J Pers Med. 2021 Dec 08;11(12). doi: 10.3390/jpm11121329.

Predictive Biomarkers of Age-Related Macular Degeneration Response to Anti-VEGF Treatment.

Journal of personalized medicine

Ana I Oca, Álvaro Pérez-Sala, Ana Pariente, Rodrigo Ochoa, Sara Velilla, Rafael Peláez, Ignacio M Larráyoz

PMID: 34945801 PMCID: PMC8706948 DOI: 10.3390/jpm11121329

Abstract

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic and local inflammation in the pathogenesis of AMD. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for choroidal neovascularization in AMD patients. However, a high number of patients do not show satisfactory responses to anti-VEGF treatment after three injections. Predictive treatment response models are one of the most powerful tools for personalized medicine. Therefore, the application of these models is very helpful to predict the optimal treatment for an early application on each patient. We analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) from AMD patients before treatment to identify biomarkers of response to ranibizumab. A classification model comprised of four mRNAs and one miRNA isolated from PBMCs was able to predict the response to ranibizumab with high accuracy (Area Under the Curve of the Receiver Operating Characteristic curve = 0.968), before treatment. We consider that our classification model, based on mRNA and miRNA from PBMCs allows a robust prediction of patients with insufficient response to anti-VEGF treatment. In addition, it could be used in combination with other methods, such as specific baseline characteristics, to identify patients with poor response to anti-VEGF treatment to establish patient-specific treatment plans at the first visit.

Keywords: PBMC; RNA-Seq; machine learning; ranibizumab; retina

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Publication Types

• Journal Article

Grant support

• PI19/01805/Instituto de Salud Carlos III
• CPII20/00029/Instituto de Salud Carlos III