Article Text

Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDR
  1. Torcato Santos1,
  2. Lewis H Warren2,
  3. Ana Rita Santos1,3,
  4. Inês Pereira Marques1,4,
  5. Sophie Kubach2,
  6. Luís G Mendes1,
  7. Luis de Sisternes2,
  8. Maria H Madeira1,4,
  9. Mary Durbin2,
  10. Jose G Cunha-Vaz1,4
  1. 1AIBILI – Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
  2. 2R&D, Carl Zeiss Meditec, Dublin, California, USA
  3. 3Department of Orthoptics, School of Health, Polytechnic of Porto, Porto, Portugal
  4. 4Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  1. Correspondence to Professor Jose G Cunha-Vaz, AIBILI, Coimbra, Coimbra, Portugal; cunhavaz{at}


Purpose To test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme.

Methods 105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control.

Results In eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43–53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47–53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43–53).

Conclusions Retinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.

  • retina
  • diagnostic tests/Investigation
  • imaging

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  • Contributors TS, ARS, IPM, LGM and MHM collected and analysed data, reviewed and edited the manuscript. LHW, and SK and LdS analysed data and contributed to writing and editing the manuscript. MD reviewed and edited the manuscript. JGC-V analysed data and wrote the manuscript. JGC-V is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding This work was supported by AIBILI and by COMPETE Portugal2020 and by Fundo de Inovação, Tecnologia e Economia Circular (FITEC) – Programa Interface (FITEC/CIT/2018/2).

  • Competing interests TS, ARS, IPM, LGM and MHM do not have financial disclosures. LHW, SK, LdS and MD: Carl Zeiss Meditec (E). JGC-V reports grants from Carl Zeiss Meditec and is consultant for Alimera Sciences, Allergan, Bayer, Gene Signal, Novartis, Pfizer, Precision Ocular, Roche, Sanofi-Aventis, Vifor Pharma, and Carl Zeiss Meditec.

  • Patient consent for publication Not required.

  • Ethics approval The tenets of the Declaration of Helsinki were followed, approval was obtained from the Institutional Ethical Review Board, and written informed consent to participate in the study was obtained from all individuals after the procedures were explained.

  • Data availability statement Data are available upon reasonable request. The dataset used for this publication was gathered from 105 diabetic patients and 38 healthy control volunteers. The dataset is composed of demographic data (gender, age) and clinical data (diabetes duration, glycated haemoglobin, best corrected visual acuity, layer retinal thickness and vessel density). Data are available upon reasonable request to José Cunha-Vaz,,

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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