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Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6

Eye volume 39, pages 2194–2203 (2025)Cite this article

Subjects

Abstract

Purpose

To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect.

Methods

Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed.

Results

A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P < 0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA > / = 54 letters alone had similar VA outcomes to eyes with both VA > / = 54 letters and central subfield thickness (CST) of <500 microns.

Conclusion

Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.

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Fig. 1: Distribution of visual acuity across time for whole cohort and for specific subgroups.
Fig. 2: OCT characteristics associated with VA at visit 2 (post single injection) and visit 4 (post initiating phase).

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Data availability

The anonymised PRECISE clinical database analysed during the current study is available from author SS on approval of a data sharing agreement with Moorfields Eye Hospital. Sharing of retinal images requires patient consent and sponsor approval.

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Funding

The investigator-initiated study was funded by Boehringer Ingelheim International GmbH (Grant number: SIVS1045). This study was also supported by the NIHR Biomedical Research Centre and Clinical Research Facility at the Moorfields Eye Hospital National Health Service Foundation Trust and the University College London Institute of Ophthalmology. Role of the Funder/Sponsor: Boehringer Ingelheim was involved in the review and approval of the manuscript. Sobha Sivaprasad reported receiving financial support from AbbVie, Alimera Science, Amgen, Apellis, Astellas, Bayer, Biogen, Boehringer Ingelheim, Clearside Biomedical, Eyebiotech, Eyepoint Phamaceuticals, Iveric Bio, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Ripple Therapeutics, Roche, Stealth Biotherapeutics and Sanofi. Sobha Sivaprasad is the Editor-in- Chief of EYE. Faruque Ghanchi has received honorarium for consultancy-advisory boards from Alimera, Allergan, Bayer, Novartis, Oxford BioElectronics, Roche; educational travel grants from Allergan, Bayer, Novartis; James Talks is a consultant for Bayer and Novartis, received grant support from Bayer, Novartis and Heidelberg Engineering, is involved in research for Allergan, Roche, Bayer, Novartis and Boehringer-Ingelheim, and is the Editor in Chief of Eye; Ian Pearce has received lecture fees from Allergan, Bayer, Heidelberg and Novartis, consultancy fees from Allergan, Alimera, Bayer and Novartis and travel fees from Allergan, Bayer and Novartis; Martin McKibbin has received lecture and advisory board honoraria from Bayer and Novartis and an educational travel grant from Bayer; Ajay Kotagiri received travel support from Novartis, Bayer, and Allergan, and speaker fees from Allergan and Bayer; Geeta Menon has conducted consultancy-advisory boards for Novartis, Bayer and Allergan, received educational travel grants from Novartis, Bayer, Allergan; Benjamin Burton is in the advisory board and received international conference attendance sponsored by Novartis and Bayer; Richard Gale has conducted consultancy-advisory boards for Novartis, Bayer and Allergan, Alimera, Santen, received educational travel grants from Novartis, Bayer, Allergan, Heidelberg Engineering.

Author information

Authors and Affiliations

  1. National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK

    Swati Chandak, Sarega Gurudas, Raheeba Pakeer Muhammed, Ayse Keskin, Sridevi Thottarath & Sobha Sivaprasad

  2. Institute of Ophthalmology, University College, London, UK

    Sarega Gurudas & Sobha Sivaprasad

  3. Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK

    Faruque Ghanchi

  4. King’s College Hospital NHS Foundation Trust, London, UK

    Anna Grabowska

  5. Newcastle Hospitals NHS Foundation Trust, Newcastle, UK

    Stephen James Talks

  6. The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust, Liverpool, UK

    Ian Pearce

  7. Leeds Teaching Hospitals NHS Trust, Leeds, UK

    Martin McKibbin

  8. South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK

    Ajay Kotagiri

  9. Frimley Health NHS Foundation Trust, Surrey, UK

    Geeta Menon

  10. James Paget University Hospitals NHS Foundation Trust, Norfolk, UK

    Benjamin J. L. Burton

  11. York Teaching Hospital NHS Foundation Trust, York, UK

    Richard Gale

Authors
  1. Swati Chandak
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  2. Sarega Gurudas
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  3. Raheeba Pakeer Muhammed
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  13. Benjamin J. L. Burton
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  14. Richard Gale
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  15. Sobha Sivaprasad
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Contributions

Conceptualization: SS; Data curation: AK, ST, RMP, SC, SG; Formal analysis: SG and SS; Funding acquisition: SS; Methodology: SC, SG, AK, ST and SS Project administration: SS; Resources: GM, BJB, IP, MM, ST, SC, RPM, AK, AKo, JT, FG, RG, AG, and SS; Supervision: SS; Visualization: SG and SC; Writing—original draft: SC, SG and SS; Writing—review & editing: SC, SG, SS. Review and approval of final manuscript: SC, SG, AK, SS, GM, BJB, IP, MM, ST, RPM, AKo, JT, AG, FG, RG.

Corresponding author

Correspondence to Sobha Sivaprasad.

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Chandak, S., Gurudas, S., Pakeer Muhammed, R. et al. Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6. Eye 39, 2194–2203 (2025). https://doi.org/10.1038/s41433-025-03797-z

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