Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion

Eye (2024)Cite this article

Subjects

Abstract

Objectives

To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula.

Methods

In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI’s extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10–15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7).

Results

Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05).

Conclusions

Perfusion macular metrics on OCT-A correlated with UWF-FA’s non-perfusion (NP), particularly in the retina’s mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data are not public, but are available from the corresponding author upon reasonable request.

References

  1. Ting DSW, Cheung GCM, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44:260–77. https://doi.org/10.1111/ceo.12696

    Article  PubMed  Google Scholar 

  2. Niki T, Muraoka K, Shimizu K. Distribution of capillary nonperfusion in early-stage diabetic retinopathy. Ophthalmology. 1984;91:1431–9. https://doi.org/10.1016/S0161-6420(84)34126-4

    Article  CAS  PubMed  Google Scholar 

  3. Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology. 1981;88:601–12. https://doi.org/10.1016/S0161-6420(81)34983-5

    Article  CAS  PubMed  Google Scholar 

  4. Silva PS, Cavallerano JD, Sun JK, Soliman AZ, Aiello LM, Aiello LP. Peripheral lesions identified by mydriatic ultrawide field imaging: Distribution and potential impact on diabetic retinopathy severity. Ophthalmology. 2013;120:2587–95. https://doi.org/10.1016/j.ophtha.2013.05.004

    Article  PubMed  Google Scholar 

  5. Price LD, Au S, Chong NV. Optomap ultrawide field imaging identifies additional retinal abnormalities in patients with diabetic retinopathy. Clin Ophthalmol. 2015;9:527–31. https://doi.org/10.2147/OPTH.S79448

    Article  PubMed  PubMed Central  Google Scholar 

  6. Silva PS, Cavallerano JD, Haddad NM, Kwak H, Dyer KH, Omar AF, et al. Peripheral lesions identified on ultrawide field imaging predict increased risk of diabetic retinopathy progression over 4 years. Ophthalmology. 2015;122:949–56. https://doi.org/10.1016/j.ophtha.2015.01.008

    Article  PubMed  Google Scholar 

  7. Wessel MM, Aaker GD, Parlitsis G, Cho M, D’Amico DJ, Kiss S. Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina. 2012;32:785–91. https://doi.org/10.1097/IAE.0b013e3182278b64

    Article  PubMed  Google Scholar 

  8. Wessel MM, Nair N, Aaker GD, Ehrlich JR, D’Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012;96:694–8. https://doi.org/10.1136/bjophthalmol-2011-300774

    Article  PubMed  Google Scholar 

  9. Fan W, Wang K, Ghasemi Falavarjani K, Sagong M, Uji A, Ip M, et al. Distribution of Nonperfusion Area on Ultra-widefield Fluorescein Angiography in Eyes With Diabetic Macular Edema: DAVE Study. Am J Ophthalmol. 2017;180:110–6. https://doi.org/10.1016/j.ajo.2017.05.024

    Article  PubMed  Google Scholar 

  10. Patel RD, Messner LV, Teitelbaum B, Michel KA, Hariprasad SM. Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema. Am J Ophthalmol. 2013;155:1038–.e2. https://doi.org/10.1016/j.ajo.2013.01.007

    Article  PubMed  Google Scholar 

  11. Silva PS, Dela Cruz AJ, Ledesma MG, van Hemert J, Radwan A, Cavallerano JD, et al. Diabetic retinopathy severity and peripheral lesions are associated with nonperfusion on ultrawide field angiography. Ophthalmology. 2015;122:2465–72. https://doi.org/10.1016/j.ophtha.2015.07.034

    Article  PubMed  Google Scholar 

  12. Silva PS, Liu D, Glassman AR, Aiello LP, Grover S, Kingsley RM, et al. Assessment of fluorescein angiography nonperfusion in eyes with diabetic retinopathy using ultrawide field retinal imaging. Retina. 2022;42:1302–10. https://doi.org/10.1097/IAE.0000000000003479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ehlers JP, Jiang AC, Boss JD, Hu M, Figueiredo N, Babiuch A, et al. Quantitative ultra-widefield angiography and diabetic retinopathy severity. Ophthalmology. 2019;126:1527–32. https://doi.org/10.1016/j.ophtha.2019.05.034

    Article  PubMed  Google Scholar 

  14. Silva PS, Marcus DM, Liu D, Aiello LP, Antoszyk A, Elman M, et al. Association of ultra-widefield fluorescein angiography-identified retinal nonperfusion and the risk of diabetic retinopathy worsening over time. JAMA Ophthalmol. 2022;140:936–45. https://doi.org/10.1001/jamaophthalmol.2022.3130

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, et al. Frequency of adverse systemic reactions after fluorescein angiography. Ophthalmology. 1991;98:1139–42. https://doi.org/10.1016/S0161-6420(91)32165-1

    Article  CAS  PubMed  Google Scholar 

  16. Fineschi V, Monasterolo G, Rosi R, Turillazzi E. Fatal anaphylactic shock during a fluorescein angiography. Forensic Sci Int. 1999;100:137–42. https://doi.org/10.1016/S0379-0738(98)00205-9

    Article  CAS  PubMed  Google Scholar 

  17. Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Prog Retin Eye Res. 2018;64:1–55. https://doi.org/10.1016/j.preteyeres.2017.11.003

    Article  PubMed  Google Scholar 

  18. Soares M, Neves C, Marques IP, Pires I, Schwartz C, Costa MÂ, et al. Comparison of diabetic retinopathy classification using fluorescein angiography and optical coherence tomography angiography. Br J Ophthalmol. 2017;101:62–8. https://doi.org/10.1136/bjophthalmol-2016-309424

    Article  PubMed  Google Scholar 

  19. Rabiolo A, Cicinelli MV, Corbelli E, Baldin G, Carnevali A, Lattanzio R, et al. Correlation analysis between foveal avascular zone and peripheral ischemic index in diabetic retinopathy: a pilot study. Ophthalmol Retin. 2018;2:46–52. https://doi.org/10.1016/j.oret.2017.05.007

    Article  Google Scholar 

  20. Hajdu D, Sedova A, Datlinger F, Hafner J, Steiner I, Kriechbaum K, et al. Association of macular perfusion status with microvascular parameters up to the far periphery in diabetic retinopathy using multimodal imaging. Int J Retin Vitr. 2020;6:1–8. https://doi.org/10.1186/s40942-020-00253-w

    Article  Google Scholar 

  21. Decker NL, Duffy BV, Boughanem GO, Fukuyama H, Castellanos Canales D, Nesper PL, et al. Macular perfusion deficits on OCTA correlate with non-perfusion on ultrawide-field FA in diabetic retinopathy. Ophthalmol Retin. 2023;(Current Opinion in Green and Sustainable Chemistry):100788. https://doi.org/10.1016/j.oret.2023.04.003

  22. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677–82. https://doi.org/10.1016/S0161-6420(03)00475-5

    Article  CAS  PubMed  Google Scholar 

  23. Zahid S, Dolz-Marco R, Freund KB, Balaratnasingam C, Dansingani K, Gilani F, et al. Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2016;57:4940–7. https://doi.org/10.1167/IOVS.16-19656

    Article  PubMed  Google Scholar 

  24. Sim DA, Keane PA, Rajendram R, Karampelas M, Selvam S, Powner MB, et al. Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography. Am J Ophthalmol. 2014;158:144–.e1. https://doi.org/10.1016/j.ajo.2014.03.009

    Article  PubMed  Google Scholar 

  25. Krawitz BD, Mo S, Geyman LS, Agemy SA, Scripsema NK, Garcia PM, et al. Acircularity index and axis ratio of the foveal avascular zone in diabetic eyes and healthy controls measured by optical coherence tomography angiography. Vis Res. 2017;139:177–86. https://doi.org/10.1016/j.visres.2016.09.019

    Article  PubMed  Google Scholar 

  26. Spaide RF, Klancnik JM, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133:45–50. https://doi.org/10.1001/jamaophthalmol.2014.3616

    Article  PubMed  Google Scholar 

  27. Sun Z, Yang D, Tang Z, Ng DS, Cheung CY. Optical coherence tomography angiography in diabetic retinopathy: an updated review. Eye. 2021;35:149–61. https://doi.org/10.1038/s41433-020-01233-y

    Article  PubMed  Google Scholar 

  28. Or C, Das R, Despotovic I, Alibhai AY, Moult E, Waheed NK, et al. Combined multimodal analysis of peripheral retinal and macular circulation in diabetic retinopathy (COPRA Study). Ophthalmol Retin. 2019;3:580–8. https://doi.org/10.1016/j.oret.2019.03.001

    Article  Google Scholar 

  29. Chen S, Moult EM, Zangwill LM, Weinreb RN, Fujimoto JG. Geometric perfusion deficits: a novel OCT angiography biomarker for diabetic retinopathy based on oxygen diffusion. Am J Ophthalmol. 2021;222:256–70. https://doi.org/10.1016/j.ajo.2020.09.007

    Article  PubMed  Google Scholar 

  30. Nesper PL, Ong JX, Fawzi AA. Deep capillary geometric perfusion deficits on OCT angiography detect clinically referable eyes with diabetic retinopathy. Ophthalmol Retin. 2022;6:1194–205. https://doi.org/10.1016/j.oret.2022.05.028

    Article  Google Scholar 

Download references

Acknowledgements

This work has been supported by the Italian Ministry of Health—Ricerca Corrente—IRCCS MultiMedica.

Author information

Authors and Affiliations

  1. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy

    Stela Vujosevic & Paolo Nucci

  2. Eye Clinic, IRCCS MultiMedica, Milan, Italy

    Stela Vujosevic & Francesca Fantaguzzi

  3. University of Milan, Milan, Italy

    Francesca Fantaguzzi

  4. Harvard Department of Ophthalmology, Joslin Diabetes Center, Beetham Eye Institute, Boston, MA, USA

    Paolo S. Silva

  5. Centre for Public Health, Queen’s University Belfast, Belfast, UK

    Recivall Salongcay & Tunde Peto

  6. Department of Medical Physics, University Hospital Maggiore della Carità, Novara, Italy

    Marco Brambilla

  7. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy

    Emanuele Torti

Authors
  1. Stela Vujosevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Fantaguzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo S. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Recivall Salongcay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marco Brambilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emanuele Torti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo Nucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tunde Peto
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SV, RS, PS, TP, FF and PN were responsible for designing the study and interpretation of results. SV and TP contributed to UWF-CF grading; PS was responsible for UWF-FA imaging analysis; ET conducted OCT-A analysis; MB conducted statistical analysis; FF contributed to data extraction and image analysis. All authors contributed to the drafting and reviewing of the manuscript ensuring accuracy and integrity of every part of the work.

Corresponding author

Correspondence to Stela Vujosevic.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vujosevic, S., Fantaguzzi, F., Silva, P.S. et al. Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion. Eye (2024). https://doi.org/10.1038/s41433-024-02989-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41433-024-02989-3

Search

Advanced search

Quick links