Aflibercept therapy in eyes with neovascular age‐related macular degeneration and its effect on choroidal thickness

Abstract

Background: The purpose of this study was to investigate changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveal choroidal thickness (SCT) after intravitreal aflibercept injections for neovascular age-related macular degeneration (NV-AMD). Methods: Eighty-nine eyes (48 treatment naive, 41 resistant) were included in this prospective study. All patients were treated with three consecutive monthly injections then every two months as required. BCVA, CMT and SCT were recorded and compared within and between the two groups. Results: The mean increase in BCVA after injections was 0.18 AE 0.34 logMAR in the naive group (p = 0.01) and 0.092 AE 0.38 logMAR in the resistant group (p = 0.131). The mean decrease in CMT was 200.3 AE 216.1 μm in the naive group and 183.3 AE 203.4 μm in the resistant group (p < 0.001 for both). The mean decrease in SCT was 22.1 AE 62.0 μm in the naive group (p = 0.014). The mean change in SCT was 22.28 AE 74.05 μm in the resistant group; this was not statistically significant (p = 0.061). Conclusion: BCVA, CMT and SCT decreased significantly after intravitreal aflibercept injections in naive patients with NV-AMD. Despite anatomic success, functional improvement was not reached and SCT did not significantly decrease after intravitreal aflibercept injections in resistant patients.

Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions

“…They reported a statistically significant decrease in the density of the choriocapillaris during the follow-up period, which was not seen in healthy age-matched controls (Hikichi and Agarie 2019). Similarly, decreased choroidal thickness was measured in neovascular AMD eyes treated with aflibercept or ranibizumab (Adhi et al 2014;Inan et al 2019;Sariyeva Ismayilov et al 2019;Ting et al 2016;Yamazaki et al 2012). Animal studies support the hypothesis that blocking VEGF may lead to choroidal Fig.…”

Design and development of new bio-gated nanodevices for targeted controlled drug release

“…In PBS a remarkable baseline was observed, which indicated that doxorubicin remained in the nanoparticles without release. For instance, cargo delivery was lower than 10% at 24 h. In contrast, cargo release in the presence of lysosomal extract was clearly found as an increase of the doxorubicin fluorescence versus time.…”

“…7 It is well known that nanocarriers shape, size and surface charge are the fundamental parameters that determine their behaviour and interaction with biological systems once administered, affecting distribution, stability, circulation time, recognition, cellular uptake, intracellular transport, accumulation and elimination. 10,24 Deep characterization of the systems developed in research laboratories is still an issue, as it results extremely complicated to analyse so many parameters (beyond those already mentioned above, composition, stability and surface coverage with ligands) separately and then establishing relationships between them. Therefore, a detailed understanding of the physico-chemical properties of nanomaterials is essential for the evaluation of their toxicological impact within acceptable pharmaceutical levels.…”

“…Otherwise, the development of biomimetic surfaces represents an alternative strategy, in which natural membrane coating enables to avoid clearance and to increase the biocompatibility of the material. 24 Targeted approaches, on the other hand, involve surface physical or chemical integration of nanomaterials with affinity ligands of overexpressed receptor or other biological targets, using a wide catalogue of biomolecules such as peptides and proteins, 33 sugars, 34 aptamers, 35 small molecules 36 and monoclonal antibodies 37 among others, with the aim to induce a recognition and a specific uptake via receptor-mediated endocytosis. 38,39 Coupling of ligands to nanotransporters surface can be achieved by covalent and non-covalent binding:…”

“…[17,22] Later, Lucentis® (ranibizumab, by Genentech/Novartis), a humanized antibody fragment that blocks the receptor binding domain of all isoforms of VEGF-A, and Eylea® (aflibercept, by Regeneron/Bayer), a recombinant fusion protein with higher affinity for VEGF-A became an established treatment for wet AMD. [17,23,24] Nevertheless, despite the desirable therapeutic outcomes obtained, these approaches still present important issues, mainly due to their route of administration (i.e. intravitreal injections) and the need of frequent applications,…”