Petra P Larsen, Marie-Noëlle Delyfer, Cédric Schweitzer, Jean-François Korobelnik, Cécile Delcourt
{"title":"神经视网膜和RPE的改变和对年龄相关性黄斑变性的易感性：来自纵向外来者研究的见解。","authors":"Petra P Larsen, Marie-Noëlle Delyfer, Cédric Schweitzer, Jean-François Korobelnik, Cécile Delcourt","doi":"10.1016/j.ophtha.2025.01.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>We assessed the associations of macular layer thicknesses, measured using spectral-domain OCT (SD-OCT), with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS).</p><p><strong>Design: </strong>Population-based cohort study PARTICIPANTS: 653 participants of the Alienor study, with biennial eye imaging from 2009 to 2024.</p><p><strong>Methods: </strong>Macular layer thicknesses of eight distinct layers and three compound layers were automatically segmented based on SD-OCT imaging of the macula. Total and pathway specific PRS were calculated from previous AMD genome-wide association studies summary statistics. Associations of macular layer thicknesses with incident intermediate and advanced AMD were analyzed using time-dependent Cox proportional hazards models. Associations of macular layer thicknesses with PRS were assessed using linear mixed models.</p><p><strong>Main outcome measures: </strong>Incident intermediate and advanced AMD based on fundus colour photographs and SD-OCT.</p><p><strong>Results: </strong>Mean age at first OCT examination of the 653 participants was 82.2 ± 4.2 years and 61.3 % were women. In multivariate adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE) - Bruch's Membrane (BM) complex in the 1 mm central circle (Hazard ratio (HR)= 1.13 for 1 μm increase; P<sub>FDR</sub>= 8.08 x 10<sup>-4</sup>). Incident advanced AMD was associated with thicker RPE-BM complex in both the central circle (HR= 1.09; P<sub>FDR</sub>= 0.005) and the inner circle (1 mm - 3 mm) (HR= 1.28; P<sub>FDR</sub>= 1.61 x 10<sup>-5</sup>). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (ß= 0.06 μm/year for 1 standard deviation increase, P<sub>FDR</sub>= 1.61 x 10<sup>-10</sup>), high complement pathway PRS (ß= 0.04 μm/year, P<sub>FDR</sub>=3.23 x 10<sup>-5</sup>), high lipid pathway PRS (ß= 0.03 μm/year, P<sub>FDR</sub>= 3.74 x 10<sup>-4</sup>) and ARMS2 (ß= 0.03 μm/year, P<sub>FDR</sub>= 0.002). Further, high total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and with thinning of the outer nuclear layer over the study period.</p><p><strong>Conclusion: </strong>These results highlight the importance of RPE-BM complex thickening in the pathophysiological sequence of AMD. Further longitudinal studies are needed, in particular to determine the value of RPE-BM thickening and PSL thinning measured using SD-OCT for the clinical follow-up of AMD patients.</p>","PeriodicalId":19533,"journal":{"name":"Ophthalmology","volume":" ","pages":""},"PeriodicalIF":13.1000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroretinal and RPE changes and susceptibility to Age-Related Macular Degeneration: insights from the longitudinal Alienor Study.\",\"authors\":\"Petra P Larsen, Marie-Noëlle Delyfer, Cédric Schweitzer, Jean-François Korobelnik, Cécile Delcourt\",\"doi\":\"10.1016/j.ophtha.2025.01.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>We assessed the associations of macular layer thicknesses, measured using spectral-domain OCT (SD-OCT), with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS).</p><p><strong>Design: </strong>Population-based cohort study PARTICIPANTS: 653 participants of the Alienor study, with biennial eye imaging from 2009 to 2024.</p><p><strong>Methods: </strong>Macular layer thicknesses of eight distinct layers and three compound layers were automatically segmented based on SD-OCT imaging of the macula. Total and pathway specific PRS were calculated from previous AMD genome-wide association studies summary statistics. Associations of macular layer thicknesses with incident intermediate and advanced AMD were analyzed using time-dependent Cox proportional hazards models. Associations of macular layer thicknesses with PRS were assessed using linear mixed models.</p><p><strong>Main outcome measures: </strong>Incident intermediate and advanced AMD based on fundus colour photographs and SD-OCT.</p><p><strong>Results: </strong>Mean age at first OCT examination of the 653 participants was 82.2 ± 4.2 years and 61.3 % were women. In multivariate adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE) - Bruch's Membrane (BM) complex in the 1 mm central circle (Hazard ratio (HR)= 1.13 for 1 μm increase; P<sub>FDR</sub>= 8.08 x 10<sup>-4</sup>). Incident advanced AMD was associated with thicker RPE-BM complex in both the central circle (HR= 1.09; P<sub>FDR</sub>= 0.005) and the inner circle (1 mm - 3 mm) (HR= 1.28; P<sub>FDR</sub>= 1.61 x 10<sup>-5</sup>). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (ß= 0.06 μm/year for 1 standard deviation increase, P<sub>FDR</sub>= 1.61 x 10<sup>-10</sup>), high complement pathway PRS (ß= 0.04 μm/year, P<sub>FDR</sub>=3.23 x 10<sup>-5</sup>), high lipid pathway PRS (ß= 0.03 μm/year, P<sub>FDR</sub>= 3.74 x 10<sup>-4</sup>) and ARMS2 (ß= 0.03 μm/year, P<sub>FDR</sub>= 0.002). Further, high total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and with thinning of the outer nuclear layer over the study period.</p><p><strong>Conclusion: </strong>These results highlight the importance of RPE-BM complex thickening in the pathophysiological sequence of AMD. Further longitudinal studies are needed, in particular to determine the value of RPE-BM thickening and PSL thinning measured using SD-OCT for the clinical follow-up of AMD patients.</p>\",\"PeriodicalId\":19533,\"journal\":{\"name\":\"Ophthalmology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":13.1000,\"publicationDate\":\"2025-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ophtha.2025.01.002\",\"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":"Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ophtha.2025.01.002","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Neuroretinal and RPE changes and susceptibility to Age-Related Macular Degeneration: insights from the longitudinal Alienor Study.
Purpose: We assessed the associations of macular layer thicknesses, measured using spectral-domain OCT (SD-OCT), with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS).
Design: Population-based cohort study PARTICIPANTS: 653 participants of the Alienor study, with biennial eye imaging from 2009 to 2024.
Methods: Macular layer thicknesses of eight distinct layers and three compound layers were automatically segmented based on SD-OCT imaging of the macula. Total and pathway specific PRS were calculated from previous AMD genome-wide association studies summary statistics. Associations of macular layer thicknesses with incident intermediate and advanced AMD were analyzed using time-dependent Cox proportional hazards models. Associations of macular layer thicknesses with PRS were assessed using linear mixed models.
Main outcome measures: Incident intermediate and advanced AMD based on fundus colour photographs and SD-OCT.
Results: Mean age at first OCT examination of the 653 participants was 82.2 ± 4.2 years and 61.3 % were women. In multivariate adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE) - Bruch's Membrane (BM) complex in the 1 mm central circle (Hazard ratio (HR)= 1.13 for 1 μm increase; PFDR= 8.08 x 10-4). Incident advanced AMD was associated with thicker RPE-BM complex in both the central circle (HR= 1.09; PFDR= 0.005) and the inner circle (1 mm - 3 mm) (HR= 1.28; PFDR= 1.61 x 10-5). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (ß= 0.06 μm/year for 1 standard deviation increase, PFDR= 1.61 x 10-10), high complement pathway PRS (ß= 0.04 μm/year, PFDR=3.23 x 10-5), high lipid pathway PRS (ß= 0.03 μm/year, PFDR= 3.74 x 10-4) and ARMS2 (ß= 0.03 μm/year, PFDR= 0.002). Further, high total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and with thinning of the outer nuclear layer over the study period.
Conclusion: These results highlight the importance of RPE-BM complex thickening in the pathophysiological sequence of AMD. Further longitudinal studies are needed, in particular to determine the value of RPE-BM thickening and PSL thinning measured using SD-OCT for the clinical follow-up of AMD patients.
期刊介绍：
The journal Ophthalmology, from the American Academy of Ophthalmology, contributes to society by publishing research in clinical and basic science related to vision.It upholds excellence through unbiased peer-review, fostering innovation, promoting discovery, and encouraging lifelong learning.
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