Randomised controlled trial on effects of topical insulin compared to artificial tears and normal saline on tear inflammatory mediator levels and clinical parameters in diabetics with dry eye disease.

Purpose: To assess the short-term effects of topical insulin (TI) as compared to topical Systane Ultra^TM (Alcon, USA) as artificial tears (AT) and topical normal saline (NS) on tear inflammatory mediators; interleukin 1-alpha (IL-1a), interleukin 6 (IL-6) and matrix metalloproteinase 9 (MMP-9) and clinical dry eye parameters in diabetics with dry eye disease (DDED).

Methods: In this randomized, multi-arm parallel single-centre trial, 73 diabetics with dry eye disease (30 female and 43 male) aged 18 to 50 years were recruited. They were randomly assigned to four weeks of treatment of either TI 0.5 unit/drop, AT or NS four times per day. Tear sample analysis and clinical parameters of dry eye (Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), corneal Oxford score and Schirmers test) were evaluated at baseline and four weeks later. Objective clinical parameters for corneal Oxford score and tear break-up time were assessed by two masked investigators.

Results: Significant reduction was seen in all inflammatory biomarkers (IL-1a, IL-6 and MMP-9) in all treatment groups at 4 weeks. In addition, inflammatory biomarkers demonstrated a significant reduction with TI (p < 0.001). Meanwhile, in AT and NS groups, reduction was also significant but less than TI group. Similarly, significant improvements were seen in all clinical parameters evaluated with all 3 treatments at 4 weeks; with TI group showing largest improvement as compared to AT and NS groups (p < 0.001). This is supported with the results as follows: mean difference -20.90 for OSDI as compared to -11.38 and -6.78 for AT and NS groups, respectively, 5.55 s for TBUT as compared to 3.00 s and 1.00 s for AT and NS group respectively, -2.40 for Oxford score as compared to -0.38 and -1.39 for AT and NS group respectively, and 5.20 mm for Schirmers test as compared to 3.00 mm and 1.00 mm for AT and NS group respectively.

Conclusion: Treatment with TI resulted in the greatest reduction in inflammatory biomarkers and ocular eye parameters, as compared to AT and NS. TI was most effective in improving clinical parameters of DDED, although all topical therapies showed significant improvements, suggesting that use of TI may be beneficial in treating DDED.