Inhibition of diclofenac formulated in hyaluronan on angiogenesis in vitroand its intraocular tolerance in the rabbit eye

Purpose: To investigate the effect of diclofenac, a potent nonsteroidal ant i-inflammatory drug, formulated in hyaluronan (diclofenac/HA) on angiognesi s in vitro and its intraocular toxicity in vivo. Methods: The effect of dic lofenac/HA on angiogenesis was determined by choriocapillary endothelial ce lls on Matrigel stimulated by vascular endothelial growth factor (VEGF). Th e tube areas were quantified by image digital analysis. For toxicity study, diclofenac/HA was injected intravitreally with a dose range from 100 to 10 80 mu g in 26 rabbits following gas compression vitrectomy, Potential toxic ity was assessed by indirect ophthalmoscopy and by histological studies (li ght and electron microscopy). Retinal function was monitored by electroreti nography (ERG) in six rabbits that received 400 mu g of diclofenac/HA. Resu lts: Diclofenac/HA, 180, 90 mu g/ml, inhibited tube formation to 24% and 55 % of the standard group (Media Ham's F12 plus 5% fetal calf serum and 50 ng /ml VEGF) respectively (P<0.01). Intravitreal injection of 540 mu g or high er doses of diclofenac/HA resulted in ocular toxicity in the rabbit, demons trated as cataract, vitreous haze and retinal damage observed by indirect o phthalmoscopy and light- and electron-microscopic examinations. No toxicity was observed in the eyes that received 400 mu g or less diclofenac/HA, whi ch was further supported by the normal ERG examined at 4 and 25 days post i njection. Conclusions: Diclofenac/HA inhibits tube formation in vitro and i s nontoxic to the rabbit retina at concentrations that are inhibitory to tu be formation. Our results suggest diclofenac/HA may be an effective candida te to inhibit ocular neovascularisation related to granulomatous reaction i n the eye.