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Nonexudative morphologic changes of neovascularization on optical coherence tomography angiography as predictive factors for exudative recurrence in age-related macular degeneration

Abstract

Purpose

To evaluate morphologic changes of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) during the nonexudative period and to correlate the features and timing of recurrence in neovascular age-related macular degeneration. (AMD).

Methods

Two hundred thirty-eight eyes with type 1 CNV were retrospectively reviewed. For cases with exudative recurrence, OCTA images were tracked for analysis between the recurrences. Qualitative parameters of morphologic changes of CNV on OCTA, including tiny branching vessels, anastomotic loops, peripheral vascular arcade, and perilesional halo, were correlated with the features of exudative recurrence.

Results

Exudative recurrence was identified in 163 cases, and among them, nonexudative morphological changes in CNV were identified using OCTA in 45 cases. For the cases with nonexudative changes on OCTA, exudative recurrence eventually developed within 0.5–3.5 months (mean, 2.3 ± 2.0 months) after identifying morphologic changes OCTA. The following changes in CNV were revealed on OCTA: tiny branching vessels in 53.3% (24/45) of cases, anastomotic loops in 40.0% (18/45), peripheral vascular arcades in 44.4% (20/45), and perilesional halo in 35.6% (16/45). Among the morphologic parameters, development of tiny branching vessels was significantly associated with early exudative recurrence (1.5 ± 1.2 months, p = 0.019), higher incidence of intraretinal fluid (IRF) (p = 0.016), and subretinal or subretinal pigment epithelial hemorrhage (p = 0.023) at recurrence, compared with other morphologic changes.

Conclusion

Development of tiny branching vessels of CNV on OCTA during the nonexudative period was associated with early exudative recurrence, including IRF or hemorrhage. Identifying the nonexudative changes of CNV on OCTA might predict exudative recurrence and provide additional parameters for monitoring neovascular AMD.

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Data availability

The data are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

References

  1. 1.

    Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358:2606–2617. https://doi.org/10.1056/NEJMra0801537

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Kaiser PK, Blodi BA, Shapiro H, Acharya NR, Group MS (2007) Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 114:1868–1875. https://doi.org/10.1016/j.ophtha.2007.04.030

    Article  PubMed  Google Scholar 

  3. 3.

    Mehta H, Tufail A, Daien V, Lee AY, Nguyen V, Ozturk M, Barthelmes D, Gillies MC (2018) Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors. Prog Retin Eye Res 65:127–146. https://doi.org/10.1016/j.preteyeres.2017.12.002

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Madhusudhana KC, Lee AY, Keane PA, Chakravarthy U, Johnston RL, Egan CA, Sim D, Zarranz-Ventura J, Tufail A, McKibbin M, Group UAES (2016) UK neovascular age-related macular degeneration database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92 976 intravitreal ranibizumab injections. Br J Ophthalmol 100:1617–1622. https://doi.org/10.1136/bjophthalmol-2015-308077

    Article  PubMed  Google Scholar 

  5. 5.

    Schmidt-Erfurth U, Waldstein SM (2016) A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration. Prog Retin Eye Res 50:1–24. https://doi.org/10.1016/j.preteyeres.2015.07.007

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Chakravarthy U, Pillai N, Syntosi A, Barclay L, Best C, Sagkriotis A (2020) Association between visual acuity, lesion activity markers and retreatment decisions in neovascular age-related macular degeneration. Eye (Lond) 34:2249–2256. https://doi.org/10.1038/s41433-020-0799-y

    CAS  Article  Google Scholar 

  7. 7.

    Jia Y, Bailey ST, Wilson DJ, Tan O, Klein ML, Flaxel CJ, Potsaid B, Liu JJ, Lu CD, Kraus MF, Fujimoto JG, Huang D (2014) Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology 121:1435–1444. https://doi.org/10.1016/j.ophtha.2014.01.034

    Article  PubMed  Google Scholar 

  8. 8.

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

    Article  PubMed  Google Scholar 

  9. 9.

    Coscas F, Lupidi M, Boulet JF, Sellam A, Cabral D, Serra R, Francais C, Souied EH, Coscas G (2019) Optical coherence tomography angiography in exudative age-related macular degeneration: a predictive model for treatment decisions. Br J Ophthalmol 103:1342–1346. https://doi.org/10.1136/bjophthalmol-2018-313065

    Article  PubMed  Google Scholar 

  10. 10.

    Bae K, Kim HJ, Shin YK, Kang SW (2019) Predictors of neovascular activity during neovascular age-related macular degeneration treatment based on optical coherence tomography angiography. Sci Rep 9:19240. https://doi.org/10.1038/s41598-019-55871-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Pilotto E, Frizziero L, Daniele AR, Convento E, Longhin E, Guidolin F, Parrozzani R, Cavarzeran F, Midena E (2019) Early OCT angiography changes of type 1 CNV in exudative AMD treated with anti-VEGF. Br J Ophthalmol 103:67–71. https://doi.org/10.1136/bjophthalmol-2017-311752

    Article  PubMed  Google Scholar 

  12. 12.

    Nakano Y, Kataoka K, Takeuchi J, Fujita A, Kaneko H, Shimizu H, Ito Y, Terasaki H (2019) Vascular maturity of type 1 and type 2 choroidal neovascularization evaluated by optical coherence tomography angiography. PLoS ONE 14:e0216304. https://doi.org/10.1371/journal.pone.0216304

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Choi M, Kim SW, Yun C, Oh J (2020) OCT angiography features of neovascularization as predictive factors for frequent recurrence in age-related macular degeneration. Am J Ophthalmol 213:109–119. https://doi.org/10.1016/j.ajo.2020.01.012

    Article  PubMed  Google Scholar 

  14. 14.

    de Oliveira Dias JR, Zhang Q, Garcia JMB, Zheng F, Motulsky EH, Roisman L, Miller A, Chen CL, Kubach S, de Sisternes L, Durbin MK, Feuer W, Wang RK, Gregori G, Rosenfeld PJ (2018) Natural history of subclinical neovascularization in nonexudative age-related macular degeneration using swept-source OCT Angiography. Ophthalmology 125:255–266. https://doi.org/10.1016/j.ophtha.2017.08.030

    Article  PubMed  Google Scholar 

  15. 15.

    Carnevali A, Sacconi R, Querques L, Marchese A, Capuano V, Rabiolo A, Corbelli E, Panozzo G, Miere A, Souied E, Bandello F, Querques G (2018) Natural history of treatment-naive quiescent choroidal neovascularization in age-related macular degeneration using OCT angiography. Ophthalmol Retina 2:922–930. https://doi.org/10.1016/j.oret.2018.02.002

    Article  PubMed  Google Scholar 

  16. 16.

    Xu D, Davila JP, Rahimi M, Rebhun CB, Alibhai AY, Waheed NK, Sarraf D (2018) Long-term progression of type 1 neovascularization in age-related macular degeneration using optical coherence tomography angiography. Am J Ophthalmol 187:10–20. https://doi.org/10.1016/j.ajo.2017.12.005

    Article  PubMed  Google Scholar 

  17. 17.

    Miere A, Butori P, Cohen SY, Semoun O, Capuano V, Jung C, Souied EH (2019) Vascular remodeling of choroidal neovascularization after anti-vascular endothelial growth factor therapy visualized on optical coherence tomography angiography. Retina 39:548–557. https://doi.org/10.1097/IAE.0000000000001964

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Spaide RF (2015) Optical coherence tomography angiography signs of vascular abnormalization with antiangiogenic therapy for choroidal neovascularization. Am J Ophthalmol 160:6–16. https://doi.org/10.1016/j.ajo.2015.04.012

    Article  PubMed  Google Scholar 

  19. 19.

    Guymer RH, Markey CM, McAllister IL, Gillies MC, Hunyor AP, Arnold JJ, Investigators F (2019) Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results. Ophthalmology 126:723–734. https://doi.org/10.1016/j.ophtha.2018.11.025

    Article  PubMed  Google Scholar 

  20. 20.

    de Massougnes S, Dirani A, Mantel I (2018) Good visual outcome at 1 year in neovascular age-related macular degeneration with pigment epithelium detachment: factors influencing the treatment response. Retina 38:717–724. https://doi.org/10.1097/IAE.0000000000001613

    Article  PubMed  Google Scholar 

  21. 21.

    Simader C, Ritter M, Bolz M, Deak GG, Mayr-Sponer U, Golbaz I, Kundi M, Schmidt-Erfurth UM (2014) Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration. Ophthalmology 121:1237–1245. https://doi.org/10.1016/j.ophtha.2013.12.029

    Article  PubMed  Google Scholar 

  22. 22.

    Dervenis N, Younis S (2016) Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration. Clin Ophthalmol 10:1117–1122. https://doi.org/10.2147/OPTH.S106734

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Waldstein SM, Simader C, Staurenghi G, Chong NV, Mitchell P, Jaffe GJ, Lu C, Katz TA, Schmidt-Erfurth U (2016) Morphology and visual acuity in aflibercept and ranibizumab therapy for neovascular age-related macular degeneration in the VIEW trials. Ophthalmology 123:1521–1529. https://doi.org/10.1016/j.ophtha.2016.03.037

    Article  PubMed  Google Scholar 

  24. 24.

    Arnold JJ, Campain A, Barthelmes D, Simpson JM, Guymer RH, Hunyor AP, McAllister IL, Essex RW, Morlet N, Gillies MC, Fight Retinal Blindness Study G (2015) Two-year outcomes of “treat and extend” intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology 122:1212–1219. https://doi.org/10.1016/j.ophtha.2015.02.009

    Article  PubMed  Google Scholar 

  25. 25.

    Stewart MW (2014) Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF. Expert Rev Clin Pharmacol 7:167–180. https://doi.org/10.1586/17512433.2014.884458

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Fauser S, Muether PS (2016) Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol 100:1494–1498. https://doi.org/10.1136/bjophthalmol-2015-308264

    Article  PubMed  Google Scholar 

  27. 27.

    Kim JM, Cho HJ, Kim Y, Jung SH, Lee DW, Kim JW (2019) Responses of types 1 and 2 neovascularization in age-related macular degeneration to anti-vascular endothelial growth factor treatment: optical coherence tomography angiography analysis. Semin Ophthalmol 34:168–176. https://doi.org/10.1080/08820538.2019.1620791

    Article  PubMed  Google Scholar 

  28. 28.

    Han JW, Cho HJ, Kang DH, Jung SH, Park S, Kim JW (2020) Changes in optical coherence tomography angiography and disease activity in type 3 neovascularization after anti-vascular endothelial growth factor treatment. Retina 40:1245–1254. https://doi.org/10.1097/IAE.0000000000002562

    CAS  Article  PubMed  Google Scholar 

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Affiliations

Authors

Contributions

Design and conduction of the study—HJC; data collection—HJC, JK, SKN, JL, CGK, and JWK; analysis and interpretation of data—HJC and JK; writing of the article—HJC; critical revision and final approval of article—JWK.

Corresponding author

Correspondence to Han Joo Cho.

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Ethics approval

The study was approved by the Institutional Review Board of Kim’s Eye Hospital, Konyang University College of Medicine.

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The need for informed consent was waived by the Institutional Review Board of Kim’s Eye Hospital, Konyang University College of Medicine.

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The authors declare no competing interests.

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Cite this article

Cho, H.J., Kim, J., Nah, S.K. et al. Nonexudative morphologic changes of neovascularization on optical coherence tomography angiography as predictive factors for exudative recurrence in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol (2021). https://doi.org/10.1007/s00417-021-05405-8

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Keywords

  • Age-related macular degeneration
  • Choroidal neovascularization
  • Optical coherence tomography angiography
  • Vascular endothelial growth factor