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Abstract
Objective To investigate if chemokine expression patterns on leucocyte subsets influence the short-term anatomical treatment response of intravitreal antivascular endothelial growth factor therapy against neovascular age-related macular degeneration (AMD).
Methods and analysis This study was conducted as a prospective observational cohort study of 79 patients with neovascular AMD. We used optical coherence tomography to quantify central retinal thickness (CRT) and to evaluate the presence of intraretinal and subretinal fluids in treatment-naive patients at baseline and after loading dose. Anatomical response was categorised into either good responders (complete regression of fluid or a reduction of >75% in CRT), partial responders (reduction of 0%–75% in CRT) or non-responders (increase of CRT). Expression levels of chemokine receptors (CCR1, CCR2, CCR3, CCR5, CXCR3 and CX3CR1) were measured on leucocyte subsets (monocytes, CD4 +T cells, and CD8 +T cells) using flow cytometry. Finally, we explored potential correlation patterns of chemokine expression between the leucocyte subsets using group-specific correlation networks.
Results Non-responders had higher CCR1 expression on monocytes (p=0.016) and lower CCR3 expression on CD8+ T cells (p=0.037). Correlation network analyses of chemokine receptor expression patterns on leucocyte subsets revealed intergroup differences.
Conclusion Short-term anatomical treatment response in neovascular AMD varies according to the leucocyte subset chemokine expression pattern, which confirms that immune dysfunction is a complex issue in AMD. Our results suggest that focusing on chemokines may be a relevant approach towards personalised treatment in neovascular AMD.
- degeneration
- immunology
- macula
- neovascularisation
- treatment medical
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Footnotes
Contributors TB, MKN and TLS designed the study. MKN, CRM, YS and TLS obtained funding. TB, MKN, CRM and YS collected the data. TB, MKN and TLS analysed and interpreted the data. TB drafted the manuscript and prepared the figures and tables. All authors critically revised the manuscript for important intellectual content.
Funding This study was made possible by grants from the Danish Eye Research Foundation (Taastrup, Denmark), Fight for Sight Denmark (Copenhagen, Denmark), the Velux Foundation (Søborg, Denmark) and the University of Copenhagen (Copenhagen, Denmark). The funding bodies had no role in the design or conduct of this research.
Competing interests None.
Patient consent for publication Not required.
Ethics approval This prospective observational cohort study was conducted in compliance with the Declaration of Helsinki and was approved by the Regional Committee of Ethics in Research in Region Zealand (journal no. SJ-385).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Dataset can be obtained from the corresponding author upon reasonable request.