Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) study protocol

Abstract

Introduction: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 55 years of age globally, being neovascular AMD (nAMD) its most aggressive form. Its treatment consists of the use of drugs that block vascular endothelial growth factor (anti-VEGF). Proteomics may allow the identification of differentially expressed proteins between responders and non-responders to each anti-VEGF drug. Thus, the objective of Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) is to find new proteomic biomarkers, predictive of response to antiangiogenic treatment in patients with nAMD.

Methods and analysis: PHARPRO-AMD is a nationwide, multicentre, prospective, observational study. Treatment-naïve patients with nAMD starting anti-VEGF therapy will be enrolled and followed up for 2 years. During this period, clinical variables will be gathered to classify treatment response. In addition, blood, tear and vitreous and aqueous humour samples will be collected and will undergo a ZenoSWATH proteomic analysis. Relevant biomarkers identified and response classification will be used to perform a multivariate logistic regression and construct receiver operating characteristic curves.

Results: The study is expected to identify a panel of proteomic biomarkers predictive of anti-VEGF treatment response. Integrating data from invasive and non-invasive biological samples may enhance clinical applicability. Once validated, these biomarkers could support the design of future clinical trials on biomarker-guided therapies, helping to optimise treatment regimens and improve visual outcomes.

Conclusions: The PHARPRO-AMD study aims to provide proof-of-concept for biomarker-guided anti-VEGF therapy in nAMD, potentially improving vision outcomes. A notable limitation is the exclusion of patients with visual acuity above 73 Early Treatment of Diabetic Retinopathy Study letters, a criterion chosen to reduce potential ceiling effects and improve response assessment accuracy.

Ethics and dissemination: Approved by the Galician Network of Ethics Committees, with nationwide validity. Anonymised data will be deposited in open-access repositories and published in peer-reviewed journals.

Trial registration number: Spanish Clinical Studies Registry (REec) (0033-2024-OBS).

Keywords: Angiogenesis; Aqueous humour; Drugs; Macula; Neovascularisation; Retina; Tears; Vitreous.

Figure 1. Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration study workflow. HPLC-MS, high-performance liquid chromatography–mass spectrometry; nAMD, neovascular age-related macular degeneration; NEI VFQ-25, National Eye Institute Visual Function Questionnaire-25.