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Advances in
eISSN: 2377-4290

Ophthalmology & Visual System

Editorial Volume 6 Issue 6

The non-Responsiveness to Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Neovascularage-Related Macular Degeneration

Burak Turgut

Department of Ophthalmology Firat University Turkey

Correspondence: Burak Turgut Associate Professor of Ophthalmology Firat University Faculty of Medicine Department of Ophthalmology 23119 Elazig Turkey, Tel +904242333555

Received: April 27, 2017 | Published: April 28, 2017

Citation: Turgut B (2017) The non-Responsiveness to Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Neovascularage-Related Macular Degeneration. Adv Ophthalmol Vis Syst 6(6): 00202 DOI: 10.15406/aovs.2017.06.00202

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In this editorial, the definition and potential risk factors of the non-responsiveness to the intravitreal applications of anti-vascular endothelial growth factors in the patients with neovascular age-related macular degeneration were summarized. To know the potential risk factors for the non-responsiveness to these agents may prevent unnecessary treatment interventions and unrealistic patient expectations.

Keywords:anti-vascular endothelial growth factor, age-related macular degeneration, non-responsiveness, definition, non-responders, potential risk factors


Anti-VEGF, anti-vascular endothelial growth factor; n-AMD, neovascular age-related macular degeneration; BVCA, best corrected visual acuity; PED, pigment epithelium detachment


The anti-vascular endothelial growth factor (anti-VEGF) agents including bevacizumab, ranibizumab, and aflibercept have been widely used in the current treatment of neovascular age-related macular degeneration (n-AMD), and they are beneficial in most n-AMD patients.1‒5 However, some patients cannot respond to the treatment as expected. In recent studies, it has been showed that the incidence for non-responsiveness to bevacizumab in treatment naïve n-AMD ranges between approximately 40 and 50% while as the percent of non-responsiveness to ranibizumab was between approximately 10-20%.6‒9 Although there is currently no more evidence in the literature, a recent report demonstrated that the rates of non-responsiveness to aflibercept in the treatment of n AMD based on best corrected visual acuity (BVCA) and fundus findings were approximately 8% and 13%, respectively.10

The absence of expected response to an anti-VEGF agent has been named in different forms as “incomplete response, poor response, non-response, unresponsive, tolerance, tachyphylaxis, rebound, treatment resistant, refractory to anti-VEGF, resistance to anti-VEGF” in current ophthalmology literature.11 However, non responsiveness is exactly different from above mentioned most nomenclatures. If the mistaken diagnosis, tachyphylaxis, and complications secondary to the drug’s itself or its application were excluded, the non-responsiveness to intravitreal anti-VEGF injection in the treatment of n-AMD is defined as the loss (more than 0.2 or 5 letters) or no change in BVCA compared to baseline with persistent macular hemorrhage in fundus examination, intraretinal or subretinal fluid on optical coherence tomography and the leakage in fluorescein angiography despite to a protocol including 3 or 6 consecutive monthly intravitreal anti-VEGF injections.6‒12 However, there is no consensus on the defining of the non responsiveness. In the light of the recent reports, it can be considered that the potential risk factors for non-responsiveness to anti-VEGF agent in the treatment of n-AMD are an initial lesion with subfoveal fibrosis or atrophy in retina pigment epithelium and photoreceptors, lesion in large size, type 1 choroidal neovascularization, serous pigment epithelium detachment (PED), haemorrhagic PED, fibrovascular PED, polypoidal choroidal vasculopathy, foveal scarring and vitreomacular traction, outer retinal tubulation, cystoid degeneration in outer retina, genetic disposition or an anti-VEGF resistance (Table 1).13-22

Possible risk factor for non-responsiveness

Subfoveal fibrosis/scarring

Atrophy in RPE and photoreceptors

Large lesion size

Type 1 CNV

Serous PED

Hemorrhagic PED

Fibrovascular/vascular PED




Cystoid degeneration in outer retina

Genetic disposition

Anti-VEGF resistance

Table 1 The possible risk factors for non-responsiveness to anti-VEGF agents in the patients with nAMD6‒22
Table Abbreviations: RPE, retina pigment epithelium; CNV, choroidal neo-vascularization; PED, pigment epithelium detachment; PCV, polypoidal choroidal vasculopathy; VMT, vitreo-macular traction; ORT, outer retinal tubulation; Anti-VEGF, anti-vascular endothelial growth factor


To know the definition and the potential risk factors of the anti-VEGF non responsiveness in the treatment of n-AMD would prevent unnecessary treatment interventions, unrealistic patient expectations, and economic consumption.



Conflicts of interest

The authors declare there are no conflicts of interest.


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