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Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study

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Abstract

Aims

Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes.

Methods

A case–control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measured by Simoa.

Results

Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAP were significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2 years of follow-up (139.1 ± 52.5 pg/mL vs. 100.2 ± 54.6 pg/mL; p = 0.04).

Conclusions

GFAP could be a useful serum biomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.

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Data availability statement

The data presented in this study are available upon request from the corresponding author.

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Funding

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration, under grant agreement no. 278040, and from Instituto de Salud Carlos III (PI20/01703). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Author information

Authors and Affiliations

  1. Diabetes and Metabolism Research Unit and CIBERDEM, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Passeig de La Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Cristina Hernández, Olga Simó-Servat & Rafael Simó

  2. Department of Medical Sciences, University of Turin, Turin, Italy

    Massimo Porta

  3. Research Unit of Ophthalmology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Jakob Grauslund & Ulrik Frydkjaer-Olsen

  4. Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, and St. Paul’s Eye Unit. Liverpool University Hospitals, Liverpool, UK

    Simon P. Harding

  5. Department of Ophthalmology, Vall d’Hebron University Hospital, Barcelona, Spain

    José García-Arumí

  6. Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal

    Luísa Ribeiro & José Cunha-Vaz

  7. Gloucestershire Hospitals National Health Service Foundation Trust, Cheltenham, UK

    Peter Scanlon

Authors
  1. Cristina Hernández
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Consortia

the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR)

Contributions

Conceptualization, CH and RS; methodology, CH, OS, MP, JG, SH, UF, JG-A, LR, PS, JC, and RS; formal analysis, CH, OS, and RS; investigation, CH, OS, MP, JG, SH, UF, JG-A, LR, PS, JC, and RS; formal analysis, CH, OS, and RS; resources, CH, OS, MP, JG, SH, UF, JG-A, LR, PS, JC, and RS; writing—original draft preparation, CH; writing—review and editing, CH and RS; project administration, CH and RS; funding acquisition, EUROCONDOR Consortium (coordinator: RS). All authors have reviewed and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Cristina Hernández.

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Conflict of interest

The authors declare no conflict of interest.

Ethical standard statement

The study was conducted in accordance with the tenets of the Declaration of Helsinki with approvals of the local scientific ethnical committees.

Informed consent

Informed consent was obtained from all subjects involved in the study.

Additional information

This article belongs to the Topical Collection "Diabetic Eye Disease", managed by Giuseppe Querques.

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Appendix

Appendix

Members of the EUROCONDOR Consortium: F. Bandello, R. Lattanzio (Scientific Institute San Raffaele, Italy), J. Cunha-Vaz, L. Ribeiro (Association for Innovation and Biomedical Research on Light and Image, Portugal), C. Egan (Moorfields Eye Hospital, UK), J. Garcıa-Arumí (Valld’Hebron University Hospital, Spain), J. Gibson (University of Aston, UK), S. Harding (University of Liverpool, UK), G. Lang (University of Ulm, Germany), P. Massin (Hôpital Lariboisière-APHP, France), E. Midena (University of Padova, Italy), B. Ponsati (BCN Peptides, Spain), M. Porta (University of Turin, Italy), P. Scanlon, S. J. Aldington (Cheltenham General Hospital, UK), R. Simó, C. Hernández (Vall d’Hebron Research Institute, Spain), J. Grauslund, U. Frydkjaer-Olsen (Odense University Hospital, Denmark).

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Hernández, C., Simó-Servat, O., Porta, M. et al. Serum glial fibrillary acidic protein and neurofilament light chain as biomarkers of retinal neurodysfunction in early diabetic retinopathy: results of the EUROCONDOR study. Acta Diabetol 60, 837–844 (2023). https://doi.org/10.1007/s00592-023-02076-1

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