Background
Glaucoma is a progressive ophthalmic disease that has the characteristics of optic disc cupping and visual field defects [
1]. A family history of glaucoma, high myopia, and high intraocular pressure (IOP) are known as risk factors of glaucoma [
2]. Among the various known risk factors, IOP is considered the most important and controllable [
3‐
5].
Although the underlying mechanism of increased IOP is still unclear, a recent study suggested that it might be associated with various health indices, such as hypertension, diabetes, and obesity [
6‐
8]. Reaven [
9] indicated that poor health indices, such as abdominal obesity, diabetes, and hypertension, share a single common mechanism that contributes to insulin resistance and glucose intolerance and therefore gave it the name “X syndrome”, which has now been changed to metabolic syndrome (MetS).
The diagnostic criteria for MetS were first announced in 1998 by the World Health Organization (WHO) [
10]. Later, the National Cholesterol Education Program-Adults Treatment Panel III of the United States proposed MetS criteria that were more clinically applicable than those announced by the WHO, and these criteria are widely used [
11]. Since then, various organizations have proposed slightly different criteria in consideration of ease in diagnosis, and, recently, in 2009, the International Diabetes Federation; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity reorganized the various criteria for MetS [
12]. Although many studies have reported on the association between MetS and IOP, the relationship between MetS components and IOP is not well known. With each component of MetS not independent but correlated, the present study aimed to identify the correlation of IOP with the number and combination of MetS components.
Discussion
Metabolic syndrome is a type of disease cluster in which the primary risk factors for cardiovascular diseases, such as hyperglycemia, hypertension, dyslipidemia, and abdominal obesity, occur simultaneously, and many studies have examined this since the WHO presented the criteria for defining MetS in 1998 [
10]. However, even before the concept of MetS was established, studies were conducted on the relationships between factors that comprise MetS and IOP. Many reports have indicated that, in people with obesity, which is one of the components of MetS, the IOP is increased because of a decrease in the aqueous humor outflow due to an increase in orbital fat and episcleral pressure [
14‐
16]. Moreover, high BP increases the pressure in the intraocular ciliary artery, which promotes the formation of the aqueous humor that increases the IOP, and, hence, the association between IOP and hypertension has been confirmed in various studies [
16,
17].
Higher serum TG, which is one of the two lipid parameters that comprise MetS, is known to increase the IOP. Klein et al. [
18] indicated that, with higher serum TG levels, there is a greater amount of orbital adipose tissue, which causes an increase in orbital pressure, which causes an increase in IOP by inducing an increase in episcleral pressure and a decrease in aqueous humor outflow [
19]. Moreover, it has been reported that higher fat intake and an increased severity of obesity results in increased TG levels, whereas HLDC, which is another component of MetS, has a low value, which is the result of increased episcleral pressure and IOP due to an increase in the vascular sclerosing changes and serum osmolality [
16].
Hyperglycemia has also been reported to be closely associated with IOP. The continuous fluid inflow into the eyeball from osmotic pressure that is caused by hyperglycemia and the autonomic nervous system dysfunction that is observed in diabetics can induce increased IOP. Additional studies are needed to find out their exact mechanism [
20‐
22].
In addition to the worldwide increase in the obese population, the prevalence of MetS is also showing an increasing trend, and it was reported that 15–25 % of Korean adults suffer from MetS [
23,
24]. For this reason, interest in MetS has risen, and many studies on the association between MetS and IOP have been published [
25‐
29]. However, up to now, there have been no reports on the correlation with IOP based on the number and combination of MetS components.
The present study showed that, even within MetS group, the presence of more components of MetS was associated with a higher IOP. As explained earlier, this is because each MetS component is causing factor of increased IOP. In the group with three components of MetS, whitch included the criteria for TG, abdominal obesity, and fasting glucose, the highest risk for IOP increased was shown. In addition, the probability of the IOP increased was significantly higher in the groups that satisfied the criteria for BP, TG, and abdominal obesity; the combination of BP, TG, and fasting glucose criteria; and the combination of BP, abdominal obesity, and fasting glucose criteria.
However, all of the cases that had the HDLC criteria as a component did not have a statistically significant higher risk of IOP. HDLC itself, as shown in Table
1, showed significant differences according to the IOP. However, in the combinations of MetS components, the effect on IOP was relatively limited and was actually influenced more by other factors. Such an interpretation can also be seen in other studies on IOP and lipid parameters, and many reports indicate that serum TG and total cholesterol are positively correlated with IOP, whereas HDLC does not show a corresponding correlation with IOP. High HDLC is negatively correlated with IOP [
17,
30,
31], but one report claims a positive correlation with IOP as well [
16]. A recent study on Koreans reported a negative correlation between HDLC and IOP in a multiple regression analysis that compensated for age, obesity, and BP [
32]. But additional studies appear to be needed to understand the influence of HDLC on IOP in depth.
In groups with four or more components of MetS, the group with BP, HDLC, abdominal obesity, and fasting glucose criteria was the only group that did not show a significant correlation with IOP increase, and, interestingly, compared to the group with all five components, the group with BP, HDLC, TG, and fasting glucose criteria as its components showed the higher risk of IOP increase. However, whether the IOP increases in MetS groups are actually different based on their component combinations is something that requires additional study, as the number of subjects was too small compared to the entire study population when the groups were subdivided according to the MetS components. The genomic variates of subjects could be one of the factors which cause the IOP increases as well [
33].
The present study had a few limitations. First, because the present study was based on the regular medical checkup in health promotion center, there was no information of cup to disc ratio and visual field analysis. So it was difficult to investigate the relationship between the glaucoma and metabolic syndrome components with their different combinations. Second, we did not measure central corneal thickness. However, if the IOP that was adjusted according to the central corneal thickness was used, it may have been possible to increase the accuracy. Third, although noncontact tonometers are reliable for testing within normal IOP ranges, the use of a Goldmann applanation tonometer would have given more accurate IOP measurements. Fourth, because the present study was a cross-sectional study, it was difficult to identify the causal relationships. Finally, there was no systemic approach about lifestyle that may have influenced IOP such as smoking history, drinking history, and the frequency of exercise.
Despite these limitations, this study has significance in that it showed not only the fact that each component of MetS is mutually dependent but also the fact that different combination of Mets components has correlation with IOP increase. If additional follow-up studies are conducted, the findings can be used as an indicator for predicting IOP increases in patients with MetS.