Evidence map›Paper›PMID 39920326›Full record

ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2025

Systemic counterregulatory response of angiopoietin-2 after intravitreal injections with faricimab for nAMD.

Anna Lena Huber, Angelika Bauer, Julius Beirer, Katharina Frede, Katharina Kirchmair, Reinhard Angermann, Matus Rehak, Claus Zehetner, Yvonne Nowosielski

Abstract read
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In one paragraph

Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
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

9 authors.

Anna Lena HuberUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Angelika BauerInstitute of Hygiene and Microbiology, Medical University Innsbruck, Schöpfstraße 41, 6020, Innsbruck, Austria.
Julius BeirerUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Katharina FredeUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Katharina KirchmairUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Reinhard AngermannDepartment of Ophthalmology, Landesklinikum Mistelbach/Gänserndorf, 2130, Mistelbach, Austria.
Matus RehakUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Claus ZehetnerUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Yvonne NowosielskiUniversity Hospital for Ophthalmology and Optometry, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. Yvonne.nowosielski@i-med.ac.at.ORCID http://orcid.org/0000-0002-2244-8645

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeRecently, a systemic counterregulatory response of angiopoietin-2 after intravitreal application of the anti vascular endothelial growth factor (anti-VEGF) drug aflibercept in neovascular age-related macular degeneration (nAMD) has been described. The aim of the study was to find out wether faricimab, a combined anti-VEGF/angiopoietin-2 drug, had an effect on systemic cytokine levels.

methods20 women and 11 men (mean age 79.5 ± 7.3 years) were included into this cohort study. Plama levels of VEGF-A and angiopoietin-2 were determined before and after intravitreal application of faricimab (6 mg/0.05 ml/eye) using ELISA-technique. These results were correlated with central macular thickness (CMT). Responders were defined as having had CMT thinning ≥ 50 μm.

resultsCMT decreased from 384.8 ± 108.8 μm prior to intravitreal injection (IVI) to 286.1 ± 63 μm one month after IVI (p < 0.0001). Angiopoietin-2 levels increased from 526.9 ± 129 pg/ml to 597.2 ± 174.8 pg/ml (p = 0.0087) one week after IVI and dropped to 547.4 ± 165 pg/ml (ns) four weeks after IVI. Responders revealed higher angiopoietin-2 (p = 0.0035) as well as higher VEGF-A (p = 0.0248) levels throughout the study period compared to non-responders. Initial CMT revealed to be the only independent factor influencing CMT 4 weeks after IVI in linear regression models with a positive correlation between initial thickness and effect size.

conclusionThe trending increase in systemic angiopoietin-2 levels, may be interpreted as an escape mechanism of the concomitant anti-VEGF component of therapy. Angiopoietin-2 levels could serve as a positive predictive factor of therapy response in the future. Further research regarding this effect as well as differences between responders and non-responders is mandatory. KEY MESSAGES: What is known Bispecific antibodies may be more beneficial compared to monospecific antibodies in neovascular age related macular degeneration (nAMD). For monospecific antibodies, there are systemic effects on systemic vascular endothelial growth factor (VEGF) levels. What is new The knew bispecific antibody faricimab entails an increase in systemic angiopoietin-2 levels, as well as a decrease in VEGF levels. The increase in systemic angiopoietin-2 may be interpreted as a counterregulatory effect. The decrease in systemic VEGF levels resembles the effects of monospecific antibodies.

Indexed as

Angiopoietin-2Wet Macular DegenerationAgedAged, 80 and overAngiogenesis InhibitorsAntibodies, BispecificEnzyme-Linked Immunosorbent AssayFemaleFluorescein AngiographyFollow-Up StudiesHumansIntravitreal InjectionsMacula LuteaMaleRecombinant Fusion ProteinsTomography, Optical CoherenceAngiogenesis InhibitorsAngiopoietin-2ANGPT2 protein, humanAntibodies, BispecificfaricimabRecombinant Fusion ProteinsVascular Endothelial Growth Factor AAngiopoietin-2Antibodies, bispecificVascular endothelial growth factor AWet macular degeneration

Identifiers

PMID39920326

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Registered trials

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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.