Experimental Study On Safety Of Fluorouracil Sustained-release Implants In Orbit

[Objective] To investigate systemic side effects of Fluorouracil Sustained Release for Implant(FSRI) after implantation in rabbit orbit. The pathological change of local conjunctiva and cornea, especially retina, optic nerve were to be observed.[Methods] 30 rabbits were randomly divided into 5 groups, A1 group (high dose group), A2 group (middle dose group), A3 group (low dose group), B group (placebo group), C group (intravenous injection control group),6 rabbits and 12 eyes per group, leukocyte (WBC) values were examed from ear vein before operation. A1 group:orbital implant FSRI 60mg; A2 group:orbital implant FSRI 40mg; A3 group:orbital implant FSRI 20mg; B group:orbital implant placebo 40mg; C group:intravenous injection fluorouracil 40mg. Observed the eyes by using slit lamp and detected WBC at 7,14,28 days after operation. Removed the rabbit eyes after 28 days. Conjunctival and subconjunctival tissue, local cornea, sclera, superior rectus, choroid, retina and optic nerve were examined in histopathology.[Results] There were different degrees of alleviation in conjunctival hyperemia and edema in each group after 10-14 days.31 eyes in A1, A2 and A3 group, which accounted for 86.1%(31/36), wound healing achieved Class A, and 4 eyes in A1 group,1 eye in A2 group, wound healing achieved B. The ratio of corneal transparency in three group was 77.8% (28/36),4 eyes in A1 group,3 eyes in A2 group,1 eye in A3 group had corneal edema. The remaining ocular examination was normal. Wound healing achieved Class A in group B, and ocular examination was normal.Pathological examination revealed different degrees of conjunctival tissue necrosis in A1, A2 and A3 group (10 eyes in A1 group,8 eyes in A2 group and 4 eyes in A3 group); fibrous tissue appeared hydropic degeneration, or accompanied by local conjunctival epithelial cells hyperplasia. Conjunctival edema appeared in site of incisal opening, which was about 3mm from implantation.4 eyes in A1 group,3 eyes in A2 group and 1 eye in A3 group appeared corneal stroma edema.2 eyes in A1 group,2 eyes in A2 group,1 eye in A3 group and 2 eyes in B group appeared superior rectus edema and muscle fiber fissure.WBC examination before the operation, showed no significant difference in each group (F=0.969, P=0.442). B group compared with the other four groups were statistically significant differences in WBC.[Conclusion] Preliminary findings show that the Fluorouracil Sustained Release for Implant(FSRI) has some security in orbital implanting, which has good prospects in obital tumor therapy. The FSRI has significant effects of chemotherapy to surrounding tissue. The impact of the drug is decided to dose and location. Control of implantation dose, can reduce the drug on the local side effects. Implantation of FSRI can significantly reduce the systemic toxicity of intravenous chemotherapy.