Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic diseases

Abstract

Macular degeneration is the leading cause of blindness in developed countries. In the treatment of neovascular age-related macular degeneration, vascular endothelial growth factor (VEGF) has emerged as a key target for therapy. The intravitreal injection of anti-VEGF drugs has been widely employed to reduce the disease progression and improve the visual outcomes of the affected patients. However, each intravitreal inoculation poses a risk of several complications as infection, inflammation, endophthalmitis, intraocular inflammation, increase of intraocular pressure and vitreous hemorrhage. This short review evaluates the efficacy and the incidence of adverse drug reactions related to intravitreal administration of the main anti-VEGF drugs actually available: Bevacizumab, ranibizumab and aflibercept.

The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

“…Nowadays, nAMD practitioners widely recur to anti-VEGF agents [79][80][81][82] for treatment, albeit with limitations or side effects: high probability of ocular infection, increased ocular pressure, cataract, vitreous hemorrhaging and retinal detachment; elevated price; transient (demands repeated intravitreal injections); limited recovery of patients' visual acuity in a long period [179][180][181][182]. Some of these issues evolve from the use of mono-factor therapies, such as anti-VEGF drugs, to address a multifactorial, multi-genetic disease, as is the case of nAMD.…”

SRPKIN-1: A Covalent SRPK1/2 Inhibitor that Potently Converts VEGF from Pro-angiogenic to Anti-angiogenic Isoform

“…While targeting VEGF with small molecules has proven difficult, the use of VEGF-blocking antibodies such as Ranibizumab has been successfully used for treating age-related macular degeneration (AMD) (Rosenfeld et al, 2006; Gragoudas et al, 2004), an intraocular neovascularization disease caused by abnormal growth of blood vessels inside the eye (Seddon and Chen, 2004). However, antibody-based therapy is often associated with multiple risk factors, including infection, inflammation, and vitreous hemorrhage (Shima et al, 2008; Ventrice et al, 2013). Therefore, small-molecule inhibitors remain desirable for patients with AMD and cancer, either as a monotherapy or in combination with other anti-cancer agents.…”

An Endostatin-lentivirus (ES-LV)-EPC gene therapy agent for suppression of neovascularization in oxygen-induced retinopathy rat model

“…VEGF can be secreted by several types of ocular cells [ 27 , 28 ]. The role of VEGF in ocular neovascularization is critical, so VEGF is an attractive target for the development of gene therapies [ 8 – 11 , 29 , 30 ]. Therefore, new effective therapeutic tools that specifically target retinal neovascularization cells and decrease VEGF secretion are urgently needed.…”

“…However, expensive charges, frequent office visits, and multiple injections are added to the burden of patients with this condition. The injections are also associated with a low risk of an increase in intraocular pressure, and the incidence of vitreous hemorrhage, uveitis, vascular occlusion, or the retinal detachment is elevated [ 9 – 11 ]. Worse, neovascularization may reappear when the therapy is over because the effect of a single injection of anti-VEGF agents is temporary [ 12 ].…”