A study recently published in Ophthalmology evaluated the extent that adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AAMD).
Give me some background.
Genetic factors contribute significantly to AMD, with heritability estimates ranging from 46 to 67% in early or intermediate disease and 71% in advanced stages.
- Genetic risk is also a strong predictor of longitudinal progression from early and intermediate AMD to advanced stages.
And in terms of this research …
A previous study by the same research team found that increased consumption of foods rich in lutein-zeaxanthin and omega-3 fatty acids during the initial non-advanced AMD stages could reduce subsequent progression to higher non-advanced and AADM severity stages.
As such: The investigators sought to expand on their findings by analyzing a high genetic risk population to examine the impact of a healthy lifestyle on the progression from early or intermediate AMD to AAMD and whether it could offset the high genetic risk for progression.
Let’s talk about the study.
In this prospective longitudinal analysis, investigators collected information on lifestyle behaviors from baseline risk and food frequency questionnaires from participants aged 55-80 years with early or intermediate AMD.
Importantly: Only subjects with a high genetic risk, defined as the third tertile of polygenic risk scores (PRS)— adjusted for age, race, and sex—were included in the analysis and tracked over 5 years.
- Eyes with early or intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study (AREDS) severity scale.
Anything else?
Risk-inducing and health-promoting lifestyle profiles were defined on dichotomous categorizations of the following in never and ever smokers:
- Smoking
- Body mass index (BMI)
- Dietary caloric intake
- Green leafy vegetables and fish
Main outcome measure: Progression to AAMD and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at two consecutive visits over 5 years of follow-up.
Findings?
Among 898 eyes with high genetic risk of progression, 207 eyes progressed to AAMD (23%).
In never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting profile (hazard ratio [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, 95% CI: 2.3-11.9, P < 0.001).
Tell me more.
High-risk lifestyle profile conferred a stronger effect for patients with GA compared to those with NV AMD:
- GA: 8- to 12-fold increased risk
- NV: 2- to 3-fold increased risk
Estimated population attributable risk (PAR) suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.
- Note: PAR describes the incidence of a disease in the population that would be eliminated if the exposure were eliminated.
Expert opinion?
The study authors emphasized the “high priority of identifying people with high genetic risk who have a much higher risk of progressing to AAMD and therefore have the highest potential gain from lifestyle modifications.”
They also recommended that “eye doctors convey to patients with a strong family history of AMD that they are not inevitably destined to develop the condition.”
- Instead, they should consider educating these patients on “how lifestyle choices can lower disease risk.”
Anything else?
Recent research sheds light on the gut microbiome-retina connection to AMD which further cements the importance of diet and genetics in relation to AMD progression.
These results emphasize the importance of comprehensive motivational lifestyle counseling—such as:
- Smoking cessation
- Maintaining a healthy weight
- Avoiding high daily caloric intake
- Incorporating foods rich in lutein-zeaxanthin and omega-3 fatty acids
Limitations?
These included:
- Self-reported dietary intake at baseline
- Information about other lifestyle behaviors—physical activity, for example—was not available in the AREDS cohort
- These results may not be generalizable to other populations since participants in clinical trials are generally well motivated, more educated, and well-nourished than the general population
So what should we take away from this?
These findings suggest that unhealthy behaviors increased the incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population.
Plus: 56-60% of AAMD incidence was attributed to modifiable factors including:
- Smoking
- High BMI
- High caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids
And finally?
These 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.