Skip to main content

Advertisement

SpringerLink
Log in

Influence of lesion location on lesion reactivation after initial treatment in neovascular age-related macular degeneration

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

Abstract

Purpose

We aim to evaluate the factors associated with the incidence of lesion reactivation after initial loading injections in patients with neovascular age-related macular degeneration (AMD).

Methods

This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three loading injections of either ranibizumab or aflibercept. After the initial treatment, patients were followed up every 1–2 months during the first year and the follow-up interval was extended to 4 months during the second year. Retreatment was administered on an as-needed basis. The incidence and timing of lesion reactivation at 24 months after diagnosis were identified. In addition, Cox’s proportional hazard model was used to evaluate the association of baseline factors with lesion reactivation. Lesion reactivation was defined re-accumulation of subretinal fluid/intraretinal fluid or the development of subretinal/intraretinal hemorrhage.

Results

A total of 284 patients (173 men and 111 women) were included in the study. The mean age of the patients was 70.5 ± 8.8 years. During the 24-month follow-up period, lesion reactivation was observed in 216 eyes (76.1%) at a mean of 8.2 ± 4.4 months after diagnosis. The incidence of lesion reactivation was 62.5% in extrafoveal macular neovascularization (MNV), 75.0% in juxtafoveal MNV, and 79.5% in subfoveal MNV. The extrafoveal MNV showed significantly lower incidence of lesion reactivation than subfoveal MNV (P = 0.041, hazard ratio = 0.64).

Conclusions

Extrafoveal MNVs showed a lower incidence of lesion reactivation after initial treatment than subfoveal MNVs. This result should be considered when interpreting the results of clinical trials with different eligibility criteria regarding lesion location.

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

Access this article

Log in via an institution

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431

    Article  CAS  PubMed  Google Scholar 

  2. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    Article  PubMed  Google Scholar 

  3. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG (2020) HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 127:72–84

    Article  PubMed  Google Scholar 

  4. Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, Figueroa MS, Lin H, Holz FG, Patel V, Lai TYY, Silverman D, Regillo C, Swaminathan B, Viola F, Cheung CMG, Wong TY (2022) Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 399:729–740

    Article  CAS  PubMed  Google Scholar 

  5. Shirley M (2022) Faricimab: First Approval. Drugs 82:825–830

    Article  CAS  PubMed  Google Scholar 

  6. Khanani AM, Guymer RH, Basu K, Boston H, Heier JS, Korobelnik JF, Kotecha A, Lin H, Silverman D, Swaminathan B, Willis JR, Yoon YH, Quezada-Ruiz C (2021) TENAYA and LUCERNE: rationale and design for the phase 3 clinical trials of faricimab for neovascular age-related macular degeneration. Ophthalmol Sci 1:100076

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ohji M, Takahashi K, Okada AA, Kobayashi M, Matsuda Y, Terano Y (2020) Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: 52- and 96-week findings from ALTAIR : a randomized controlled trial. Adv Ther 37:1173–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mitchell P, Holz FG, Hykin P, Midena E, Souied E, Allmeier H, Lambrou G, Schmelter T, Wolf S (2021) Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: the ARIES study: a randomized clinical trial. Retina 41:1911–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brown GC, Brown MM, Rapuano S, Boyer D (2020) Cost-utility analysis of VEGF inhibitors for treating neovascular age-related macular degeneration. Am J Ophthalmol 218:225–241

    Article  CAS  PubMed  Google Scholar 

  10. Prenner JL, Halperin LS, Rycroft C, Hogue S, Williams Liu Z, Seibert R (2015) Disease burden in the treatment of age-related macular degeneration: findings from a time-and-motion study. Am J Ophthalmol 160(725-731):e721

    Google Scholar 

  11. Iglicki M, González DP, Loewenstein A, Zur D (2021) Longer-acting treatments for neovascular age-related macular degeneration-present and future. Eye (Lond) 35:1111–1116

    Article  PubMed  Google Scholar 

  12. Meer EA, Oh DH, Brodie FL (2022) Time and distance cost of longer acting anti-VEGF therapies for macular degeneration: contributions to drug cost comparisons. Clin Ophthalmol 16:4273–4279

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kuroda Y, Yamashiro K, Miyake M, Yoshikawa M, Nakanishi H, Oishi A, Tamura H, Ooto S, Tsujikawa A, Yoshimura N (2015) Factors associated with recurrence of age-related macular degeneration after anti-vascular endothelial growth factor treatment: a retrospective cohort study. Ophthalmology 122:2303–2310

    Article  PubMed  Google Scholar 

  14. Kim JH, Kim JW, Kim CG (2021) Five-year reactivation after ranibizumab or aflibercept treatment for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. J Ocul Pharmacol Ther 37:525–533

    Article  CAS  PubMed  Google Scholar 

  15. Kim JH, Kim JW, Kim CG (2022) Difference in lesion reactivation between pure type 2 and mixed type 1 and 2 macular neovascularization and its influence on long-term treatment outcomes. Semin Ophthalmol:1–7

  16. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B (1990) Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina 10:1–8

    Article  CAS  PubMed  Google Scholar 

  17. Parodi MB, Iacono P, La Spina C, Iuliano L, Lo Giudice G, Introini U, Bandello F (2014) Intravitreal ranibizumab for naive extrafoveal choroidal neovascularization secondary to age-related macular degeneration. Retina 34:2167–2170

    Article  CAS  PubMed  Google Scholar 

  18. Giacomelli G, Giansanti F, Finocchio L, Biagini I, Bacherini D, Virgili G, Menchini U (2014) Results of intravitreal ranibizumab with a prn regimen in the treatment of extrafoveal and juxtafoveal neovascular membranes in age-related macular degeneration. Retina 34:860–867

    Article  CAS  PubMed  Google Scholar 

  19. Ladas ID, Chatziralli IP, Kotsolis AI, Douvali M, Georgalas I, Theodossiadis PG, Rouvas AA (2012) Intravitreal ranibizumab versus thermal laser photocoagulation in the treatment of extrafoveal classic choroidal neovascularization secondary to age-related macular degeneration. Ophthalmologica 228:93–101

    Article  CAS  PubMed  Google Scholar 

  20. Ying GS, Maguire MG, Pan W, Grunwald JE, Daniel E, Jaffe GJ, Toth CA, Hagstrom SA, Martin DF (2018) Baseline predictors for five-year visual acuity outcomes in the comparison of AMD treatment trials. Ophthalmol Retina 2:525–530

    Article  PubMed  PubMed Central  Google Scholar 

  21. Augsburger M, Sarra GM, Imesch P (2019) Treat and extend versus pro re nata regimens of ranibizumab and aflibercept in neovascular age-related macular degeneration: a comparative study. Graefes Arch Clin Exp Ophthalmol 257:1889–1895

    Article  CAS  PubMed  Google Scholar 

  22. Chin-Yee D, Eck T, Fowler S, Hardi A, Apte RS (2016) A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol 100:914–917

    Article  PubMed  Google Scholar 

  23. Chaikitmongkol V, Sagong M, Lai TYY, Tan GSW, Ngah NF, Ohji M, Mitchell P, Yang CH, Ruamviboonsuk P, Wong I, Sakamoto T, Rajendran A, Chen Y, Lam DSC, Lai CC, Wong TY, Cheung CMG, Chang A, Koh A (2021) Treat-and-extend regimens for the management of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy: consensus and recommendations from the Asia-Pacific vitreo-retina society. Asia Pac J Ophthalmol (Phila) 10:507–518

    Article  CAS  PubMed  Google Scholar 

  24. Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, Hoyng CB, Hykin P, Staurenghi G, Heldner S, Bogumil T, Heah T, Sivaprasad S (2015) Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol 99:220–226

    Article  PubMed  Google Scholar 

  25. Kvannli L, Krohn J (2017) Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration. Acta Ophthalmol 95:678–682

    Article  CAS  PubMed  Google Scholar 

  26. Hatz K, Prunte C (2016) Changing from a pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration. Br J Ophthalmol 100:1341–1345

    Article  PubMed  Google Scholar 

  27. Kim JH, Kim JW, Kim CG (2022) Comparison of 24-month treatment outcomes between as-needed treatment and switching to treat-and-extend in type 3 macular neovascularization. Sci Rep 12:22546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gillies MC, Hunyor AP, Arnold JJ, Guymer RH, Wolf S, Pecheur FL, Munk MR, McAllister IL (2020) Macular atrophy in neovascular age-related macular degeneration: a randomized clinical trial comparing ranibizumab and aflibercept (RIVAL study). Ophthalmology 127:198–210

    Article  PubMed  Google Scholar 

  29. Kim JH, Chang YS, Kim JW, Kim CG, Lee DW (2019) Age-related differences in the prevalence of subtypes of Neovascular age-related macular degeneration in the first diagnosed eye. Graefes Arch Clin Exp Ophthalmol 257:891–898

    Article  PubMed  Google Scholar 

  30. 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 127:1179–1188

    Article  PubMed  Google Scholar 

  31. Kim YH, Lee B, Kang E, Oh J (2021) Clustering of eyes with age-related macular degeneration or pachychoroid spectrum diseases based on choroidal thickness profile. Sci Rep 11:4999

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gunter R, Szeto E, Jeong SH, Suh S, Waters AJ (2020) Cigarette smoking in South Korea: a narrative review. Korean J Fam Med 41:3–13

    Article  PubMed  Google Scholar 

  33. Shin HT, Yoon BW, Seo JH (2021) Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups. BMC Ophthalmol 21:97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shah AM, Bressler NM, Jampol LM (2011) Does laser still have a role in the management of retinal vascular and neovascular diseases? Am J Ophthalmol 152:332–339.e331

    Article  PubMed  Google Scholar 

  35. Macular Photocoagulation Study Group (1991) Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol 109:1109–1114

    Google Scholar 

  36. Kim JH, Kim JW, Kim CG (2021) Eyes that do not meet the eligibility criteria of clinical trials on age-related macular degeneration: proportion of the real-world patient population and reasons for exclusion. J Ophthalmol 2021:6635467

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Kim’s Eye Hospital (Seoul, South Korea) provided funding for English editing support. The sponsor had no role in the design or conduct of the study.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kim’s Eye Hospital, #156 Youngdeungpo-dong 4ga, Youngdeungpo-gu, Seoul, 150-034, South Korea

    Jae Hui Kim, Jong Woo Kim & Chul Gu Kim

Authors
  1. Jae Hui Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jong Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chul Gu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae Hui Kim.

Ethics declarations

Ethical approval

This study was approved by the Institutional Review Board of Kim’s Eye Hospital (Seoul, South Korea) and conducted in accordance with the tenets of the Declaration of Helsinki.

Informed consent

Informed consent was not obtained as no participant information was identified in this study.

Conflict of interest

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

Kim, J.H., Kim, J.W. & Kim, C.G. Influence of lesion location on lesion reactivation after initial treatment in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 261, 3139–3148 (2023). https://doi.org/10.1007/s00417-023-06144-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-023-06144-8

Keywords

Search

Navigation