Study finds direct link between diabetes, elevated intraocular pressure
Individuals with diabetes or long-term hyperglycaemia appear to have higher intraocular pressure (IOP), with central corneal thickness (CCT) representing a meagre proportion of mediating effect to the total effect of diabetes on IOP, according to a cross-sectional study from Singapore.
“Our findings suggest that higher IOP associated with diabetes is not primarily mediated through thicker CCT,” the investigators pointed out. “[T]his … may have pathophysiologic significance with respect to the risk of glaucoma among persons with diabetes.”
The study included 8,636 individuals (mean age 57.7 years; 49.5 percent male) participating in the Singapore Epidemiology of Eye Diseases study, among whom 2,524 (29.23 percent) had diabetes. Compared with participants who had no diabetes, those who did were older, had higher systolic blood pressure, higher body mass index, poorer best-corrected visual acuity and shorter axial length. [Invest Ophthalmol Vis Sci 2018;59:2205-2211]
Notably, CCT did not significantly differ between participants with and without diabetes (mean CCT, 545.05 vs 544.56 μm, respectively; p=0.542), whereas IOP was markedly higher in diabetic participants (mean, 15.92 vs 14.86 mm Hg; p<0.001) of both sexes (males: 0.55 mm Hg higher; females: 0.83 mm Hg higher; p<0.001 for both).
In multivariate regression models, diabetes, higher serum glucose and glycated haemoglobin (HbA1c) levels were all associated with higher IOP (p<0.01 for all). Further analysis revealed that CCT partially and minimally mediated the total effect of diabetes on IOP, and the proportion of mediating effect of CCT was 11.09 percent.
Factors such as axial length and spherical equivalent did not mediate the association between diabetes and IOP. The observations were consistent across three ethnicity groups: Malay, Indian and Chinese.
While the exact physiological mechanism underlying the association between diabetes and higher IOP is unclear, the investigators explained that long-term hyperglycaemia might induce changes that increase IOP given that HbA1c levels were associated with IOP irrespective of diabetes status.
The said changes could be related to the accumulation of advanced glycation end products, which have been reported to promote cellular senescence and induce apoptosis of human trabecular meshwork cells. Dysfunction of the trabecular meshwork may in turn lead to an increase in IOP. [Ophthalmol 2012;26:123-131]
Another potential mechanism pertains to the effects of TGF-β, the concentration of which is known to be heightened in the aqueous humor and trabecular meshwork of eyes of patients with diabetes or glaucoma. [Jpn J Ophthalmol 2002;46:249-253]
Despite the study’s strengths including a large sample population from three ethnic groups with high participation rates (response rate, 75.6 percent), the investigators admitted that the study design prevented inferences of causality and that they were not able to investigate the contribution of other factors that may explain the link between diabetes and higher IOP.