Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions

Abstract

Aims: To determine the characteristics of ''non-responders'' to intravitreal bevacizumab treatment in choroidal neovascularisation (CNV). Methods: Forty-three patients with visual loss due to neovascular age-related macular disease (ARMD) (44 eyes) underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab and were followed up every 4 weeks for 2, 3 or 6 months. Re-injection was performed when persistent leakage of the CNV was determined by fluorescein angiography and retinal oedema was assessed by optical coherence tomography (OCT). Non-responders were defined as those patients having reduced or stable visual acuity at the last follow-up. Results: 45% of the patients were non-responders. In this group the initial CNV size was significantly larger than in the responders. Initial reading ability was significantly lower in non-responders, but the initial foveal oedema was similar in both groups. Gains in mean visual acuity and reading ability were independent of lesion type. The proportion of non-responders to responders in the different lesion type groups was equally distributed. Only patients with the classic type of CNV seemed to respond better. Conclusions: In this study initial reasons for non-responders to intravitreal bevacizumab treatment in CNV are given. The efficiency of bevacizumab depends on initial lesion size and initial reading ability, but is independent of the amount of intraretinal and subretinal fluid. There was no general ineffectiveness of bevacizumab with any particular lesion type.

Surgical management of subfoveal choroidal neovascular membranes in age-related macular degeneration by macular relocation: experiences of an early-stopped randomised clinical trial (MARAN Study)

“…However, despite the effectiveness of anti-VEGF therapies in most patients with AMD, there may still remain indications for MR surgery in some, such as in patients with large subretinal haemorrhages 20 or in Anti-VEGF non-responders. 21 In this respect, the results of the MARAN study will help to refine patient selection and expectations from MR surgery. …”

Progression of macular atrophy after PDT combined with the COX-2 inhibitor Nabumetone in the treatment of neovascular ARMD

“…Though studies comparing PDT and anti-VEGF therapy show the greater efficacy of anti-VEGF therapy 19 , there are still a number of patients who do not respond to anti-VEGF therapy 20 . These patients could potentially benefit from PDT in combination with other treatment options than anti-VEGF therapy.…”

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

“…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][7][8][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].…”

“…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]. Table 1: The possible risk factors for non-responsiveness to anti-VEGF agents in the patients with nAMD [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

“…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][7][8][9][10][11][12]. However, there is no consensus on the defining of the non responsiveness.…”