Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment

Abstract

The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients.

Optical Coherence Tomography Angiography to Quantify Choroidal Neovascularization in Response to Aflibercept

“…However, complete regression of CNV cannot be achieved with anti-VEGF monotherapy. Therefore, some cases are refractory to anti-VEGF monotherapy, while some cases exhibit high recurrence [6]. …”

Early Changes of Retinal Morphology in Therapy of Neovascular Age-Related Macular Degeneration with Three Commonly Used Anti-VEGF Agents

“…Previous studies regarded the presence of IRF as a negative prognostic biomarker for the functional outcome [24,25] . Interestingly, we observed a decrease of intraretinal edema on average by 80% within the first 7 days after an intravitreal injection.…”

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

“…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.…”