Exploring the Causal Relationships between Lipid Biomarkers and Anti-VEGF Treatment Response in Patients with Neovascular Age-related Macular Degeneration

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-01-13 DOI:10.1016/j.xops.2025.100711

Feixiang He MS , Qifang Chen MS , Peilin Gu MS , Xuemei Liu MS , Yinglian Chen PhD , Ting Liu PhD, MD , Chongyi Li PhD, MD

{"title":"Exploring the Causal Relationships between Lipid Biomarkers and Anti-VEGF Treatment Response in Patients with Neovascular Age-related Macular Degeneration","authors":"Feixiang He MS , Qifang Chen MS , Peilin Gu MS , Xuemei Liu MS , Yinglian Chen PhD , Ting Liu PhD, MD , Chongyi Li PhD, MD","doi":"10.1016/j.xops.2025.100711","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD).</div></div><div><h3>Design</h3><div>A bidirectional and multivariable Mendelian randomization study.</div></div><div><h3>Participants</h3><div>The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 genetic variants available for analysis.</div></div><div><h3>Methods</h3><div>Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes.</div></div><div><h3>Main Outcome Measures</h3><div>Thirteen lipid biomarkers, VA, and CRT.</div></div><div><h3>Results</h3><div>A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD.</div></div><div><h3>Conclusions</h3><div>This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 4","pages":"Article 100711"},"PeriodicalIF":3.2000,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmology science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666914525000090","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD).

Design

A bidirectional and multivariable Mendelian randomization study.

Participants

The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 genetic variants available for analysis.

Methods

Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes.

Main Outcome Measures

Thirteen lipid biomarkers, VA, and CRT.

Results

A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD.