Damian McNamara

May 24, 2013

SEATTLE, Washington — Age-related macular degeneration is significantly associated with a higher risk for all-cause mortality and death related to circulatory disease, according to the nearly 10 years of follow-up to a longitudinal randomized clinical trial, conducted by researchers from the University of Illinois at Chicago.

This secondary analysis of the Age-Related Eye Disease Study (AREDS) provides a more definitive link between age-related macular degeneration and death; previous shorter-duration research yielded mixed results, Charlotte Joslin, PhD, told Medscape Medical News.

"This study had enough time to look at mortality," said Dr. Joslin. "We know the cardiovascular risks of death are higher in men than in women." We found that "death from any cause was statistically significantly higher, but more was seen in men than women."

Of the 4116 patients enrolled in AREDS (mean follow-up, 9.6 years), 1096 people with macular degeneration died.

"On a multivariate analysis, even after adjustment for possible confounders, age-related macular degeneration was still an independent predictor of increased risk for death," Dr. Joslin said during a poster presentation here at the Association for Research in Vision and Ophthalmology 2013 Annual Meeting.

Table. Hazard Ratio for Death Related to Circulatory Disease by Category of Age-Related Macular Degeneration

Patients Category 1 (None) Category 2 (Early) Category 3 (Intermediate) Category 4 (Advanced)
All 1.00 1.34 1.43 1.98
Men 1.00 1.48 1.48 2.18
Women 1.00 1.14 1.31 1.75


Patients need to be educated about their risks, study coauthor Lawrence Ulanski, MD, told Medscape Medical News. When a patient comes to your office with an eye problem, your response should be, "yes, you have an eye problem, but it's also an important marker of a systemic problem. You need to be concerned about other aspects of your health."

Dr. Ulanski noted that some patients with macular degeneration are at increased risk for stroke. He is principal investigator on a separate analysis of the AREDS population, and reported that 77 incident strokes occurred during the follow-up period.

Yes, you have an eye problem, but it's also an important marker of a systemic problem.

"When we looked at stroke...for women, it was not a significant problem, but men have a significantly increased risk," he said.

On a multivariable Cox regression analysis, men with more severe category 3 or 4 macular degeneration were at significantly greater risk for stroke than those with milder disease (P < .05). This increased risk was not seen in women, said Dr. Ulanski.

Interestingly, in the mortality study by Dr. Joslin's team, the risk for death related to circulatory disease declined over time. The strength of the association was stronger at 5 years than at 7 or 10 years. This could be because of death from other causes, Dr. Joslin explained.

In contrast, the relation between macular degeneration and the risk for all-cause mortality did not vary significantly over time.

Macular degeneration, stroke, and cardiovascular disease, including all circulatory disease, share risk factors and a similar pathogenesis, Dr. Joslin and colleagues note. They classified cause of death on the basis of hospital records and death certificates collected during AREDS and a search of the National Death Index after the study ended.

Brian Proctor, MD, from Gottlieb Memorial Hospital in Melrose Park, Illinois, who was asked by Medscape Medical News to comment on the findings, noted that the shared etiology between stroke and death related to circulatory disease includes damage to blood vessels from smoking.

"This study shows what ophthalmologists have felt in our gut for a long time," he said. "People who smoke have a faster rate of macular degeneration than nonsmokers. For that reason, we advise our patients not to smoke and to control their blood pressure."

Funding support for AREDS was provided by the National Eye Institute and the Research to Prevent Blindness organization. Dr. Joslin and Dr. Proctor have disclosed no relevant financial relationships. Dr. Ulanski reports being a consultant for Allergan.

Association for Research in Vision and Ophthalmology (ARVO) 2013 Annual Meeting: Abstracts D0090 and D0077. Presented May 5, 2013.


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