Abstract
BackgroundNeovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Low-grade inflammation is well-known as one of the pathogenic mechanisms in nAMD. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, although macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. Here, we show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment.MethodsTwenty-eight nAMD patients received three consecutive monthly IVA, followed by a pro re nata regimen for 2 years. AH specimens were collected before first IVA (pre-IVA) and before third IVA (post-IVA). AH cytokine levels, visual acuity (VA), and central retinal thickness (CRT) were measured.ResultsTwo-year incidence of MA was 21.4%. In nAMD eyes developing MA [MA (+) group], pre-IVA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1β, VEGF and post-IVA level of MCP-1 were higher than those in nAMD eyes without MA [MA (−) group]. In hierarchical cluster analysis, pre-IVA MCP-1 and VEGF were grouped into the same subcluster, as were post-IVA MCP-1 and CRT. In principal component analysis, principal component loading (PCL) of pre-IVA interferon-γ-inducible protein 10 (IP-10) was 0.61, but PCL of post-IVA IP-10 decreased to −0.09. In receiver operating characteristic analysis and Kaplan–Meier curves, pre-IVA MCP-1, MIP-1β, and VEGF and post-IVA interleukin-6, MCP-1, and MIP-1β were detected as predictive factors for MA incidence. In 2-year clinical course, changes of VA in groups with high levels of pre-IVA MIP-1β (over 39.9 pg/ml) and VEGF (over 150.4 pg/ml) were comparable to those in MA (+) group.ConclusionSubstantial loss of IP-10 effects and persistent inflammation contribute to incidence of MA, and screening of AH cytokine levels could be a useful method to predict MA incidence in nAMD eyes under anti-VEGF therapy.
Highlights
In developed countries, age-related macular degeneration (AMD) is a severe ocular disease in people older than 50 years [1]
Total Neovascular age-related macular degeneration (nAMD) group was composed of 10 eyes (35.7%) classified as typical AMD subdivided into type I choroidal neovascularization (CNV) (Type I: five eyes, 17.9%) and type II CNV (Type II: five eyes, 17.9%), 18 eyes (64.3%) as polypoidal choroidal vasculopathy (PCV), and 0 eye as retinal angiomatous proliferation (RAP)
The present study examined macula atrophy (MA)-associated factors and identified significant biomarkers that predict MA incidence in nAMD eyes under intravitreal injection of aflibercept (IVA) treatment for 2 years
Summary
Age-related macular degeneration (AMD) is a severe ocular disease in people older than 50 years [1]. AMD leads to approximately 1% of visual impairment and some 5% of blindness [2]. Neovascular AMD (nAMD) is associated with choroidal neovascularization (CNV), leading to subretinal and intraretinal macular edema, hemorrhage, and fibrosis, resulting in visual impairment [4]. Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. We show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment
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