Aqueous humor mediator levels as biomarkers of anti-VEGF response in age-related macular degeneration

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-03-26 DOI:10.1016/j.cyto.2025.156921

Stéphanie Baillif , Sacha Nahon-Esteve , Tanguy Pace-Loscos , Gilles Pagès , Maeva Dufies

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引用次数: 0

Abstract

Purpose

To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response.

Design

Interventional, monocentric, prospective, clinical study.

Participants

Treatment-naïve nAMD patients.

Methods

Aqueous humor samples (100–200 μL) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1β, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1α and TNFα) using multiplex arrays.

Main outcomes measures

The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4.

Results

Fifteen eyes were included in the study. BCVA remained stable throughout the study (p = 0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (p < 0.0001, p < 0.0001, p < 0.001 and p < 0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p < 0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels ≤50 pg/mL: they showed higher baseline IL-6 levels (p = 0.05), and elevated IL-6 (p = 0.03), PlGF (p = 0.02), VEGF-C (p = 0.005), IL-8 (p = 0.04), and TNFα (p = 0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (p = 0.007). Patients who required a fourth IVI within 8 weeks of the loading dose had higher baseline TNFα levels (p = 0.05); higher MIP-1α levels after the first IVI (p = 0.045); and elevated TNFα (p = 0.026) and IL-8 (p = 0.029) levels after the second IVI.

Conclusions

The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval > 8 weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.