Solar Exposure and Residential Geographic History in Relation to Exfoliation Syndrome in the United States and Israel

Abstract

Importance

Residential (geographic) history and extent of solar exposure may be important risk factors for exfoliation syndrome, but detailed lifetime solar exposure has not been previously evaluated in exfoliation syndrome.

Objective

To assess the relation between residential history, solar exposure and exfoliation syndrome.

Design

Clinic-based, case control studies.

Setting

A clinical center in the United States and in Israel.

Participants

Exfoliation syndrome cases and controls (all 60+ years old Caucasians) enrolled from 2010 to 2012 (United States: 118 cases and 106 controls; Israel: 67 cases and 72 controls).

Main Outcomes and Measures

Weighted lifetime average latitude of residence and average number of hours per week spent outdoors as determined by validated questionnaires.

Results

In multivariable analyses, each degree of weighted lifetime average residential latitude away from the equator was associated with an 11% increased odds of exfoliation syndrome (pooled odds ratio = 1.11; 95% CI: 1.05-1.17; p < .001). Furthermore, every hour per week spent outdoors during the summer, averaged over a lifetime, was associated with a 4% increased odds of exfoliation syndrome (pooled odds ratio = 1.04; 95% CI: 1.00-1.07; p = .03). For every 1% of average lifetime summer time between 10 a.m. and 4 p.m. that sunglasses were worn, the odds of exfoliation syndrome decreased by 2% (odds ratio = 0.98; 95% CI: 0.97-0.99; p < .001) in the United States, but not in Israel (odds ratio = 1.00; 95% CI: 0.99-1.01; p = .92; p for heterogeneity = .005). In the United States, after controlling for important environmental covariates, history of work over water or snow was associated with increased odds of exfoliation syndrome (odds ratio = 3.86; 95% CI: 1.36-10.9); in Israel, there were too few people with such history for analysis. We did not identify an association between brimmed hat wear and exfoliation syndrome (p>.57).

Conclusion and Relevance

Lifetime outdoor activities may contribute to exfoliation syndrome. The association with work over snow or water and the lack of association with brimmed hat wear suggests that ocular exposure to light from reflective surfaces may be an important type of exposure in exfoliation syndrome etiology.

INTRODUCTION

Exfoliation syndrome (XFS) is a form of deleterious ocular aging categorized by increased risk of climatic droplet keratopathy,^1,2 age-related cataract,^3-5 late-onset spontaneous intraocular lens subluxation,⁶ elevated intraocular pressure with glaucomatous optic neuropathy,⁷ and retinal vein occlusion.^8,9 The discovery that common variants of LOXL1 are present in 99% of XFS cases represents a significant advance in understanding this condition.¹⁰ However, 80% of controls also harbor these variants and the ratio of cases to controls with trait-related variants is fairly similar in regions where XFS is hyper-endemic¹¹ and regions where the condition is relatively rare.¹² This suggests that other genetic or environmental factors contribute to XFS.

There is considerable evidence that climatic factors contribute to XFS. For example, aboriginal Australians who spend substantial time outdoors have a higher prevalence of XFS¹³ (11%) compared to a mix of urban, rural and nursing home residents from Victoria, Australia (1%).¹⁴ Taylor found that XFS was particularly common in Australian stockmen who looked after livestock.¹⁵ On the island of Rab in the Adriatic Sea, the frequency of XFS was 23% among 480 villagers categorized as agriculturists and fishermen but no cases were detected in 61 urban dwellers.¹⁶ Stein et al.¹⁷ concluded that people with XFS tended to reside at higher latitude in the continental United States (US), a finding that was supported by the Nurses’ Health Study and Health Professionals Follow-up Study.¹⁸ When state-specific climatic data was considered, colder ambient temperature and increased number of sunny days was associated with increased risk of XFS.¹⁷

The relation between ultraviolet radiation (UVR) and XFS deserves further study because some reports have not been consistent with a positive association between UVR and XFS. For instance, Forsius et al. found virtually no XFS among Inuit people residing in Greenland where UVR exposure is high.¹⁹ Forsius et al. did find at least one type of solar ophthalmopathy –specifically, pterygium, climatic keratopathy or pronounced pingecula - was at least as common, or more common in individuals with XFS compared to unaffected individuals, in various populations. Yet, because the frequency of XFS in tropical countries (Tunisia and India) lagged behind that in countries at higher latitudes (Finland, Iceland and Russia) in their worldwide personal survey, they concluded, “climate does not appear to influence the occurrence of XFS.”¹⁹ Finally, no relation between time spent outdoors and risk of XFS was found in the Reykjavik Eye Study.²⁰

To further clarify the UVR-XFS relationship, we conducted a clinic-based, case-control study in the US and Israel. We administered validated questionnaires to explore the relation between residential (geographic) history and solar exposure from birth to age 60 in relation to XFS.

METHODS

We conducted a clinic-based, case-control study at two ophthalmic centers: Massachusetts Eye and Ear in the US and the Goldschleger Eye Institute in Israel. The Israeli site was chosen because we wanted to assess the previously reported association between increasing latitude and XFS in Europe, and the Goldschleger Eye Institute cares for people from throughout Europe. The Human Subject Committee at each institution approved this study and written informed consent was obtained from participants.

All participants were at least 60 years old and recruited from November 2010 to December 2012. Cases had evidence of exfoliation precipitates in at least one eye with or without evidence of glaucoma. Controls had no exfoliation material on any available examinations, including at least one dilated slit lamp examination prior to cataract surgery in both eyes if the participant was pseudophakic. Controls could have forms of glaucoma other than exfoliation glaucoma. We collected data regarding a family history of glaucoma, diabetes, hypertension and eye color from medical record review.

Assessment of residential history and solar exposure

Measurement of residential history and solar exposure were based on The Residential History and The Ocular Exposure to Ultraviolet Light instruments found in the PhenX Toolkit,²¹ a repository of freely available validated instruments designed to assess traits related to complex disease (www.phenxtoolkit.org). The questionnaires were administered by phone or in person by trained interviewers (AZJ, TZ-D, and AM), who were masked to participants’ ophthalmic status.

For residential history, we asked the participants where they lived from birth to age 60, capturing all moves to new locations. We recorded the latitude of each residence with a Google map application prior to its retirement in August 2013 (http://maps.google.com/latitude). We calculated the weighted lifetime average latitude from birth to age 60, which accounted for the time spent at each residential location.

We asked participants to provide information on the activities listed below during the age periods of 10-19, 20-29, 30-39, 40-49 and 50-59 years:

1. The number of hours per week spent outdoors between 10am and 4pm during the summer and the percentage of that time eyeglasses, sunglasses (including clip-on, wrap-around or other forms of ocular UV protection), and brimmed hats or visors were worn;

2. Whether time was spent in regular leisure activity over snow or a body of water (such as the ocean, lake or pond). We defined “regular” leisure activity as an activity performed at least one whole week in the aggregate (or the equivalent of engaging in an activity from 10 a.m. to 4 p.m. for the equivalent of 7 day or ~42 hours) during a year;

3. Whether time was spent working over snow in activities like ski instructing or winter landscaping (snow shoveling for personal housekeeping was excluded as it does not constitute a regular environmental exposure).

As an ancillary component to the solar exposure questionnaire, we asked about the age when participants experienced their first sunburn, defined as a solar exposure that caused redness and pain for approximately 12+ hours, even if it only involved a small patch of skin.

Statistical analysis

We used SAS version 9.3 (SAS Institute, Cary NC) for all statistical analyses. We performed multiple logistic regression models separately for the US and Israeli groups. In our various models, we adjusted for sex, age in years, light eye color (hazel, green, blue green, blue or gray), diabetes mellitus, hypertension, family history of glaucoma, lifetime average number of hours spent outside per week and weighted lifetime average latitude of residence. Latitude of residence was defined by the absolute value of the latitude from the equator (e.g.,10° latitude South and 10° latitude North were treated the same). We performed statistical tests for heterogeneity to assess whether it was appropriate to pool site-specific results.²²

RESULTS

We recruited 118 XFS cases and 106 controls in the US, and 67 XFS cases and 72 controls in Israel - all were self-reported Caucasians (Table 1). At both sites, cases were older than controls, had a higher frequency of a family history of glaucoma and had light colored irides (Table 1). While fewer cases had diabetes mellitus at the US site, the opposite was true at the Israeli site. At both sites, cases lived farther from the equator and spent more time outdoors in summer than controls. A smaller percentage of cases reported ever wearing sunglasses compared to controls at both sites. Fewer cases compared to controls wore brimmed hats at the US site but the opposite was true at the Israeli site. At both sites, a higher percent of cases than controls reported ever spending leisure time over water or snow. At the US site, more cases than controls spent any time working over snow or water but few people at the Israeli site reported these activities.

Table 1.

Age and age-adjusted characteristics of United States and Israeli study participants¹

	Participants
	United States		Israel
Characteristic	Case (n=118)	Control (n=106)	Case (n=67)	Control (n=72)
Age, mean years [SD]	75.2 [7.6]	69.7 [7.3]	74.4 [7.0]	71.6 [7.0]
Women, %	57	63	43	64
Family history of glaucoma, %	33	27	28	25
Light color irides, %	63	52	49	26
Diabetes mellitus, %	7	17	28	24
Hypertension, %	65	53	52	65
Weighted lifetime average latitude of residence2 [SD]	42.6 [3.1]	41.9 [2.0]	39.7 [8.1]	34.0 [4.2]
Weighted lifetime average above the median latitude of residence,2 %	53	52	62	38
Lifetime average number of hours/week spent outdoors3 [SD]	18.5 [9.1]	16.2 [7.4]	16.7 [7.6]	13.5 [5.8]
Lifetime average % above the median number of hours/week spent outdoors,3 %	56	51	64	40
Sunburn,4 % childhood	51	51	55	58
Ever sunglass wear, %	73	87	62	73
Lifetime average of % time worn sunglasses3 [SD]	24.1 [26.1]	43.8 [30.5]	28.8 [29.4]	35.5 [33.6]
Lifetime average of % time worn brimmed hat3 [SD]	14.2 [23.1]	16.3 [23.3]	24.0 [31.5]	17.1 [25.3]
Any lifetime leisure time spent over water, %	88	82	86	74
Any lifetime leisure time spent over snow, %	59	52	28	12
Any lifetime work spent over water, %	15	8	0	2
Any lifetime work spent over snow, %	12	0	0	0

¹Values are means (standard deviations) or percentages and are standardized to the age distribution of the study population.

²Refers to residence from birth to age 60 with latitudes determined using Google maps. Absolute values for latitudes were used to account for residence in the southern hemisphere.

³Refers to ages 11-59 years and between the hours of 10 a.m. - 4 p.m. during the summer.

⁴Sunburn is defined as recalled burn during childhood (before age 10 years) that produced redness or pain and lasted 12 or more hours regardless of severity, even if only involving a small part of the body surface.

Abbreviation used SD= standard deviation

To explore the inter-relationships between the main exposure of lifetime latitude and other potential confounders, we assessed the distribution of covariates in controls by greater than or less than the median latitude of each cohort (Table 2). At both sites, compared with those residing close to the equator, a greater percentage of people farther from the equator reported any sunburns (70% vs. 52% at the US site, p = .07; 65% vs. 60% at the Israeli site, p = .57) and spending more time outside (16.2 vs. 15.6 hours per week in the US site, p = .98; 15.0 vs. 13.0 in the Israeli site, p = .20). People farther from the equator also wore brimmed hats a greater percentage of the time than those closer to the equator (22.1% vs. 14.5% at the US site, p = .22; 21.4% vs. 13.5% at the Israeli site, p = .09). More people residing farther from the equator than those living closer wore sunglasses a higher percent of the time at the US site (53.6% vs. 42.5%, p = .27) though there was little difference at the Israeli site (31.7% vs. 32.2%, p = .85).

Table 2.

Age and age- adjusted characteristics of United States and Israeli by latitude among controls^1,2

	Latitude, %
	United States		Israel
	Latitude below the median (<42.2 degrees) (n=56)	Latitude above the median (>42.2 degrees) (n=50)	Latitude below the median (<32.7 degrees) (n=43)	Latitude above the median (≥32.7 degrees) (n=29)
Age, mean years [SD]	68.7 [7.3]	70.7 [7.1]	71.4 [5.7]	71.8 [4.9]
Women, %	65	53	66	57
Family history of glaucoma, %	31	29	31	15
Light eye color, %	45	70	20	31
Diabetes mellitus, %	14	14	32	18
Hypertension, %	47	56	72	53
Sunburn,3 % childhood	52	70	60	65
Ever sunglass wear, %	91	87	67	78
Lifetime average number of hours/week spent outdoors (standard deviation)3 [SD]	15.6 [7.2]	16.2 [8.3]	13.0 (5.1)	15.0 (5.3)
Lifetime average % above the median number of hours/week spent outdoors3, %	46	44	35	55
Lifetime average of % time worn sunglasses [SD]3	42.5 [28.3]	53.6 [35.6]	32.2 [32.1]	31.7 [24.7]
Lifetime average of % time worn brimmed hat [SD]3	14.5 [19.8]	22.1 [26.1]	13.5 [20.1]	21.4 [23.4]
Weighted lifetime average latitude of residence [SD]2	41.1 [1.7]	43.1 [2.2]	32.0 [0.6]	37.6 [4.5]
Any lifetime leisure time spent over water, %	78	87	80	72
Any lifetime leisure time spent over snow, %	38	59	2	28
Any lifetime work spent over water, %	8	6	2	5
Any lifetime work spent over snow, %	2	0	0	0

¹Values are means (standard deviations) or percentages and are standardized to the age distribution of the study population.

²Refers to residence from birth to age 60 with latitudes determined using Google maps. Absolute values for latitudes were used to account for residence in the southern hemisphere.

³Details regarding how sunburns, time spent outdoors, sunglass wear and hat wear was collected can be found in the footnotes to Table 1.

Abbreviation used: SD= standard deviation

In pooled analyses (Table 3), after adjusting for age, sex, iris color, family history of glaucoma, diabetes mellitus and systemic hypertension, each 1-degree in weighted average lifetime residential latitude away from the equator was associated with an 11% increased odds of XFS (pooled OR = 1.11; 95% CI: 1.05-1.17; p < 0.001). Furthermore, every extra hour per week spent outdoors, averaged over ages 10-59, was associated with a 4% increased odds of XFS (pooled OR = 1.04; 95% CI: 1.00-1.07; p = .03; Table 3). In secondary analysis, we calculated weighted average residential latitude for three age periods: 0-20, 21-40, and 41-59 years. In pooled multivariable analysis, average weighted residential latitude during young adulthood (age 21-40 years) was independently associated with XFS (pooled OR = 1.17; 95% CI: 1.05-1.31; p = .01; See Table 4) even after adjusting for residence at other time periods and other confounders. A similar analysis of time spent outdoors during various age periods in relation to XFS was inadequately powered and did not reveal any associations (data not shown).

Table 3.

Relative risk of exfoliation syndrome by time spent outdoors and residential latitude.

	US		Israel		Pooled
Variable	OR (95% CI)	p-value1	OR (95%CI)	p-value1	OR (95% CI)	p-value1
Female gender	0.82 (0.43, 1.55)	.53	0.43 (0.19, 0.97)	.04	0.62 (0.33, 1.16)	.14
Age in years	1.10 (1.06, 1.15)	<.0001	1.07 (1.01, 1.14)	.02	1.09 (1.06, 1.13)	<.0001
Light eye color	1.32 (0.72, 2.44)	.37	2.25 (0.95, 5.33)	.07	1.58 (0.96, 2.61)	.07
Diabetes mellitus1	0.22 (0.08, 0.59)	.003	1.87 (0.72, 4.86)	.20	0.65 (0.08, 5.22)	.68
Hypertension1	1.95 (1.03, 3.7)	.04	0.41 (0.16, 1.01)	.05	0.92 (0.20, 4.29)	.92
Family history of glaucoma	1.95 (1.00, 3.82)	.05	1.11 (0.45, 2.73)	.83	1.59 (0.93, 2.73)	.09
Lifetime average number of hours/week spent outdoors2	1.04 (1.00, 1.08)	.04	1.03 (0.97, 1.09)	.35	1.04 (1.00, 1.07)	.03
Weighted lifetime average latitude of residence2	1.10 (0.97, 1.24)	.13	1.11 (1.04, 1.19)	.001	1.11 (1.05, 1.17)	<.001

¹P for heterogeneity<.05. Diabetes mellitus: p for heterogeneity=.002, hypertension: p for heterogeneity=.006.

²Details regarding how data pertaining to time spent outdoors and weighted lifetime average latitude was collected is provided in the footnote to Table 1.

Abbreviations used: US=United States; OR=odds ratio; CI=confidence interval

Table 4.

Relative risk of exfoliation syndrome by average residential latitude during various life periods.

	US		Israel		Pooled
Variable	OR (95% CI)	p-value1	OR (95% CI)	p-value1	OR (95% CI)	p-value1
Female gender	0.77 (0.40, 1.49)	.44	0.44 (0.17, 0.93)	.03	0.59 (0.31, 1.11)	.10
Age	1.11 (1.07, 1.17)	<.001	1.09 (1.02, 1.16)	.01	1.11 (1.07, 1.15)	<.001
Light irides	1.32 (0.71, 2.45)	.38	2.48 (1.00, 5.95)	.05	1.64 (0.93, 2.91)	.09
Diabetes mellitus1	0.20 (0.07, 0.56)	.002	1.95 (0.74, 5.16)	.18	0.63 (0.07, 5.80)	.69
Hypertension1	1.85 (0.97, 3.53)	.06	0.41 (0.16, 1.05)	.06	0.91 (0.21, 3.94)	.90
Family history of glaucoma	2.02 (1.02, 3.99)	.04	1.05 (0.42, 2.62)	.91	1.57 (0.84, 2.92)	.16
Lifetime average number of hours spent outside per week2	1.04 (1.00, 1.08)	.04	1.03 (0.97, 1.09)	.39	1.04 (1.00, 1.07)	.03
Weighted average latitude of residence during age: 0-203	0.97 (0.85, 1.11)	.67	0.95 (0.87, 1.04)	.28	0.96 (0.89, 1.03)	.26
Weighted average latitude of residence during age: 21-403	1.17 (0.99, 1.38)	.06	1.17 (1.00, 1.37)	.05	1.17 (1.05, 1.31)	.01
Weighted average latitude of residence during age: 41-603	0.94 (0.80, 1.10)	.43	0.99 (0.85, 1.16)	.92	0.97 (0.86, 1.08)	.54

¹P for heterogeneity<0.05. Diabetes mellitus p for heterogeneity = .002, hypertension p for heterogeneity = .01.

²Details regarding how data pertaining to time spent outdoors are provided in the footnote to Table 1.

³Average latitude during each time period (ages 0-20; 21-40 and 41-60) is derived from the residential history.

Abbreviations used: US=United States; OR=odds ratio; CI=confidence interval

In a separate model, the association between sunglass wear and XFS was different between the two sites (p for heterogeneity = .005). At the US site, for every percentage point increase in the lifetime average number of hours sunglasses were worn in the summer between 10 a.m. and 4 p.m., the odds of XFS decreased by 2% (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001); however, no association was observed at the Israeli site (OR = 1.00; 95% CI: 0.99-1.01; p = .92). An association between brimmed hat or visor wear and XFS was not identified (pooled p ≥ .57; models not shown).

Leisure time spent over water or snow was not related to XFS in the US site (data not shown). However, in the US site, any history of work activity over water or snow was associated with a nearly 4-fold increased odds of XFS (OR = 3.86; 95% CI: 1.36-10.93; p = .01) after further adjustment for weighted average lifetime residential latitude, sunglass wear, average lifetime hours spent outdoors and brimmed hat wear. In Israel, there were too few participants who worked or spent leisure time over water or snow for meaningful analysis.

DISCUSSION

In our US and Israeli case-control groups, we observed a positive association between residential latitude away from the equator and XFS. This association was driven largely by the varied residential histories of the Israeli participants who lived throughout Europe and in countries of the southern hemisphere. More time spent outdoors in the summer over a lifetime was associated with XFS. Brimmed hat wear was not associated with XFS, while at the US site, sunglass wear was associated with reduced odds of XFS. Taken with the evidence that work over water or snow in the US was associated with an increased odds of XFS, our data suggests that ocular exposure to light from reflective surfaces is important for XFS development.

In the Reykjavik Eye Study, time spent outdoors was not associated with an increased risk of XFS;²⁰ however, in that study, only most recent exposures were considered, which does not necessarily correlate with critical earlier exposures. In youth, people spend more time outdoors²³ and have larger pupils,²⁴ making them vulnerable to anterior segment UV damage. Our survey asked participants to recall their exposures at every decade from ages 10 to 59, and we observed associations with greater time spent outdoors averaged over a lifetime.

The amount of UVR incident on the horizontal terrain relates to the ocular UVR dosing in a complicated manner. Using a UV sensing contact lens, Sydenham et al.²⁵ reported that the ratio of ocular-to-ambient UV exposure ranged from 4% to 23%, indicating that ambient UV exposure is not the major source of ocular solar exposure. Indeed, in our study, brimmed hat wear, which may protect against ambient UV exposure but not radiation reflected from the ground and into the eye, was not associated with XFS. Interestingly, fresh snow reflects as much as 80% of UV-B (290-320nm) during mid-day,²⁶ while sand is an intermediate reflecting surface (~7-18%) and grass is a poor reflector of UVR (~2-4%). At the US site, working over snow or water was associated with nearly 4-fold increased odds of XFS, even after controlling for important potentially confounding factors including residential latitude. In our study sunglass wear at the US site, but not the Israeli site, was associated with reduced odds of XFS. The reason for the difference between the sites is unclear but the data suggests sunglass wear could be associated with reduced odds of XFS by virtue of blocking reflected UVR. The importance of reflected UVR in relation to XFS is further supported by the relatively high prevalence of XFS in Saudi Arabia (9%) where there is considerable sand and sun exposure.²⁷

If UVR is important in XFS as our study suggests, then XFS could be considered as an ophthalmoheliosis (solar-related ophthalmic condition) and the association between other ophthalmohelioses in relation to XFS warrant study to further test the UVR – XFS hypothesis. Climatic droplet keratopathy is a classic ophthalmoheliosis linked to XFS in several studies.^1,2,28,29 Pterygium is another ophthalmoheliosis related to UVR that typically presents at a much younger age than XFS.³⁰ While Taylor¹³ found a connection between pterygium and XFS in Aboriginal Australians, this association is not well documented in other populations. Pterygia are thought to result from the Coroneo effect³¹ where horizontal UVR rays reflect across the corneal dome to focus on the nasal limbus, and not from light rays directly entering the iris, an important focus of UVR-related pathophysiology in XFS; thus, the association between ptyergia and XFS may not be particularly strong. Cataract is associated with UVB exposure,^32-34 and has also been associated with XFS.^35-40.

One needs to reconcile the role UVR plays in XFS with the positive relation between latitude and XFS.^17,18 It is interesting to note that during the summer, UV doses to the horizon at higher latitude is comparable to that recorded at lower latitude. For example, Godar et al.⁴¹ estimated that the terrestrial erythema weighted solar UV dose during summer in Boston, Massachusetts (Latitude, 42.4° North) was 272,113 J/m²and 296,436 J/m²in Atlanta, Georgia (Latitude, 33.7° North). This fact coupled with the higher snow accumulation which may reflect UVR into the eye during winter months may explain why Stein et al.found that Massachusetts had a higher hazards ratios (HR) for XFS (HR=3.2) relative to Missouri, the geographical center of the US.¹⁷In our analysis of the relation between time spent outdoors and XFS, we measured participant exposure during the summer months when UVR is highest (10 a.m. to 4 p.m.)²⁶ and we controlled for residential latitude.

It is important to also consider the relatively low prevalence of XFS in Greenland Inuits and Peruvian people,^19,43 despite their exposure to considerable reflected sunlight from snow that could contribute to XFS. In addition, while pterygium is a common problem in China,⁴⁴ XFS is relatively uncommon.⁴⁵ It should be noted that while the frequency of LOXL1 gene variants related to XFS are unknown among Inuits and Peruvians, these polymorphisms are common in China.^46,47 We speculate that Inuits and Peruvians, like Asian Chinese have relatively thick irides that may ameliorate uveal tract damage caused by the expected high degree of reflected UVR.⁴⁸

Several limitations of this study should be considered. The questionnaires used to assess ocular UV are subjective and imprecise. Also, they are vulnerable to inaccurate recall of exposures from the distant past even though UV exposure during young adulthood may be important in XFS. Interviewer bias cannot be ruled out but was minimized with the use of trained interviewers who were masked to ophthalmic status. Another source of bias in our study is that XFS cases may differentially recall more UV exposure than controls but it is unlikely that cases would equate working over snow with XFS or appreciate that brimmed hats might be ineffective at blocking reflected UV light from entering the eye. Our XFS cases may have more UV exposure than typical XFS cases and our controls may have had less UV exposure than subjects drawn from the general population. However, our data showing an association between time spent outdoors and XFS in 2 sites is consistent with data showing that indigenous people, who generally spend considerable time outdoors have higher rates of XFS than people living in comparable urban settings. For example, the prevalence of XFS in Navajo Indians in Arizona was 6%⁴⁹ compared to clinic-based estimates from southeastern US of 1.4 to 3%.^50.51

In conclusion, this work provides evidence for a role of reflected UV rays in contributing to XFS. It by no means excludes other genetic and environmental mechanisms in XFS pathogenesis. If confirmed in other studies, there could be reason to consider more widespread use of UV blocking eyewear in the prevention of XFS.