Quantifying Effects of Diet and Lifestyle Changes on Progression to Advanced Age Related Macular Degeneration in High Genetic Risk Individuals.

Abstract

We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AAMD) to address concerns of family members of affected patients. Prospective, longitudinal analysis. Eyes with early or intermediate age-related macular degeneration (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. 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), dietary caloric intake, and consumption of 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 of AMD. Progression to AAMD and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years of follow-up. 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 with an ideal health-promoting profile (HR, 3.3; 95% confidence interval [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 with NV. Estimated PARs suggested that adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers. Unhealthy behaviors increased incidence of AAMD by 3- to 5-fold among a highly genetically susceptible population, and 56% to 60% of AAMD incidence was due 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 populations at high risk of progression, such as patients with a high GRS, to reduce progression from early or intermediate AMD to advanced vision-threatening stages. Clinical management of patients, including those with a strong family history of AMD, should incorporate education on healthy lifestyle choices. Proprietary or commercial disclosure may be found after the references.