Development of Macular Atrophy in Patients with Wet Age-Related Macular Degeneration Receiving Anti-VEGF Treatment

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGF). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularisation (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterised as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

Photo‐mediated ultrasound therapy for the treatment of retinal neovascularization in rabbit eyes

“…While the use of anti-VEGF therapies has revolutionized the treatment of ocular neovascularization, anti-VEGF therapy could potentially lead to retinal atrophy, and blockage of VEGF-A during retinal stress could lead to accelerated retinal cell death and is an area of active investigation. [3][4][5][6][7][8][9][10][11][12] In addition, 15%-40% of eyes fail to or only partially respond to anti-VEGF therapies. 13 Further, anti-VEGF therapy involves frequent, often monthly, intravitreal injections of anti-VEGF agents, which are costly and inconvenient for patients, and carry a risk of eye infection or endophthalmitis.…”

“…Treatment of RNV includes anti‐vascular endothelial growth factor (VEGF) therapy and laser therapy. While the use of anti‐VEGF therapies has revolutionized the treatment of ocular neovascularization, anti‐VEGF therapy could potentially lead to retinal atrophy, and blockage of VEGF‐A during retinal stress could lead to accelerated retinal cell death and is an area of active investigation 3–12 . In addition, 15%–40% of eyes fail to or only partially respond to anti‐VEGF therapies 13 .…”

PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

“…However, in view of the success of anti‐VEGF biologics in treating the latter disorders, 96 much more compelling clinical evidence is needed for PAF receptor antagonists to be progressed into development and for future approvals by health agencies. Given that maculopathy develops after long‐term anti‐VEGF treatment, 108 perhaps it is time to consider PAF receptor antagonists as another treatment option for AMD. For this to happen, the PAF antagonist molecules would need to be hydrophobic enough to enter the affected cells in order to block the intracellular PAF receptors on the nuclear membranes.…”

Introduction to the Department of Cardiology in Nanjing First Hospital of Nanjing Medical University, China

“…Neovascular age-related macular degeneration (nAMD) is a main subtype of AMD. As the intravitreal vascular endothelial growth factor (VEGF) level elevates, choroidal neovasculars invade the avascular outer retina and severely damage photoreceptors, resulting in rapid vision loss [1]. At present, anti-VEGF injection is considered the preferred nAMD therapy [2].…”

“…t 2 , f j t 2 to z j t 1 , z j t 2 , z j t 2 for evolution reinforcement learning:z = h(f ) = W (2) (ReLU (W (1) • GAP (f )))(8)where W(1) , W(2) are weight matrixes, GAP (•) indicates global average pooling. We hope predicted z j t 2 and real z j t 2 should be as similar as possible, while predicted z j t 2 and real z j t 1 should be different.…”