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Assessing and monitoring abnormal retinal blood circulation for early detection of pre-structural damage and enhanced diabetic retinopathy staging using non-invasive, high-resolution biophotonic imaging technology

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Abstract

Biophotonic imaging technology offers a non-invasive solution for objectively and quantitatively staging diabetic retinopathy (DR) and detecting pre-DR before structural damage occurs. Integrating this technology into clinical practice enables more accurate staging, early risk management, and prediction of treatment outcomes, ultimately reducing DR-related structural damage. The platform featured a novel physics-based retinal oximetry algorithm, built on Saccadic-Phase Spatial Frequency Domain Imaging (SP-SFDI). This technology measured an oxygen saturation analogue (αSO2) in tissue with high resolution, detecting oxygenation changes <3% using two snapshots capturing phase shifts in spatially modulated light. Its first application, BioxyDR™, focused on measuring αSO2 in the superficial retinal vasculature for accurate DR staging and early detection. For clinical validation, the study included 63 DR patients, 60 diabetes mellitus (DM) patients without DR (DM no DR), and 18 controls (no DM, no known ocular diseases). Retinal venous αSO2 significantly differed (p = 0.007) between controls and patient groups, including proliferative (PDR) and non-proliferative DR (NPDR). 100% of controls and DR patients were correctly classified per standard-of-care (SOC) criteria. Among DM no DR patients, 8 were classified as pre-DR, and 7 (87%) developed DR within 18 months. Notably, all patients classified as not pre-DR (100%) remained DR-free. Initial studies across various ocular diseases showed distinct classifications based on venous and arterial αSO2. Taken together, these findings suggest that venous αSO2 measured with SP-SFDI may serve as a biomarker for DR progression, with higher αSO2 levels indicating greater disease severity. αSO2 also shows promise as a metric for staging pre-DR.

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Correspondence and requests for materials should be addressed to Dr. Quan Dong Nguyen.

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Acknowledgements

The authors would like to acknowledge the Bay Area Retina Associates (BARA) for facilitating this project. We also extend our gratitude to John Maroney for his dedicated commitment to the project.

Funding

This work was supported by the National Science Foundation (NSF) through the Small Business Innovation Research (SBIR) programme and was funded in part by Research to Prevent Blindness (Byers Eye Institute at Stanford) and NIH grant P30-EY026877 (Byers Eye Institute at Stanford).

Author information

Authors and Affiliations

  1. Bioxytech Retina, Inc, Oakland, CA, USA

    Ali Basiri, Caesar Luo, Mohammad Shokoohi-Yekta, Hossein Taheri, Jacob Bryan, Mohammad Soheilypour, Payman Amiri & Ahmed Abou ElHassan

  2. Bay Area Retina Associates, Walnut Creek, CA, USA

    Caesar Luo

  3. Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, CA, USA

    Theodore Leng, Christopher Or, Jia-Horung Hung & Quan Dong Nguyen

  4. University Medical Center Utrecht, Utrecht, Netherlands

    Herke Jan Noordmans

Authors
  1. Ali Basiri
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  2. Caesar Luo
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  3. Mohammad Shokoohi-Yekta
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  4. Theodore Leng
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  5. Hossein Taheri
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  6. Herke Jan Noordmans
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  7. Jacob Bryan
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  8. Mohammad Soheilypour
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  9. Payman Amiri
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  10. Christopher Or
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  11. Jia-Horung Hung
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  12. Ahmed Abou ElHassan
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  13. Quan Dong Nguyen
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Contributions

Conception/Design/Acquisition/Analysis/Interpretation (AB), Analysis/Interpretation (MSY), Acquisition/Interpretation (CL) Design/Acquisition (MS, JB), Design (HT), Interpretation (PA, TL, QDN), Drafting/Revision (all authors), Final Approval (all authors), Agreement of Accountability (all authors).

Corresponding author

Correspondence to Quan Dong Nguyen.

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Competing interests

AB, MSY, and MS are full-time employees of Bioxytech and hold equity in the company; they have also received payment. JB is a part-time employee of Bioxytech and has received payment. CL, TL, and QDN serve as consultants to Bioxytech and hold equity in the company. The remaining authors declare no competing interests.

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Basiri, A., Luo, C., Shokoohi-Yekta, M. et al. Assessing and monitoring abnormal retinal blood circulation for early detection of pre-structural damage and enhanced diabetic retinopathy staging using non-invasive, high-resolution biophotonic imaging technology. Eye (2025). https://doi.org/10.1038/s41433-025-04032-5

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  • DOI: https://doi.org/10.1038/s41433-025-04032-5

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