Publication

Silicone oil emulsification

Emulsification seems to be a time-dependent phenomenon after retina-vitreous surgery. A number of factors have been involved, including:
• Difference in density of intraocular fluids and the oil;
• Biological “detergents” e.g. fibrinogen, fibrin, albumin and serum;
• Absorption of low and high molecular weight compounds from ocular fluids, blood, or tissue, such as retinol, cholesterol, lipoproteins, blood ghost cells, plasma and lymphocytes;
• Head and saccadic eye motion;
• Impurities in silicone oil.

The role of each of these factors is explained in details below.
1. Interfacial surface tension
While the bubble’s internal pressure of gas or air is greater than intraocular pressure, in a silicone oil bubble it is lower. A practical consequence of this is that, once a large silicone oil bubble divides into smaller ones (emulsification), the higher pressure acting on these prevents them from coalescing back to the original size, as would normally occur with air or gas. In a static situation, an oil bubble will theoretically remain intact unless the interfacial tension drops to less than about 6 mN/m. However, it has been shown that several factors may contribute to decreasing the interfacial tension of the silicone oil bubble once it is injected in the vitreous cavity:
• Interfacial surface tension is lower against ionized solutions, such as biological fluids, than against pure water (e.g. the interfacial surface tension of silicone oil 1.000 was found to be 33 mM/m against physiologic fluids, as compared to 40 mN/m against water);
• Interfacial surface tension is also lower in the presence of physiological surfactants such as proteins and lipids (e.g. the interfacial surface tension of silicone oil 1.000 dropped from 40 mN/m against water to 16 mN/m against bovine vitreous humour);
• The presence of blood in the vitreous cavity might also expected to lower the interfacial surface tension to less than 14 mN/m, because of denaturation of absorbed proteins;
• In some instances, viscoelastic solutions are used during vitreoretinal surgery. Although these solution are normally aspirated before substitution with silicone oil, sufficient material will remain at the retinal surface to influence the resultant interfacial surface tension (e.g. the interfacial tension of the silicone oil bubble was found to be drastically lowered to less than 25 mN/m in the presence of viscoelastics);
• Interfacial surface tension can further be reduced due to silicone oil having the capacity to absorb various molecules and proteins from the aqueous humour and ocular tissues during the postoperative period (e.g. the interfacial tension of the silicone oil bubble was found to be instantaneously lowered to 14 nM/m by 10 mg/ml lipoprotein. The absorbance of lipophilic substances, particularly retinol and cholesterol was confirmed by Refojo et al. Concentration of these biological emulsifiers is increased in case of hemorrhage or inflammation.

2. Postoperative period
Emulsification has been reported to occur as soon as within a few days after surgery, but more typically it is not seen until several months later. In particular, a study by Federman & Schubert reported emulsification to occurs in 1% of eyes at 1 month, 11% at 3 months, 85% at 6 month, and 100% at 1 year (Federman JL, Schubert HD. Ophthalmology, 95:870-76, 1988). Because
emulsification in patients appear to be time-dependent, it can be postulated that it is provoked by a combination of:
• Head and saccadic eye motion, which impart oscillatory microvortex currents both within and outside the air bubble;
• The difference in density of the intraocular fluids and the oil (see 1);
• The gradual decrease of interfacial surface tension of the oil against intraocular fluids brought about by the absorption of surface-active components from the physiological milieu (see 1).

3. Other factors
Other interdependent factors related to silicone oil have been studies such as:
• Interfacial surface tension of the oil;
• Viscosity of the oil;
• Chemical composition;
• Presence of low-MW siloxane compounds or other impurities;

Generally, all of these factors will affect intrinsic or in situ interfacial surface tension of the air bubble, its susceptibility to emulsification, or the time required for the onset of the emulsification. Silicone oil with a viscosity of 5000 cS is more stable than oils with a viscosity up to 4.000 cS. However, it is also true that low-viscosity oils are both easier to inject and subsequently to remove. No difference in the resistance to mechanical emulsification were found in commercial-grade, medical-grade, purified and refined silicone oils of similar viscosity. However polymerization catalyst residues may be responsible for the spontaneous emulsification, without mechanical action observed with commercial-grade and some medical-grade high viscosity (12500 cS). Silicone oils require purification before use in ophthalmology. According to the European Pharmacopoeia, the accepted limit of volatile content is 0.3%.
4. Conclusions
Notwithstanding these concerns of tendency to emulsification to lessen the biocompatibility of silicone tamponades, the rate of occurrence of adverse histopathological effects or ocular intolerance remains quite low.

Reference:
Parel J-M, Milne P, Gautier S, Jallet V, Franck Villain: Silicone oils: Physico-Chemical properties. In: SJ Ryan (ed), Surgical Retina, Fourth Edition, Philadelphia, Elsevier Mosby, 2006; Ch 129, pp 2191-2210.