Tackling the Coming AMD Epidemic

Although its incidence has declined in younger generations, overall age-related macular degeneration (AMD) numbers are rising rapidly due to global population ageing. Already the third leading cause of blindness, AMD is predicted to affect about 288 million patients worldwide by 2040, up from about 196 million in 2020. 

So, what can the global eye care community do, given it is already beset by labour and other resource shortages? “Prevention, prevention, prevention is really important,” Emily Y Chew MD stressed in her ARVO Proctor Medal Lecture.

Harnessing the knowledge gained from research such as the Age-Related Eye Disease Studies 1 and 2 (AREDS and AREDS2) and supplementing it with new research into the causes and mechanisms of AMD could help expand prevention beyond the secondary role of adding supplements for patients already diagnosed with intermediate disease. Dr Chew suggested catching and discouraging AMD before it appears or progresses will help relieve the disproportionate burden it creates in later stages for patients, practitioners, and health systems as well.

The role of supplements

Conducted from 1991 through 2001 with follow-up through 2005, AREDS is a landmark in AMD prevention. It examined the impact on AMD of taking daily doses of 500 mg vitamin C, 400 IU vitamin E, 2 mg cupric oxide, 80 mg zinc, and 15 mg beta-carotene.

“Much to our surprise, we found supplements can reduce the risk of AMD progression from intermediate to late disease by as much as 25% in 5 years,” Dr Chew said.

A study extension found the effect lasted at least 10 years, and a 2023 Cochrane review of existing studies that randomised to supplements or no supplements showed supplements reduced progression to late AMD, with neovascular disease risk declining most.

However, beta-carotene increases the risk of developing lung cancer in smokers and former smokers, nearly doubling it in one study. Begun in 2006, AREDS2 found that substituting the carotenoids lutein 10 mg and zeaxanthin 2 mg for beta-carotene reduced the risk of progression to late AMD by about 10% over 10 years compared with the beta-carotene, without raising cancer or other health risks, Dr Chew said. Therefore, smokers and non-smokers are advised to take AREDS2 rather than AREDS supplements. Adding omega-3 fatty acids was found to have no bearing on AMD progression.

New post-hoc data analysis by the US National Eye Institute suggests that in about two-thirds of patients with geographic atrophy, it does not start in the centre of the retina, so it doesn’t have as much impact. Adding AREDS or AREDS2 supplements reduced the risk of central progression by about 36%. “That’s pretty significant,” Dr Chew said. Further investigation is needed to better understand this finding, she added.

Food as medicine

Dietary questionnaires were also included in AREDS and AREDS2, Dr Chew noted. Data from these and other research suggest that eating fish, greens, and other elements of the Mediterranean diet may cut AMD progression by 25–40%, or even prevent it from developing in the first place. For example, patients who reported not eating any greens on AREDS2 had about a 25% greater chance of AMD progression. “Clearly, it has an impact,” Dr Chew said.

Similarly, the Mediterranean diet, which is high in plant-based oils and includes very little red meat or dairy fat, has been shown to cut cardiovascular disease risk by about 30% and slow AMD progression. An analysis of nine diet elements found fish to be especially protective, Dr Chew said. Those who reported eating fish twice a week had about a 30% reduction in risk of progression to late AMD, including geographic atrophy and neovascular disease. For patients with no or early AMD, a Mediterranean diet reduces the risk of developing large drusen—a sign of intermediate disease—by about 25%. “Food really is medicine,” Dr Chew said. “It’s never too late to start the Mediterranean diet.”

A way forward

Better evidence of the preventive effects of treatment and diet, as well as the natural history of AMD and the mechanisms that drive or slow its progression, are needed to expand treatment, Dr Chew said. Animal studies are currently underway to better characterise the effects of the antioxidants on fatty acids in the blood and retina, genetic and metabolic factors that drive AMD occurrence and progression, and how AREDS supplements or other treatments might affect those mechanisms. The effects of the Mediterranean diet are also being studied for a better understanding of how they affect fatty acid signalling, and how this may influence AMD progression. Such research could reveal new treatment targets for drugs and other treatments.

Analysis of blood samples collected during AREDS and AREDS2 may help find genomic, metabolomic, and proteomic markers of AMD risk and progression, Dr Chew added. Developing AI programs that can analyse OCT and other diagnostic images to detect AMD earlier and better track its progression will also help alleviate eye care professional shortages and growing AMD workloads. There is even potential for an AREDS3 investigating prevention and early progression risk reduction, which will also reduce AMD burdens.

“Prevention is indeed very important,” she concluded.

Dr Chew presented the Proctor Medal Lecture at ARVO 2024 in Seattle, US.

Emily Y Chew MD, FARVO is director of the Division of Epidemiology and Clinical Applications, at the US’s National Eye Institute, the National Institutes of Health (NIH), and is an NIH distinguished investigator in Bethesda, Maryland, US. Among other research, she chairs the Age-Related Eye Disease Study 2 (AREDS2) and the eye study of the Actions to Control Cardiovascular Risk in Diabetes (ACCORD) Trial. echew@nei.nih.gov