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Sunlight and the 5-Year Incidence of Early Age-Related Maculopathy
The Beaver Dam Eye Study
Arch Ophthalmol. 2001;119:246-250.
ABSTRACT
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Objective To investigate the relation of sunlight exposure and indicators of sun
sensitivity with the 5-year incidence of early age-related maculopathy (ARM).
Design Longitudinal, population-based study. Participants (aged 43-86 years
at baseline) in the Beaver Dam Eye Study were reexamined from 1993 to 1995,
5 years after the baseline examination. Questionnaire data about sunlight
exposure and sun sensitivity were obtained at baseline. Additional information
about earlier life patterns of exposure was ascertained at follow-up. Stereoscopic
color fundus photographs were graded to determine the presence of ARM at the
5-year follow-up in eyes free from signs of early ARM at the baseline examination.
Results Leisure time spent outdoors while persons were teenagers (aged 13-19
years) and in their 30s (aged 30-39 years) was significantly associated with
the risk of early ARM (odds ratio, 2.09; 95% confidence interval, 1.19-3.65).
There was a slight, but nonsignificant, protective effect associated with
use of hats and sunglasses while persons were teenagers and in their 30s (odds
ratio, 0.72; 95% confidence interval, 0.50-1.03). People with red or blond
hair were slightly more likely to develop early ARM than people with darker
hair (odds ratio, 1.33; 95% confidence interval, 0.97-1.83). There were no
associations between estimated ambient UV-B exposure or markers of sun sensitivity
and the incidence of early ARM.
Conclusion Exposure to sunlight may be associated with the development of early
ARM.
INTRODUCTION
IDENTIFYING primary prevention strategies for age-related maculopathy
(ARM) is an important goal for epidemiologic research as there are no effective
sight-saving therapies for most patients with this vision-threatening disease.
There is growing evidence that genes1-3
and environmental factors4-9
(including lifestyle factors such as smoking and other chronic diseases such
as atherosclerosis) may be important in the multifactorial etiology of ARM.
Thus far, however, much of the epidemiologic evidence for environmental influences
has been from cross-sectional cohort and case-control studies. Ocular exposure
to sunlight (blue light) has been associated with ARM in a cohort of men with
high levels of sunlight exposure during work (Maryland watermen).5 In the Beaver Dam Eye Study,9
people who reported spending most of their leisure time outdoors in the summer
were more likely to have late maculopathy (odds ratio [OR], 2.19; 95% confidence
interval, 1.12-4.25). Longitudinal studies are needed to investigate this
association and strengthen the evidence for a causal relation. The present
study describes the relations between reported sunlight exposure and the 5-year
incidence of early ARM in the Beaver Dam cohort.
PARTICIPANTS AND METHODS
The Beaver Dam Eye Study is a population-based study of age-related
ocular disorders. Details of the methods have been published previously.10-14
A private census was conducted to identify all persons between the ages of
43 and 84 years who were residents of the city or township of Beaver Dam,
Wis, from 1987 to 1988.10 Of the 5925 eligible
persons identified, 4926 (83.1%) were examined during the baseline examination
(March 1, 1988, through September 15, 1990), 225 (3.8%) died before examination,
91 (1.5%) had moved out of the area, 23 (0.4%) could not be located, 269 (4.5%)
completed a questionnaire only, and 391 (6.6%) refused to participate (percentages
may not total 100 because of rounding). Nonparticipants were older than participants.
From 1993 to 1995, a 5-year follow-up examination of the cohort was
conducted using the same methods as used in the first examination.12, 14 Of the 4541 surviving baseline participants,
3684 (81.1%) participated in the follow-up examination, 423 (9.3%) refused
to participate, 259 (5.7%) completed a questionnaire only, 171 (3.8%) died
before examination, and 4 (0.1%) could not be located. Surviving participants
who were not reexamined in the follow-up eye study (n = 686) were older, had
less education, had a lower income, had poorer visual acuity, were more likely
to have a history of cardiovascular disease, and smoked more than participants
in the 5-year follow-up examination.14 After
adjusting for age and sex, there were no significant differences between nonparticipants
and participants in baseline sunlight exposure variables (data not shown).
During each examination, a medical history questionnaire was administered.
Participants were asked about residential history; time spent outdoors during
leisure and work; and use of eyeglasses for distance vision, hats with brims,
and sunglasses.9 At the 5-year follow-up examination,
additional questions were added to ascertain sunlight-related behaviors during
their teenage years (age 13-19 years) and their 30s (age 30-39 years).
An index of ambient UV-B exposure was constructed from the baseline
residential history, weighting time spent outside of Wisconsin by the ratio
of the total ambient UV-B light present in that area to the level for 1 year
in Wisconsin (Wisconsin sun year).9 The average
annual ambient UV-B exposure was calculated by dividing the cumulative ambient
exposure by age. Most participants had spent most of their lives in Wisconsin,
resulting in a highly skewed distribution of average annual exposure, so this
variable was used to categorize participants into 2 levels of exposure. Between
the baseline and the follow-up examinations, some people had migrated out
of Beaver Dam to other regions with higher UV-B levels or had spent vacation
time in areas with higher UV-B levels. Therefore, an additional index was
created using the same weighting procedure as used for the historical data,
to capture additional exposure during follow-up to areas with higher UV-B
levels than Wisconsin.
The amounts of time participants reported using hats and sunglasses
at the baseline examination were combined in a weighted fashion into levels
of increasing protection from UV-B light (none, low, moderate, and high).
A high protection level was defined as wearing hats,
sunglasses, or both at least half of the time spent outdoors.9
Indexes of sunlight exposure and use of hats and sunglasses while aged
13 to 19 years and 30 to 39 years were created. Participants who reported
being outside in summer for 5 or more hours per day in both age periods were
considered to have high exposure, those who reported being outside less than
2 hours per day in both age periods were considered to have low exposure,
and those with 2 to 5 hours of exposure per day or exposure that varied by
age period were considered to have intermediate exposure. Similarly, participants
who reported they wore hats or sunglasses at least half the time while outside
in the summer in both age periods were considered to have used them often
and have a "high" level of protection. People who reported "rarely" using
either hats or sunglasses in both age periods were considered to have a low
level of protection. Participants who reported variable patterns of use were
considered to have intermediate levels of protection.
Age-related maculopathy was assessed by grading stereoscopic 30°
color fundus photographs taken at the baseline and 5-year follow-up examinations
using the Wisconsin Age-Related Maculopathy Grading System.13-15
Stereoscopic photographs were taken centered on the disc (Diabetic Retinopathy
Study standard field 1) and macula (Diabetic Retinopathy Study standard field
2), and a nonstereoscopic color fundus photograph was taken temporal to but
including the fovea of each eye.
Among eyes free from ARM at baseline, the incidence
of early ARM was defined as the presence, at follow-up, of soft indistinct
drusen or any type of drusen associated with either retinal pigment epithelial
depigmentation or increased retinal pigment. The 5-year incidence of late
ARM was low (0.9%), so this end point was excluded from further analyses.14
SAS statistical software, version 6.09 (SAS Institute Inc, Cary, NC),
was used to calculate the  2 statistic to test for overall
associations, to test for trends in proportions, and to determine logistic
regression models. Binary logistic regression models were used to examine
the relations of sun-related variables with the incidence of early ARM, controlling
for the effects of age and other covariates. Sun-related exposure variables
were also entered into logistic regression models in combinations to test
for associations while controlling for the potentially important modifying
effects of other exposure measures.
RESULTS
Overall, the incidence of early ARM was 8.2% (Table 1). The incidence was higher for older vs younger age groups.
In univariate analyses (Table 2),
the 5-year incidence of early ARM was significantly higher among those who
reported having blond or red hair than among people with brown or black hair.
The incidence of early ARM was lower among those who reported, at the time
of the baseline examination (1988-1990), usually using hats and sunglasses
while outside. A similar pattern was found for use of these protective devices
in earlier age periods. The incidence of early ARM was 6.9% for frequent users
of hats, sunglasses, or both while persons were teenagers and in their 30s
compared with 9.8% for those who rarely used either hats or sunglasses.
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Table 1. Five-Year Incidence of Early ARM by Age at Baseline and Sex:
The Beaver Dam Eye Study (1988-1990 and 1993-1995)*
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Table 2. Five-Year Incidence of Early ARM by Reported Sunlight Exposure
and Measures of Sun Sensitivity, Beaver Dam, Wis*
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The age- and sex-adjusted ORs are given in Table 3. Leisure time spent outdoors in summer while persons were
aged 13 to 19 and 30 to 39 years was significantly associated with the incidence
of early ARM. There were slight, but nonsignificant, associations (P  .05) with the use of hats and sunglasses during the same age
periods and with having blond or red hair compared with dark hair. None of
the other sunlight exposure variables or sun sensitivity variables were associated
with the incidence of early ARM. There was no association with the marker
of ambient UV-B exposure based on residential history at baseline and the
5-year incidence of early ARM. Including a measure of ambient UV-B exposure
during the 5-year follow-up period did not alter this finding (data not shown).
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Table 3. Age- and Sex-Adjusted ORs for the Associations of Sunlight
Exposure and Sun Sensitivity Variables and the 5-Year Incidence of Early ARM,
Beaver Dam, Wis (1988-1990 and 1993-1995)*
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Additional age- and sex-adjusted models testing the effects of combinations
of the sun-related variables (exposure and sensitivity) were evaluated, and
interaction terms were included as appropriate. The final model retained,
in addition to age and sex, leisure time spent outdoors in the summer while
persons were teenagers and in their 30s, use of hats and sunglasses during
those periods, and hair color (Table 4).
While the latter 2 variables were not statistically significantly associated
with the incidence of early ARM, they did modify the strength of the association
between time spent outdoors and incidence. Participants who spent 5 or more
hours per day outside during leisure time when they were aged 13 to 19 and
30 to 39 years were twice as likely to develop early ARM as those who reported
spending less than 2 hours a day outside.
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Table 4. Sunlight-Related Risk Factors for the 5-Year Incidence of
Early ARM, Beaver Dam, Wis (1988-1990 and 1993-1995)*
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Cigarette smoking has been demonstrated, in the Beaver Dam cohort, to
be associated with the incidence of ARM.6 Therefore,
an additional model was run, adding indicator variables for current and past
smoking (vs never smoking). Leisure time spent outdoors while persons were
teenagers and in their 30s remained significantly associated with the risk
of early ARM (OR, 2.09; 95% confidence interval, 1.19-3.65). Adding additional
lifestyle variables of beer drinking and vitamin use did not alter this association
(data not shown).
COMMENT
In this study, people who reported spending 5 or more hours per day
outside in the summertime during their teenage years and 30s appeared to have
a greater risk of developing early ARM as older adults than people who spent
little time outside. There was a slight attenuating effect of wearing hats
and sunglasses during these age periods. These data are consistent with the
cross-sectional epidemiologic studies5, 9
that found that extended exposure to bright light may be associated with ARM.
Animal studies16-19
also have suggested that exposure to bright sunlight can induce retinal changes.
Among humans, retinal damage has been found with sun gazing and prolonged
exposure to intense, bright light at the beach or in the desert.20
While the incidence of late ARM was too low to permit evaluating the link
with the development of the more severe, vision-threatening forms of ARM,
this is the first prospective study, to our knowledge, to find a link between
sunlight exposure and risk of early ARM.
There was no association between UV radiation exposure and early ARM
incidence in this cohort. To date, in spite of experimental studies that suggest
that the retina is susceptible to UV-B damage, there is no evidence from epidemiologic
studies of any risk, suggesting that the filtering effects of the lens provide
ample protection throughout the life course.21
Interestingly, aphakic individuals in Beaver Dam were more likely to develop
late ARM.22
There were no statistically significant associations between baseline
sunlight exposure variables and the 5-year incidence of early ARM, which may
reflect the smaller number of older adults still spending time outdoors in
summer and winter. In fact, the point estimate suggests a weak link between
time spent outside in winter at baseline and the incidence of early ARM.
The slight, but not significant, excess risk for blond- or red-haired
people may reflect their lighter pigmentation and, therefore, less protection
from the damaging effects of light, which may suggest some genetic predisposition
that clusters within certain ethnic backgrounds, or may represent a chance
finding. Vinding,23 in a cross-sectional study,
found no association between hair color and risk of late ARM.
The Blue Mountains Eye Study24 recently
reported an association between abnormal skin sensitivity to sunlight (either
increased or decreased) and ARM. We found no association between skin sensitivity
and early ARM. Reasons for this discrepancy are not clear, but may relate
to the differences in amount of exposure to sunlight in the Australian population
compared with this population, who have spent most of their lives in a northern
region of the United States, where opportunities to tan or burn are few. A
recent case-control study25 in Australia, which
measured ocular exposure to sunlight by retrospective questionnaire, found
that among poor tanners, the average exposure was more than 600 hours per
year.
In our study, only retrospective information about time spent outside
during 2 earlier periods was available. Clearly, long ago habits may be poorly
and inaccurately recalled by older adults. However, the respondents were asked
to broadly classify habits, which may have lessened recall problems. The true
impact of possible misclassification bias cannot be assessed. These results
may be spurious and reflect uncontrolled confounding, as people who spend
major portions of their time outside differ in many ways from those who tend
to be indoors. Models including markers of other health habits did not alter
the association, but there may have been unmeasured confounders of this relation.
Although these data should be viewed with caution, accurate assessment of
past sunlight exposure and long-term studies with prospectively measured exposures
will remain problematic.
These results fit with a small body of epidemiologic evidence that indicates
that exposure to bright sunlight may be a risk factor for early ARM. Furthermore,
they support the idea that ARM may be partly preventable through modification
of lifestyle factors.6, 26-27
Longer follow-up times or larger cohort studies are necessary to have sufficient
power to evaluate the link with late-stage ARM, a critical step in determining
the etiologic significance of sunlight in the pathogenesis of ARM.
AUTHOR INFORMATION
Accepted for publication July 6, 2000.
This study was supported by grant EY06594 from the National Institutes
of Health, Bethesda, Md (Drs R. Klein and B. E. K. Klein); and by the Lew
R. Wasserman Award from Research to Prevent Blindness Inc, New York, NY (Dr
Cruickshanks).
Corresponding author and reprints: Karen J. Cruickshanks, PhD, Department
of Ophthalmology and Visual Sciences, University of Wisconsin, 610 N Walnut
St, Room 460, WARF Building, Madison, WI 53705-2397 (e-mail: cruickshanks{at}epi.ophth.wisc.edu).
Karen J. Cruickshanks, PhD;
Ronald Klein, MD;
Barbara E. K. Klein, MD;
David M. Nondahl, MS
From the Departments of Ophthalmology and Visual Sciences (Drs Cruickshanks,
R. Klein, and B. E. K. Klein and Mr Nondahl) and Preventive Medicine (Dr Cruickshanks),
University of Wisconsin, Madison.
REFERENCES
1. Heiba IM, Elston RC, Klein BEK, Klein R. Sibling correlations and segregation analysis of age-related maculopathy:
the Beaver Dam Eye Study. Genet Epidemiol. 1994;11:51-67. [published correction appears in Genet Epidemiol. 1994;11:571].
FULL TEXT
|
ISI
| PUBMED
2. Myers SM. A twin study on age-related macular degeneration. Trans Am Ophthalmol Soc. 1994;92:775-844.
PUBMED
3. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997;123:199-206.
ISI
| PUBMED
4. Hyman LG, Lilienfeld AM, Ferris III FL, Fine SL. Senile macular degeneration: a case-control study. Am J Epidemiol. 1983;118:213-227.
FREE FULL TEXT
5. West SK, Rosenthal FS, Bressler NM, et al. Exposure to sunlight and other risk factors for age-related macular
degeneration. Arch Ophthalmol. 1989;107:875-879.
ABSTRACT
6. Klein R, Klein BEK, Moss SE. Relation of smoking to the incidence of age-related maculopathy: the
Beaver Dam Eye Study. Am J Epidemiol. 1998;147:103-110.
FREE FULL TEXT
7. Vingerling JR, Dielemans I, Bots ML, Hofman A, Grobbee DE, de Jong PT. Age-related macular degeneration is associated with atherosclerosis:
the Rotterdam Study. Am J Epidemiol. 1995;142:404-409.
FREE FULL TEXT
8. Smith W, Mitchell P, Leeder SR, Wang JJ. Plasma fibrinogen levels, other cardiovascular risk factors, and age-related
maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol. 1998;116:583-588.
FREE FULL TEXT
9. Cruickshanks KJ, Klein R, Klein BEK. Sunlight and age-related macular degeneration: the Beaver Dam Eye Study. Arch Ophthalmol. 1993;111:514-518.
ABSTRACT
10. Linton KLP, Klein BEK, Klein R. The validity of self-reported and surrogate-reported cataract and age-related
macular degeneration in the Beaver Dam Eye Study. Am J Epidemiol. 1991;134:1438-1446.
FREE FULL TEXT
11. Klein R, Klein BEK, Linton KLP, DeMets DL. The Beaver Dam Eye Study: visual acuity. Ophthalmology. 1991;98:1310-1315.
ISI
| PUBMED
12. Klein R, Klein BEK, Lee KP. The changes in visual acuity in a population: the Beaver Dam Eye Study. Ophthalmology. 1996;103:1169-1178.
ISI
| PUBMED
13. Klein R, Klein BEK, Linton KLP. Prevalence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1992;99:933-943.
ISI
| PUBMED
14. Klein R, Klein BEK, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy:
the Beaver Dam Eye Study. Ophthalmology. 1997;104:7-21.
ISI
| PUBMED
15. Klein R, Davis MD, Magli YL, et al. The Wisconsin Age-Related Maculopathy Grading System. Ophthalmology. 1991;98:1128-1134.
ISI
| PUBMED
16. Young RW. Solar radiation and age-related macular degeneration. Surv Ophthalmol. 1988;32:252-269.
FULL TEXT
|
ISI
| PUBMED
17. Borges J, Li Z-Y, Tso MOM. Effects of repeated photic exposures on the monkey macula. Arch Ophthalmol. 1990;108:727-733.
ABSTRACT
18. Tso MO. Photic maculopathy in rhesus monkey: a light and electron microscopic
study. Invest Ophthalmol. 1973;12:17-34.
FREE FULL TEXT
19. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Guerry III D, Guerry RK. Action spectrum for retinal injury from near-ultraviolet radiation
in the aphakic monkey. Am J Ophthalmol. 1982;93:299-306.
ISI
| PUBMED
20. Ewald RA, Ritchey CL. Sun gazing as the cause of foveomacular retinitis. Am J Ophthalmol. 1970;70:491-497.
ISI
| PUBMED
21. Boettner EA, Wolter JR. Transmission of the ocular media. Invest Ophthalmol. 1962;1:776-783.
22. Klein R, Klein BEK, Jensen SC, Cruickshanks KJ. The relationship of ocular factors to the incidence and progression
of age-related maculopathy. Arch Ophthalmol. 1998;116:506-513.
FREE FULL TEXT
23. Vinding T. Pigmentation of the eye and hair in relation to age-related macular
degeneration: an epidemiological study of 1000 aged individuals. Acta Ophthalmol (Copenh). 1990;68:53-58.
24. Mitchell P, Smith W, Wang JJ. Iris color, skin sun sensitivity, and age-related maculopathy: the
Blue Mountains Eye Study. Ophthalmology. 1998;105:1359-1363.
FULL TEXT
|
ISI
| PUBMED
25. Darzins P, Mitchell P, Heller RF. Sun exposure and age-related macular degeneration: an Australian case-control
study. Ophthalmology. 1997;104:770-776.
ISI
| PUBMED
26. Seddon JM, Willett WC, Speizer FE, Hankinson SE. A prospective study of cigarette smoking and age-related macular degeneration
in women. JAMA. 1996;276:1141-1146.
ABSTRACT
27. Christen WG, Glynn RJ, Manson JE, Ajani UA, Buring JE. A prospective study of cigarette smoking and risk of age-related macular
degeneration in men. JAMA. 1996;276:1147-1151.
ABSTRACT
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