Title : Formation of water-in-oil droplets in intraocular silicone oil: In vivo evidence of a protein-active multiphase system
Abstract:
Silicone oil (SO) is widely used as a long-term intraocular tamponade in retinal detachment surgery; however, its multiphase behavior in vivo remains incompletely understood. Although oil-in-water (O/W) emulsification has been extensively investigated, the potential formation of water-in-oil (W/O) droplets within the oil phase has not been systematically evaluated. The aim of this study was to experimentally verify the formation of W/O droplets during prolonged vitreous tamponade and to elucidate the mechanisms governing their formation and stability. Using a controlled porcine model complemented by analysis of explanted human SO samples, we provide the first systematic in vivo evidence of W/O droplet formation during long-term intraocular tamponade. Water-in-oil droplets were directly detected within the vitreous cavity, demonstrating that intraocular SO does not behave as a strictly continuous single-phase fluid but rather as a dynamic multiphase soft material. Droplet size distribution was strongly influenced by sampling conditions. Aspiration through narrow-gauge needles resulted in shear-induced fragmentation of pre-existing droplets, whereas co-aspiration of aqueous fluid during infusion generated substantial artifacts. These findings indicate that clinical explantation represents a microcapillary shear process capable of significantly altering ex vivo microstructural assessment. Oil viscosity modulated the sensitivity of the system to shear stress but did not determine droplet occurrence. Complementary in vitro experiments confirmed that needle passage fragments existing droplets rather than inducing de novo formation. Integration of in vivo observations with in vitro phase behavior and interfacial viscoelasticity data supports a mechanistic framework in which shear-driven emulsification in protein-containing environments, together with protein-mediated interfacial stabilization, governs the formation, persistence, and fragmentation of water/oil droplets in oil-dominant biological systems. Although clinical outcomes were not directly assessed, the presence of water-containing inclusions may influence optical properties, tamponade mechanics, and interactions with intraocular tissues. These findings reconceptualize intraocular SO as a protein-active, closed multiphase biomaterial system and highlight the critical role of interfacial phenomena and sampling-induced artifacts in the interpretation of viscous biological materials.
