Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy
Xuan Cao, … , Silvia Montaner, Akrit Sodhi
Xuan Cao, … , Silvia Montaner, Akrit Sodhi
Published December 7, 2021
Citation Information: J Clin Invest. 2022;132(2):e144469. https://doi.org/10.1172/JCI144469.
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Clinical Research and Public Health Ophthalmology

Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy

Abstract

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.Funding This work was supported by the National Eye Institute, National Institutes of Health grants R01EY029750, R01EY025705, and R01 EY27961; the Research to Prevent Blindness, Inc.; the Alcon Research Institute; and Johns Hopkins University through the Robert Bond Welch and Branna and Irving Sisenwein professorships in ophthalmology.Conclusion Aqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.

Authors

Xuan Cao, Jaron Castillo Sanchez, Aumreetam Dinabandhu, Chuanyu Guo, Tapan P. Patel, Zhiyong Yang, Ming-Wen Hu, Lijun Chen, Yuefan Wang, Danyal Malik, Kathleen Jee, Yassine J. Daoud, James T. Handa, Hui Zhang, Jiang Qian, Silvia Montaner, Akrit Sodhi

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Figure 1

Heatmap comparing fluid over time for eyes of patients who required sustained anti-VEGF treatment versus those who were successfully weaned from anti-VEGF therapy by 12 months.

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Heatmap comparing fluid over time for eyes of patients who required sust...
OCT images were obtained from all 102 eligible patients who underwent the TEP/M approach for at least 12 months. Presence of fluid on OCT was graded independently by 2 investigators for the presence of no fluid, subretinal fluid (SRF), intraretinal fluid (IRF), or both at time points 0, 1, 2, 3, 6, and 12 months after initiation of protocol. Fluid status overtime for each individual patient is graphically represented with dark blue denoting no fluid; light blue, SRF; light green, IRF; and yellow, both. Patients were grouped into 2 categories: those not weaned (requiring sustained treatment every 4–12 weeks) and those weaned off treatment. Within each group, patients were sorted by severity of fluid (none < SRF < IRF < both).