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Wide-field OCTA quantified peripheral nonperfusion areas predict the risk of subclinical neovascularization

Eye volume 39, pages 2467–2473 (2025)Cite this article

Subjects

Abstract

Purpose

To demonstrate the capabilities of single-shot widefield swept-source OCT angiography (SS-OCTA) in detecting subclinical retinal neovascularization (RNV), quantifying nonperfusion areas (NPAs), and exploring the relations between NPAs and subclinical RNV in eyes graded as nonproliferative diabetic retinopathy (NPDR).

Methods

Eyes clinically graded as moderate to severe NPDR underwent SS-OCTA imaging. Expert graders identified subclinical RNV, defined as vessels with a flow signal above the internal limiting membrane on OCTA that are not visible on dilated fundus examination. This identification was based on a combination of en face OCT, en face OCTA, and cross-sectional OCTA overlaid on OCT. NPA index was calculated as a percentage of automatically quantified NPA over the area in the posterior pole, the mid-periphery, and the total imaged area.

Results

Totally 37 eyes, including 21 had severe NPDR and 16 had moderate NPDR. Subclinical RNV was present in 14 eyes (37.8%). The eyes with RNV had significantly higher mid-peripheral and total NPA indices but not in the posterior region (mid-peripheral NPA: 31.97% ± 7.02% vs. 24.80% ± 6.60%, p = 0.041; total NPA: 27.96% ± 6.36% vs. 21.61% ± 5.65%, p = 0.046; all values are reported as mean ± standard deviation). The total NPA index showed the highest diagnostic accuracy for subclinical RNV detection (AUC: 0.761; 95% CI, 0.592–929, with a sensitivity of 64.3% and a specificity of 87% at a cutoff value of 28.84%).

Conclusion

Widefield SS-OCTA can detect subclinical RNV. The eyes with higher mid-peripheral NPA indices are more likely to have subclinical RNV, indicating that the NPA index may be a useful biomarker for identifying eyes at risk of RNV.

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Fig. 1: Representative en face angiogram of the entire retinal layer from cases with and without subclinical retinal neovascularization (RNV).
Fig. 2: Receiver operating characteristic curves for evaluating the predictive accuracy of the nonperfusion area (NPA) index in detecting subclinical retinal neovascularization (RNV).

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Data availability

The datasets generated and analyzed in this study are available from the corresponding author upon reasonable request. Access may be subject to restrictions to protect patient confidentiality and institutional policy.

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Funding

This work was supported by grants from National Institutes of Health (R01 EY 036429, R01 EY035410, R01 EY024544, R01 EY027833, R01 EY031394, R43EY036781, P30 EY010572, T32 EY023211, UL1TR002369); the Jennie P. Weeks Endowed Fund; the Malcolm M. Marquis, MD Endowed Fund for Innovation; Unrestricted Departmental Funding Grant and Dr. H. James and Carole Free Catalyst Award from Research to Prevent Blindness (New York, NY); Edward N. & Della L. Thome Memorial Foundation Award, and the Bright Focus Foundation (G2020168, M20230081). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA

    An-Lun Wu, Yukun Guo, Tristan T. Hormel, Christina J. Flaxel, Merina Thomas, Steven T. Bailey, Dong-Wouk Park, Yali Jia & Thomas S. Hwang

  2. Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu, Taiwan

    An-Lun Wu

  3. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA

    Yukun Guo & Yali Jia

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  1. An-Lun Wu
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Contributions

AW designed the methodology, collected data, conducted analysis, interpreted results, and drafted the original manuscript. YG contributed to data review, analysis, and result interpretation. TTH provided critical manuscript revisions. CJF, MT, STB, and DP assisted with data collection, offered clinical insights, and reviewed and edited the manuscript. YJ provided expertise in OCTA, contributed to study design and data interpretation, and critically revised the manuscript. TSH conceptualized the study, supervised the research process, interpreted results, and provided critical revisions and final approval. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Thomas S. Hwang.

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Competing interests

YG: Visionix/Optovue (P), Genentech (R), Ifocus Imaging (P); TTH: Ifocus Imaging (I); STB: Visionix/Optovue (F); YJ: Visionix/Optovue (P, R), Roche/Genentech (P, R, F), Ifocus Imaging (I, P), Optos (P), Boeringer Ingelheim (C), Kugler (R). These potential conflicts of interest have been reviewed and managed by OHSU. Other authors declare no conflicts of interest related to this article.

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Wu, AL., Guo, Y., Hormel, T.T. et al. Wide-field OCTA quantified peripheral nonperfusion areas predict the risk of subclinical neovascularization. Eye 39, 2467–2473 (2025). https://doi.org/10.1038/s41433-025-03891-2

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