Recent advances in treating age-related macular degeneration and diabetic retinopathy: Current therapies and emerging novel approaches.

The incidence of retinopathies is expected to increase globally as our population ages and diabetes becomes more prevalent. Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR) are major causes of severe vision loss. These ophthalmological conditions are associated with neovascularization caused by excessive vascular endothelial growth factor (VEGF) secretion. This review focuses on the milestones achieved during the last few decades in treating retinopathies, presents a meta-analysis of key human clinical trials, and finally describes various novel therapies, some of which could potentially eliminate the need for intravitreal injections of anti-VEGF in the future. According to data from clinical trials and everyday medical practice, treatments targeting VEGF are efficient; however, they can cause various systemic (such as stroke) and ocular adverse events. The most frequently experienced adverse reactions (such as endophthalmitis or retinal detachment) are related to the injection process itself. These complications warrant the efforts invested in developing novel approaches, including gene therapy-based products and inhibitors of VEGF receptors. We discuss here the strengths and drawbacks of gene therapy and highlight the potential of small-molecule tyrosine kinase inhibitors (TKIs) as alternative anti-neovascularization agents. TKIs have recently been tested via numerous administration routes, including simple oral dosing of oral formulations in addition to intravitreal implants, which allow for a slow release, intravitreal depots, and suprachoroidal injections. All of which have shown different safety and efficacy profiles. We conclude that gene therapy products, especially TKIs, have the potential to become inhibitors of ocular neovascularization in the upcoming years.