Abstract
Purpose.:
To develop new blends of emulsification-resistant silicone oil based on high molecular weight (HMW) silicone oil for use as an endotamponade in vitreoretinal surgery.
Methods.:
Viscosity and elasticity of various silicone oil blends (Siluron 1000, Siluron 2000, Siluron 5000, 7% HMW + Siluron 1000, 10% HMW + Siluron 1000, and 15% HMW + Siluron 1000; Fluoron GmbH, Ulm, Germany) were measured using a piezoelectric axial vibrator. Emulsification was induced using a sonication device. Pluronic 10%, plasma, and serum were used as emulsifiers. The emulsion area was photographed and measured using ImageJ software (developed by Wayne Rasband, National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index.html).
Results.:
Viscosity increased proportionally to HMW concentrations. Fluid elasticity was optimum using 10% HMW. Emulsification was at a minimum when using 10% or 15% HMW blends.
Conclusions.:
A new silicone oil–based tamponade was developed with a viscosity similar to Siluron 5000 (at 37°C) but with significantly less emulsification tendency than Siluron 5000 or Siluron 2000. HMW concentration increases the fluid elasticity, thereby reducing the emulsification tendency.
Silicone oil as endotamponade is used in vitreoretinal surgery, particularly in complicated cases of retinal detachment. Because of emulsification, silicone oil can lead to secondary glaucoma, inflammation, and epiretinal membrane reproliferation.
1,2 Therefore, silicone oils with little tendency to emulsify in the eye are preferable.
Williams et al.
3,4 showed that the addition of high molecular weight (HMW) silicone oil polymer increases the extensional viscosity of silicone oil blends at high strain rates. An important factor of silicone oil stability is its viscoelastic behavior. Viscosity describes a fluid's resistance to flow, and elasticity is the property that causes a material to take up its original shape after distortion. Viscoelastic substances possess both properties.
Viscoelasticity is studied by using dynamic mechanical analysis. An oscillatory force (stress) is applied to a material and the resulting displacement (strain) is measured. An important parameter of viscoelastic behavior is the complex shear modulus G*. The complex shear modulus is composed of a viscous part (loss modulus G′′) and an elastic part (storage modulus G′). The loss modulus describes the part of leaded energy that dissipates as heat. The storage modulus describes the ability of a material to store and recover energy to get its original shape back. This parameter can be used to measure the elastic component of a sample. Another factor that describes the elastic part of a fluid is the equilibrium creep compliance Je0. Higher Je0 means higher elasticity. Normal silicone oils show only a small elastic portion. It is known from applications like offset printing that the addition of HMW polymers increases the elastic portion. This is important because a low elastic portion in printer's ink would result in rupturing of the ink filaments. Small droplets would occur. The same phenomenon is the reason for silicone oil emulsification. In polymers like polystyrene, the addition of up to 10% of HMW polymer increases the elastic portion. Importantly, addition of a higher amount of HMW polymer results in a decrease of the elastic portion.
Previously, we could reduce the emulsification rate of Siluron 2000 (Fluoron GmbH, Ulm, Germany) by adding 5% very long chain silicone oil molecules.
5 Siluron 2000 has about the same emulsification tendency as Siluron 5000, but is suitable for small-gauge surgery.
6
In this study, we developed a silicone oil that was suitable for 20-gauge surgery and yet emulsified less than Siluron 2000 or Siluron 5000. In addition, we showed that the tendency of silicone oil to emulsify depends on the elastic part of the blend.
For the purpose of viscosity and elasticity measurements, the following silicone oils and silicon oil blends were used: Siluron 1000, Siluron 5000 and Siluron 2000 (a mixture of 5% HMW + Siluron 1000; Fluoron GmbH). Blends were produced by mixing various amounts of Siluron 1000 and 423-kDa HMW (7%, 10%, and 15% HMW) for 48 hours at 100 rpm in a glass reactor using a KPG stirrer (IKA Eurostar power control-visc, Fa.; KGW-Isotherm, Karlsruhe, Germany).
The viscoelastic properties of the silicone oil blends were determined by oscillatory testing. Measurements were performed with a piezoelectric axial vibrator (PAV) with 0.025 mm (low frequency) to 0.2 mm (high frequency) gap thickness (Institute for Dynamic Materials Testing, University of Ulm, Germany). The PAV consists of a thin-walled rectangular tube glued to a rigid base and surrounded by a hollow cylinder. Both the tube and cylinder are tightly covered by a plate with a circular ditch of thin-walled floor to create an axial vibrating inner part of radius R, excited by four piezo elements and detected by another four glued onto the tube walls. Four lead zirconate titanate (PZT) elements have proved suitable to avoid direct coupling between them. By using a distance ring, it can be hermetically closed with the upper plate, leaving a circular gap of width d to be filled by squeeze flow of a droplet of soft material during closing. The principle of the measurement is the piezoelectric stimulation and detection of axial oscillations of the upper plate. From the complex ratio ×0/× of the dynamic displacements in unloaded and loaded measurements, it is possible to calculate the viscoelastic functions.
To analyze the viscoelastic behavior of silicone oil, one drop of the oil was squeezed into the PAV. Measurements were performed at frequencies from 1 to 10,000 Hz. To simulate the behavior of the oil in the eye, measurements were taken at 37°C. The viscous part (loss modulus G′′) and elastic part (storage modulus G′) were determined. Equilibrium creep compliance (i.e., the elastic part of the compliance at low frequencies) was calculated as Je0. Shear viscosity was calculated by using the Cox–Merz rule, which correlates the linear dynamic moduli as a function of frequency to the steady shear flow viscosity as a function of shear rate.
We used the modified technique previously described by Savion et al.,
6 which we used previously to measure silicone oil emulsification.
5 Six different silicone oil blends (500 μL) along with 500-μL emulsifier (Pluronic 10%, plasma, or serum) were pipetted into a glass cuvette (inner dimension 4 × 10 × 40 mm). Plasma and serum were collected from one individual on a single day. They were kept frozen at −80°C until use. Informed consent was provided from the individual, and the procedure adhered to the declaration of Helsinki. We have previously published this method.
5 We repeated the experiments, and the results published here were performed with other plasma and serum samples (i.e., not the same samples reviewed in the previous paper).
5 The glass cuvette was then put into a water-filled sonication device (Sonorex TK 30, Bandelin Electronic, Berlin, Germany) for 3 minutes. The water temperature was kept at 20°C to 24°C. The entire system was then centrifuged at 5000
g for 30 minutes. After centrifugation, the nonemulsified oil was on top, followed by emulsified oil in the middle and the aqueous solution at bottom. The glass cuvette was then photographically documented. Each oil blend was tested four times.
The area of the emulsified oil was measured using ImageJ software (developed by Wayne Rasband, National Institutes of Health, Bethesda, MD; available at
http://rsb.info.nih.gov/ij/index.html). The area of emulsified oil was presented as area in percent (i.e., area of emulsified oil (%) = (area of emulsified oil × 100%)/(area of nonemulsified oil + area of emulsified oil + area of aqueous solution). Statistical analysis was performed using the number cruncher statistical system (version 2004; NCSS, Kaysville, UT). All data are presented as mean ± SD.
P < 0.05 was considered statistically significant.
Figure 1 shows the complex shear modulus (G*). G* is composed of a viscous part (loss modulus G′′) and an elastic part (storage modulus G′). Overall viscosity and elasticity increases with increasing HMW concentration. Siluron 1000 exhibits only a small elastic part that cannot be measured at low frequencies. Elasticity rises with increasing HMW concentration. Interestingly, a silicone oil blend with 15% HMW shows elastic parts over the total frequency range. Elasticity (equilibrium creep compliance) of the silicone oil blends is presented in
Figure 2 and
Table 1. Elasticity is at minimum for Siluron 1000 and at maximum for 10% HMW + Siluron 1000. Siluron 5000, although having about the same shear viscosity as 10% HMW + Siluron 1000, shows lesser elasticity. Elasticity increases with HMW concentration up to 10%. Increasing the concentration of HMW beyond 10% results in decreasing elasticity. Shear viscosity increases proportionally with increasing concentration of HMW (
Fig. 3;
Table 2).
Figure 3 shows the shear viscosity of silicon oils and silicone oil blends at shear rates from 6 to 100 seconds
-1 at 37°C. Viscosity rises with increasing concentration of HMW. The blend with 10% HMW exhibits nearly the same viscosity as Siluron 5000.
The emulsification area is presented in
Table 3 and
Figure 4. When using a strong emulsifier (i.e., Pluronic 10%), emulsification was at maximum for Siluron 1000 and at minimum for 10% HMW + Siluron 1000 and 15% HMW + Siluron 1000. According to the viscosity and elasticity data calculation, a silicone oil blend using 10% HMW was chosen because it has nearly the same viscosity as Siluron 5000 and was determined to have the greatest elasticity, thereby having the least tendency to emulsify.
Silicone oil has the viscoelastic properties of a non-Newtonian fluid. It exhibits both viscous and elastic properties. Viscosity presents the resistance to stress, while elasticity represents the ability to return into its original shape after stress. Previous studies have shown that the addition of HMW silicone oil molecules increases the extensional viscosity
4 and thereby reduces the emulsification tendency.
5 In this study, we measured both the elasticity and viscosity of silicone oil blends. We found that by increasing the HMW concentration in the silicone oil blends, we were able to increase both the viscosity and the elasticity of oil, thereby decreasing the emulsification tendency to a minimum. Emulsification occurs when a silicone oil droplet separates from the rest of the oil after stress is applied. Silicone oil with high viscosity tends to withstand this stress better. As in silicone oil with high elasticity, after stress is applied, the silicone oil mass tends to snap back into its original form, thereby reducing the tendency of building smaller droplets.
We found that using 10% HMW + Siluron 1000 would be ideal, because this blend has about the same shear viscosity as Siluron 5000 and yet has even lesser emulsification tendency. The blend using 15% HMW has about the same emulsification tendency as 10% HMW blend. This indicates that addition of > 10% HMW would not further enhance the emulsification stability of the silicone oil tamponade. In addition, blends with > 10% HMW are more viscous, making handling during vitreoretinal surgery more complicated. Because a mixture with 10% HMW has the highest elastic portion, a relationship between the elastic portion of an oil mixture and its emulsification tendency is evident.
Emulsification in vivo is influenced by rheologic characteristics of the oil, amounts of surfactant in the eye,
7 eye movements,
8 and impurities in the oil.
9 –12 While most parameters cannot be influenced, rheologic properties of silicone oil can be optimized. We have previously published the emulsification data of Siluron 1000, Siluron 2000, and Siluron 5000 using plasma and serum as emulsifiers.
5 The results from this study differed, however, from the previously published data. These differences occured because we were using different plasma and serum samples as those used in the previously published data.
This study shows the development of an emulsification-resistant silicone oil–based endotamponade in vitro. These findings have to be confirmed in vivo; however, at this time, no appropriate in vivo models for assessing silicone oil emulsification are known. Different aspects mentioned above also influence the emulsification tendency in vivo, making emulsification measurement in vivo difficult to quantify.
In this study, we developed a silicone oil with a shear viscosity similar to Siluron 5000. Therefore, it might be less suitable for small-gauge surgery. However, the lesser tendency of emulsification compared to Siluron 2000 and 5000 might be helpful for eyes with high amounts of endogenous emulsifier, such as eyes with hemorrhages or eyes with extensive blood–retinal barrier breakdown.