Evidence map›Paper›PMID 41347874›Full record

ArticleInvestigative ophthalmology & visual science2025

Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.

Omer Trivizki, Charles C Wykoff, Magda A Smoor, David Rabinovitch, Avery Zhou, Jessica A Cao, Yara T E Lechanteur, Lambert van den Heuvel, Alain J van Gool, Jolein Gloerich and 2 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 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. 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

12 authors.

Omer TrivizkiTel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Charles C WykoffRetina Consultants of Texas, Houston, Texas, United States.
Magda A SmoorDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
David RabinovitchTel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Avery ZhouRetina Consultants of Texas, Houston, Texas, United States.
Jessica A CaoRetina Consultants of Texas, Houston, Texas, United States.
Yara T E LechanteurDepartment of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Lambert van den HeuvelDepartment of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.
Alain J van GoolTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Jolein GloerichTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Joëlle E VergroesenDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
Caroline C W KlaverDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects. Methods: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction. Results: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased. Conclusions: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.

Indexed as

Aqueous HumorGeographic AtrophyProteomeAgedAged, 80 and overChromatography, LiquidComplement C3FemaleHumansMaleMiddle AgedProspective StudiesProteomicsTandem Mass SpectrometryComplement C3Proteome

Identifiers

PMID41347874
PMCPMC12700176

What Socratic holds

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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 Socratic graph.