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. 2025 Mar;14(3):585-597.
doi: 10.1007/s40123-025-01095-1. Epub 2025 Feb 3.

Treatment Interval Progression and Adherence to Observe-and-Plan Regimen for Neovascular Age-Related Macular Degeneration Treated with Aflibercept 2 mg

Leyla Turan  1 , Andreas Arnold-Vangsted  1 , Morten la Cour  1   2 , Delila Hodzic-Hadzibegovic  1 , Javad N Hajari  1   2 , Oliver N Klefter  1   2 , Miklos Schneider  1   3 , Yousif Subhi  4   5   6
Affiliations

Treatment Interval Progression and Adherence to Observe-and-Plan Regimen for Neovascular Age-Related Macular Degeneration Treated with Aflibercept 2 mg

Leyla Turan et al. Ophthalmol Ther. 2025 Mar.

Abstract

Introduction: Treatment burden of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD) can be reduced with the Observe-and-Plan (O&P) regimen, which allows for an individualized treatment while reducing the number of injections and assessment visits. In this study, we evaluate detailed characteristics of treatment interval adjustment through individual follow-ups and evaluate adherence to the O&P regimen in a real-world setting in one of the largest centers in Europe.

Methods: This was a retrospective cohort study of treatment-naïve eyes with neovascular AMD that were treated with intravitreal aflibercept 2 mg in an O&P regimen who had persisting exudation after completion of loading dose. We evaluated decisions on adjustment of treatment intervals and adherence to the O&P regimen from a total of 5 follow-up visits. Data from visits and decision on treatment intervals were extracted from a treatment database.

Results: A total of 561 eyes were eligible for this study. Treatment intervals gradually increased from a 4-weeks interval (loading dose) to a wide distribution of intervals from 4-weeks to 12-weeks, and at the 5th follow-up 24.9% were followed without any treatment. In total, 209 eyes (49.5%) at the 5th follow-up (of 422 eyes present at the 5th follow-up) adhered to the treatment algorithm.

Conclusion: Aflibercept 2 mg in an O&P treatment regimen leads to a variety of treatment intervals, and some eyes may be overtreated. An important proportion of eyes deviate from the intended O&P treatment regimen. Our study contributes to understanding real-world implications of personalized treatment regimens.

Keywords: Adherence to treatment regimen; Aflibercept; Neovascular age-related macular degeneration; Observe-and-plan; Treatment interval.

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Conflict of interest statement

Declarations. Conflicts of Interest: Leyla Turan, Andreas Arnold-Vangsted, Morten la Cour, Javad Nouri Hajari, and Oliver Niels Klefter declare that they have no competing interests. Delila Hodzic-Hadzibegovic declares to have served as an advisory board member for Roche. Miklos Schneider declares to have served as an advisory board member for Novartis and Roche and Bayer, to have acted as a consultant for AbbVie, received speaker fees from AbbVie and Roche, and received travel grants from AbbVie, Bayer and Roche, not related to this work. Yousif Subhi declares to have received speakers fee from Bayer and Roche, and to be the inventor of a patent related to the use of biomarkers of polypoidal choroidal vasculopathy (WO2020007612A1), not related to this work. Yousif Subhi is Section Editor of Ophthalmology and Therapy. Yousif Subhi was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: We obtained permission for this database study from the Local Department Research Committee (jr. nr. 6-FSU-2023-13) and the Regional Data Protection Agency (jr. no.: R-20052134). Further approvals were not required due to the retrospective nature of the study. All aspects of this study adhered to the Declaration of Helsinki and its later amendments.

Figures

Fig. 1
Fig. 1
The observe-and-plan treatment regimen. Exudative activity (red arrow) leads to continuation of treatment. Dry macula (green arrow) leads to increasing treatment interval or the eyes were observed without treatment
Fig. 2
Fig. 2
Distribution of treatment intervals at follow-up (FU) visits. The x-axis indicates visits, and the y-axis indicates number of eyes
Fig. 3
Fig. 3
Proportion of eyes with treatment interval (TI) of 8-weeks or longer at follow-up (FU) visits. The x-axis indicates visits, and the y-axis indicates percentage of eyes that commence in ≥ 8-weeks treatment interval
Fig. 4
Fig. 4
Distribution of eyes with neovascular age-related macular degeneration throughout the algorithm. Only eyes adhering to the treatment regimen are included
See this image and copyright information in PMC

References

    1. Vision Loss Expert Group of the Global Burden of Disease Study, GBD 2019 Blindness and Vision Impairment Collaborators. Global estimates on the number of people blind or visually impaired by age-related macular degeneration: a meta-analysis from 2000 to 2020. Eye (London). 2024;2024(38):2070–82. - PMC - PubMed
    1. Sedeh FB, Scott DAR, Subhi Y, Sørensen TL. Prevalence of neovascular age-related macular degeneration and geographic atrophy in Denmark. Dan Med J. 2017;64:A5422. - PubMed
    1. Vangsted A, Thinggaard BS, Nissen AHK, Hajari JN, Klefter ON, Krogh Nielsen M, Sørensen TL, Grauslund J, Subhi Y. Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: a systematic review with meta-analyses and forecasting study. Acta Ophthalmol. 2023;101:857–68. - PubMed
    1. Bloch SB, Larsen M, Munch IC. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010. Am J Ophthalmol. 2012;153:209-213.e2. - PubMed
    1. Feng C, Krogh Nielsen M, Sørensen TL, Subhi Y. Systemic levels of C-reactive protein in patients with age-related macular degeneration: a systematic review with meta-analyses. Mech Ageing Dev. 2020;191: 111353. - PubMed

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