Skip to main content

Advertisement

SpringerLink
Log in

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up)

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

Abstract

Purpose

To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space).

Methods

This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections.

Results

Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45 µm vs 191 ± 52 µm, p = 0.01) before treatment and (170 ± 47 µm vs 179 ± 48 µm, p = 0.24) after 60 months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60 months. CMT in group 1 vs group 2 was (398 ± 154 µm vs 382 ± 103 µm, p = 0.86) before treatment and (297 ± 68 µm vs 283 ± 67 µm, p = 0.14) after 60 months. The number of injections per eye over a period of 60 months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60 months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03).

Conclusion

Over the full 60 months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Jonas JB, Cheung CMG, Panda-Jonas S (2017) Updates on the epidemiology of age-related macular degeneration. Asia Pac J Ophthalmol 6(6):493–497. https://doi.org/10.22608/APO.2017251

    Article  Google Scholar 

  2. Augustin AJ, Kirchhof J (2009) Inflammation and the pathogenesis of age-related macular degeneration. Expert Opin Ther Targets 13(6):641–651. https://doi.org/10.1517/14728220902942322

    Article  CAS  PubMed  Google Scholar 

  3. Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G (2020) Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev 5(5):CD012208. https://doi.org/10.1002/14651858.CD012208.pub2

    Article  PubMed  Google Scholar 

  4. Schouten JS, La Heij EC, Webers CA, Lundqvist IJ, Hendrikse F (2009) A systematic review on the effect of bevacizumab in exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 247(1):1–11. https://doi.org/10.1007/s00417-008-0952-y

    Article  CAS  PubMed  Google Scholar 

  5. Gass JD (1994) Biomicroscopic and histopathologic considerations regarding the feasibility of surgical excision of subfoveal neovascular membranes. Trans Am Ophthalmol Soc 92:91–111 (discussion 111-6)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Freund KB, Zweifel SA, Engelbert M (2010) Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina 30(9):1333–1349. https://doi.org/10.1097/IAE.0b013e3181e7976b

    Article  PubMed  Google Scholar 

  7. Mathis T, Holz FG, Sivaprasad S, Yoon YH, Eter N, Chen LJ, Koh A, Cunha de Souza E, Staurenghi G (2023) Characterisation of macular neovascularisation subtypes in age-related macular degeneration to optimise treatment outcomes. Eye (Lond) 37(9):1758–1765. https://doi.org/10.1038/s41433-022-02231-y

    Article  PubMed  Google Scholar 

  8. Spaide RF, Jaffe GJ, Sarraf D, Freund KB, Sadda SR, Staurenghi G, Waheed NK, Chakravarthy U, Rosenfeld PJ, Holz FG, Souied EH, Cohen SY, Querques G, Ohno-Matsui K, Boyer D, Gaudric A, Blodi B, Baumal CR, Li X, Coscas GJ, Brucker A, Singerman L, Luthert P, Schmitz-Valckenberg S, Schmidt-Erfurth U, Grossniklaus HE, Wilson DJ, Guymer R, Yannuzzi LA, Chew EY, Csaky K, Monés JM, Pauleikhoff D, Tadayoni R, Fujimoto J (2020) Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group. Ophthalmology 127(5):616–636. https://doi.org/10.1016/j.ophtha.2019.11.004

    Article  PubMed  Google Scholar 

  9. Giovannini A, Mariotti C, Ripa E, Scassellati B, Tittarelli R (1994) Choroidal filling in age-related macular degeneration: indocyanine green angiographic findings. Ophthalmologica 208(4):185–191. https://doi.org/10.1159/000310483

    Article  CAS  PubMed  Google Scholar 

  10. Koizumi H, Kano M, Yamamoto A, Saito M, Maruko I, Kawasaki R, Sekiryu T, Okada AA, Iida T (2015) Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration. Am J Ophthalmol 159(4):627–633. https://doi.org/10.1016/j.ajo.2014.12.025

    Article  CAS  PubMed  Google Scholar 

  11. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S (2012) Subfoveal choroidal thickness after ranibizumab therapy for neovascular age-related macular degeneration: 12-month results. Ophthalmology 119(8):1621–1627. https://doi.org/10.1016/j.ophtha.2012.02.022

    Article  PubMed  Google Scholar 

  12. Ellabban AA, Tsujikawa A, Ogino K, Ooto S, Yamashiro K, Oishi A, Yoshimura N (2012) Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization. Clin Ophthalmol 6:837–844. https://doi.org/10.2147/OPTH.S30907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ogasawara M, Maruko I, Sugano Y, Ojima A, Sekiryu T, Iida T (2012) Retinal and choroidal thickness changes following intravitreal ranibizumab injection for exudative age-related macular degeneration. Nippon Ganka Gakkai Zasshi 116(7):643–649

    PubMed  Google Scholar 

  14. Abdin AD, Suffo S, Bischoff-Jung M, Daas L, Pattmöller M, Seitz B (2020) Advantages of a designated IVI center for a German university eye hospital. Ophthalmologe 117(1):50–57. https://doi.org/10.1007/s00347-019-0911-5

    Article  PubMed  Google Scholar 

  15. Serra R, Coscas F, Cabral D et al (2022) Polypoidal choroidal neovascularization versus Type 1 choroidal neovascularization in age-related macular degeneration: a fractal analysis study. Retina 42(6):1005–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chae B, Jung JJ, Mrejen S, Gallego-Pinazo R, Yannuzzi NA, Patel SN, Chen CY, Marsiglia M, Boddu S, Freund KB (2015) Baseline predictors for good versus poor visual outcomes in the treatment of neovascular age-related macular degeneration with intravitreal anti-VEGF therapy. Invest Ophthalmol Vis Sci 6(9):5040–5047. https://doi.org/10.1167/iovs.15-1649

    Article  Google Scholar 

  17. Mrejen S, Jung JJ, Chen C, Patel SN, Gallego-Pinazo R, Yannuzzi N, Xu L, Marsiglia M, Boddu S, Freund KB (2015) Long-term visual outcomes for a treat and extend anti-vascular endothelial growth factor regimen in eyes with neovascular age-related macular degeneration. J Clin Med 4(7):1380–1402. https://doi.org/10.3390/jcm4071380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Abdin AD, Aljundi W, El Jawhari K, Suffo S, Weinstein I, Seitz B (2022) First year real life experience with intravitreal brolucizumab for treatment of refractory neovascular age-related macular degeneration. Front Pharmacol 13:860784. https://doi.org/10.3389/fphar.2022.860784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang S, Zhao J, Sun X (2016) Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther 10:1857–1867

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lee CS, Kim AJ, Baughman D et al (2018) Visual acuity improvement when switching from ranibizumab to aflibercept is not sustained. Retina 38(5):951–956

    Article  PubMed  PubMed Central  Google Scholar 

  21. Empeslidis T, Storey M, Giannopoulos T, Konidaris V, Tranos PG, Panagiotou ES, Voudouragkaki IC, Konstas AG (2019) How successful is switching from bevacizumab or ranibizumab to aflibercept in age-related macular degeneration? A systematic overview. Adv Ther 36(7):1532–1548. https://doi.org/10.1007/s12325-019-00971-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wallsh JO, Gallemore RP (2021) Anti-VEGF-resistant retinal diseases: a review of the latest treatment options. Cells 10(5):1049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gale RP, Pearce I, Eter N et al (2020) Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study. Br J Ophthalmol 104(4):493–499

    Article  PubMed  Google Scholar 

  24. Kiss S, Campbell J, Almony A, Shih V, Serbin M, LaPrise A, Wykoff CC (2020) Management and outcomes for neovascular age-related macular degeneration: analysis of United States electronic health records. Ophthalmology 127(9):1179–1188. https://doi.org/10.1016/j.ophtha.2020.02.027

    Article  PubMed  Google Scholar 

  25. Siktberg J, Kim SJ, Sternberg P Jr, Patel S (2023) Effectiveness of bevacizumab step therapy for neovascular age-related macular degeneration. Eye (Lond) 37(9):1844–1849. https://doi.org/10.1038/s41433-022-02253-6

    Article  CAS  PubMed  Google Scholar 

  26. Invernizzi A, Nguyen V, Teo K, Barthelmes D, Fung A, Vincent A, Gillies M (2019) Five-year real-world outcomes of occult and classic choroidal neovascularization: data from the Fight Retinal Blindness! Project. Am J Ophthalmol 204:105–112. https://doi.org/10.1016/j.ajo.2019.03.001

    Article  PubMed  Google Scholar 

  27. Abdin AD, Devenijn M, Fulga R, Langenbucher A, Seitz B, Kaymak H (2023) Prevalence of geographic atrophy in advanced age-related macular degeneration (AMD) in daily practice. J Clin Med 12(14):4862. https://doi.org/10.3390/jcm12144862

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sadda SR, Tuomi LL, Ding B, Fung AE, Hopkins JJ (2018) Macular atrophy in the HARBOR Study for neovascular age-related macular degeneration. Ophthalmology 125(6):878–886. https://doi.org/10.1016/j.ophtha.2017.12.026

    Article  PubMed  Google Scholar 

  29. Chung SE, Kang SW, Lee JH, Kim YT (2011) Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration. Ophthalmology 118(5):840–845. https://doi.org/10.1016/j.ophtha.2010.09.012

    Article  PubMed  Google Scholar 

  30. Ting DS, Ng WY, Ng SR, Tan SP, Yeo IY, Mathur R, Chan CM, Tan AC, Tan GS, Wong TY, Cheung CM (2016) Choroidal thickness changes in age-related macular degeneration and polypoidal choroidal vasculopathy: a 12-month prospective study. Am J Ophthalmol 164:128–36.e1. https://doi.org/10.1016/j.ajo.2015.12.024

    Article  PubMed  Google Scholar 

  31. Inan S, Baysal Z, Inan UU (2019) Long-term changes in submacular choroidal thickness after intravitreal ranibizumab therapy for neovascular age-related macular degeneration: 14-mo follow-up. Curr Eye Res 44(8):908–915. https://doi.org/10.1080/02713683.2019.1600195

    Article  CAS  PubMed  Google Scholar 

  32. Rahman W, Chen FK, Yeoh J, da Cruz L (2013) Enhanced depth imaging of the choroid in patients with neovascular age-related macular degeneration treated with anti-VEGF therapy versus untreated patients. Graefes Arch Clin Exp Ophthalmol 251(6):1483–1488. https://doi.org/10.1007/s00417-012-2199-x

    Article  CAS  PubMed  Google Scholar 

  33. Ünlü C, Erdogan G, Onal Gunay B, Sezgin Akcay BI, Kardes E (2015) Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for neovascular age-related macular degeneration. Int J Ophthalmol 8(4):849–851. https://doi.org/10.3980/j.issn.2222-3959.2015.04.38

    Article  PubMed  PubMed Central  Google Scholar 

  34. Shahar J, Avery RL, Heilweil G, Barak A, Zemel E, Lewis GP, Johnson PT, Fisher SK, Perlman I, Loewenstein A (2006) Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina 26(3):262–269. https://doi.org/10.1097/00006982-200603000-00002

    Article  PubMed  Google Scholar 

  35. Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M (2007) Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res 85(4):425–430. https://doi.org/10.1016/j.exer.2007.05.008

    Article  CAS  PubMed  Google Scholar 

  36. Hood JD, Meininger CJ, Ziche M, Granger HJ (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 274(3):H1054–H1058. https://doi.org/10.1152/ajpheart.1998.274.3.H1054

    Article  CAS  PubMed  Google Scholar 

  37. Grossniklaus HE, Green WR (2004) Choroidal neovascularization. Am J Ophthalmol 137(3):496–503. https://doi.org/10.1016/j.ajo.2003.09.042

    Article  PubMed  Google Scholar 

  38. Christenbury JG, Phasukkijwatana N, Gilani F, Freund KB, Sadda S, Sarraf D (2018) Progression of macular atrophy in eyes with type 1 neovascularization and age-related macular degeneration receiving long-term intravitreal anti–vascular endothelial growth factor therapy: an optical coherence tomographic angiography analysis. Retina 38(7):1276–1288. https://doi.org/10.1097/IAE.0000000000001766

    Article  CAS  PubMed  Google Scholar 

  39. Kang HM, Kwon HJ, Yi JH, Lee CS, Lee SC (2014) Subfoveal choroidal thickness as a potential predictor of visual outcome and treatment response after intravitreal ranibizumab injections for typical exudative age-related macular degeneration. Am J Ophthalmol 157(5):1013–1021. https://doi.org/10.1016/j.ajo.2014.01.019

    Article  PubMed  Google Scholar 

  40. Sadda SR, Abdelfattah NS, Lei J, Shi Y, Marion KM, Morgenthien E, Gune S, Balasubramanian S (2020) Spectral-domain OCT analysis of risk factors for macular atrophy development in the HARBOR Study for neovascular age-related macular degeneration. Ophthalmology 127(10):1360–1370. https://doi.org/10.1016/j.ophtha.2020.03.031

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Saarland University Medical Center UKS, Kirrberger Strasse 100, Bldg. 22, 66421, Homburg, Saar, Germany

    Alaa Din Abdin, Omar Hanifa, Wissam Aljundi, Cristian Munteanu, Berthold Seitz & Shady Suffo

Authors
  1. Alaa Din Abdin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omar Hanifa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wissam Aljundi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristian Munteanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Berthold Seitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shady Suffo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by OH. The first draft of the manuscript was written by ADA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alaa Din Abdin.

Ethics declarations

Ethical approval

This study was approved by the Ethics Committee of the Medical Association of Saarland, Germany (Nr. 123/20). 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. This article does not contain any studies with animals performed by any of the authors.

Informed consent

For this type of retrospective study, formal consent is not required. However, all patients provided written informed consent before each IVI, as usual approach in our clinical practice.

Competing interest

• Financial interests: Abdin AD has received speaker and consultant honoraria from Novartis and Bayer Company. Other authors declare they have no financial interests.

• Non-financial interests: none.

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

Abdin, A.D., Hanifa, O., Aljundi, W. et al. Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up). Graefes Arch Clin Exp Ophthalmol 262, 457–468 (2024). https://doi.org/10.1007/s00417-023-06278-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-023-06278-9

Keywords

Search

Navigation