Evidence map›Paper›PMID 40326420›Full record

Trial reportActa ophthalmologica2025

Comparison of treatment routine using aflibercept: Strict vs. relaxed retreatment regimen (TOLERANT study)-A non-inferiority, randomized controlled trial.

Damian Jaggi, Lieselotte E Berger, Sandrine Zweifel, Matthias D Becker, Stephan Michels, Odile Stalder, Joel-Benjamin Lincke, Oussama Habra, Sebastian Wolf, Martin S Zinkernagel

Abstract readMulticenter StudyRandomized Controlled TrialClinical Trial, Phase IV
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Acta ophthalmologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Damian JaggiDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID https://orcid.org/0000-0002-3670-6983
Lieselotte E BergerDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sandrine ZweifelDepartment of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Matthias D BeckerSpross Research Institute, Department of Ophthalmology, Zürich City Hospital, Zürich, Switzerland.
Stephan MichelsAugenklinik Zürich West, Switzerland.
Odile StalderCTU Bern, University of Bern, Bern, Switzerland.
Joel-Benjamin LinckeDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Oussama HabraDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sebastian WolfDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Martin S ZinkernagelDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Funding

Bayer
6 · The paper itself

Abstract

purposeThis trial evaluated the noninferiority of a relaxed compared to a strict treat-and-extend treatment strategy in patients with neovascular Age-related macular degeneration (AMD).

methodsMulticenter, randomized, controlled, phase IV, non-inferiority clinical trial. Patients with treatment-naïve nAMD were randomized 1:1 to a relaxed or strict treat-and-extend treatment regimen. Aflibercept 2 mg/0.05 mL was used. In the relaxed regimen, up to 100 μm subfoveal subretinal fluid was tolerated, vs. no tolerance of any fluid in the strict regimen. The primary outcome was the change in best corrected visual acuity (BCVA; ETDRS letters) from baseline to the end of the study at week 104 and its difference between the two treatment arms, with a 5-letter non-inferiority margin.

resultsWe randomized 150 patients. The full analysis showed non-inferiority of the relaxed treatment, with a mean difference of -0.12 letters (95%-CI: -3.45 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.008), and a visual acuity gain of 7.3 (4.82; 9.78) vs. 7.01 (3.67; 10.36) letters in the strict vs. relaxed regimen, respectively. Many patients deviated from the protocol due to Covid-19. Per-protocol analysis showed a mean difference of -1.78 letters (95%-CI: -6.61 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.136). Fewer injections were needed in the relaxed regimen, with a mean difference of -2.34 (95%-CI: -4.11 to -0.56, p = 0.01).

conclusionTolerating up to 100 μm subfoveal subretinal fluid achieves good visual outcomes in our 24-month follow-up period, in patients treated with aflibercept for nAMD, with significantly fewer injections needed.

Indexed as

Receptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVisual AcuityWet Macular DegenerationAgedAged, 80 and overAngiogenesis InhibitorsFemaleFluorescein AngiographyFollow-Up StudiesFundus OculiHumansIntravitreal InjectionsMaleMiddle AgedRetreatmentafliberceptAngiogenesis InhibitorsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVascular Endothelial Growth Factor AafliberceptAMDanti‐VEGFsubretinal fluidtolerancetreat‐and‐extend

Identifiers

PMID40326420
PMCPMC12340175

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.