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Sunlight and the 10-Year Incidence of Age-Related Maculopathy
The Beaver Dam Eye Study
Sandra C. Tomany, MS;
Karen J. Cruickshanks, PhD;
Ronald Klein, MD, MPH;
Barbara E. K. Klein, MD, MPH;
Michael D. Knudtson, MS
Arch Ophthalmol. 2004;122:750-757.
ABSTRACT
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Objective To examine the association of sunlight exposure and indicators of sun sensitivity with the 10-year incidence of age-related maculopathy (ARM).
Design Population-based cohort study.
Participants We included persons aged 43 to 86 years at the baseline examination from 1988 to 1990, living in Beaver Dam, Wis, of whom 3684 persons underwent 5-year follow-up and 2764 underwent 10-year follow-up.
Methods Data on sun exposure and indicators of sun sensitivity were obtained from a standardized questionnaire administered at baseline and/or follow-up. We determined ARM status by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.
Main Outcome Measures Incidence and progression of ARM.
Results While controlling for age and sex, we found that participants exposed to the summer sun for more than 5 hours a day during their teens, in their 30s, and at the baseline examination were at a higher risk of developing increased retinal pigment (risk ratio [RR], 3.17; 95% confidence interval [CI], 1.24-8.11; P = .01) and early ARM (RR, 2.14; 95% CI, 0.99-4.61; P = .05) by 10 years than those exposed less than 2 hours per day during the same periods. In participants reporting the highest summer sun exposure levels in their teens and 30s, the use of hats and sunglasses at least half the time during the same periods was associated with a decreased risk of developing soft indistinct drusen (RR, 0.55; 95% CI, 0.33-0.90; P = .02) and retinal pigment epithelial depigmentation (RR, 0.51; 95% CI, 0.29-0.91; P = .02). Participants who experienced more than 10 severe sunburns during their youth were more likely than those who experienced 1 or no burn to develop drusen with a 250-µm diameter or larger (RR, 2.52; 95% CI, 1.29-1.71; P = .01) by the 10-year examination. No relationships were found between UV-B exposure, winter leisure time spent outdoors, skin sun sensitivity, or number of bad sunburns experienced by the time of the baseline examination and the 10-year incidence and progression of ARM or its associated lesions.
Conclusions Few significant relationships between environmental exposure to light and the 10-year incidence and progression of ARM were found in the Beaver Dam Eye Study. Consistent with results from the baseline and 5-year follow-up examinations, significant associations were found between extended exposure to the summer sun and the 10-year incidence of early ARM and increased retinal pigment. A protective effect of hat and sunglasses use by participants while in their teens and 30s against the 10-year incidence of soft indistinct drusen and retinal pigment epithelial depigmentation was also found, but only in those who reported the highest amount of sun exposure during the same periods.
INTRODUCTION
Age-related maculopathy (ARM) is the leading cause of vision loss in older Americans.1-6 The pathogenesis of the disease is poorly understood,6-7 but it is thought to be multifactorial, involving both genetic8-10 and environmental factors.11-14 With the exception of antioxidant vitamins and zinc, few sight-saving therapies are available to treat patients with this disease.15 For this reason, it is important to identify primary prevention strategies. It has been suggested that exposure to sunlight may play a role in the etiology of ARM. Previous studies examining the relationship between sunlight exposure and ARM have produced inconsistent results.16-22 At the time of the 5-year follow-up examination in the Beaver Dam Eye Study,19 persons who reported spending most of their summer leisure time outdoors during their teens and 30s were found to be at increased risk for incident early ARM (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.19-3.65). This article examines the association of sunlight exposure and measures of sun sensitivity with the 10-year incidence of early ARM in the Beaver Dam, Wis, population and further examines the relationships between these sun exposure variables and additional ARM incidence and progression outcomes.
METHODS
STUDY POPULATION
Methods to identify and describe the population have appeared previously.23-31 A private census of the population of Beaver Dam was performed from September 15, 1987, to May 4, 1988, to identify all residents in the city or township aged 43 to 84 years. Of the 5924 eligible individuals, 4926 participated in the baseline examination between March 1, 1988, and September 14, 1990.23 Of the population, 99% was white. Of those surviving, 3684 (81.1%) participated in the 5-year follow-up examination between March 1, 1993, and June 14, 1995. Comparisons between participants and nonparticipants at the time of the baseline and 5-year follow-up examinations have appeared elsewhere.26 Additional analysis of sun exposure–related variables showed that after adjusting for age and sex, participants were more likely than nonparticipants to wear protective hats and sunglasses at baseline.
Prior to the 10-year follow-up examination on March 1, 1998, 350 participants (9.5%) from the 5-year examination died. Of the 3334 surviving participants from the baseline and second examinations, 2764 (82.9%) participated in the second follow-up examination between March 1, 1998, and June 9, 2000. Of the nonparticipants, 1 could not be located, 42 (1.3%) permitted an interview only, 38 (1.1%) had moved out of the area and did not participate, 337 (10.1%) refused to participate, and 152 (4.6%) died after the start of the 10-year follow-up period prior to being examined. The mean time between the baseline and 10-year follow-up examinations was 10.1 ± 0.4 years, and the median was 10.0 years. Comparisons between participants and nonparticipants at the 10-year follow-up examinations have been presented elsewhere.27 Additional analyses found participants less likely than nonparticipants to work outdoors and spend time outside during the summer while in their 30s.
PROCEDURES
Similar procedures were used at both the baseline and follow-up examinations and are described in detail elsewhere.24-25 Informed consent was obtained from each participant. A standardized questionnaire was administered. Participants were asked about their residential history, time spent outdoors for leisure activities and work, and use of brimmed hats and sunglasses. At the 5-year follow-up examination, participants were asked about sun-related behaviors while in their teens (aged 13-19 years) and 30s (aged 30-39 years).
An index of ambient UV-B exposure was constructed from the baseline residential history, weighting the time spent outside 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-years).18 The mean ambient UV-B sun exposure was calculated by dividing the cumulative ambient sun exposure by age. Most participants had spent most of their lives in Wisconsin, resulting in a highly skewed distribution of mean annual exposure, so this variable was used to categorize participants into 2 levels of exposure: those with an index of 1.01 or lower and those with an index higher than 1.01. Between baseline and follow-up, some people had migrated out of Beaver Dam to other regions with higher UV-B levels. Therefore, an additional index was created with the same weighting procedure used for the historical data to capture additional exposure during follow-up in areas with higher UV-B levels than Wisconsin.19
The amounts of time that 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).18 A high protection level was defined as wearing hats, sunglasses, or both at least half of the time spent outdoors. An index of hat and sunglasses use while aged 13 to 19 years and 30 to 39 years was created.19 Participants who reported wearing hats or sunglasses at least half of the time when outside in the summer during both periods were considered to have used them often and to have a high level of protection. People who reported rarely using sunglasses or hats during both periods were considered to have a low level of protection. Participants who reported various patterns of use were considered to have intermediate levels of protection.
The amount of time participants spent outdoors in the summer at baseline was reported as more than 75%, 25% to 75%, or less than 25% of the day. The amount of time spent outdoors in the teens and 30s was obtained at the 5-year follow-up examination and reported as more than 5 hours, 2 to 5 hours, or less than 2 hours per day. These data were used to create a sun exposure index. Participants who reported being outdoors in the summer more than 5 hours a day in both their teens and 30s were considered to have high exposure; those who reported less than 2 hours of exposure during both periods, low exposure; and those with 2 to 5 hours per day or exposure that varied by age, intermediate exposure.19
A measure of cumulative sun exposure was similarly created by combining baseline summer sun exposure with that in the teens and 30s. Participants who reported the highest level of exposure during all periods were categorized as high exposure, those who reported the lowest level of ISD exposure during all periods were categorized as low exposure, and all others were classified as moderate exposure. For those with moderate exposure, a variable indicating the period in which the participant spent the most time outdoors was created; in cases of ties, the earliest period with the highest value was selected.
The number of bad sunburns, or burns with pain lasting longer than 1 day, experienced by a participant during youth (<21 years) and prior to the baseline examination was ascertained through the questionnaire and classified as none, 1, 2 to 10, or more than 10 burns. Skin sun sensitivity was characterized in response to a question asking participants how their skin reacted when exposed to the sun for half an hour without sunscreen and was recorded as "skin burns but never tans," "skin burns, then tans," "skin never burns but tans," or "skin never burns or tans." A person was classified as a nonsmoker if he or she had smoked fewer than 100 cigarettes in his or her lifetime, as an ex-smoker if he or she had smoked more than this number of cigarettes in his or her lifetime but had stopped smoking before the baseline examination, and as a current smoker if he or she had not stopped smoking. A subject was classified as a current vitamin user if he or she had taken at least 1 vitamin per week in the month prior to the baseline examination, as a past vitamin user if he or she had ever regularly taken vitamins at least once a week in the past but not in the last month, and as never using vitamins if he or she had never regularly taken vitamins at least once a week. Age was defined as the age at the time of the baseline examination.
Stereoscopic 30° color fundus photographs centered on the disc (Diabetic Retinopathy Study28 standard field 1) and macula (standard field 2) and a nonstereoscopic color fundus photograph temporal to but including the fovea of each eye were taken. For purposes of this article, the 2663 people (3570 at the first 2 examinations) with at least 1 eye free of confounding lesions (eg, retinal detachment or non–age-related chorioretinal scarring) at all 3 examinations (right eye: n = 2592 [3475 at the first 2 examinations]; left eye: n = 2600 [3501 at the first 2 examinations]; both eyes: n = 2529 [3406 at the first 2 examinations]) are included in the analyses.
The Wisconsin Age-Related Maculopathy Grading System28 was used to assess the presence and severity of lesions associated with ARM. Grading procedures, lesion descriptions, and detailed definitions for the presence and severity as well as 10-year incidence of specific lesions have appeared elsewhere.26, 31 Incidence implies the appearance of a lesion at follow-up when it was absent in any of the subfields that could be graded at the baseline and follow-up examinations. Progression implies either the incidence of disease or the presence of a lesion at baseline with a worsening at follow-up.26
Incidence was determined for maximum drusen size and type, increased retinal pigment, retinal pigment epithelial (RPE) depigmentation, pigmentary abnormalities (defined as RPE depigmentation or increased retinal pigment), signs of exudative macular degeneration, and pure geographic atrophy. For example, if none of the subfields had soft indistinct drusen at baseline and soft indistinct drusen were present in 1 or more subfields at the 5- or 10-year follow-up examination, the eye would be considered to have incident soft indistinct drusen.
Early ARM was defined by the presence of soft indistinct drusen or any type of drusen associated with RPE depigmentation or increased retinal pigment. Late ARM was defined by exudative macular degeneration or pure geographic atrophy.
Progression for a participant was defined as an increase in maculopathy severity on a 6-level scale. The cutpoints used were based on previous observations in the Beaver Dam Eye Study of an increased risk of developing late ARM associated with larger areas of large soft drusen and pigmentary abnormalities.31 An increase in severity in either eye by 2 or more steps from level 1 through 3, or 1 or more steps from level 4 to 5, was defined as progression. A detailed description appears elsewhere.14
STATISTICAL METHODS
We examined the relationships between risk factors at baseline and the incidence of each maculopathy lesion, the incidence of 2 end points of disease severity (early and late ARM), and the progression of ARM. We used SAS statistical software (SAS Institute Inc, Cary, NC) to analyze the data. The analytical approaches used allowed persons who were right censored (not seen after the 5-year examination as a result of death or nonparticipation) to contribute information to the estimates. Cumulative events were estimated using the Kaplan-Meier (product-limit) survival approach.32 Multivariate risk ratios (RRs) and 95% confidence intervals (CIs) were calculated from the discrete linear logistic model.33 Age- and sex-adjusted models were constructed by outcome for each of the potential risk factors. Final models were then created by outcome for each risk factor by further adjusting the models for vitamin use and smoking history. When multivariate models included eye-specific risk factors (such as iris color or history of cataract), data were analyzed using the generalized estimating equation approach.34 This method adjusts for correlations between the two eyes.
RESULTS
Table 1 shows the distribution of sunlight-related risk factors. Few participants reported spending most of their days outdoors, either during the winter or summer (3.0% and 19.8%, respectively), at the baseline examination, and most (65.6%) reported spending an intermediate amount of time outdoors while in their teens and 30s. About half of the participants reported wearing hats and sunglasses rarely or not at all, both at baseline and in their teens and 30s. Less than half had experienced more than 1 bad sunburn in their lifetime, and most persons had skin that either burned and then tanned or tanned and never burned. Women reported spending more time indoors and being more likely to wear sunglasses and hats than men. They also reported fewer bad sunburns and had less UV-B exposure. Older participants reported spending less time outdoors in both the summer and winter than younger participants (data not shown). Older participants were more likely to report never or rarely wearing sunglasses in their teens and 30s and at baseline and to have experienced fewer bad sunburns, both in youth and at baseline, than younger participants (data not shown). Participants who experienced the greatest number of bad burns in their youth and at baseline were more likely to report wearing protective hats and sunglasses often and spending less than 25% of their time outdoors during the summer than persons who experienced the fewest burns (data not shown).
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Table 1. Distribution of Risk Factors by Sex*
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Table 2 gives overall incidence estimates, without adjustment, for early and late ARM and the progression of ARM. No significant relationships were found between the amount of time spent outdoors for work or winter or summer leisure activities, either at baseline or in the teens and 30s, and the incidence of early or late ARM or the progression of ARM. Participants who reported wearing sunglasses and hats during their teens and 30s had a significantly lower incidence of early ARM than those who never or rarely wore hats and sunglasses. This relationship, although not significant, held for baseline use of sunglasses and hats as well. Participants who reported frequent use of hats and sunglasses at baseline were also less likely to experience progression of ARM. Participants who experienced 2 or more burns had a lower incidence of early and late ARM than those who experienced none or 1 bad burn. Participants with 2 or more bad sunburns during youth were also less likely to have progression than their counterparts. No significant relationships were found between mean annual ambient UV-B exposure and incidence or progression of ARM. Participants who reported that their skin tanned but never burned when exposed to the sun were more likely than any of the other skin sensitivity groups to experience progression of ARM.
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Table 2. Association of Sunlight Variables With the 10-Year Incidence and Progression of Age-Related Maculopathy*
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The RRs for sun-related factors and the 10-year incidence and progression of ARM are presented in Table 3. All models are age and sex adjusted. Participants with the highest levels of sun exposure during all 3 periods as well as those with moderate levels of sun exposure during all 3 periods were significantly more likely to develop early ARM (RR, 2.20 and 1.94, respectively) and increased retinal pigment (RR, 2.99 and 2.42, respectively) by the 10-year follow-up examination than those reporting the lowest levels of sun exposure during all 3 periods. Participants exposed to the summer sun for more than 5 hours a day both during their teens and 30s had a higher risk of developing increased retinal pigment (RR, 2.53; 95% CI, 1.22-5.26; P = .01) and early ARM (RR, 2.02; 95% CI, 1.08-3.79; P = .03) at 10 years than those who were exposed less than 2 hours per day during the same periods. Only a marginal relationship between level of sun exposure at baseline and the 10-year incidence of increased retinal pigment was found (RR, 1.39; 95% CI, 0.94-2.04; P = .10). The relationship between cumulative sun exposure and increased retinal pigment and early ARM was further examined by adding previously identified risk factors (smoking and vitamin use) for ARM. The relationships between sun exposure during the teens and 30s and incidence of early ARM and increased retinal pigment remained (RR, 2.01 and 2.51, respectively), as did the relationships between high and moderate sun exposure during all 3 periods and incident increased retinal pigment (RR, 2.40 and 2.95, respectively). The relationship between high sun exposure during all 3 periods and incident early ARM, however, was reduced to moderate significance. Other factors for which sun exposure could be a surrogate, including use of photosynthesizing drugs, cataract, cataract surgery, aphakia, and iris color, were added to all significant models. None of these risk factors explained the relationship previously found (data not shown). For participants reporting variable sun exposure during the 3 periods, the relationships between the period in which the participant spent the most time outdoors and the 10-year incidence of early ARM and increased retinal pigment were examined. No significant relationships were found (data not shown).
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Table 3. Relationship of Sun-Related Risk Factors to the 10-Year Incidence and Progression of Age-Related Maculopathy Controlling for Age and Sex in the Beaver Dam Eye Study*
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As indicated in Table 3, participants who experienced more than 10 sunburns during their youth were more likely than those who experienced 1 or no burn to have drusen at least 250 µm in diameter (RR, 2.52; 95% CI, 1.29-4.94; P = .01) and soft indistinct drusen (RR, 1.71; 95% CI, 0.97-2.99; P = .06) by the 10-year examination. Those who experienced 2 to 10 burns in their youth were significantly more likely to develop late ARM (RR, 2.32; 95% CI, 1.01-5.31; P = .05) but significantly less likely to develop soft indistinct drusen (RR, 0.72; 95% CI, 0.51-1.00; P = .05) than participants reporting 1 or no burn. None of the participants who experienced more than 10 burns during youth (n = 177) developed late ARM by 10 years. All relationships besides that between soft indistinct drusen and number of bad sunburns in youth held after further adjusting the models for smoking status and vitamin use (risk of incident large drusen in those experiencing more than 10 burns: 2.40; 95% CI, 1.22-4.71; P = .01; risk of incident late ARM in those experiencing 1 to 9 burns: 2.31; 95% CI, 1.00-5.32; P = .05).
After adjusting for age and sex, the use of hats and sunglasses by participants at baseline or in their teens and 30s was not found to protect against the 10-year incidence or progression of ARM. However, in those who reported having the highest summer sun exposure levels in their teens and 30s, the use of hats and sunglasses at least half the time was associated with a decreased risk of developing soft indistinct drusen (RR, 0.55; 95% CI, 0.33-0.90; P = .02) and RPE depigmentation (RR, 0.51; 95% CI, 0.29-0.91; P = .02), but no significant associations were found between increased retinal pigment (RR, 1.36; 95% CI, 0.76-2.42; P = .30), incident early ARM (RR, 0.83; 95% CI, 0.48-1.43; P = .50), incident late ARM (RR, 0.73; 95% CI, 0.22-2.37; P = .60), and progression of ARM (RR, 0.93; 95% CI, 0.55-1.59; P = .80).
COMMENT
In the Beaver Dam Eye Study, extended sun exposure was associated with the 10-year incidence of early ARM and increased retinal pigment. Our results confirm those from the baseline and 5-year follow-up examinations.18-19 At baseline, summer sun exposure was related to increased retinal pigment in men, and at the 5-year follow-up examination, summer leisure time spent outdoors while participants were in their teens and 30s was significantly related to the incidence of early ARM. However, a study by Taylor et al17 found that exposure to visible light was associated with late ARM, and other studies have found no associations between sunlight exposure and ARM.20, 22
If cumulative sun exposure is related to the incidence of increased retinal pigment or early ARM, it is hypothetically the effect of exposure to visible rather than UV light. Previous studies have not found ARM to be associated with cumulative UV-A or UV-B exposure16-17,22 but support associations between ARM and ocular exposure to visible blue light.17, 35-36 The results of a study by Winkler et al37 in which photoporphyric mice exposed to blue light developed sub-RPE fibrillogranular deposits, as well as other animal studies,38-39 are consistent with this hypothesis. Some studies have suggested that excessive blue-light exposure results in photic damage to the RPE induced by photochemical or photo-oxidative mechanisms,35-36 possibly contributing to ARM.
A study by Delcourt et al22 found subjects who used sunglasses regularly to have a decreased risk of soft drusen (OR, 0.81; 95% CI, 0.66-1.00; P = .05). In the Beaver Dam Eye Study, after adjusting for age and sex, no significant associations between use of hats and sunglasses and 10-year incidence or progression of ARM were found. However, in those who reported the highest summer sun exposure levels in their teens and 30s, the use of hats and sunglasses at least half the time was associated with a decreased risk of developing soft indistinct drusen and RPE depigmentation but not with the 10-year incidence of increased retinal pigment or early ARM, the 2 outcomes for which participants with excessive sun exposure were at significantly higher risk. Our lack of findings indicate that the use of sunglasses with UV protection may not provide benefits against the development of some signs of ARM.
Results of analyses of the relationship between the number of bad sunburns experienced during youth and the incidence and progression of ARM were inconsistent. No participants with more than 10 bad burns during youth developed late ARM. However, those experiencing 2 to 10 burns during youth had a significantly higher incidence of late ARM than those with 1 or no burn. Participants experiencing 1 or no burn in their youth were less likely than those experiencing more than 10 burns, but more likely than those experiencing 2 to 10 burns, to develop soft indistinct drusen. One possible explanation for these inconsistent findings is that participants who experienced the highest number of burns during youth were more likely to take measures protective against sun exposure later in life. A second possible explanation is that these statistically significant associations are a type I error (ie, due to chance alone when no associations exist). Our study found no relationships between number of severe burns experienced at the baseline examination and the 10-year incidence or progression of ARM. This is consistent with the Blue Mountains Eye Study.21
No relationships were found between mean annual ambient UV-B exposure and incidence or progression of ARM at 10 years in the Beaver Dam Eye Study. This is consistent with our earlier findings,18 a study by Delcourt et al,22 and the Maryland Watermen Study,17 which reported no significant associations between UV-B exposure and late ARM. A study by Delcourt et al22 found that subjects exposed to high ambient solar radiation had a decreased risk of pigmentary abnormalities (OR, 0.61; 95% CI, 0.39-0.93; P = .02), but we did not find this association.
Any conclusions or explanations regarding associations, or lack thereof, described in this article must be made with caution for several reasons. First, the concomitant incidence of some lesions (eg, exudative macular degeneration) may limit our ability to detect meaningful relationships. Second, the analyses conducted for this study include the examination of associations between many risk factors and outcomes. There is a distinct possibility that some statistical associations reported in our article are type I errors. Third, it is also possible that some relationships were not found or were attenuated because persons with these factors who developed ARM did not live to participate in the follow-up examination. However, nonparticipation as a result of death is unlikely to bias our findings because ARM has not been associated with mortality.40 Fourth, differences in the participation rates of survivors at the follow-up examinations by level of sun exposure may have masked or accentuated some associations. Finally, it is difficult to capture an adequate history of sun exposure with a questionnaire. Recall of behaviors occurring long ago may be poor or inaccurate. Insensitivity may limit our ability to find an association when one exists, and misclassification can result in spurious findings.
In summary, few significant relationships between environmental exposure to light and the 10-year incidence and progression of ARM were found in the Beaver Dam Eye Study. However, the power to detect relationships between sunlight exposure and late ARM is limited by the rarity of the disease. A significant association was found between extended exposure to the summer sun and the 10-year incidence of early ARM and increased retinal pigment. This is consistent with results from the baseline and 5-year follow-up examinations. A protective effect of hat and sunglasses use by participants while in their teens and 30s against the 10-year incidence of soft indistinct drusen and RPE depigmentation was also found, but only in those who reported the highest amount of sun exposure during the same periods. These results support previous findings indicating a possible link between extended sunlight exposure and the incidence of early ARM. Further follow-up is needed if conclusions about the relationship between sunlight exposure and incidence of late ARM are to be reached.
AUTHOR INFORMATION
Corresponding author: Ronald Klein, MD, MPH, Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison, 610 N Walnut St, 450 WARF, Madison, WI 53726 (e-mail: kleinr{at}epi.ophth.wisc.edu).
Submitted for publication February 19, 2003; final revision received August 27, 2003; accepted October 1, 2003.
This study was supported by grant EY06594 (Drs R. Klein and B. Klein) from the National Institutes of Health, Bethesda, Md, and in part by the Senior Scientific Investigator Award (Dr R. Klein) and Lew R. Wasserman Award (Dr Cruickshanks) from Research to Prevent Blindness, New York, NY.
Reprints not available from the author.
From the Department of Ophthalmology and Visual Sciences (Ms Tomany, Drs R. Klein and B. Klein, and Mr Knudtson) and Department of Population Health Science, University of Wisconsin Medical School, Madison. The authors have no relevant financial interest in this article.
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