Abstract
Purpose: :
Several studies have shown that insulin has no effect on intraocular pressure (IOP). However, in wake of recent renaissance of early insulin intervention in type 2 diabetes (see for example: Lancet 2008;371:1753), unexpected ocular findings from follow-ups of patients starting insulin therapy have justified a reassessment. Therefore, the present study aims at investigating the effect of insulin on IOP.
Methods: :
Type 2 diabetes patients, with no diabetic retinopathy and without therapy that could affect IOP, were periodically examined starting from 3 weeks before the initiation of SC insulin therapy. Animal studies on 48 female albino rabbits were done to investigate the tolerability of ocular insulin administration and insulin effect on IOP. Controls and negative controls received denaturated insulin and balanced salt solution (BSS) respectively. Examinations included body mass index (BMI) determinations (Humans), and measurements of IOP (Humans: Goldmann applanation tonometer; Rabbits: Tonopen AVIA, Reichert), blood glucose level at time of IOP measurement (Optium-Xceed, Abbott), and central corneal thickness (CCT) (SP 100, Tomey).
Results: :
21 patients have completed >6 months of follow-up on insulin therapy. There were no statistically significant differences in IOP compared to baseline in first month of insulin therapy. Though statistically significant differences were prominent by the end of third month with Insulin IOP lowering effect being inversely correlated to the BMI (31.26±4.0, 12.74±8.6, and 9.81±5.91 % lower IOP, for BMI groups of less/=25.0, >25.0-30.0, and >30.0 Kg/m2 respectively). In rabbits, 6 daily instillations of 8 µl of Insulin (Humulin 70/30, Lilly) on corneal surface was the most tolerated and effective protocol in lowering IOP. In treated eyes of this protocol, IOP was statistically significant lower than baseline at days 26-32 and from day 34 on, being 35.23±4.7 % less at 2 months after initiation of insulin (7.24±5.08 and 5.14±4.28 % for the denaturated insulin and BSS respectively). In both humans and rabbits, no correlation was found with blood glucose and there were no statistically significant changes in CCT compared to baseline.
Conclusions: :
The association between IOP and insulin resistance was reported previously. However, this is the first report to suggest an ocular hypotensive effect of insulin, not correlated to changes in blood glucose or CCT. More studies are needed due to the small sample size of this observational study and more preclinical studies should be done to address formulation challenges. Clinical studies are invited to address the effect of insulin on IOP in non-diabetic subjects.
Keywords: intraocular pressure • diabetes • drug toxicity/drug effects