Hae Min Kang, Kevin M Mendez, Inês Laíns, Krupa Sourirajan, Roshni Bhat, Archana Nigalye, Raviv Katz, Georgiy Kozak, Hanna Choi, Augustine Bannerman, Rodrigo A Alvarez, David Wu, Ivana K Kim, Liming Liang, John B Miller, Demetrios G Vavvas, Joan W Miller, Jessica Lasky-Su, Deeba Husain
{"title":"treatment-naïve新生血管性年龄相关性黄斑变性患者玻璃体内注射抗血管内皮生长因子后血浆代谢物与治疗反应的关系","authors":"Hae Min Kang, Kevin M Mendez, Inês Laíns, Krupa Sourirajan, Roshni Bhat, Archana Nigalye, Raviv Katz, Georgiy Kozak, Hanna Choi, Augustine Bannerman, Rodrigo A Alvarez, David Wu, Ivana K Kim, Liming Liang, John B Miller, Demetrios G Vavvas, Joan W Miller, Jessica Lasky-Su, Deeba Husain","doi":"10.1136/bmjophth-2025-002149","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aims: </strong>To investigate the association between plasma metabolomic profiles and treatment response after intravitreal anti-vascular endothelial growth factor (VEGF) injections in treatment-naïve neovascular age-related macular degeneration (nAMD).</p><p><strong>Methods: </strong>This is part of a prospective longitudinal study that included patients with treatment-naïve nAMD who have undergone three loading intravitreal anti-VEGF injections. All patients underwent ophthalmological examinations including spectral domain optical coherence tomography (SD OCT). Fasting blood samples were collected at the time of study enrolment (not to first anti-VEGF injection) and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry. Treatment response was defined as no evidence of any subretinal and intraretinal fluid on SD OCT 4-6 weeks after the third injection. Multilevel mixed-effects linear modelling was used to assess associations between plasma metabolites and treatment response. Multiple comparisons were accounted for using the effective number of tests to explain 80% of the variance (ENT80), with a p value threshold of 0.0017.</p><p><strong>Results: </strong>We included 131 eyes of 101 patients, and 69 patients (68.3%) were female. 51 eyes (38.9%) were treatment responders. Taurodeoxycholate (TDCA) was the only plasma metabolite significantly associated with treatment response (β=1.6, ENT80=0.001).</p><p><strong>Conclusion: </strong>In our study, TDCA was the most significant plasma metabolite associated with treatment response after three-loading dose of anti-VEGF therapy in patients with nAMD. Bile acids may have a beneficial impact on treatment response in nAMD through their neuroprotective property. Plasma metabolites may be used as biomarkers to predict responses to initial anti-VEGF therapy in patients with nAMD, providing a more individualised treatment plan.</p>","PeriodicalId":9286,"journal":{"name":"BMJ Open Ophthalmology","volume":"10 1","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911696/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of plasma metabolites with treatment response after intravitreal anti-vascular endothelial growth factor injections in treatment-naïve neovascular age-related macular degeneration.\",\"authors\":\"Hae Min Kang, Kevin M Mendez, Inês Laíns, Krupa Sourirajan, Roshni Bhat, Archana Nigalye, Raviv Katz, Georgiy Kozak, Hanna Choi, Augustine Bannerman, Rodrigo A Alvarez, David Wu, Ivana K Kim, Liming Liang, John B Miller, Demetrios G Vavvas, Joan W Miller, Jessica Lasky-Su, Deeba Husain\",\"doi\":\"10.1136/bmjophth-2025-002149\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aims: </strong>To investigate the association between plasma metabolomic profiles and treatment response after intravitreal anti-vascular endothelial growth factor (VEGF) injections in treatment-naïve neovascular age-related macular degeneration (nAMD).</p><p><strong>Methods: </strong>This is part of a prospective longitudinal study that included patients with treatment-naïve nAMD who have undergone three loading intravitreal anti-VEGF injections. All patients underwent ophthalmological examinations including spectral domain optical coherence tomography (SD OCT). Fasting blood samples were collected at the time of study enrolment (not to first anti-VEGF injection) and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry. Treatment response was defined as no evidence of any subretinal and intraretinal fluid on SD OCT 4-6 weeks after the third injection. Multilevel mixed-effects linear modelling was used to assess associations between plasma metabolites and treatment response. Multiple comparisons were accounted for using the effective number of tests to explain 80% of the variance (ENT80), with a p value threshold of 0.0017.</p><p><strong>Results: </strong>We included 131 eyes of 101 patients, and 69 patients (68.3%) were female. 51 eyes (38.9%) were treatment responders. Taurodeoxycholate (TDCA) was the only plasma metabolite significantly associated with treatment response (β=1.6, ENT80=0.001).</p><p><strong>Conclusion: </strong>In our study, TDCA was the most significant plasma metabolite associated with treatment response after three-loading dose of anti-VEGF therapy in patients with nAMD. Bile acids may have a beneficial impact on treatment response in nAMD through their neuroprotective property. Plasma metabolites may be used as biomarkers to predict responses to initial anti-VEGF therapy in patients with nAMD, providing a more individualised treatment plan.</p>\",\"PeriodicalId\":9286,\"journal\":{\"name\":\"BMJ Open Ophthalmology\",\"volume\":\"10 1\",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911696/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Ophthalmology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjophth-2025-002149\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Ophthalmology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/bmjophth-2025-002149","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Association of plasma metabolites with treatment response after intravitreal anti-vascular endothelial growth factor injections in treatment-naïve neovascular age-related macular degeneration.
Background/aims: To investigate the association between plasma metabolomic profiles and treatment response after intravitreal anti-vascular endothelial growth factor (VEGF) injections in treatment-naïve neovascular age-related macular degeneration (nAMD).
Methods: This is part of a prospective longitudinal study that included patients with treatment-naïve nAMD who have undergone three loading intravitreal anti-VEGF injections. All patients underwent ophthalmological examinations including spectral domain optical coherence tomography (SD OCT). Fasting blood samples were collected at the time of study enrolment (not to first anti-VEGF injection) and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry. Treatment response was defined as no evidence of any subretinal and intraretinal fluid on SD OCT 4-6 weeks after the third injection. Multilevel mixed-effects linear modelling was used to assess associations between plasma metabolites and treatment response. Multiple comparisons were accounted for using the effective number of tests to explain 80% of the variance (ENT80), with a p value threshold of 0.0017.
Results: We included 131 eyes of 101 patients, and 69 patients (68.3%) were female. 51 eyes (38.9%) were treatment responders. Taurodeoxycholate (TDCA) was the only plasma metabolite significantly associated with treatment response (β=1.6, ENT80=0.001).
Conclusion: In our study, TDCA was the most significant plasma metabolite associated with treatment response after three-loading dose of anti-VEGF therapy in patients with nAMD. Bile acids may have a beneficial impact on treatment response in nAMD through their neuroprotective property. Plasma metabolites may be used as biomarkers to predict responses to initial anti-VEGF therapy in patients with nAMD, providing a more individualised treatment plan.
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