Intravitreal anti-VEGF agents and cardiovascular risk

Abstract

Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) are widely administered by intravitreal injection for the treatment of ocular pathologies such as Age-related Macular Degeneration, Diabetic Macular Edema, Proliferative Diabetic Retinopathy and occlusion of retinal vessels. Anti-VEGF agents, in particular bevacizumab, were introduced in oncology to inhibit tumor-induced angiogenesis feeding neoplastic tissues. Subsequently, other specific agents were developed for intraocular administration.Whereas systemic administration of anti-VEGF agents in oncology is burdened by increased risk of arterial hypertension and embolism, agents administered for ophthalmic indications are delivered locally into the eye globe in much smaller quantities. Nevertheless, clinical observations have raised the possibility that, even in these conditions, anti-VEGF agents may increase cardiovascular risk in patients who, being elderly and/or diabetic, are intrinsically prone to such events. This paper aims at reviewing the current knowledge on VEGF and its pharmacologic antagonists from mechanistic and side-effect points of view, with specific reference to patients with sight-threatening conditions. Internists should be aware of the need to collaborate with ophthalmologists and pharmacovigilance operators to define as best as possible the risk/benefit balance of intravitreal agents in patients who might lose their sight if left untreated, or increase their risk of suffering a cardiovascular event if treated.

Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?

“…However, these treatments are not effective for every patient and they are associated with risks of complications. In particular, anti-VEGF agents have been linked to adverse effects on the photoreceptors and choroidal vessels as well as on the kidney and cardiovascular system [11][12][13]. Moreover, none of these treatments addresses neuronal damage or promotes tissue repair.…”

Soluble Vegfr3 gene therapy suppresses multi‐organ metastasis in a mouse mammary cancer model

“…sVEGFR‐2, an endogenous soluble isoform of the VEGF‐C receptor, was reported to function as a specific inhibitor of lymphatic vessel growth, 46 a subsequent study revealed that sVEGFR‐2 suppressed tumor growth and lymph node metastasis in a mouse mammary model specifically through inhibition of lymphangiogenesis by sequestering VEGF‐C, while it did not affect angiogenesis 26 . As VEGF‐A maintains blood vessel integrity, prolonged systemic administration of anti‐VEGF‐A agents in cancer is accompanied by side‐effects (due to lack of normal VEGF functioning) such as increased risk of arterial hypertension and embolism 47 . It influences the survival of blood vessels in healthy tissues 48 as well.…”

“…26 As VEGF-A maintains blood vessel integrity, prolonged systemic administration of anti-VEGF-A agents in cancer is accompanied by side-effects (due to lack of normal VEGF functioning) such as increased risk of arterial hypertension and embolism. 47 It influences the survival of blood vessels in healthy tissues 48 as well. Therefore, sVEGFR-3 therapy may prevent side-effects through anti-angiogenesis.…”

Does conventional laser photocoagulation still have a place in the treatment of diabetic macular edema?

“…Anti-VEGF treatment necessitates several monthly injections to achieve desirable results during treatment of DME and causes treatment burden both financially and related to patient attendance [ 16 ]. Moreover, every injection may carry some risks such as endophthalmitis, cerebrovascular accidents even if they are seen very rarely [ 19 , 20 ].…”