Silicone Oil Emulsification Research Articles

Emulsified silicone oil is taken up by and induces pro-inflammatory response in primary retinal microglia

PurposeSilicone oil is used as endotamponade in combination with vitrectomy. Thinning of retinal layers and loss of retinal cells under silicone oil use have been found. Here, we investigate the influence of silicone oil on primary microglia cells.MethodsPrimary microglia cells were prepared from the porcine retina. Microglia identity was assessed with Iba1 staining. Silicone oil was emulsified by sonification. Cell morphology and silicone oil uptake were evaluated by light microscopy after Coomassie blue staining. Cytokine secretion was evaluated with ELISA. Toxicity of silicone oil on microglia and toxic effect of silicone oil–treated microglia on neuronal cell line PC12 were evaluated by MTT or WST assay, respectively.ResultsMicroglia took up silicone oil droplets after 72 h of incubation. Silicone oil induced no toxicity but increased the metabolism in microglial cells. In addition, the secretion of IL-6 and IL-8, but not of IL-1ß or TNF-α, was induced. Silicone oil–treated microglia did not exert any neurotoxic effect on differentiated PC12 cells but induced an increase in metabolism.ConclusionEmulsified silicone oil changes the activity level of microglia and induces the secretion of IL-6 and IL-8. Neurotoxicity is not induced. Further experiments are required to investigate the long-term effect of silicone oil on microglia and their consequent effect on neuronal cells.

Quantitative Differentiation of Protein Aggregates From Other Subvisible Particles in Viscous Mixtures Through Holographic Characterization

We demonstrate the use of holographic video microscopy to detect individual subvisible particles dispersed in biopharmaceutical formulations and to differentiate them based on material characteristics measured from their holograms. The result of holographic analysis is a precise and accurate measurement of the concentrations and size distributions of multiple classes of subvisible contaminants dispersed in the same product simultaneously. We demonstrate this analytical technique through measurements on model systems consisting of human IgG aggregates in the presence of common contaminants such as silicone oil emulsion droplets and fatty acids. Holographic video microscopy also clearly identifies metal particles and air bubbles. Being able to differentiate and characterize the individual components of such heterogeneous dispersions provides a basis for tracking other factors that influence the stability of protein formulations including handling and degradation of surfactant and other excipients.

Analysis of the rates of emulsification in intraocular silicone oil tamponades of differing viscosities.

To investigate the rates of emulsification in silicone oil (SO) tamponades of differing viscosities used during pars plana vitrectomy (PPV) in the treatment of complicated vitreoretinal diseases. This study was a prospective randomized clinical trial. Totally 290 cases with greater likelihoods of secondary detachment were included and randomly grouped into either Siluron 2000 (n=143) or Siluron 5000 (n=147) SO tamponades with 23-gauge PPV. Patient follow-ups and data analyses were conducted 1, 3, 6, and 12mo post-surgery. The time of the SO emulsification ranged from 1 to 17mo, with a mean of 7.3±4.2mo. The Siluron 5000 group showed a slower emulsification rate in comparison to the Siluron 2000 group. The Siluron 2000 group took a shorter time to show signs of emulsification, necessitating earlier SO removal. However, there were no significant differences in the occurrence of complications, including secondary retinal detachment, cataract, corneal abnormality, high intraocular pressure and hypotony. The Siluron 2000 SO tamponade shows a faster rate of emulsification than the Siluron 5000 SO, necessitating earlier removal. Both groups show similar results in terms of anatomical success and visual acuity outcome, and there is no significant difference between the SOs regarding the occurrence of complications.

Evaluation of emulsified silicone oil with spectral domain-optical coherence tomography and fluorescein angiography.

To report emulsified particles and related complications after removal of silicone oil (SO) by spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA). A prospective, single-center investigation was performed using SD-OCT, FA and flare cell photometry measurements to evaluate in a cohort of eyes with emulsified silicone particles after removal of long-term SO tamponade. Nineteen eyes of the 19 patients with emulsified silicone particles detected in ophthalmoscopic exam were included in the study: 13 (68%) were male, and 6 (31.6%) were female, and their mean age was 52.75 ± 16.06years. Preoperative diagnoses were rhegmatogenous retinal detachment in all eyes. The mean duration of the silicone oil's presence in the eye was found as 12.63 ± 4.87 (7-26) months. SD-OCT examination postoperatively showed small, round and hyper-reflective structures compatible with emulsified silicone particles on preretinal surface in 7 (36.8%) eyes, intraretinally in 6 (31.6%) eyes and in the vitreous in 12 (63%) eyes. FA imaging demonstrated pearl-like hyper-fluorescence at early and late phases on the large blood vessels in 9 (47.4%) eyes. Late phase hyper-fluorescence due to leakage on the macula was observed in 17 (89.5%) eyes. Diffuse peripheral leakage and hyper-fluorescence was detected in 11 (57.9%) eyes. Flare levels were higher in eyes with emulsified SO compared to unaffected fellow eyes (p < 0.05). Emulsified silicone particles that remain in the eye may lead to retinal complications and inflammation in addition to their known complications such as keratopathy and glaucoma. The particles that lead to inflammation and presence of inflammation may be examined by imaging methods such as SD-OCT and FA. Removing the SO before emulsification would be suitable for avoiding such complications.

Дренажная хирургия вторичной «силиконовой» глаукомы

«Российская офтальмология онлайн» - электронное информационное издание, создается с 1 марта 2010 года под эгидой Российского общества офтальмологов. Основная задача проекта - научно-информационная поддержка специалистов в области офтальмологии.

Silicone Oil Emulsification after Vitrectomy for Rhegmatogenous Retinal Detachment.

Purpose To investigate the characteristics of silicone oil (SO) emulsification after vitrectomy for rhegmatogenous retinal detachment and their possible correlations with clinical factors. Methods The first 2 mL of washing out fluid after SO removal was collected, and used for the measurement of the size and number of SO droplets using a Multisizer® 3 Coulter counter (Beckman Coulter, USA). The correlations between SO droplets and clinical factors were analyzed. Results A total of 38 patients (23 males, 15 females) who underwent primary PPV with SO injection for RRD and whose retina stayed attached for ≥3 months after SO removal were included in the study. The average number of oil droplets was 1.96 × 106 ± 3.95 × 106/mL (range 0.17 × 106 to 21.71 × 106/ml), and 80.8% (range 64.23%–99.07%) of the droplets were 1-2 μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all P > 0.05). When the emulsified SO droplets were divided into groups by their diameter, multiple linear regression revealed that age was negatively correlated with the numbers of 5–7-μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all P > 0.05). When the emulsified SO droplets were divided into groups by their diameter, multiple linear regression revealed that age was negatively correlated with the numbers of 5–7-μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all P > 0.05). When the emulsified SO droplets were divided into groups by their diameter, multiple linear regression revealed that age was negatively correlated with the numbers of 5–7-Conclusion Using a Multisizer® Coulter counter, we successfully determined the number and size of SO droplets after emulsification. We found that the number of 5–12-μm-diameter droplets was higher in younger-age patients and was higher in patients using antiglaucoma eyedrops.μm in diameter. The total number of emulsified SO droplets was not correlated with any clinical factor (all

Emulsification of Different Viscosity Silicone Oil in Complicated Retinal Detachment Surgery: A Randomized Double-Blinded Clinical Trial.

ObjectiveTo study silicone oil (SO) emulsification, anatomic and visual outcome after complicated retinal detachment surgery by pars plana vitrectomy (PPV) with intraocular SO tamponade, comparing between low and high viscosity SO.DesignRandomized, double-blinded, controlled trial.Patients and MethodsPatients with complicated retinal detachment who had been surgically treated by PPV and intraocular SO tamponade were randomly divided into low viscosity (Group 1) or high viscosity (Group 2). Main Outcome Measures were rate of silicone oil emulsification, anatomic retinal reattachment and visual outcome, assessed at 1,3,6,9 and 12 months.ResultsOne hundred patients were divided into 50 patients in each group. The rate of silicone oil emulsification in Group 1 (63.64%) was higher than Group 2 (40%), but the difference was not statistically significant (p = 0.08). Rates of anatomic retinal reattachment were 88% in Group 1 and 90% in Group 2 (p = 0.76). For functional visual outcome, final best-corrected visual acuity (BCVA) at Month 12 compared with the baseline BCVA was improved vision 52% in Group 1 and 58% in Group 2 (p = 0.82).ConclusionSO emulsification rate in low viscosity group is non-significantly higher than high viscosity group, but results in a comparable reattachment rate and final visual recovery. Emulsification in both groups is detected at as early as 1 month and mostly within 3 months. We recommend using either low or high viscosity SO in complicated retinal detachment surgery and removing it as early as possible to prevent the consequent serious complications.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT02988583.

Inverse Pseudohypopyon from Emulsified Silicone Oil in the Macula

Inverse Pseudohypopyon from Emulsified Silicone Oil in the Macula

Myopic retinoschisis with intraretinal emulsified silicone oil appearing as a macular hyperoleon.

Myopic retinoschisis with intraretinal emulsified silicone oil appearing as a macular hyperoleon.

Study on the effectiveness and safety of Foldable Capsular Vitreous Body implantation

BackgroundFoldable capsular vitreous body (FCVB) was designed to treat severe retinal detachment. The aim of this study was to evaluate the efficacy and safety of the implantation of foldable capsular vitreous body in 1-year follow-up.MethodsA retrospective analysis was conducted for 20 patients with severe ocular trauma or silicone oil (SO) dependent eyes underwent vitrectomy and FCVB implantation in a 1-year follow-up. All treated eyes were peformed clinical examinations involved the visual acuity (VA) examination, Goldmann applanation tonometer, noncontact specular microscopy, fundus photography, B-Scan examination and optical coherence tomography (OCT). The groups were compared with t-test and the McNemar - Bowker test.ResultsIn 1-year follow-up, 20 eyes were evaluated in the study. FCVB well supported the vitreous retina in all treated eyes, and 6 treated eyes achieved retinal reattachment 12 months after FCVB implantation. There were no significant differences in VA before and after FCVB implantation (P = 1.000). In addition, the postoperative IOP markedly elevated from the preoperative IOP of 12.90 ± 7.06 mmHg to 15.15 ± 3.36 mmHg (P = 0.000017). The intraocular pressure (IOP) of 10 eyes maintained at a normal level after surgeries. The other 10 eyes showed slightly lower IOP within the acceptable level. Though two patients developed keratopathy and ocular inflammation respectively, other treated eyes were symmetric with fellow eyes showing satisfactory appearance. Moreover, there was no SO emulsification or leakage happened in the observation.ConclusionsFCVB implantation was an effective and safe treatment in the eyes with severe retinal detachment.

A NOVEL FINDING OF HYPERREFLECTIVE MATERIAL IN THE SILICONE-RETINA INTERFACE: An Optical Coherence Tomographic and Histopathological Study.

To describe novel findings of hyperreflective material in the silicone-retina interphase on spectral domain optical coherence tomography (SD-OCT) imaging in eyes with silicone oil tamponade. Retrospective observational clinical study of consecutive patients who underwent primary pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment. Repeat clinical examination and spectral domain optical coherence tomography macular imaging performed 3 months after surgery were evaluated to identify any macular pathologies, including formation of epiretinal membranes, intraretinal changes, subretinal fluid, and edema before scheduled secondary vitrectomy for silicone oil removal. Eighty-two patients (mean age 54 years, range 22-89) were included. Twelve eyes (14%) showed discrete preretinal hyperreflective organized coarse material in the silicone-retina interphase on spectral domain optical coherence tomography. The material was scattered in the posterior pole, with several foci showing additional hyperreflectivity of the inner retinal layers beneath. These findings did not resemble silicone oil emulsification in size, shape, or reflectivity. This is the first report on hyperreflective material detected by spectral domain optical coherence tomography in the silicone-retina interphase in eyes with silicone oil tamponade. These findings may represent an inflammatory response to silicone oil exposure that may be the initial manifestation of a future proliferative process, warranting a rigorous follow-up protocol for affected patients.

Amphiphilic additives in silicone oil tamponade and emulsification: an eye-on-a-chip study.

Recently, chemically modified silicone oil has been demonstrated as a reservoir for sustained release of intraocular drugs, many of which might be amphiphilic in nature. In this work, we study the effect of amphiphilic additives in silicone oil on emulsification under eye-like movements. Three silicone-oil-soluble surfactants, namely DC749, MQ1640 and FZ2233, were used as model amphiphilic additives. The change of viscosity was measured by a rheometer in the cone-and-plate geometry. The interfacial tension (IFT) between silicone oil and model aqueous phase was measured by pendant drop tensiometry. Emulsification of silicone oil was induced by simulated saccadic eye movements on a cell-coated eye-on-a-chip platform for 4 days. The number of emulsified silicone oil droplets observed in the aqueous phase was assessed daily by optical microscopy. Significantly more emulsified droplets were formed in silicone oil with DC749 or MQ1640 (P<0.05). However, such increase was not directly related to the change in IFT nor viscosity. Moreover, water droplets were also found in the silicone oil, but not in the control silicone oil without additive. The amphiphilic substances in silicone oil promoted emulsification. Besides typical oil-in-water drops that normally affect the eye, water-in-oil drops were also formed. Before silicone oil could be considered as a vehicle for drug delivery, the nature of the drug and its possible effect on emulsification and therefore on the pharmacokinetics needs to be investigated. An additional concern is that water-in-oil droplets in the eye would affect the optical clarity of silicone oil and might cause visual symptoms.

Silicone Oils and their Properties used in Rhegmatogenous Retinal Detachment Surgery

Silicone oils are polymer structures including siloxane repeats in the center. Copolymers formed by combining these polymers at different ratios constitute different silicone structures with different physical and chemical properties. The presence of several factors such as trauma, giant retinal tear, proliferative vitreoretinopathy and retinal tear in posterior localization is the main medical indications for the use of silicone oils in the surgery of rhegmatogenous retinal detachment. Problems associated with the need for a second surgical intervention to remove silicone oil, the emulsification of silicone oil with the problem this emulsification, and the presence of foreign structure in eye globe are the most important conditions limiting the use of silicone oil.

Intraretinal Migration of Emulsified Silicone Oil: Association With Cystoid Macular Edema and Surgical Treatment

Purpose: The purpose of this article is to report the detailed stages of intraretinal silicone oil infiltration, and to describe a new surgical treatment for this condition. Methods: An observational case series is presented. Results: We report 2 patients who had undergone repair of complex diabetic retinal detachment and subsequently developed intraretinal migration of emulsified silicone oil, cystoid macular edema (CME), and lamellar macular hole (LMH). Surgical removal of the incarcerated oil bubbles rapidly restored foveal anatomy in both cases. Possible risk factors for intraretinal oil migration are discussed. Conclusions: Emulsified silicone oil droplets can penetrate the retina, resulting in CME and LMH. While severe CME in this setting is usually recalcitrant to pharmacotherapy, vitrectomy with expression of oil droplets may result in rapid and longstanding resolution.

This Issue of ACTA

This Issue of ACTA

Backgrounded Membrane Imaging (BMI) for High-Throughput Characterization of Subvisible Particles During Biopharmaceutical Drug Product Development

Backgrounded membrane imaging (BMI) is a novel automated, 96-well plate-based microscopic approach for subvisible particle analysis. We scientifically evaluated BMI with respect to sizing and counting accuracy, working range, impact of refractive index, and interferences by silicone oil droplets, and compared BMI to state-of-the-art dynamic image analysis (DIA). Image quality was found to be comparable to current DIA methodologies. However, with the first versions of BMI image analysis software, an undersizing of polystyrene beads was observed. BMI linear concentration range was found to reach an upper limit (7.1 × 105 particles/mL) similar to DIA. In the absence of silicone oil droplets, BMI and DIA showed good agreement in total particle concentrations (particle diameter ≥2 μm) but differences in size distributions for particle sizes ≥4 μm. Analyses of prefilled syringe products and silicone oil emulsions demonstrated the removal of silicone oil in BMI sample processing. In contrast to DIA, particle counting by BMI remained unaffected by changes in refractive index. Overall, we demonstrated BMI to be a promising orthogonal method for subvisible particle characterization. Aspects like low required sample volume, high throughput, and ease of handling can make BMI a valuable alternative or complement to DIA in particular for formulation screening.

Analysis of the causative factors related to earlier emulsification of silicone oil.

The aim of this study is to report and analyze the factors related with earlier occurrence of silicone oil (SO) emulsification in patients underwent pars plana vitrectomy and SO injection in our hospital. We retrospectively reviewed consecutive case series undergone both SO injection and removal in our hospital, and 182 ones were eligible. Possible related independent factors included: macula status (on/off), concomitant phacoemulsification with the surgery of SO tamponading, concomitant status of proliferative vitreoretinopathy, combined surgery of retinotomy, time to have emulsification (<6mo/≥6mo after primary SO injection), route of SO injection (anterior/posterior), lens status (aphakic/pseudophakic/phakic), anesthesia (local/general), brands and type of SO, with/without episcleral cryotherapy, with/without hypertension, with/without diabetes, with/without intraoperative use of triamcinolone acetonide. The study revealed that brand and type of SO was the significant factor related with earlier emulsification of SO. Further study was warranted to find out the underlying causes.

Ahmed Glaucoma Valves versus EX-PRESS Devices in Glaucoma Secondary to Silicone Oil Emulsification.

Objective To evaluate and compare the clinical effects of Ahmed glaucoma valves (AGVs) and EX-PRESS implants on glaucoma secondary to silicone oil (SO) emulsification. Methods A retrospective case-series study was designed. A total of 23 eyes with late intraocular pressure (IOP) elevation secondary to SO emulsification were included in the study. Antiglaucoma surgery with implantation of AGVs or EX-PRESS devices was performed. Pre- and postoperative ocular parameters were recorded at each visit during a 1-year follow-up period. The rates of complete success (IOP < 21 mmHg without medication) and qualified success (IOP < 21 mmHg with ≤3 glaucoma medications) were analyzed. Results A total of 14 eyes underwent AGV implantation, and 9 underwent EX-PRESS implantation. The mean IOP and number of medications used at the last follow-up decreased significantly compared with that before surgery (P < 0.001). The total success rate for all eyes including complete success (7/23) and qualified success (7/23) was 60.9% (14/23) at 1 year. The total success rate in the AGV group was 78.6% (11/14), whereas it was 33.3% (3/9) in the EX-PRESS group; the difference between the 2 groups was significant (P < 0.05). Conclusion For glaucoma secondary to SO emulsification, glaucoma implants could be effective at lowering IOP, and AGVs might produce better outcomes than EX-PRESS devices.

Unusual Rapid Progression of Silicone Oil Emulsification

Unusual Rapid Progression of Silicone Oil Emulsification

This issue of ACTA

The cover illustration shows a prolene thread inserted into Schlemm′s canal as reported by Grieshaber et al. in this issue of Acta. Klemp et al. in Copenhagen describe exudative retinal detachment, cataract formation and melanocytic tumours as the characteristic ocular findings in uveal melanocytic proliferation. Campos et al. in Portugal consider the role of the choroid in diabetic macular oedema and how OCT studies of the choroid advance this field of research. Jørstad et al. in Oslo found positive results with aflibercept in AMD eyes which were resistant to ranibizumab and bevacizumab injections. Many eyes required more than bimonthly aflibercept injections. Vujosevic et al. in Italy emphasize inflammatory biomarkers in diabetic macular oedema such as hyperreflective retinal spots, subfoveal neuroretinal detachment and increased foveal autofluorescence. These biomarkers improved with dexamethasone treatment. Subhi and Lykke Sørensen in Denmark correlated systemic leucocyte activity with onset and size of neovascular lesions in AMD. They suggest that inflammation plays a role in the pathophysiology. Sauer et al. in Germany used fluorescence lifetime imaging to map pigment distribution and evaluate its role in macular hole formation. Hamoudi et al. in Denmark found no difference in corneal endothelial density between combined and separated phacoemulsification and vitrectomy for epiretinal membrane. Makdoumi et al. in Sweden and the USA used blue light and riboflavin to kill resistant staphylococci and suggest this approach may work in corneal infections. Margulis et al. in the Netherlands, Spain and Denmark examined use of nonsteroidal anti-inflammatory eye drops. These were used with cataract surgery and for allergic conjunctivitis. Pärssinen and Kauppinen in Finland found astigmatism to increase with myopia. Corneal astigmatism predominates. Grieshaber et al. in South Africa and Switzerland recommend the Stegmann Schlemm′s canal expander to lower intraocular pressure in patients with moderate to advanced open angle glaucoma. Quérat and Chen in Sweden recommend ICARE® self-tonometry. Day-to-day variations are seen in most patients. Mrowicka et al. in Poland propose that insufficient antioxidant capacity may play a role in age related macular degeneration. This hypothesis is based on study of enzymes and genes related to antioxidant activity. Pilat et al. in UK used hand-held OCT to image anterior segment dysgenesis in children. The following articles are published electronically only and are accessible on www.actaophtalmologica.com, where you can also access the printed articles. Nitta et al. in Japan report an increase in retinal oximetry readings in retinal venules following glaucoma surgery and lowering of intraocular pressure. Tanito et al. in Japan recommend microhook trabeculotomy in glaucoma patients. It lowers IOP and reduces need for glaucoma medications. Mansouri and Shaarawy in the USA and Switzerland fond similar outcomes with scanning laser trabeculoplasty and selective laser trabeculoplasty. Lanza et al. in Italy used light backscattering with in vivo corneal confocal microscopy to evaluate changes in corneal layers in patients with Sjögren syndrome and dry eyes. Shimada et al. in Japan found reduced anterior chamber bacterial contamination with either 0.025% povidone-iodine or 0.0025% polyvinyl alcohol iodine irrigation of ocular surface. Peiretti et al. in Italy, the Netherlands, Saudi Arabia and the USA examined retinal folds following retinal detachment repair. This was not influenced by use of heavy liquids in surgery or postoperative positioning. Chan et al. in Hong Kong, Singapore and UK seek ways to measure and control emulsification of intraocular silicone oil. Kang et al. in Korea measured greater choroidal thickness in eyes with vitreoretinal traction. This was reversed following epiretinal membrane surgery and release of the traction. Jonas et al. in India and Germany found myopic retinopathy to be rare in rural India. It was associated with open angle glaucoma. Carreño et al. in Spain, USA and UK measured several inflammatory cytokines in tear fluid in uveitis patients. Bray et al. in UK suggest that portable electronic vision enhancement systems are cost-effective to improve near vision. However, it may not provide cost-effective improvement in quality of life. Babeau et al. in France comment on an article on using adaptive optics for screening chloroquine retinopathy. Parrovano et al. in Italy used OCT angiography to monitor reduction in neovascular lesions. Van Asten et al. in the Netherlands found positive outcomes with aflibercept in AMD patients unresponsive to bevacizumab. Lytvynchuk in Ukraine surgically removed a retinal branch artery embolus. Dimopoulos et al. in Germany used autologous thrombocyte serum for macular hole surgery. Grewal et al. in USA used intraoperative OCT to guide placement of Argus II retinal prosthesis. Huynh et al. in the USA found no benefit from dilated fundus examination in patients with spontaneous subconjunctival haemorrhage. Qu-Knafo et al. in France suggest that eyes with DME and serous retinal detachment may show greater improvement with ranibizumab than eyes without serous detachment. I hope you are enjoying a pleasant summer and Acta fits into your summer reading schedule.