The prevalence of ES is known to vary worldwide, with a gradient by latitude. Reported ES prevalences in Sri Lanka (latitude, 7°N),51 South India (12°N),52 Pakistan (30°N),53 Greece (39°N),54 and Sweden (62°N)33 are 1.1%, 3.8%, 6.5%, 11.9%, and 23%, respectively. In 2 clinic-based US studies, which might overestimate the burden of ES because of referral bias, the prevalences were low: 3% in adults 60 years or older in North Carolina (latitude, 35°N)46 and 1.4% in Louisiana (30°N).55 In the present study, crude prevalences of ES in various US states were considerably lower than previously reported estimates for Europe and Asia. Mississippi (latitude, 32°N) had the lowest crude prevalence (0.23%), whereas Minnesota (45°N) had the highest (2.84%) (data not shown). The lower prevalences in the present study have many possible explanations. Nevertheless, in this study, where patients' residences spanned a latitude range of 15°, living in the northern continental US tier was associated with an increased hazard for ES; residing in North Dakota was associated with the highest risk of ES relative to living in Missouri. The association with latitude was the same in white and nonwhite beneficiaries, suggesting that a trend toward genetically predisposed Northern Europeans populating northern-tier states does not explain these findings. Colder temperatures in summer and winter months increased the hazard of ES. Many of the highest reported ES prevalences are from countries with cold mean temperatures. For example, ES prevalences in Icelanders, Finns, and Lapps are greater than 20%.32,34,56- 57One explanation may be that the extracellular deposits of ES represent a nucleation reaction58 that is prone to develop at lower temperatures. Although the temperature in the vascular iris may be close to the core body temperature, the temperatures in the avascular ocular segments, such as the anterior chamber and lens, may be susceptible to ambient temperatures.15 One notable exception to the cold-precipitation hypothesis was a study59 in which the ES prevalence in Inuits in Alaska, Canada, and Greenland was 0%. Perhaps in Inuits a thicker iris and more abundant periorbital fat help to keep ocular temperatures high enough to prevent extracellular deposit formation.60 Alternatively, the finding could be related to cultural practices—style of dress or housing design—that may modulate climate impact.