Objectives: In this pilot study, the effect of 970 mg Chi-Ju-Di-Huang-Wan (CJDHW) plus 30 mg four-substance decoction (Si Wu Tang; CJDHWSWT) was evaluated, in terms of its ability to alleviate dry eye symptoms and its therapeutic mechanism. Methods: This double-masked prospective investigation has recruited dry eye patients who have been randomly selected into two groups, namely treatment (n = 15) versus nontreatment (n = 15). In the treatment group, a daily oral intake of CJDHWSWT plus eye drops systane ultra was given for 90 consecutive days. In the nontreatment group, only defined eye drops were prescribed. The examinations included Schirmer's test, fluorescein-stained superficial punctate keratitis (SPK), artificial tear consumption, tear vascular endothelium growth factor (VEGF) level, and ocular surface disease index. The drug safety tests included liver and kidney functions, and complete blood counts. The candidates were observed during the screening visit and the following three monthly follow-ups. The data were analyzed by unpaired Student's t-test. Results: Compared to no significance in the nontreatment group, CJDHWSWT significantly (p = 0.03) increased the tear secretion after 3 months of intake. Furthermore, in contrast to no significance in the treatment group, there were significant alterations, including (i) increased fluorescein-stained SPK areas (p = 0.03); (ii) increased artificial tear instillation amount (p = 0.03); (iii) elevated tear VEGF protein levels (p = 0.03) in the nontreatment group; and (iv) significant improvement in clinically relevant phenomenon (e.g., reading limit and uncomfortable feeling in windy conditions), after treatment of artificial tear plus oral intake of CJDHWSWT. As shown by the post-treatment normal defined laboratory data, there were no adverse drug effects. Conclusions: This study has supported that CJDHWSWT is safe and effective in relieving dry eye's clinically relevant symptoms/phenomena. CJDHWSWT avoided the tear VEGF upregulation probably induced by dry eye-associated hypoxia/ischemia.
Keywords: Chi-Ju-Di-Huang-Wan; Si Wu Tang; dry eye; ischemia; tear vascular endothelium growth factor.