Here we investigated whether seasonal climatic changes affect the incidence of RVO in Japan, and found a significant variation among six 2-month periods in a year. We found increased incidence in January/February and May/June periods compared to the trough July/August period. Interestingly, statistically significant two-peak/one-trough pattern was detected only in the subpopulation of females, although similar tendency was observed for most of the subpopulations. The results in some previous studies [17-19] were similar to those in this study, with a higher incidence of RVO in winter (January/February) and a lower incidence in summer (July/August). However, studies conducted in Iowa City, Iowa, USA and (countrywide) in Armenia did not find any seasonal variation in the onset of CRVO [20, 21]. The average monthly temperatures in each of the previous study locations are shown in Figure 5. A study investigating seasonal variation in stroke onset found that there was only an association in locations where the annual temperature differential was greater than 10 °C [16, 22] . In the aforementioned studies that found significant seasonal variation in the onset of RVO, the annual temperature differential was more than 10 °C. However, the studies conducted in Iowa City and Armenia, which did not find any seasonal variation in the onset of RVO, were also in regions that have an annual temperature differential of more than 10 °C. Therefore, the conclusion regarding the impact of the temperature differential is not universally applicable. It is anticipated that factors such as patient race and access to heating equipment could influence these findings, and future studies will need to elucidate the impact of those factors, as well as explore additional geographical regions, to clarify the influence of weather conditions on RVO.
In this study, RVO tended to develop more in January/February and May/June and less in July/August. The RVO rates may be related to low temperatures in January and February and high humidity in May and June (the rainy season in Japan). A bimodal pattern was also reported in London [18], where the first peak is observed in winter and the second peak coincides with the beginning of rainy season (September). In another vascular occlusive disease, cerebral infarction, some studies showed that its occurrence was highest in summer [9], some in winter [10]. As possible mechanisms contributing to vascular occlusion, it has been suggested that arteriosclerosis and venous obstruction are more prominent during winter, with dehydration prevalent in the summer [23]. As we found the incidence of RVO to be lowest during the summer, dehydration may not be a risk factor for the onset of this condition. In addition, the onset of cerebral hemorrhage and myocardial infarction have been found to be lower in summer and higher in winter [24, 25], which is in accordance with the findings of this study. Also, some studies show the existence of a highly significant seasonal pattern in the occurrence of DVT, characterized by a winter peak [14, 15] and DVT is associated with high vapor pressure [15]. These studies suggest that lower temperature and high vapor pressure may lead to the higher incidence of vein thrombosis. It is tempting to hypothesize that our observation of another peak in the May/June period might be due to the high vapor pressure, in spring, before reaching the high temperatures of summer. However, it needs to be determined whether this pattern of bimodal peaks is repeatedly observed, especially in other countries with rainy seasons.
Another factor that may account for the seasonal variation is blood pressure fluctuation. Hypertension has been reported to be a major risk factor for cerebral hemorrhage and myocardial infarction, and is believed to also be important for the development of RVO [4]. However, we did not found any statistically significant effect of the patients’ history of hypertension. This could be due, at least in part, to the fact that some of the patients were already on treatment for hypertension. However, this does not exclude an effect of seasonal changes in blood pressure on the incidence of RVO. For example, a negative correlation between atmospheric pressure and systolic blood pressure has been observed [26]. In addition, respiratory and circulatory system parameters, such as ventilation, heart rate, blood pressure and red blood cell count, increase when the temperature or atmospheric pressure decreases [11]. In addition to the blood pressure changes, the climate in winter has been shown to affect the parameters that explain the increased risk of arteriosclerosis, vein occlusion and hypertension during that season. For instance, catecholamines, cholesterol and vasopressin increase during winter [27]. Low temperature is associated with an increase in blood viscosity. Low temperature may also cause an increase in platelets, erythrocytes and fibrinogen, and a decrease in antithrombin III [6, 7]. It has also been suggested that lower blood levels of vitamin D in winter may be related to an increased incidence of CRVO [28].
This study had some limitations. There was a recruitment bias with our cohort, whereby patients were only eligible to be included in the study if they visited the hospital. This excluded patients who were asymptomatic or those who did not visit the hospital because of a lack of concern about their condition. Of the patients who did visit the hospital, those for whom the date of RVO onset could not be established were excluded from the study; which may also introduce some bias. In addition, the effect of cardiovascular risk factors other than hypertension, such as smoking, diabetes and hypercholesterolemia, were not investigated in our study. Finally, as this study was only conducted over a short period (48 months) and at a single facility, future studies should focus on longer-term recruitment and multiple sites.