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Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration

Abstract

Purpose

To assess retinal vascular perfusion and choroidal vascularity biomarkers correlated with drusen volume and severity of age-related macular degeneration (AMD).

Methods

Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) (PlexElite-9000). Eyes with geographic atrophy or neovascular AMD were excluded. Retinal thickness, retinal perfusion including superficial (SCP) and deep capillary plexuses (DCP), foveal avascular zone (FAZ), drusen volume, choroidal thickness (ChT) and choroidal vascularity index (CVI) were assessed through the Advanced Research and Innovation Network. Linear mixed model and Spearman test were used for statistical analysis.

Results

We assessed 81 eyes from 57 subjects (34 early-stage, 47 intermediate-stage AMD). The mean age was 74.95 ± 8.79 years. The mean LogMar visual acuity (VA) was 0.16 ± 0.18 (early-stage: 0.12 ± 0.17, intermediate-stage: 0.19 ± 0.18, P = 0.122). Between early and intermediate AMD, no significant differences were seen in SCP and DCP vascular perfusion (P = 0.368, 0.859, respectively), FAZ (p = 0.836) and retinal thickness within the 6-mm area (P = 0.680). Drusen volume showed a significant difference (early-stage: 0.0706 ± 0.1272, intermediate-stage: 0.2102 ± 0.2211mm3, P < 0.01). Intermediate-stage AMD had significantly lower mean ChT (266.40 ± 115.55 vs. 204.97 ± 70.69 µm, P = 0.038) and CVI (0.605 ± 0.021 vs. 0.591 ± 0.015, P = 0.004) within the 5-mm area. Drusen volume was negatively correlated with ChT (r = −0.198, P = 0.017) and CVI (r = −0.209, P = 0.029). No significant correlation was found between drusen volume and VA (r = 0.051, P = 0.143), retinal thickness (−0.03, P = 0.393), FAZ (r = −0.023, P = 0.150), SCP (r = −0.011, P = 0.307), and DCP (r = −0.022, P = 0.190).

Conclusion

Drusen volume, a key AMD severity marker, correlates more strongly with choroidal parameters like ChT and CVI than retinal thickness and perfusion. It may serve as a biomarker for dry AMD severity, with choroidal biomarkers showing earlier disease changes.

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Fig. 1: Advanced research and innovation (ARI) network algorithms in an eye with early-stage age-related macular degeneration (AMD).
Fig. 2: Advanced research and innovation (ARI) network algorithms in an eye with intermediate-stage age-related macular degeneration (AMD).
Fig. 3

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Sadeghi E, Valsecchi N, Ibrahim MN, Du K, Davis E, Bollepalli SC, et al. Three-Dimensional Choroidal Vessels Assessment in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2024;65:39.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sadeghi E, Vupparaboina SC, Bollepalli SC, Vupparaboina KK, Agarwal K, Sahel J-A, et al. Incidence and risk factors of fellow-eyes wet conversion in unilateral neovascular age-related macular degeneration over 15-year follow-up. Graefe Arch Clin Ophthamol. 2024;263:77–86.

    Article  Google Scholar 

  3. Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharm Rep. 2006;58:353–63.

    CAS  Google Scholar 

  4. Taylor TRP, Menten MJ, Rueckert D, Sivaprasad S, Lotery AJ. The role of the retinal vasculature in age-related macular degeneration: a spotlight on OCTA. Eye. 2024;38:442–9.

    Article  PubMed  Google Scholar 

  5. Friedman E, Krupsky S, Lane AM, Oak SS, Friedman ES, Egan K, et al. Ocular blood flow velocity in age-related macular degeneration. Ophthalmology. 1995;102:640–6.

    Article  CAS  PubMed  Google Scholar 

  6. Ciulla TA, Harris A, Chung HS, Danis RP, Kagemann L, McNulty L, et al. Color Doppler imaging discloses reduced ocular blood flow velocities in nonexudative age-related macular degeneration. Am J Ophthalmol. 1999;128:75–80.

    Article  CAS  PubMed  Google Scholar 

  7. Ikram MK, van Leeuwen R, Vingerling JR, Hofman A, de Jong PT. Retinal vessel diameters and the risk of incident age-related macular disease: the Rotterdam Study. Ophthalmology. 2005;112:548–52.

    Article  PubMed  Google Scholar 

  8. Liew G, Kaushik S, Rochtchina E, Tan AG, Mitchell P, Wang JJ. Retinal vessel signs and 10-year incident age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology. 2006;113:1481–7.

    Article  PubMed  Google Scholar 

  9. Toto L, Borrelli E, Di Antonio L, Carpineto P, Mastropasqua R. Retinal vascular plexuses’ changes in dry age-related macular degeneration, evaluated by means of optical coherence tomography angiography. Retina. 2016;36:1566–72.

    Article  CAS  PubMed  Google Scholar 

  10. Shin Y-I, Kim JM, Lee M-W, Jo Y-J, Kim J-Y. Characteristics of the foveal microvasculature in Asian patients with dry age-related macular degeneration: an optical coherence tomography angiography study. Ophthalmologica. 2020;243:145–53.

    Article  PubMed  Google Scholar 

  11. Jeganathan VSE, Kawasaki R, Wang JJ, Aung T, Mitchell P, Saw S-M, et al. Retinal vascular caliber and age-related macular degeneration: the Singapore Malay Eye Study. Am J Ophthalmol. 2008;146:954–9.

    Article  PubMed  Google Scholar 

  12. Yang K, Zhan SY, Liang YB, Duan X, Wang F, Wong TY, et al. Association of dilated retinal arteriolar caliber with early age-related macular degeneration: the Handan Eye Study. Graefe Arch Clin Ophthamol. 2012;250:741–9.

    Article  Google Scholar 

  13. Jabs DA, Van Natta ML, Pak JW, Danis RP, Hunt PW. Association of retinal vascular caliber and age-related macular degeneration in patients with the acquired immunodeficiency syndrome. Invest Ophthalmol Vis Sci. 2018;59:904–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Toulouie S, Chang S, Pan J, Snyder K, Yiu G. Relationship of Retinal Vessel Caliber with Age-Related Macular Degeneration. J Ophthalmol. 2022;2022:8210599.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sadeghi E, Valsecchi N, Rahmanipour E, Ejlalidiz M, Hasan N, Vupparaboina KK, et al. Choroidal biomarkers in age-related macular degeneration. Surv Ophthalmol. 2024;70:167–83.

    Article  PubMed  Google Scholar 

  16. Vaghefi E, Hill S, Kersten HM, Squirrell D. Quantification of Optical Coherence Tomography Angiography in Age and Age-Related Macular Degeneration Using Vessel Density Analysis. Asia Pac J Ophthalmol. 2020;9:137–43.

    Article  Google Scholar 

  17. Parisi V, Ziccardi L, Costanzo E, Tedeschi M, Barbano L, Manca D, et al. Macular functional and morphological changes in intermediate age-related maculopathy. Invest Ophthalmol Vis Sci. 2020;61:11.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Reiter GS, Told R, Schlanitz FG, Baumann L, Schmidt-Erfurth U, Sacu S. Longitudinal association between drusen volume and retinal capillary perfusion in intermediate age-related macular degeneration. Invest Ophthalmol Vis Sci. 2019;60:2503–8.

    Article  PubMed  Google Scholar 

  19. Can GD, Gelisken O. Evaluation of retinal vessel density and foveal avascular zone in unilateral exudative choroidal neovascularization by optical coherence tomography angiography. Beyoglu Eye J. 2022;7:83.

    PubMed  PubMed Central  Google Scholar 

  20. Stavrev V, Sivkova N, Koleva-Georgieva D. Quantitative assessment of foveal avascular zone in patients with early and intermediate nonexudative age-related macular degeneration using optical coherence tomography-angiography. Open J Ophthalmol. 2018;8:133–9.

    Article  Google Scholar 

  21. Grunwald JE, Metelitsina TI, DuPont JC, Ying G-S, Maguire MG. Reduced foveolar choroidal blood flow in eyes with increasing AMD severity. Invest Ophthalmol Vis Sci. 2005;46:1033–8.

    Article  PubMed  Google Scholar 

  22. Ferris FL III, Wilkinson C, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844–51.

    Article  PubMed  Google Scholar 

  23. Zhou H, Dai Y, Shi Y, Russell JF, Lyu C, Noorikolouri J, et al. Age-related changes in choroidal thickness and the volume of vessels and stroma using swept-source OCT and fully automated algorithms. Ophthalmol Retin. 2020;4:204–15.

    Article  Google Scholar 

  24. Zhou H, Chu Z, Zhang Q, Dai Y, Gregori G, Rosenfeld PJ, et al. Attenuation correction assisted automatic segmentation for assessing choroidal thickness and vasculature with swept-source OCT. Biomed Opt Express. 2018;9:6067–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vitale S, Agrón E, Clemons TE, Keenan TD, Domalpally A, Danis RP, et al. Association of 2-year progression along the AREDS AMD scale and development of late age-related macular degeneration or loss of visual acuity: AREDS Report 41. JAMA Ophthalmol. 2020;138:610–7.

    Article  PubMed  Google Scholar 

  26. Seddon JM, De D, Rosner B. The role of nutritional factors in transitioning between early, mid, and late stages of age-related macular degeneration: prospective longitudinal analysis. Am J Clin Nutr. 2024;120:1387–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cheung R, Trinh M, Tee YG, Nivison-Smith L. RPE curvature can screen for early and intermediate AMD. Invest Ophthalmol Vis Sci. 2024;65:2.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pappuru RR, Ouyang Y, Nittala MG, Hemmati HD, Keane PA, Walsh AC, et al. Relationship between outer retinal thickness substructures and visual acuity in eyes with dry age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:6743–8.

    Article  PubMed  Google Scholar 

  29. Schlanitz FG, Baumann B, Kundi M, Sacu S, Baratsits M, Scheschy U, et al. Drusen volume development over time and its relevance to the course of age-related macular degeneration. Br J Ophthalmol. 2017;101:198–203.

    Article  PubMed  Google Scholar 

  30. Abdelfattah NS, Zhang H, Boyer DS, Rosenfeld PJ, Feuer WJ, Gregori G, et al. Drusen volume as a predictor of disease progression in patients with late age-related macular degeneration in the fellow eye. Invest Ophthalmol Vis Sci. 2016;57:1839–46.

    Article  CAS  PubMed  Google Scholar 

  31. Ou WC, Denlar RA, Csaky KG. The relationship between Central Drusen volume and low-luminance deficit in Age-Related Macular Degeneration. Transl Vis Sci Technol. 2020;9:10.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Toto L, Borrelli E, Mastropasqua R, Di Antonio L, Doronzo E, Carpineto P, et al. Association between outer retinal alterations and microvascular changes in intermediate stage age-related macular degeneration: an optical coherence tomography angiography study. Br J Ophthalmol. 2017;101:774–9.

    Article  PubMed  Google Scholar 

  33. Trinh M, Kalloniatis M, Nivison-Smith L. Vascular changes in intermediate age-related macular degeneration quantified using optical coherence tomography angiography. Transl Vis Sci Technol. 2019;8:20.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Trinh M, Kalloniatis M, Nivison-Smith L. Radial peripapillary capillary plexus sparing and underlying retinal vascular impairment in intermediate age-related macular degeneration. Invest Ophthalmol Vis Sci. 2021;62:2.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wei X, Ting DSW, Ng WY, Khandelwal N, Agrawal R, Cheung CMG. CHOROIDAL VASCULARITY INDEX: A Novel Optical Coherence Tomography Based Parameter in Patients With Exudative Age-Related Macular Degeneration. RETINA. 2017;37:1120–5.

    Article  PubMed  Google Scholar 

  36. Sacconi R, Vella G, Battista M, Borrelli E, Balasubramanian S, Querques L, et al. Choroidal Vascularity Index in Different Cohorts of Dry Age-Related Macular Degeneration. Transl Vis Sci Technol. 2021;10:26.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Grunwald JE, Hariprasad SM, DuPont J. Effect of aging on foveolar choroidal circulation. Arch Ophthalmol. 1998;116:150–4.

    Article  CAS  PubMed  Google Scholar 

  38. Vidal-Oliver L, Spissinger S, Herzig-de Almeida E, Garzone D, Finger RP. Longitudinal changes in choroidal thickness and choroidal vascularity index in age-related macular degeneration. Ophthalmic Res. 2024;67:654–61.

    Article  PubMed  Google Scholar 

Download references

Funding

NIH CORE Grant P30 EY08098 supported this work to the Department of Ophthalmology, the Eye and Ear Foundation of Pittsburgh, and from an unrestricted grant from Research to Prevent Blindness, New York, NY.

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Authors and Affiliations

Authors

Contributions

ES: conceptualization, data gathering, data analysis, drafting, revision, final approval. AS: data gathering, final approval. SCV: data analysis, final approval. SRS: revision, final approval. NH: revision, final approval. SCB: revision, final approval. KKV: revision, final approval. JAS: revision, final approval. AWE: revision, final approval. JC: conceptualization, data preparation, revision, final approval.

Corresponding author

Correspondence to Jay Chhablani.

Ethics declarations

Competing interests

JAS: Avista Therapeutics, Tenpoint, Code C (Consultant/Contractor), Clinical Trials: Gensight, SparingVision, Meira, Code F (Financial Support), Netramind Innovations, Gensight, Sparing Vision, Avista, Tenpoint, Prophesee, Chronolife, Tilak Healthcare, SharpEye, Cilensee, Vegavect, Code O (Owner), Allotopic Expression, Rod-derived Cone Viability Factor and related patents., Code P (Patent), Patent Royalties, Gensight, Code R (Recipient), Observer: Gensight, SparingVision, Avista, Vegavect. President: Fondation Voir et Entendre, Paris; President: StreetLab, Paris., Code S (non-remunerative); JC: Netramind Innovations, Code O (Owner). KKV: Netramind Innovations, Code O (Owner). SCB: Netramind Innovations, Code O (Owner).

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Sadeghi, E., Schulman, A., Vupparaboina, S.C. et al. Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration. Eye 39, 2231–2237 (2025). https://doi.org/10.1038/s41433-025-03847-6

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