Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

Abstract

Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

“…Also this aspect could be of particular relevance in clinics. Hence, there are emerging signals that anti-VEGF treatment can potentially increase development of RPE atrophy and even macular atrophy, leading to geographic atrophy (GA) [39, 40]. …”

miR‐30a‐5p inhibition promotes interaction of Fas+endothelial cells and FasL+microglia to decrease pathological neovascularization and promote physiological angiogenesis

“…Often, these ischemic events lead to abnormal angiogenesis, a hallmark of many retinopathies, and this in turn leads to neurodegeneration resulting in visual impairment. Currently, therapies employing anti‐vascular endothelial growth factor (VEGF) agents to target abnormal angiogenesis are used to treat ischemic retinal diseases including age‐related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP) (Chawla & Darlow, ; Duh, Sun, & Stitt, ; Gemenetzi, Lotery, & Patel, ; Stewart, ). While anti‐VEGF agents represent a major breakthrough in the treatment of retinal diseases with an angiogenic component, they have been used with limited success (Usui et al, ).…”

“…While anti‐VEGF agents represent a major breakthrough in the treatment of retinal diseases with an angiogenic component, they have been used with limited success (Usui et al, ). Not all patients respond to anti‐VEGF treatment (Ashraf, Souka, Adelman, & Forster, ; Chin‐Yee, Eck, Fowler, Hardi, & Apte, ) and increasing evidence suggests that, in some cases, prolonged treatment with anti‐VEGF may lead to hypoxia, exacerbate retinal ischemia (Lee, Kang, & Koh, ; Toy, Schachar, Tan, & Moshfeghi, ) and lead to degeneration of retinal neurons and retinal pigment epithelium (RPE) (Ashraf et al, ; Gemenetzi et al, ; Keir et al, ). Thus, there is a large unmet medical need to develop new, targeted therapies that will either improve efficacy or reduce off‐target effects when used in combination with anti‐VEGF drugs.…”

“…VEGF may lead to hypoxia, exacerbate retinal ischemia (Lee, Kang, & Koh, 2017;Toy, Schachar, Tan, & Moshfeghi, 2016) and lead to degeneration of retinal neurons and retinal pigment epithelium (RPE) (Ashraf et al, 2016;Gemenetzi et al, 2017;Keir et al, 2017). Thus, there is a large unmet medical need to develop new, targeted therapies that will either improve efficacy or reduce off-target effects when used in combination with anti-VEGF drugs.…”

Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases

“…Intravitreal drug delivery has been a dominant method in treating vitreoretinal diseases for the last few decades, and it comprises direct intravitreal injection and intravitreal implantable device technology as well as bioerodible and nonbioerodible intravitreal implantable devices [22] . Via this effective technique, clinicians can administer drugs such as anti-VEGF [23][24][25][26][27] and steroids [28][29][30][31] , among others, or gene therapy such as vectors containing specific genes [32][33][34] , stem cells [35,36] , etc., directly into the back of the eye to increase drug concentration in the vitreous and the retina. However, the complications associated with this method have emerged, gaining increasing attention from clinicians.…”