Can You Eat Away the Risk for Blindness?

Medscape

26-05-2025

Many clinicians wonder if their advice about smoking cessation, diet, and exercise has much effect on patients. But people with family histories of age-related macular degeneration (AMD) may be more receptive than others.
Given the dearth of effective treatments once patients have reached the late stage of the disease, they may be motivated by hearing to lifestyle changes early in the course of the condition may help preserve their vision.
Paul Bernstein, MD, PhD
'When I first started in this field 30 years ago, there was really not much we could do for the patients,' said Paul Bernstein, MD, PhD, a professor of ophthalmology and ocular science at the Moran Eye Center at the University of Utah in Salt Lake City. Intravitreal injection therapy with anti-vascular endothelial growth factor (VEGF) agents has made a dramatic difference in the care of the wet form of advanced AMD, or choroidal neovascularization (CNV). CNV results from abnormal growth of blood vessels in the back of the eye and accounts for most cases of blindness from AMD.
But 80% of patients with AMD suffer from the dry form of the condition, or geographical atrophy, which is characterized by enlarging areas of photoreceptor and retinal pigment epithelium atrophy. Two recently-approved drugs for dry AMDinhibit steps in the complement pathway and slower the growth of atrophic lesions but do not prevent loss of vision.
AMD is to blame for nearly half of the cases of blindness in people older than 40 years. In 2019, an estimated 20 million people older than 40 years in the United States, or about 12.4% of the population, had AMD, of whom 1.5 million had late stages of the condition, when vision loss typically occurs.
The Role of Nutrition
Age is the biggest nonmodifiable risk factor for AMD, while genetics accounts for 71% of the risk of developing the disorder.
Even so, experts say patients need to know that certain behaviors can increase — or reduce — their odds both of developing AMD and slowing its progression.
Smoking has long been recognized as an important contributor to the risk for AMD, with a two- to three-fold risk for advanced AMD in current smokers compared with nonsmokers. But 20 years after quitting smoking, the risk returns to that of a nonsmoker.
Exercise can help, too. A 2017 meta-analysis of studies examining the relationship between exercise and AMD suggested that regular physical activity could reduce the development of late disease by 40%.
Some of the strongest data support the role of nutrition in preventing AMD. 'In terms of things that people can do to lower their risk beyond smoking, nutrition is really kind of the biggest thing that people can do,' Bernstein said.
The macula lutea derives its name from the Latin for 'yellow spot.' To Bernstein, that's a clue: 'Lutein and zeaxanthin that we get from our diet come from green leafy vegetables, and orange and yellow fruits and vegetables. Both these compounds are very actively concentrated in the macula of the eye,' he said. 'When the eye goes out of its way to accumulate a nutrient in the retina, that nutrient is likely to be important for the functioning' of the organ.
Bernstein's theory has been buttressed by two randomized trials of vitamin supplementation. The Age-Related Eye Disease Study (AREDS1), which ran from 1992-2001, demonstrated patients with intermediate AMD treated with vitamins C, E, and beta-carotene, along with zinc, showed a 25% decrease in the risk of progressing to late AMD after 6 years of follow-up.
But given concerns about an increase in lung cancer in patients with a history of smoking who received high doses of beta-carotenoids, the AREDS2 trial replaced the beta-carotene component with lutein and zeaxanthin. That substitution removed the risk for lung cancer while still protecting against progression from intermediate to advanced AMD, and the AREDS2 vitamins have become the standard of care for patients with intermediate forms of the disease.
But can preventive efforts be helpful before AMD progresses to its intermediate stage?
Tiarnán Keenan, MD, PhD
Tiarnán Keenan, MD, PhD, of the National Eye Institute, has used data from AREDS1 and 2 to explore the role of diet in patients already taking supplements.
'The Mediterranean diet, the anti-inflammatory diet pattern, or low glycemic diets are all really strongly associated with reduced risk of disease,' Keenan said. His research has found adherence to a Mediterranean diet in particular can reduce the risk for progression from early to intermediate AMD by 21%, while also lowering the risk for the dry form of late AMD by nearly 30%.
The main protective drivers were consuming fish at least twice per week; fruits twice per day; and at least 200 g per day of vegetables. The consumption of six to seven servings of red meat a week for women and nine or more servings a week for men was found to be harmful.
Keenan and his colleagues from the AREDS/AREDS2 Research Groups were able to control the use of dietary supplements and a history of smoking, meaning the decreases in risk associated with eating fish and vegetables occurred in addition to the lower risks seen with taking vitamins. 'The answer comes up very clearly that you get additional benefits,' he said.
Keenan has encountered patients who don't think they need to change their diets because they already are taking ALREDS2 vitamins, or who have made dietary changes and do not want to take supplements.
'But that's not true. Dietary changes and supplements are complementary,' he said. Keenan told them supplements are mostly helpful in decreasing the risk of developing wet AMD, whereas eating fish, fruits, and vegetables can prevent progression to advanced disease from geographical atrophy.
For patients who have a family history of AMD, diet can largely overcome their genetic risk. Participants in the Coimbra Eye Study underwent ophthalmological exams, completed dietary histories, and received genetic testing for variants associated with AMD. Adherence to a Mediterranean diet was associated with a lower risk for the condition overall, but the most significant findings — a 60% reduction in risk — was observed in those with the greatest genetic predisposition.
Screening Gaps
The American Academy of Ophthalmology (AAO) recommends a formal eye exam, which includes a dilated slit lamp exam, starting at age 40 years even in people without any loss of visual acuity. Because the risk for cataracts, glaucoma, and AMD rises with age, patients should visit an ophthalmologist or optometrist more frequently as they age (Table).
But the National Health Interview Survey showed that in 2017 only 40% of patients at high risk for vision loss — people with self-reported diabetes, a self-reported history of vision and eye problems, or who are age 65 years or older — had the appropriate exam in the last year.
Steven Bailey, MD
Steven Bailey, MD, a professor of ophthalmology at the Casey Eye Institute at Oregon Health and Science University in Portland, Oregon, helped write the AAO's most recent practice guidelines for AMD. 'In general, evaluations for age-related macular degeneration are recommended starting at 50,' he said, as it is uncommon to see AMD before age 50 years even in individuals with a family history.
Bailey also said patients with a family history of AMD presenting before age 50 years should be referred earlier as their family member's eye disease may not have been AMD, but something else, such as a macular dystrophy.
Primary care clinicians also can educate patients with a family history about the early warning signs of AMD, such as difficulty performing tasks under low light conditions, visual distortion, or symptoms of blurred vison or difficulty focusing, which are red flags indicating need for a referral to an eye specialist.
Although the guidelines do not recommend AREDS2 vitamins for patients with a family history of AMD or those with early disease — largely because of lack of efficacy at that stage — Bailey said primary care clinicians can support their patients by encouraging lifestyle changes.
'The low hanging fruit is healthy diet and active lifestyle, and those overlap with so many other benefits,' he said. 'The thought of vision changes can help patients decide, 'This is actually worth it.''
For patients who have progressed to intermediate AMD, Bailey stressed the importance of making sure patients are taking supplements and that they receive regular dilated slit lamp exams. Some people start vitamins and take them for years without seeking additional follow-up from an ophthalmologist.
Patients also should be reminded about the importance of tools such as the Amsler grid or electronic home monitoring for detection of warning signs for progression of disease. An Amsler grid, which Bailey prefers for home use, is unlikely to detect changes in someone with early AMD.
'Regular Amsler grid testing would probably be most important for someone who has intermediate AMD or more advanced AMD in one eye,' as it can identify early changes in the good eye, he said. 'If you develop wet macular degeneration, we want to catch that as soon as we can, because the treatment is very effective at halting progression,' he added.
Patients undergoing monthly treatments with anti-VEGF drugs should be reminded of the importance of adhering to a regular regimen. 'It's a treatment, not a cure,' Bailey said. 'If you withhold that treatment, sometimes they can lose ground that we can't regain.'
But helping patients avoid late AM — and the need for intravitreal injections — should be the goal. Bernstein said he has seen some people with early AMD who have already developed visual problems. He often finds they have low levels of macular pigment related to poor diet or some type of malabsorption syndrome. He starts them on supplements and looks forward to seeing them at follow-up. 'I have patients come back, and they're seeing better,' he said. 'A lot of their symptoms better.'
Bernstein reported research support from Kemin, Bausch + Lomb, and Heidelberg Engineering. He also has been a speaker for DSM-Firmenich and OmniActive.
Bailey and Keenan reported no conflicts of interest.