Abstract
Purpose :
A comparative assessment of the distribution and safety of cyclophosphamide (CPA) in anterior ocular segment and blood samples following subtenon sustained controllable drug infusion (SSCI) and traditional intravenous injection (IV) route.
Methods :
Sixty New Zealand white rabbits were randomly divided into two groups: SSCI group and IV group. Thirty rabbits received CPA (20mg/ml) via SSCI method with the flow rate of 0.1ml/h for 10h. The IV group, CPA (6mg/kg) was administrated to 30 rabbits via IV route. Concentrations of CPA in the ocular tissues (aqueous humor, cornea, iris/ciliary body, lens) and plasma were measured at 1 hour, 3 hours, 6 hours, 10 hours and 24 hours, and analyzed by ultra-high-performance liquid chromatographic method. Random series of 6 rabbits were humanly killed at 1 hour, 3 hours, 6 hours, 10 hours and 24 hours in each group. The eyeballs were clinically examined and then prepared for histopathologic examination to evaluate the safety of CPA in both groups.
Results :
The mean aqueous CPA concentration in SSCI group showed significantly higher than that in IV group at 1,3,6,10,24 hours (t=6048, 4.184, 6.097, 8.480, 3.342; p=0.000, 0002, 0.000, 0.000, 0.007 respectively). At 24 hours, mean CPA concentration for SSCI and IV groups were as follows: plasma 5.66±2.92ng/ml, 7.59±3.08ng/ml (p=0.00); aqueous: 53.47±31.63ng/ml, 9.77±5.10ng/ml (p=0.00); lens:75.42±21.93ng/g, 10.14±571ng/g (p=0.00); iris body 312.9±99.75ng/g, 89.14±9.47ng/g (p=0.00) respectively. The mean CPA concentration at 24 hours in the cornea and lens were significantly higher in SSCI group. Peak CPA concentration in SSCI group was at 3 hours in iris body, and at 1 hour in the aqueous, cornea and lens. Histological examination results showed no inflammation and tissue damage in ocular tissues of all rabbits in this study.
Conclusions :
Our results suggest that SSCI can delivery moderately higher and sustained CPA concentration in the anterior ocular segment comparison to IV in rabbit eyes, thus indicating that SSCI might be a therapeutic alternative to treat a variety of intractable anterior segment diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.