Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

Abstract

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

“…Some of these therapies cause neovascular membrane regression and can potentially improve outcomes when used in combination with anti-VEGF therapies (Hanout et al, 2013;Kaiser, 2013). Anti-PDGF medication (Fovista™, Ophthotech, US), in combination with anti-VEGF medications, prevent PDGF from binding to its natural receptor on pericytes, enhancing the effect of anti-VEGF drugs on new vessel regression.…”

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids

“…With the introduction of anti-VEGF antibody therapy in 2006, and more recently the introduction of the recombinant fusion protein aflibercept, 6 about 30%–40% of nvAMD patients regain three or more lines of visual acuity with stabilization occurring in 90% of the remaining patients. However, in addition to the fact that the majority of nvAMD patients do not regain vision with anti-VEGF therapy, the frequent, often monthly, intravitreal injections are a significant impediment to compliance, considering that these patients are old and visually impaired.…”

Advances in pharmacotherapy for wet age-related macular degeneration

“…siRNAs cross the cellular membrane and are incorporated into the RNA-induced silencing complex (RISC), enhancing the helicase activity of this complex and leading to selective degradation of mRNA molecules containing a complementary sequence [82]. siRNAs can be engineered to match a specific nucleotide sequence of a target mRNA [83].…”

“…Preclinical data show good anti-angiogenic and anti-tumor activity [90]. In humans, topical pazopanib is safe and well tolerated [83]. However, a recent study of Csaky KG et al found that daily pazopanib eye drops in patients with wet AMD did not result in therapeutic benefit beyond that obtained with ranibizumab alone [91].…”