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 (SD) OCT, with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRSs).</p><p><strong>Design: </strong>Population-based cohort study.</p><p><strong>Participants: </strong>A total of 653 participants from the ALIENOR study, with biennial eye imaging from 2009 through 2024.</p><p><strong>Methods: </strong>Macular layer thicknesses of 8 distinct layers were automatically segmented based on SD-OCT imaging. Total and pathway-specific PRSs 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 color 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, 61.3% of which were women. In multivariable adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE)-Bruch membrane (BM) complex in the 1-mm central circle (hazard ratio [HR], 1.13 for 1-μm increase; P = 8.08 × 10<sup>-</sup><sup>4</sup> with false discovery rate [FDR] correction). Incident advanced AMD was associated with thicker RPE-BM complex in both the central (HR, 1.09; P<sub>FDR</sub> = 0.005) and inner circle (1- to 3 mm; HR, 1.28; P<sub>FDR</sub> = 1.61 × 10<sup>-</sup><sup>5</sup>). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (β = 0.06 μm/year for 1-standard deviation increase; P<sub>FDR</sub> = 1.61 × 10<sup>-</sup><sup>10</sup>), high complement pathway PRS (β = 0.04 μm/year; P<sub>FDR</sub> = 3.23 × 10<sup>-</sup><sup>5</sup>), high lipid pathway PRS (β = 0.03 μm/year; P<sub>FDR</sub> = 3.74 × 10<sup>-</sup><sup>4</sup>), and ARMS2 (β = 0.03 μm/year, P<sub>FDR</sub> = 0.002). High total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and longitudinal thinning of the outer nuclear layer.</p><p><strong>Conclusions: </strong>These findings highlight RPE-BM complex thickening in the pathophysiologic 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 patients with AMD.</p><p><strong>Financial disclosure(s): </strong>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p>","PeriodicalId":19533,"journal":{"name":"Ophthalmology","volume":" ","pages":""},"PeriodicalIF":13.1000,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroretinal and Retinal Pigment Epithelium 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 (SD) OCT, with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRSs).</p><p><strong>Design: </strong>Population-based cohort study.</p><p><strong>Participants: </strong>A total of 653 participants from the ALIENOR study, with biennial eye imaging from 2009 through 2024.</p><p><strong>Methods: </strong>Macular layer thicknesses of 8 distinct layers were automatically segmented based on SD-OCT imaging. Total and pathway-specific PRSs 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 color 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, 61.3% of which were women. In multivariable adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE)-Bruch membrane (BM) complex in the 1-mm central circle (hazard ratio [HR], 1.13 for 1-μm increase; P = 8.08 × 10<sup>-</sup><sup>4</sup> with false discovery rate [FDR] correction). Incident advanced AMD was associated with thicker RPE-BM complex in both the central (HR, 1.09; P<sub>FDR</sub> = 0.005) and inner circle (1- to 3 mm; HR, 1.28; P<sub>FDR</sub> = 1.61 × 10<sup>-</sup><sup>5</sup>). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (β = 0.06 μm/year for 1-standard deviation increase; P<sub>FDR</sub> = 1.61 × 10<sup>-</sup><sup>10</sup>), high complement pathway PRS (β = 0.04 μm/year; P<sub>FDR</sub> = 3.23 × 10<sup>-</sup><sup>5</sup>), high lipid pathway PRS (β = 0.03 μm/year; P<sub>FDR</sub> = 3.74 × 10<sup>-</sup><sup>4</sup>), and ARMS2 (β = 0.03 μm/year, P<sub>FDR</sub> = 0.002). High total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and longitudinal thinning of the outer nuclear layer.</p><p><strong>Conclusions: </strong>These findings highlight RPE-BM complex thickening in the pathophysiologic 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 patients with AMD.</p><p><strong>Financial disclosure(s): </strong>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p>\",\"PeriodicalId\":19533,\"journal\":{\"name\":\"Ophthalmology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":13.1000,\"publicationDate\":\"2025-01-09\",\"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 Retinal Pigment Epithelium 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 (SD) OCT, with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRSs).
Design: Population-based cohort study.
Participants: A total of 653 participants from the ALIENOR study, with biennial eye imaging from 2009 through 2024.
Methods: Macular layer thicknesses of 8 distinct layers were automatically segmented based on SD-OCT imaging. Total and pathway-specific PRSs 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 color photographs and SD-OCT.
Results: Mean age at first OCT examination of the 653 participants was 82.2 ± 4.2 years, 61.3% of which were women. In multivariable adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE)-Bruch membrane (BM) complex in the 1-mm central circle (hazard ratio [HR], 1.13 for 1-μm increase; P = 8.08 × 10-4 with false discovery rate [FDR] correction). Incident advanced AMD was associated with thicker RPE-BM complex in both the central (HR, 1.09; PFDR = 0.005) and inner circle (1- to 3 mm; HR, 1.28; PFDR = 1.61 × 10-5). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (β = 0.06 μm/year for 1-standard deviation increase; PFDR = 1.61 × 10-10), high complement pathway PRS (β = 0.04 μm/year; PFDR = 3.23 × 10-5), high lipid pathway PRS (β = 0.03 μm/year; PFDR = 3.74 × 10-4), and ARMS2 (β = 0.03 μm/year, PFDR = 0.002). High total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and longitudinal thinning of the outer nuclear layer.
Conclusions: These findings highlight RPE-BM complex thickening in the pathophysiologic 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 patients with AMD.
Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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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