humor levels of angiogenic and pro-angiogenic proteins including VEGF-A, VEGF-C, interleukin 8, endothelin 1, HGF (Hepatocyte growth factor), HB-EGF (Heparin-binding epidermal growth factor-like growth factor), follistatin, and angiopoietin 2 were also found to be elevated after intravitreal injection of bevacizumab 20 .…”

Section: Discussionmentioning

confidence: 98%

Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

Sharma

Battu

Singh

et al. 2022

Sci Rep

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Age-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.

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“…Factors associated with a poor response to or shorter durability of aflibercept in neovascular AMD remain unclear. Higher body mass index and geographic atrophy are considered potential indicators for a poor response to aflibercept [ 20 ]. Remnant polyps and PED morphology are associated with recurrence of PCV after aflibercept treatment [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration

Lee¹,

Kim²,

Kim³

2022

JCM

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We investigated the efficacy of monthly alternating injections of aflibercept and bevacizumab (MAAB) for maintenance treatment in patients with neovascular age-related macular degeneration (AMD) who showed improvement with the initial monthly injections but presented with rapid worsening after conversion to bimonthly injections. We included 72 patients with neovascular AMD who showed improvement with loading injections of aflibercept. For maintenance treatment, bevacizumab was administered every alternate month between the bimonthly aflibercept injections in 24 (33.3%) eyes showing worsening (MAAB group). The other eyes were treated with aflibercept (BiA group) bimonthly. Baseline low retinal thickness, thick choroid, and presence of intraretinal fluid were associated with worsening after extending the injection intervals. Visual improvement was lower in the MAAB group than in the BiA group, but the final visual outcomes were comparable. Additional bevacizumab stabilized the early fluctuation of retinal thickness, thus maintaining long-term visual stability without increasing the risk of geographic atrophy or disciform scar until the second year. Previously treated eyes or those with polypoidal choroidal vasculopathy responded less to the initial loading doses and showed worsening under the bimonthly regimen. MAAB was effective in preventing anatomical and functional deterioration when bimonthly aflibercept proved insufficient for the maintenance treatment of neovascular AMD.

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Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration

Abstract: BMI and geographic atrophy may be considered as potential indicators for poor response to aflibercept after switching from ranibizumab or bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:458-465.].

Cited by 3 publications

References 51 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

Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration

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