Chemical stability of silicone oil in the human eye after prolonged clinical use.

OBJECTIVE: To investigate the assumption that silicone oil is chemically stable in the human eye after prolonged clinical use as a vitreous substitute. DESIGN: Experimental study. MATERIAL: Samples of silicone oil recovered from the vitreous cavities of 25 consecutive patients up to 26 months (mean, 9.2 months) after implantation and 4 different batches of original highly purified silicone oil with a kinematic viscosity of 5000 mPa.s were analyzed. Visible silicone oil emulsification was present in 18 of the 25 eyes. INTERVENTION: Gas chromatography/mass spectroscopy (GC/MS) was used to detect and characterize low-molecular weight components (LMWC). Gel permeation chromatography (GPC) was used to determine the molecular weight distribution of the silicone oils. Functional groups of the silicone oils were quantified and characterized by infrared (IR) spectroscopy and 1H nuclear magnetic resonance (1H NMR) spectroscopy. MAIN OUTCOME MEASURES: The sample oils explanted from the eyes were compared to the original oils with regard to LMWC, molecular weight distribution, and type and amount of functional groups. RESULTS: The GC/MS chromatograms showed no peaks indicative of LMWC in any of the 25 sample oils explanted from the eyes or any of the original oils. In the GPC chromatograms, the peak position occurred at the same retention times with identical signal shape in all original and sample oils, indicating that the molecular weight and the molecular weight distribution did not change after prolonged implantation. The IR spectroscopy and 1H NMR spectroscopy showed characteristic absorption bands at 1260 cm(-1) related to symmetric deformation vibration of the Si-CH3 group and at 800 cm(-1) related to the Si-(CH3)2 group. This was identical for all sample and original oils. CONCLUSIONS: Highly purified 5000-mPa.s silicone oils, used as prolonged retinal tamponades in patients with proliferative vitreoretinopathy, proliferative diabetic retinopathy, and tractional retinal detachment after central retinal vein occlusion, are chemically stable in the human eye and do not undergo chemical modification. The LMWC do not play a substantial role in the variations of oil emulsification.

Complement inhibition by FUT-175 and K76-COOH in a pig-to-human lung xenotransplant model.

Two complement inhibitors, FUT-175 (FUT) and K76-COOH (K76), were studied as single agents in an ex vivo, in situ model of pig lung rejection by human blood. Pulmonary toxicity (primarily increased pulmonary vascular resistance [PVR]) was seen with FUT at a dose which inhibited complement in vitro (0.4 mg/ml); a lower dose (0.1 mg/ml) was therefore used. K76 had little apparent toxicity at a dose which inhibited complement in vitro (6 mg/ml), but activated complement, leading to C3a elaboration. Efficacy was then assessed by 1) deposition of complement pathway components in the lung and 2) lung survival during perfusion with human blood. Neither agent consistently prolonged median lung survival (FUT: 50 min. +/- 28 SEM; K76: 37 +/- 16), blocked thromboxane production, or prevented PVR elevation compared to experiments using unmodified human blood (survival 9 min. +/- 2). At the doses used, both agents prevented deposition of terminal complement complex (TCC) in the lung. This finding demonstrates that the various phenomena associated with hyperacute lung rejection (thromboxane release, PVR elevation, capillary leak, and intraalveolar hemorrhage) can all occur despite abrogation of membrane attack complex formation. We can not exclude a contribution by drug toxicity or complement damage (mediated by C3a or other complement pathway components proximal to TCC) to the observed lung injury. We conclude that, although both FUT and K76 inhibit deposition of TCC in the lung, at the dose tested neither drug is useful as a single agent to prolong survival in a pig-to-human lung xenograft model.