JAMA Ophthalmology Journal Club Slides: Generational Differences in the 5-Year Incidence of Age-Related Macular Degeneration Cruickshanks KJ, Nondahl DM, Johnson LJ, et al. Generational differences in the 5-year incidence of age-related macular degeneration. JAMA Ophthalmol. Published online November 16, 2017. doi:10.1001/jamaophthalmol.2017.5001

Introduction Importance: Rapid declines in the incidence of noncommunicable diseases are strong evidence they are partially preventable. The Beaver Dam Eye Study (BDES) studied declining age-related macular degeneration (AMD) by birth year (1903 to 1942). It is not known if the declining risk extends to the Baby Boom generation (born 1946-1964) or later generations. The Baby Boom generation are turning 65 years of age at the rate of 10 000 individuals per day, so these data are important to plan for eye health care needs in the 21st century. Objective: To determine whether the 5-year risk of AMD declined by generation and to identify factors that contributed to improvement in risk.

Methods Study Design, Setting, and Participants: Longitudinal cohort studies: Population-based BDES included residents of the city and town of Beaver Dam, WI, aged 43 to 84 years in 1987 to 1988. Participants were examined from 1988 to 1990 and from 1993 to 1995. The Beaver Dam Offspring Study (BOSS) included adult children, aged 21 to 84 years, of the BDES participants seen for the ancillary study (Epidemiology of Hearing Loss Study) from 2005 to 2008 and from 2010 to 2013. N=4819 at risk for AMD. Main Outcomes and Measures Five-year incidence of AMD as measured by fundus images graded using the Wisconsin Age-related Maculopathy Grading System.

Methods Limitations: Cohorts predominately consisted of non-Hispanic white individuals, and known racial/ethnic differences in risk exist, with higher risk for non-Hispanic white individuals. The offspring were not geographically constrained; risk for AMD varies by geographic location among non-Hispanic white individuals. Changes in imaging methods (BDES, film-based; BOSS, digital); systems yield comparable results and decline began before change.

Results Age- and Sex-Adjusted 5-Year Incidence of AMD by Generation The mean age was 54 years, and 43.9% of participants were men. The overall incidence of AMD was 4.2%

Generation Effect on 5-year Incidence of AMD Results Generation Effect on 5-year Incidence of AMD Adjusting for age and sex, each generation was more than 65% less likely to develop AMD than the previous generation. Adjusting for potential AMD risk factors only slightly attenuated this association.

Results Estimated 5-Year Incidence of AMD by Generation and Age The incidence of AMD was lower among the Baby Boom generation than the Silent generation, which was lower than the Greatest generation. Generation X is young, but the trend appears to continue.

Comment The 5-yr incidence of AMD was 60% lower for each successive generation (in the multivariable model). This dramatic decline in the incidence across 3 generations suggests environmental and/or behavioral factors and are important risk factors in the cause of AMD because rapid genetic changes are unlikely. The results of this study are consistent with previously reported decline in risk for participants born before 1943. This study extends the findings to people born during the Baby Boom and represents the largest cohort of aging adults to date. Results are consistent with reports of declining AMD prevalence in Europe and with declines in incidence of cardiovascular disease, dementia, and cancers.

Comment The change was not attributable to changes in educational attainment, smoking, exercise, high-sensitivity C-reactive protein, non–high-density lipoprotein cholesterol, or use of nonsteroidal anti-inflammatory drugs, statins, or multivitamins. It is difficult to accurately estimate the number of adults needing treatment for AMD by the middle of the 20th century. The number of older adults will increase, but AMD may be associated with mortality and previous gains in life expectancy may not continue (obesity and diabetes). These results suggest the current epidemic of AMD may wane as the Baby Boom generation ages. Future research may identify new opportunities for primary prevention.

Conflict of Interest Disclosures Contact Information If you have questions, please contact the corresponding author: Karen J. Cruickshanks, PhD, Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin–Madison, 610 Walnut St, 1038 WARF, Madison, WI 53726 (kjcruick@wisc.edu). Funding/Support This study was supported by grant R01AG021917 from the National Institute on Aging and the National Eye Institute (Dr Cruickshanks), grant U10EY06594 from the National Eye Institute (Drs B. E. Klein and R. Klein), and an unrestricted grant from Research to Prevent Blindness. Conflict of Interest Disclosures All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.