We identified 288 incident EG/EGS cases in the NHS and 60 incident EG/EGS cases in the HPFS during the study period. The total accrued person-time was 1,761,676 person-years (1,289,264 in the NHS and 472,412 in the HPFS). Of the 78,955 women and 41,191 men who ever contributed person-time, 5,482 (7.0%) women and 4,591 (11.2%) men reported Scandinavian ancestry, 12,967 (16.4%) women and 9,484 (23.0%) men reported Southern European ancestry, 58,662 (74.3%) women and 25,248 (61.3%) men reported other Caucasian ancestry, 1,119 (1.4%) women and 357 (0.9%) men reported African ancestry, 568 (0.7%) women and 671 (1.6%) men reported Asian ancestry and 157 (0.2%) women and 840 (2.0%) men reported Native American or Hawaiian ancestry. Hispanic/non-Hispanic ethnicity was only assessed in the NHS (n=656; 0.8% of women).
The mean age at diagnosis of EG/EGS was 68.1 ± 6.6 years in women and 70.8 ± 6.9 years in men (); female cases were much more likely to be diagnosed before age 65 years compared with men. The maximum IOP at diagnosis averaged 27.8 ± 6.3 mm Hg in women and 29.2 ± 7.6 mm Hg in men. There was a strong unilateral presentation of EG/EGS, where in 59% of the women and 63% of the men were affected in just one eye, although the right and left eyes were similarly affected. In about 41% of all EG/EGS cases, at least one abnormal VF in the eye(s) with exfoliation material was documented. Among all cases, 90% of women and 92% of men had elevated IOP; 55% of women and 60% of men had abnormal optic discs or glaucomatous VF loss in the affected eye. Family history of glaucoma, history of cataract and high cholesterol were more common in female cases than in male cases, whereas diabetes was less common in female cases than in male cases ().
Descriptive factors of exfoliation glaucoma cases in Nurses’ Health Study (n=288) and Health Professionals’ Follow-up Study (n=60) a
In the women, the percentage of the total person time from the northern, middle and southern tiers were 36%, 48% and 16%, respectively, while in men, the percentages were 32%, 39% and 29%, respectively. Most characteristics such as Scandinavian ancestry were evenly distributed across geographic tiers. More men with northern tier residence reported Southern European ancestry. Residence at birth, age 15 and age 25/30 were strongly associated with current residence, especially for the northern and middle tiers, indicating more migration to southern tiers in later life. Any differences in the distribution of variables that might confound the relation between geographic tier and EG/EGS were adjusted for in multivariable analysis.
Multivariable analysis indicates that EG/EGS is a strongly age-related condition (). Compared to those aged 40–55y, the risk of EG/EGS in those 75 years of age or older was 46.22-fold in pooled analysis (95% CI, 22.77 – 93.80). A family history of any glaucoma was associated with a doubling of risk of EG/EGS (MVRR = 2.29; 95% CI, 1.39 – 3.78). Men were 68% less likely to develop EG/EGS than women (MVRR = 0.32; 95% CI, 0.23 – 0.46). Among the covariates we adjusted for in multivariable analyses, vascular conditions such as DM, hypertension, history of myocardial infarction and hypertension were not significantly associated with EG/EGS risk (data not shown). Increasing BMI appeared to be inversely associated with EG/EGS risk, with significant associations for the BMI 26 to 28 kg/m2 category compared to BMI <22 kg/m2 (MVRR = 0.55; 95% CI, 0.37 – 0.83).
Age-adjusted and multivariable adjusted rate ratios for various risk factors for exfoliation glaucoma
People of Scandinavian (MVRR = 0.75; 95% CI, 0.48 – 1.17) and Southern European ancestry (MVRR = 0.98; 95% CI, 0.56 – 1.72) were not at increased risk of EG/EGS compared to the reference group of mostly other Caucasians, African-Americans, Asian-Americans and Americans of other racial heritage ().
Among men in whom eye color information was available, compared to those with blue or light eye color, having medium eye color (MVRR = 0.87; 95% CI, 0.43 – 1.74) or dark eye color (MVRR = 0.84; 95% CI, 0.42 – 1.68) was not associated with EG/EGS ().
Participants who reported current residence in the middle (MVRR = 0.59; 95% CI, 0.47 – 0.75) and southern tier (MVRR = 0.51; 95% CI, 0.37 – 0.69) had markedly reduced risks of EG/EGS compared to participants currently living in the northern tier ().
We also evaluated whether there may be associations with the longitude of current residence that were independent of latitude. We observed that longitude (in 3 categories: east coast to −84°, −84° to −104°, −105° to west coast) was indeed independently associated: compared with residence in the east, residence in the middle and western US was associated with lower risk (MVRR = 0.56; 95% CI, 0.36 – 0.88 and MVRR = 0.49; 95% CI, 0.32 – 0.76, respectively). However, the association with longitude was not observed in the northern tier but was most evident in the middle and southern tiers, which was in contrast to the association with latitude, which was apparent in all the longitude categories.
Similar strong significant inverse associations with living in the middle and southern tiers in relation to EG/EGS were observed when we evaluated multivariable models substituting current residence with residence at birth, residence at age 15 or residence at age 25/30 (data not shown). Because current residence was strongly correlated with residence at other life periods, and there may be different associations between residence and EG/EGS depending on the life period, we examined multivariable models for current residence that also simultaneously controlled for residence at birth, age 15 and age 25/30 (). Indeed, the association with current residence in the southern tier remained significantly inverse, but it was attenuated (MVRR = 0.67; 95% CI, 0.45 – 0.98) as was the association with residence in the middle tier, which was no longer significant (MVRR = 0.76; 95% CI, 0.53 – 1.10). Interestingly, in this model, residence at birth and age 25/30 were not independently associated with risk of EG/EGS, but residence at age 15 at either the middle or southern tier was strongly, significantly and independently associated with EG/EGS risk (middle tier: MVRR = 0.55; 95% CI, 0.32 – 0.94; southern tier: MVRR = 0.40; 95% CI, 0.16 – 0.99).
When we examined the long-term cumulative life residential history from birth to the current residence, compared to those who consistently lived only in the northern tier, those who consistently lived in the middle tier had a 47% reduced risk of EG/EGS (MVRR = 0.53; 95% CI, 0.40 – 0.71) and those who consistently lived in the southern tier had a 75% reduced risk of EG/EGS (MVRR = 0.25; 95% CI, 0.09 – 0.71) ().