Skip to main content

Advertisement

SpringerLink
Log in

Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration

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

Abstract

Purpose

To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD).

Methods

Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3 mg aflibercept, 0.75 mg or 1.0 mg ranibizumab, and 1.8 mg or 2.5 mg bevacizumab. The eyes were analyzed at standardized time points up to 48 months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6 months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate.

Results

There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7–6.4 weeks). Mean follow-up was 22.8 months.

Conclusions

Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.

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

Available.

Code availability

Not applicable.

References

  1. GBD 2019 Blindness and Vision Impairment Collaborators and Vision Loss Expert Group of the Global Burden of Disease Study (2021) Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to vision 2020: the right to sight: an analysis for the global burden of disease study. Lancet Glob Health 9:e144-160

    Article  Google Scholar 

  2. Mettu PS, Allingham MJ, Cousins SW (2020) Incomplete response to Anti-VEGF therapy in neovascular AMD: exploring disease mechanisms and therapeutic opportunities. Prog Retin Eye Res. 82:100906

    Article  Google Scholar 

  3. Sharma S et al (2016) Macular Morphology and visual acuity in the second year of the comparison of age-related macular degeneration treatments trials. Ophthalmology 123:865–875

    Article  Google Scholar 

  4. Broadhead GK, Hong T, Chang AA (2014) Treating the untreatable patient: current options for the management of treatment-resistant neovascular age-related macular degeneration. Acta Ophthalmol 92:713–723

    Article  CAS  Google Scholar 

  5. Muller S et al (2017) Treatment of age-related neovascular macular degeneration: the patient’s perspective. Graefes Arch Clin Exp Ophthlmol 255:2237–2246

    Article  CAS  Google Scholar 

  6. Iglicki M et al (2021) Longer-acting treatments for neovascular age-related macular degeneration – present and future. Eye (Lond) 35(4):1111–1116

    Article  Google Scholar 

  7. You QS et al (2018) High-dose high-frequency aflibercept for recalcitrant neovascular age-related macular degeneration. Retina 38:1156–1165

    Article  CAS  Google Scholar 

  8. Forooghian F et al (2009) Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration. Retina 29:723–731

    Article  Google Scholar 

  9. Brown D et al (2013) Super-dose anti-VEGF (SAVE) trial: 2.0 mg intravitreal ranibizumab for recalcitrant neovascular macular degeneration – primary end point. Ophthalmol 120:349–354

    Article  Google Scholar 

  10. Verritti D, Lanzetta P (2013) Triple therapy for anti-vascular endothelial growth factor nonresponders in neovascular age-related macular degeneration: impact of different photodynamic therapy parameters. Ophthalmologica 230:131–137

    Article  Google Scholar 

  11. Barikian A et al (2017) Intravitreal dexamethasone implant as adjuvant treatment for bevacizumab and ranibizumab-resistant neovascular age-related macular degeneration: a pilot study. Retina 37:1337–1344

    Article  CAS  Google Scholar 

  12. Chang AC et al (2014) Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration. Ophthalmology 121:188–192

    Article  Google Scholar 

  13. Marquis L-M, Mantel I (2020) Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 258:1591–1596

    Article  CAS  Google Scholar 

  14. Felfeli T et al (2019) Hypotensive efficacy of topical brimonidine for intraocular pressure spikes following intravitreal injections of antivascular endothelial growth factor agents: a randomised crossover trial. Br J Ophthalmol 103:1388–1394

    Article  Google Scholar 

  15. Spooner K et al (2019) Long-term outcomes of switching to aflibercept for treatment-resistant neovascular age-related macular degeneration. Acta Ophthalmol 97:e706–e712

    CAS  PubMed  Google Scholar 

  16. Fung AT et al (2012) Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with persistent/recurrent macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study). Eye (Lond) 26:1181–1187

    Article  CAS  Google Scholar 

  17. Wykoff CC et al (2013) Two year SAVE outcomes: 2.0 mg ranibizumab for recalcitrant neovascular AMD. Ophthalmology 120:1945–1946

    Article  Google Scholar 

  18. Busbee BG et al (2013) Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 120:1046–1056

    Article  Google Scholar 

  19. Eshtiaghi A et al (2021) Geographic atrophy incidence and progression following intravitreal anti-vascular endothelial growth factor agenets for age-related macular degeneration: a meta-analysis. Retina 41: 2424–2435

  20. Spooner KL et al (2020) Macular atrophy incidence and progression in eyes with neovascular age-related macular degeneration treated with vascular endothelial growth factor inhibitors using a treat-and-extend or a pro re nata regimen: four-year results of the MANEX study. Ophthalmology 127:1663–1673

    Article  Google Scholar 

  21. Gillies MC et al (2020) Macular atrophy in neovascular age-related macular degeneration: a randomized clinical trial comparing ranibizumab and aflibercept (RIVAL Study). Ophthalmology. 127:198–210

    Article  Google Scholar 

  22. Sadda SR et al (2018) Macular atrophy development in the HARBOR study for neovascular age-related macular degeneration. Ophthalmology 125:878–886

    Article  Google Scholar 

Download references

Funding

This research was supported by the Intramural Research Program of the NIH, National Eye Institute.

Author information

Authors and Affiliations

  1. Division of Epidemiology & Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Geoffrey K. Broadhead, Tiarnan D. L. Keenan, Emily Y. Chew, Henry E. Wiley & Catherine A. Cukras

Authors
  1. Geoffrey K. Broadhead
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiarnan D. L. Keenan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily Y. Chew
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henry E. Wiley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Catherine A. Cukras
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherine A. Cukras.

Ethics declarations

Ethics approval

Ethics approval for this study was provided by the Institutional Review Board of the National Institutes of Health.

Consent to participate

All participants had previously provided written consent for their clinical data to be used for research purposes. In view of the retrospective nature of this study, specific consent for inclusion in this retrospective study was not required by the IRB.

Consent for publication

Not applicable.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Broadhead, G.K., Keenan, T.D.L., Chew, E.Y. et al. Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 260, 2239–2247 (2022). https://doi.org/10.1007/s00417-021-05547-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-021-05547-9

Keywords

Search

Navigation