INTRAVITREAL INJECTION OF OCTREOTIDE ACETATE

This study was conducted to determine the feasibility of injecting the somatostatin analogue, octreotide acetate (OA), into the vitreous cav ity. Previous work suggests that octreotide effectively inhibits angio genesis in vitro, thus its use in vivo may slow the progression of pro liferative eye disease. Fifty micrograms of aqueous OA in 50 mu l aque ous solution was injected into the mid-vitreous of kitten eyes (n=6), and OA levels were monitored over 4 days. A long-acting release form o f octreotide (OA-LAR) was also injected into the mid-vitreous of rabbi t eyes at doses of 0.36 (n=16), 1.1 (n=1), 2.1 (n=1), 4.05 (n=1), 8.2 (n=1), and 36 mg (n=3) in solution; and octreotide concentrations were measured at various time points over 42 days. OA concentrations were determined by a highly specific radioimmunoassay. Aqueous octreotide w as eliminated rapidly (t1/2=16 hours) from the vitreous of the kitten eye, with only negligible amounts recoverable 4 days post-injection. I n the long-acting form, OA in the rabbit eye reached peak levels at 28 days. By 42 days, OA levels had declined to the 14-day level. Doses o f OA-LAR of 1.1 mg or less produced no gross evidence of clinical toxi city and elicited no grossly visible ocular side effects. Doses greate r than 1.1 mg produced significant toxicity, including cataracts and r ubeosis. The 28-day peak release for long-acting OA implies that month ly intravitreal injections could provide continual high levels of OA. Intravitreal injection of long-acting OA provides sustained, high conc entrations of drug, and deserves further study as a potential treatmen t of proliferative eye diseases.