Skip to main content

Advertisement

SpringerLink
Log in

Topography of choriocapillaris flow deficit predicts development of neovascularization or atrophy in age-related macular degeneration

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the relationship between choriocapillaris (CC), flow deficits (FD), and structural optical coherence tomography (OCT) biomarkers, and the progression of intermediate age-related macular degeneration (iAMD) to complete retinal pigment epithelial and outer retinal atrophy (cRORA) or macular neovascularization (MNV).

Methods

Consecutive patients with iAMD were sequentially reviewed to define three equal sized groups: progressed to MNV, progressed to cRORA, or remained stable over 12 months of follow-up. Odds ratios for progression to cRORA and MNV were estimated by logistic regression for intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDDs), high central drusen volume, fellow eye with late AMD, and peripheral and central CC FD.

Results

Thirty iAMD eyes from 30 patients were enrolled into each group. The CC FD was greater in the peripheral sectors of the macula of eyes which progressed to cRORA compared to the other two groups (P < 0.0001). The central CC FD was also significantly impaired in eyes that progressed to cRORA or MNV compared to eyes that did not progress (P = 0.001 and P = 0.02, respectively). CC FD in the peripheral macula was significantly and independently associated with the development of cRORA, while CC FD in the center was significantly and independently associated with the development of MNV.

Conclusions

While the CC is diffusely impaired throughout the macula in iAMD eyes that progress to cRORA, it is relatively spared in the more peripheral macula among eyes which progress to MNV. These differential findings may have implications for the pathophysiology of the different late-stage manifestations of AMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data relevant to the study are included in the article or uploaded as supplementary information.

References

  1. Schmitz-Valckenberg S, Steinberg JS, Fleckenstein M, Visvalingam S, Brinkmann CK, Holz FG (2010) Combined confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging of reticular drusen associated with age-related macular degeneration. Ophthalmology 117:1169–1176

    Article  Google Scholar 

  2. Bressler SB, Maguire MG, Bressler NM, Fine SL (1990) Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study Group. Arch Ophthalmol 108:1442–1447

    Article  CAS  Google Scholar 

  3. Ferris FL, Davis MD, Clemons TE et al (2005) A simplified severity scale for age-related macular degeneration: AREDS Report No.18. Arch Ophthalmol 123:1570–1574

    Article  Google Scholar 

  4. Klein R, Klein BEK, Knudtson MD, Meuer SM, Swift M, Gangnon RE (2007) Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114:253–262

    Article  Google Scholar 

  5. Abdelfattah NS, Zhang H, Boyer DS et al (2016) Drusen volume as a predictor of disease progression in patients with late age-related macular degeneration in the fellow eye. Invest Ophthalmol Vis Sci 57:1839–1846

    Article  CAS  Google Scholar 

  6. Finger RP, Chong E, McGuinness MB et al (2016) Reticular pseudodrusen and their association with age-related macular degeneration: the Melbourne Collaborative Cohort Study. Ophthalmology 123:599–608

    Article  Google Scholar 

  7. Spaide RF, Ooto S (2018) Curcio CA (2018) Subretinal drusenoid deposits AKA pseudodrusen. Surv Ophthalmol 63:782–815

    Article  Google Scholar 

  8. Lei J, Balasubramanian S, Abdelfattah NS, Nittala MG, Sadda SR (2017) Proposal of a simple optical coherence tomography-based scoring system for progression of age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 255:1551–1558

    Article  Google Scholar 

  9. Nassisi M, Lei J, Abdelfattah NS et al (2019) OCT risk factors for development of late age-related macular degeneration in the fellow eyes of patients enrolled in the HARBOR Study. Ophthalmology 126:1667–1674

    Article  Google Scholar 

  10. Chirco KR, Sohn EH, Stone EM, Tucker BA, Mullins RF (2017) Structural and molecular changes in the aging choroid: implications for age-related macular degeneration. Eye (Lond) 31:10–25

    Article  CAS  Google Scholar 

  11. Querques G, Querques L, Forte R, Massamba N, Coscas F, Souied EH (2012) Choroidal changes associated with reticular pseudodrusen. Invest Ophthalmol Vis Sci 53:1258–1263

    Article  Google Scholar 

  12. Corvi F, Souied EH, Capuano V et al (2017) Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images. Br J Ophthalmol 101:348–352

    Article  Google Scholar 

  13. Corvi F, Su L, Sadda SR (2021) Evaluation of the inner choroid using OCT angiography. Eye (Lond) 35:110–120

    Article  Google Scholar 

  14. Nasir MA, Sugino I, Zarbin MA (1997) Decreased choriocapillaris perfusion following surgical excision of choroidal neovascular membranes in age-related macular degeneration. Br J Ophthalmol 81:481–489

    Article  CAS  Google Scholar 

  15. Thulliez M, Zhang Q, Shi Y et al (2019) Correlations between choriocapillaris flow deficits around geographic atrophy and enlargement rates based on swept-source OCT imaging. Ophthalmol Retina 3:478–488

    Article  Google Scholar 

  16. Alagorie AR, Verma A, Nassisi M, Sadda SR (2019) Quantitative assessment of choriocapillaris flow deficits in eyes with advanced age-related macular degeneration versus healthy eyes. Am J Ophthalmol 205:132–139

    Article  Google Scholar 

  17. Corradetti G, Tiosano L, Nassisi M et al (2020) Scotopic microperimetric sensitivity and inner choroid flow deficits as predictors of progression to nascent geographic atrophy. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2020-316893

  18. Corvi F, Tiosano L, Corradetti G et al (2020) Choriocapillaris flow deficit as a risk factor for progression of age-related macular degeneration. Retina. https://doi.org/10.1097/IAE.0000000000002990

  19. Moult EM, Alibhai AY, Rebhun C et al (2020) Spatial distribution of choriocapillaris impairment in eyes with choroidal neovascularization secondary to age-related macular degeneration: a Quantitative OCT Angiography Study. Retina 40:428–445

    Article  Google Scholar 

  20. Alagorie AR, Verma A, Nassisi M et al (2020) Quantitative assessment of choriocapillaris flow deficits surrounding choroidal neovascular membranes. Retina. https://doi.org/10.1097/IAE.0000000000002878

  21. Alagorie AR, Nassisi M, Verma A et al (2020) Relationship between proximity of choriocapillaris flow deficits and enlargement rate of geographic atrophy. Graefes Arch Clin Exp Ophthalmol 258:995–1003

    Article  Google Scholar 

  22. Moult EM, Alibhai AY, Lee B et al (2020) A framework for multiscale quantitation of relationships between choriocapillaris flow impairment and geographic atrophy growth. Am J Ophthalmol 214:172–187

    Article  Google Scholar 

  23. Ferris FL, Wilkinson CP, Bird A et al (2013) Clinical classification of age-related macular degeneration. Ophthalmology 120:844–851

    Article  Google Scholar 

  24. Sadda SR, Guymer R, Holz FG et al (2018) Consensus definition for atrophy associated with age-related macular degeneration on OCT: classification of atrophy report 3. Ophthalmology 125:537–548

    Article  Google Scholar 

  25. Spaide RF, Jaffe GJ, Sarraf D et al (2020) Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group. Ophthalmology 127:616–636

    Article  Google Scholar 

  26. Ho J, Witkin AJ, Liu J et al (2011) Documentation of intraretinal retinal pigment epithelium migration via high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 118:687–693

    Article  Google Scholar 

  27. Lee SY, Stetson PF, Ruiz-Garcia H, Heussen FM, Sadda SR (2012) Automated characterization of pigment epithelial detachment by optical coherence tomography. Invest Ophthalmol Vis Sci 53:164–170

    Article  Google Scholar 

  28. Gregori G, Wang F, Rosenfeld PJ et al (2011) Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration. Ophthalmology 118:1373–1379

    PubMed  Google Scholar 

  29. Byon I, Alagorie AR, Ji Y, Su L, Sadda SR (2020) Optimizing the repeatability of choriocapillaris flow deficit measurement from optical coherence tomography angiography. Am J Ophthalmol 219:21–32

    Article  Google Scholar 

  30. Lane M, Moult EM, Novais EA et al (2016) Visualizing the choriocapillaris under drusen: comparing 1050-nm swept-source versus 840-nm spectral-domain optical coherence tomography angiography. Invest Ophthalmol Vis Sci 57:OCT585–OCT590

    Article  Google Scholar 

  31. Chu Z, Cheng Y, Zhang Q et al (2020) Quantification of choriocapillaris with Phansalkar local thresholding: pitfalls to avoid. Am J Ophthalmol 213:161–176

    Article  Google Scholar 

  32. Zhang Q, Shi Y, Zhou H et al (2018) Accurate estimation of choriocapillaris flow deficits beyond normal intercapillary spacing with swept source OCT angiography. Quant Imaging Med Surg 8:658–666

    Article  Google Scholar 

  33. Choi W, Moult EM, Waheed NK et al (2015) Ultrahigh-speed, swept-source optical coherence tomography angiography in nonexudative age-related macular degeneration with geographic atrophy. Ophthalmology 122:2532–2544

    Article  Google Scholar 

  34. Moult EM, Waheed NK, Novais EA et al (2016) Swept-source optical coherence tomography angiography reveals choriocapillaris alterations in eyes with nascent geographic atrophy and drusen-associated geographic atrophy. Retina Suppl 1:S2–S11

    Article  Google Scholar 

  35. Nattagh K, Zhou H, Rinella N et al (2020) OCT angiography to predict geographic atrophy progression using choriocapillaris flow void as a biomarker. Transl Vis Sci Technol 9:6

    PubMed  PubMed Central  Google Scholar 

  36. Christenbury JG, Folgar FA, O’Connell RV, Chiu SJ, Farsiu S, Toth CA (2013) Progression of intermediate age-related macular degeneration with proliferation and inner retinal migration of hyperreflective foci. Ophthalmology 120:1038–1045

    Article  Google Scholar 

  37. Schmidt-Erfurth U, Waldstein SM, Klimscha S et al (2018) Prediction of individual disease conversion in early AMD using artificial intelligence. Invest Ophthalmol Vis Sci 59:3199–3208

    Article  CAS  Google Scholar 

  38. Veerappan M, El-Hage-Sleiman A-KM, Tai V et al (2016) Optical coherence tomography reflective drusen substructures predict progression to geographic atrophy in age-related macular degeneration. Ophthalmology 123:2554–2570

    Article  Google Scholar 

  39. Ouyang Y, Heussen FM, Hariri A, Keane PA, Sadda SR (2013) Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration. Ophthalmology 120:2656–2665

    Article  Google Scholar 

  40. Corvi F, Cozzi M, Invernizzi A, Pace L, Sadda SR, Staurenghi G (2020) Optical coherence tomography angiography for detection of macular neovascularization associated with atrophy in age-related macular degeneration. Graefe’s Arch Clin Exp. https://doi.org/10.1007/s00417-020-04821-6

  41. Faridi A, Jia Y, Gao SS et al (2017) Sensitivity and specificity of OCT angiography to detect choroidal neovascularization. Ophthalmol Retina 1:294–303

    Article  Google Scholar 

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Doheny Eye Institute, University of California at Los Angeles, Los Angeles, CA, USA

    Federico Corvi, Giulia Corradetti, Liran Tiosano & Srinivas R. Sadda

  2. Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Federico Corvi, Giulia Corradetti & Srinivas R. Sadda

  3. Eye Clinic, Department of Biomedical and Clinical Science “Luigi Sacco”, Sacco Hospital, University of Milan, Milan, Italy

    Federico Corvi

  4. Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Liran Tiosano

  5. Department of Ophthalmology, Retina Centre of Ottawa, University of Ottawa, Ottawa, ON, Canada

    John Adam McLaughlin & Thomas K. Lee

Authors
  1. Federico Corvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Corradetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liran Tiosano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Adam McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas K. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Srinivas R. Sadda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FC: study conception, design, analysis, data acquisition, interpretation of data, drafting and revising, final approval. GC, LT, JAM, and TKL: data acquisition and data analysis, revising, and final approval. SRS: study conception, design, interpretation of data, drafting and revising, final approval.

Corresponding author

Correspondence to Srinivas R. Sadda.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

F. Corvi, G. Corradetti, L. Tiosano, J.A. McLaughlin, T.K. Lee declare no conflict of interest. S.R. Sadda reports consulting fees from Amgen, Allergan, Regeneron, Roche/Genentech, Novartis, Merck, 4DMT, Optos, Heidelberg, and Centervue. He also receives research instruments from Topcon, Nidek, Heidelberg, Centervue, Optos, and Carl Zeiss Meditec, outside the submitted work.

Additional information

Publisher’s note

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

Supplementary information

Supplemental Figure 1.

Scatter plot showing the duration of the follow-up visit (in months) on the y-axis and the individual subject on x-axis for each group: intermediate age-related macular degeneration (iAMD) patients who remained stable over follow-up (black dot), iAMD who progressed to MNV (white square), and iAMD who progressed to cRORA (white dot) (PNG 7661 kb)

High resolution image (TIFF 2202 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Corvi, F., Corradetti, G., Tiosano, L. et al. Topography of choriocapillaris flow deficit predicts development of neovascularization or atrophy in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 259, 2887–2895 (2021). https://doi.org/10.1007/s00417-021-05167-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-021-05167-3

Keywords

Search

Navigation