EFFECTS OF AN INTRAVITREAL DAUNOMYCIN IMPLANT ON EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY - SIMULTANEOUS PHARMACOKINETIC AND PHARMACODYNAMIC EVALUATIONS

Intravitreal daunomycin (D) effectively suppresses cellular proliferat ion in experimental proliferative vitreoretinopathy (PVR) but has a na rrow therapeutic safety range. Studies were undertaken to reduce toxic ity of D by preparing a slow-release implant using polysulfone capilla ry fiber (PCF). Fabrication of the implant involved loading PCF with 1 % D in tristearin (w/w), an excipient with diffusion-retardant propert ies. Two dose levels of the PCF-D device (15 mu g and 30 mu g/device) were prepared and sterilized prior to use. To examine the kinetics and efficacy of the device, rabbits were randomized and eyes were implant ed as follows: 1) control group (PCF vehicle); 2) PCF-D (15 mu g/devic e); 3) PCF-D (30 mu g/device). Immediately after implantation, all eye s received an intravitreal injection of 2.5 x 10(5) retinal pigmented epithelial (RPE) cells. Thereafter, tractional retinal detachments (TR D) were graded by ophthalmoscopic examination. Also, fluorophotometry scanning from the retina to the anterior chamber was performed to dete rmine the intraocular bioavailability of D. Results showed a therapeut ically sustained level of D up to 21 days after device implantation. M idvitreous concentration of D was greater in group 3 than group 2 at a ll time points examined, indicating a dose-proportional increase in D release. Results of the PVR study showed that by 7 days after treatmen t, all eyes implanted with the PCF vehicle developed stage 2 TRD or gr eater; only 1 eye in each of groups 2 and 3 developed stage 2. By 2 we eks, most eyes in groups 2 and 3 remained in stages 1 and 2 with only 2 eyes progressing to stages 3 and 4 TRD. By 5 weeks, all eyes in grou p 1 showed stages 4 and 5 TRD, while most eyes in groups 2 and 3 remai ned in stages 1 and 2. The device with 30 mu g D was more effective in preventing TRD. In conclusion, these data indicate that PCF can reduc e the toxicity of D and may be a useful implant for treatment of PVR.