Endothelin-1 Plasma and Aqueous Humor Levels in Different Types of Glaucoma: A Systematic Review and Meta-Analysis

Author:

Lampsas Stamatios1ORCID,Kandarakis Stylianos A.2ORCID,Vakalopoulos Dionysios G.2ORCID,Lampsa Aikaterini1,Oikonomou Evangelos3,Siasos Gerasimos4,Kymionis George D.2

Affiliation:

1. Second Department of Ophthalmology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece

2. First Department of Ophthalmology, “G. Gennimatas” Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece

3. Third Department of Cardiology, Thoracic Diseases General Hospital Sotiria, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece

4. Cardiovascular Division, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115, USA

Abstract

Background and Objectives: Several studies suggest the complex relationship between Endothelin-1 (ET-1) levels with various types of glaucoma. This systematic review and meta-analysis explore ET-1 levels in plasma and aqueous humor among different types of glaucoma. Materials and Methods: A literature search (PubMed, ScienceDirect, Cochrane Library) was made up to April 2024 (PROSPERO: CRD42023430471). The results were synthesized according to PRISMA Guidelines. Results were presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 2597 subjects (1513 patients with glaucoma vs. 1084 healthy controls) from 23 studies were included in a meta-analysis. Notably, patients with glaucoma reported significantly higher plasma levels of ET-1 compared to controls (SMD: 1.21, 95% CI: 0.59–1.82, p < 0.001). Particularly, plasma ET-1 levels were higher in primary open-angle glaucoma (POAG) (SMD: 0.87, 95% CI: 0.09–1.65, p < 0.05), normal-tension glaucoma (SMD: 0.86, 95% CI: 0.27–1.46, p = 0.05), and angle-closure glaucoma patients (SMD: 1.03, 95% CI: 0.43–1.63, p < 0.001) compared to healthy controls. Moreover, ET-1 aqueous humor levels were significantly higher in patients with glaucoma compared to controls (SMD: 1.60, 95% CI: 1.04–2.15, p < 0.001). In particular, aqueous humor levels were higher in POAG patients (SMD: 2.03 95% CI: 1.00–3.14, p < 0.001), and pseudoexfoliative glaucoma patients (SMD: 2.03, 95% CI: 1.00–3.07, p < 0.001) compared to controls. Conclusions: This meta-analysis indicates that elevated levels of ET-1 plasma and aqueous humor are significantly associated with different types of glaucoma. The pathogenesis of ET-1-related mechanisms may vary across different glaucoma types, indicating that possible therapeutic approaches targeting ET-1 pathways should be tailored to each specific glaucoma type.

Publisher

MDPI AG

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