Smoking Hikes Risk of Age-Related Macular Degeneration

SIDNEY, Australia, Aug. 14 -- Age-related macular degeneration is four times more likely to affect current smokers than those who never smoked, found researchers here.

Current smokers had a nearly four-fold higher risk of the serious late, but not early, macular degeneration compared with those who had never smoked, the researchers said.

The risk also held for past smokers who were three times likelier to have geographic atrophy, Jie Jin Wang, M.Med., Ph.D., of the University of Sydney here, and colleagues, reported in the July issue of the Archives of Ophthalmology.

Late age-related macular degeneration, the more severe form of the eye disorder with the poorest prognosis, is thought to share risk factors with cardiovascular disease. Although there was a suggestion of a causal relationship between lipid levels and the eye disease, the interactions were not statistically significant, the researchers reported.

The findings emerged from a prospective study of 2,454 Australians, ages 49 and older at baseline (1992 through 1993), with a mean age of 64.4. Of the participants 57.6% were women.

Participants were examined five years or 10 years later, or both. Retinal photographs were used to assess macular degeneration, while smoking status was recorded at each interview. Body mass index and blood pressure were also measured.

After controlling for age, sex, and other factors, current smokers had a 3.9 times relative risk (95% confidence interval, 1.7-8.8), on average five years earlier than never smokers.

Past smokers had 3.4 relative risk of geographic atrophy (CI, 1.2-9.7), suggesting some benefit from smoking cessation and supporting a likely causal effect between smoking and macular degeneration, the researchers said.

The effect of past smoking was not evident at five years, the researchers said, but appeared after 10 years, with the risk persisting above that of never-smokers for a considerable time after quitting smoking.

Past smokers were divided above and below the median of 17 years for smoking cessation. The risk of late age-related macular degeneration was 1.9 (CI, 0.8-4.4) for those who quit fewer than 17 years earlier, and 1.2 (CI 0.6-2.7) for those with 17 or more years smoke-free.

Combined exposure to current smoking and the lowest level of HDLs, the highest ratio for total cholesterol to HDL cholesterol, or low fish consumption was associated with a higher risk of the eye disease than the effect of any risk factor alone. However, these interactions were not statistically significant, the researchers said.

Data from other studies have not shown a consistent association between lipid levels and age-related macular degeneration. The present findings, the investigators said, should therefore be interpreted with caution, as chance findings cannot be excluded.

A biological model involving atherosclerosis could explain the joint effects of smoking and lipid levels on risk. For example, it has been postulated that lipid accumulation in the sclera and the Bruch's membrane increases choroidal vascular resistance, causing leakage and deposition of proteins and lipids in the membrane.

Animal models support a role for cholesterol and the possibility of joint effects in the pathogenesis of macular degeneration, the researchers said.

Furthermore, they added, high levels of polyunsaturated fatty acids in the retina support the biological plausibility of a protective effect from fatty acids derived from fish intake.

The researchers wrote that this is only the second (after the Beaver Dam Eye Study) prospective population-based study to assess the long-term association between baseline smoking and age-related macular degeneration. A strength of the study, they wrote, included its long follow-up, and detailed side-by-side comparison of the eye-examination photographs.

An important source of bias in this study was the loss to follow-up of about 25% of the survivors. Those alive but lost to follow-up were more likely to be current smokers at baseline, leading to an underestimation of the relationship between current smoking and macular degeneration.

Alternatively, smokers diagnosed with macular degeneration may have been more likely to attend follow-up than smokers without vision problems, leading to an apparent association between smoking and the vision disorder when none was really present.

These findings add evidence to a possible causal relationship between smoking and the long-term risk of late, but not early, age-related macular degeneration, the researchers wrote.

In addition, these results suggest a possibly greater joint effect in persons with low HDLs, a high ratio of total cholesterol to HDLs, and low fish consumption.

"This supports speculation that macular degeneration is a condition with multiple etiologic factors, and such joint effects contributing to the pathogenesis of macular degeneration could mirror the pathogenesis of cardiovascular disease," Dr. Wang concluded.