{"title":"Quantifying Effects Of Lifestyle Changes On Progression To Advanced Age-Related Macular Degeneration In High Genetic Risk Individuals.","authors":"Johanna M Seddon, Dikha De, Bernard Rosner","doi":"10.1016/j.ophtha.2025.09.030","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.</p><p><strong>Design: </strong>Prospective longitudinal analysis PARTICIPANTS: Eyes with early/intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score (GRS) for progression, adjusted for age, race and sex.</p><p><strong>Methods: </strong>Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.</p><p><strong>Main outcome: </strong>Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years follow-up.</p><p><strong>Results: </strong>Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a high risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.</p><p><strong>Conclusion: </strong>Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to modifiable factors: smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. Results underscore the importance of lifestyle interventions in high genetic risk populations, such as relatives of affected patients and/or patients with a high GRS, to reduce progression from early/intermediate AMD to advanced vision-threatening stages.</p>","PeriodicalId":19533,"journal":{"name":"Ophthalmology","volume":" ","pages":""},"PeriodicalIF":9.5000,"publicationDate":"2025-10-09","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.2025.09.030","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.
Design: Prospective longitudinal analysis PARTICIPANTS: Eyes with early/intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score (GRS) for progression, adjusted for age, race and sex.
Methods: Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.
Main outcome: Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years follow-up.
Results: Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a high risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.
Conclusion: Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to modifiable factors: smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. Results underscore the importance of lifestyle interventions in high genetic risk populations, such as relatives of affected patients and/or patients with a high GRS, to reduce progression from early/intermediate AMD to advanced vision-threatening stages.
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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