In vitro silicone oil emulsification in retinal detachment treatment: Methods, designs, and future strategies

Silicone oils are widely used as intraocular tamponade agents in vitreoretinal surgery, particularly in the treatment of complex retinal detachments and other severe posterior segment pathologies such as proliferative diabetic retinopathy, macular holes, ocular trauma, or endophthalmitis. While they offer mechanical support for retinal reattachment, their prolonged intraocular presence is associated with the risk of emulsification, i.e., a process in which the oil phase breaks into subvisible droplets that can obstruct aqueous outflow and compromise visual outcomes. Although emulsification is frequently attributed to interfacial shear stresses generated during ocular motion, especially saccades, the underlying mechanisms remain poorly understood due to the multifactorial nature of the intraocular environment. This review provides a comprehensive analysis of experimental approaches used to investigate silicone oil emulsification, including vortex systems, mechanical shakers, artificial eye chambers, and microfluidic eye-on-a-chip platforms. We critically evaluate the physicochemical and biomechanical parameters influencing droplet formation. Despite significant progress, data from current in vitro models remain heterogeneous and often difficult to compare due to differences in design, fluid composition, and analytical endpoints. Based on the collective evidence, we propose a set of experimental recommendations aimed at emulsification in vitro, including the use of high-molecular-weight modified oils, standardized fluid compositions, advanced eye-mimicking platforms, and improved experimental and analytical protocols. Finally, we highlight the potential of next-generation testing platforms and biocompatible tamponades to offer physiologically relevant, reproducible, and standardized assessment of emulsification resistance. These insights aim to guide the rational design of improved tamponade agents and testing methodologies in future vitreoretinal applications. STATEMENT OF SIGNIFICANCE: Silicone oils are widely used as tamponades in retinal detachment surgery, yet their long-term stability is compromised by emulsification, leading to severe complications such as glaucoma. Although many in vitro studies have attempted to model this process, their findings remain fragmented and often contradictory. This review provides the first systematic, cross-platform analysis of silicone oil emulsification, critically comparing mechanical, chamber-based, and eye-on-a-chip approaches. By identifying unifying trends, methodological gaps, and underexplored parameters such as interfacial rheology and biomechanics, it establishes a roadmap toward standardized, physiologically relevant testing. These insights are significant not only for improving current tamponade materials but also for guiding the design of next-generation biomaterials and experimental platforms at the interface of ophthalmology, biomaterials science, and fluid mechanics.