Abstract
We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal anti-VEGF injections for CNV. The VEGF level decreased significantly (P < 0.001), while the C3a and C4a levels increased significantly (P < 0.001 for both comparisons) 1 month after two monthly anti-VEGF injections. The VEGF level was correlated with the C3a (R = 0.328, P = 0.007) and C4a (R = − 0.237, P = 0.055) levels at baseline, but the correlation between the VEGF and C3a levels (R = − 0.148, P = 0.242) changed significantly (P = 0.028 by analysis of covariance) after anti-VEGF treatment. The C3a increase after anti-VEGF therapy did not change the visual outcomes in eyes with CNV for 1 year. Dysregulation of the complement system can be induced after anti-VEGF therapy.
Highlights
We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy
The patients with drusen-associated neovascular AMD (nAMD) were a median age of 73.0 years and the controls were a median age of 69.0 years (IQR 67.0–74.5) (P = 0.118)
There were no significant differences in age (P = 0.054), sex (P = 0.218), logarithm of the minimum angle of resolution (P = 0.212), axial length (P = 0.902), equivalent spherical power (P = 0.166), incidence of subretinal fluid (SRF) (P = 0.06), intraretinal fluid (IRF) (P = 0.288), pigmentary abnormalities (P = 0.501), greatest linear dimension (GLD) (P = 0.916), CNV lesion size (P = 0.146), and central retinal thickness (CRT) (P = 0.349) among the three subtypes
Summary
We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal antiVEGF injections for CNV. The C3a increase after anti-VEGF therapy did not change the visual outcomes in eyes with CNV for 1 year. AMD is classified as atrophic or neovascular AMD; the former is characterized by atrophy of the photoreceptors and retinal pigment epithelium (RPE) without exudative changes and the latter by choroidal neovascular membranes (CNV) and retinal edema at the macula. Histopathologic studies reported that complement activation products deposit in the drusen on the RPE cells, Bruch’s membrane, and choriocapillaris[5,6]. Elevated C3a in the intraocular fluid in neovascular AMD (nAMD) suggests the involvement of the complement s ystem[8]
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