TY - JOUR
T1 - Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy
AU - Cao, Xuan
AU - Sanchez, Jaron Castillo
AU - Dinabandhu, Aumreetam
AU - Guo, Chuanyu
AU - Patel, Tapan P.
AU - Yang, Zhiyong
AU - Hu, Ming Wen
AU - Chen, Lijun
AU - Wang, Yuefan
AU - Malik, Danyal
AU - Jee, Kathleen
AU - Daoud, Yassine J.
AU - Handa, James T.
AU - Zhang, Hui
AU - Qian, Jiang
AU - Montaner, Silvia
AU - Sodhi, Akrit
N1 - Publisher Copyright:
Copyright: © 2022, Cao et al.
PY - 2022/1/18
Y1 - 2022/1/18
N2 - BACKGROUND. To reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear. METHODS. Eyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients’ response to treatment. RESULTS. At the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients’ response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV. CONCLUSION. Aqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.
AB - BACKGROUND. To reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear. METHODS. Eyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients’ response to treatment. RESULTS. At the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients’ response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV. CONCLUSION. Aqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.
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U2 - 10.1172/JCI144469
DO - 10.1172/JCI144469
M3 - Article
C2 - 34874918
AN - SCOPUS:85123651640
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
M1 - 144469
ER -