Octreotide,a Somatostatin Analogue,Fails to Inhibit Hypoxia-induced Retinal Neovascularization in the Neonatal Rat

Objective: Octreotide, a somatostatin analogue, hasbeen shown to prevent angiogenesis in diverse invitro models. We evaluated its effect on retinal neovascularizationin vivo, using a neonatal rat retinopathymodel. Methods: We used, on alternating days, hypoxia(10% O₂) and hyperoxia (50% O₂) during the first 14days of neonatal rats, to induce retinal neovascularization.Half of the rats were injected subcutaneouslywith octreotide 0.7 μg/g BW twice daily. Atday 18 the eyes were evaluated for the presence ofepiretinal and vitreal hemorrhage, neovascularizationand epiretinal proliferation. Octreotide pharmacokineticsand its effect on serum growth hormone(GH) and insulin-like growth factor I (IGF-I) wereexamined in 28 rats. Results: Serum octreotide levels were 667 μg/1 twohours after injection, 26.4 μg/1 after nine hours and3.2 μg/1 after 14 hours. GH levels were decreasedby 40% (p = 0.002) two hours after injection butthereafter returned to baseline. IGF-I levels were unchangedtwo hours after injection and were elevatedby 26% 14 hours after injection (p = 0.02). Epiretinalmembranes were highly associated with epiretinalhemorrhages (p < 0.001), while retinal neovascularizationwas notably associated with vitreal hemorrhages (p < 0.001). Conclusions: Twice-daily injections of octreotidefailed to produce sustained decrease in serum GH,but produced rebound elevation of serum IGF-I.Accordingly, no statistically significant effect of injectionson retinal pathology was noted. This finding,however, does not contradict our assumptionthat GH suppression may decrease the severity ofretinopathy.