Anne M Lynch, Nathan C Grove, Brandie D Wagner, Alan G Palestine, V Michael Holers, Ashley A Frazer-Abel, Ramya Gnanaraj, Andres Lisker-Cervantes, Jennifer L Patnaik, Talisa E de Carlo Forest, Emily A Auer, Arden J McReynolds, Marc T Mathias, Niranjan Manoharan, Santiago Rodriquez De Cordoba, Naresh Mandava
{"title":"随着时间的推移，全身性补体激活发展为晚期老年性黄斑变性的动态风险。","authors":"Anne M Lynch, Nathan C Grove, Brandie D Wagner, Alan G Palestine, V Michael Holers, Ashley A Frazer-Abel, Ramya Gnanaraj, Andres Lisker-Cervantes, Jennifer L Patnaik, Talisa E de Carlo Forest, Emily A Auer, Arden J McReynolds, Marc T Mathias, Niranjan Manoharan, Santiago Rodriquez De Cordoba, Naresh Mandava","doi":"10.1001/jamaophthalmol.2025.1608","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.</p><p><strong>Objective: </strong>To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).</p><p><strong>Design, setting, and participants: </strong>This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.</p><p><strong>Exposures: </strong>Complement factors.</p><p><strong>Main outcomes and measures: </strong>Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.</p><p><strong>Results: </strong>Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P = .03), C4b (HR, 60.4; 95% CrI, 6.5-544; P < .001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P < .001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P < .001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14 877; P = .003), and factor I (HR, 525.9; 95% CrI, 5.5-107 589; P = .02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P = .01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P < .001) were associated with the hazard of GA.</p><p><strong>Conclusions and relevance: </strong>Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.</p>","PeriodicalId":14518,"journal":{"name":"JAMA ophthalmology","volume":" ","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163720/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dynamic Risk of Systemic Complement Activation With Time to Progression to Advanced Age-Related Macular Degeneration.\",\"authors\":\"Anne M Lynch, Nathan C Grove, Brandie D Wagner, Alan G Palestine, V Michael Holers, Ashley A Frazer-Abel, Ramya Gnanaraj, Andres Lisker-Cervantes, Jennifer L Patnaik, Talisa E de Carlo Forest, Emily A Auer, Arden J McReynolds, Marc T Mathias, Niranjan Manoharan, Santiago Rodriquez De Cordoba, Naresh Mandava\",\"doi\":\"10.1001/jamaophthalmol.2025.1608\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.</p><p><strong>Objective: </strong>To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).</p><p><strong>Design, setting, and participants: </strong>This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.</p><p><strong>Exposures: </strong>Complement factors.</p><p><strong>Main outcomes and measures: </strong>Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.</p><p><strong>Results: </strong>Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P = .03), C4b (HR, 60.4; 95% CrI, 6.5-544; P < .001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P < .001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P < .001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14 877; P = .003), and factor I (HR, 525.9; 95% CrI, 5.5-107 589; P = .02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P = .01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P < .001) were associated with the hazard of GA.</p><p><strong>Conclusions and relevance: </strong>Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.</p>\",\"PeriodicalId\":14518,\"journal\":{\"name\":\"JAMA ophthalmology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163720/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAMA ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamaophthalmol.2025.1608\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamaophthalmol.2025.1608","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Dynamic Risk of Systemic Complement Activation With Time to Progression to Advanced Age-Related Macular Degeneration.
Importance: Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.
Objective: To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).
Design, setting, and participants: This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.
Exposures: Complement factors.
Main outcomes and measures: Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.
Results: Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P = .03), C4b (HR, 60.4; 95% CrI, 6.5-544; P < .001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P < .001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P < .001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14 877; P = .003), and factor I (HR, 525.9; 95% CrI, 5.5-107 589; P = .02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P = .01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P < .001) were associated with the hazard of GA.
Conclusions and relevance: Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.
期刊介绍：
JAMA Ophthalmology, with a rich history of continuous publication since 1869, stands as a distinguished international, peer-reviewed journal dedicated to ophthalmology and visual science. In 2019, the journal proudly commemorated 150 years of uninterrupted service to the field. As a member of the esteemed JAMA Network, a consortium renowned for its peer-reviewed general medical and specialty publications, JAMA Ophthalmology upholds the highest standards of excellence in disseminating cutting-edge research and insights. Join us in celebrating our legacy and advancing the frontiers of ophthalmology and visual science.
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