Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products.

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety.

Sub-Visible Particle Classification and Label Consistency Analysis for Flow-Imaging Microscopy Via Machine Learning Methods.

Sub-visible particles can be a quality concern in pharmaceutical products, especially parenteral preparations. To quantify and characterize these particles, liquid samples may be passed through a flow-imaging microscopy instrument that also generates images of each detected particle. Machine learning techniques have increasingly been applied to this kind of data to detect changes in experimental conditions or classify specific types of particles, primarily focusing on silicone oil. That technique generally requires manual labeling of particle images by subject matter experts, a time-consuming and complex task. In this study, we created artificial datasets of silicone oil, protein particles, and glass particles that mimicked complex datasets of particles found in biopharmaceutical products. We used unsupervised learning techniques to effectively describe particle composition by sample. We then trained independent one-class classifiers to detect specific particle populations: silicone oil and glass particles. We also studied the consistency of the particle labels used to evaluate these models. Our results show that one-class classifiers are a reasonable choice for handling heterogeneous flow-imaging microscopy data and that unsupervised learning can aid in the labeling process. However, we found agreement among experts to be rather low, especially for smaller particles (< 8 µm for our Micro-Flow Imaging data). Given the fact that particle label confidence is not usually reported in the literature, we recommend more careful assessment of this topic in the future.

Silicone oil-free syringes, siliconized syringes and needles: quantitative assessment of silicone oil release with drugs used for intravitreal injection.

PURPOSE: This study aimed to quantify the amount of silicone oil (SO) released across a variety of syringe and needle models routinely used for intravitreal injection. METHODS: The release of SO was assessed in eight models of syringes, two of which were reported to be 'SO-free', and eleven models of needles with unknown SO content. To evaluate SO release within the context of anti-VEGF therapeutics, syringes were evaluated using aflibercept, bevacizumab, buffer, ziv-aflibercept and formulation buffer. All syringe tests were performed with or without agitation by flicking for syringes. Needles were evaluated without agitation only. Samples were fluorescently labelled to identify SO, and triplicate measurements were collected using imaging flow cytometry. RESULTS: Seven out of 8 syringe models showed a statistically significant increase in the SO particle count after agitation. The two SO-free syringe models (HSW Norm-Ject, Daikyo Crystal Zenith) released the least SO particles, with or without agitation, whereas the BD Ultra-Fine and Saldanha-Rodrigues syringes released the most. More SO was released when the syringes were prefilled with formulation buffer than with ziv-aflibercept. Syringes filled with aflibercept and bevacizumab had intermediate levels. Agitation increased the release of SO into each of the drug solutions. Silicone oil (SO) was detected in all needles. CONCLUSIONS: Agitation of the syringe by flicking leads to a substantial increase in the number of SO particles. Silicone oil (SO)-free syringes had the best performance, but physicians must also be aware that needles are siliconized and also contribute to the injection of SO into the vitreous.

Analysis of Silicone Oil in Prefilled Syringes and Biopharmaceutical Drug Products Using High-Performance Liquid Chromatography.

As the packaging of choice for many therapeutic proteins, prefilled syringes have been widely used in biopharmaceutical industry as primary containers, where silicone oil is applied to ensure their proper functionality. Adequate lubrication from sufficient amount of silicone oil and its appropriate distribution across syringe barrels is crucial for successful administration of drug product (DP) from the prefilled syringes; however, silicone oil is also susceptible to leaching from the syringe surface into the formulation with the potential to interact with therapeutic proteins, which could lead to the formation of visible and sub-visible aggregates and/or particles that are potentially immunogenic. Accurate determination and careful control of silicone oil levels in both empty syringes and protein drug products are therefore critical in process development to ensure syringe functionality, drug product quality, and patient safety. On the other hand, analysis of silicone oil can be challenging especially when the analysis is performed on formulated protein drug products, where matrix effects could be significant. It is demonstrated in this study that silicone oil in empty syringes or formulated drug products can be extracted effectively using organic solvents and quantitatively determined using high-performance liquid chromatography (HPLC) coupled with a universal detector. It was also shown that direct extraction of silicone oil from formulated protein drug products can be very challenging, but pretreatment of the protein drug products with pepsin enzymatic digestion facilitated the extraction process, which enabled the analysis of silicone oil in the drug product at low ppm levels.

Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections.

Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.

Silicone oil droplets in repackaged anti-vascular endothelial growth factors for intravitreal injections: In search of the main source of contamination.

INTRODUCTION: Repackaging of anti-vascular endothelial growth factors in polypropylene syringes lubricated with silicone oil for intravitreal use is associated with the presence of intravitreal silicone oil droplets. The objective of this study is to assess how the use of silicone-free syringes (for storage and/or administration) would reduce the amount of silicone oil droplets in the product to be administered. METHODS: Two 16 mL vials of bevacizumab were repackaged at the compounding pharmacy to obtain four sets of product, each consisting of three 1.2 mL tubes of the drug repackaged in different ways. Set A was repackaged according to routine practice, that is, the drug was placed into 1 mL siliconized syringes and 60 µL aliquots were extracted with 0.5 mL insulin siliconized syringes until reaching 1.2 mL. In set B, a 1-mL silicone-free syringe was used, followed by a 0.5 mL siliconized syringe. In set C, only 0.5 mL siliconized syringes were used. In set D, only the 1-mL silicone-free syringe was used. Micro-Flow Imaging technology was used for quantifying silicone oil droplet-like particles below 25 µm. RESULTS: Silicone oil droplet-like particles were absent in set D. Set C had the highest average frequency of these particles, which was much lower in sets A and B. Set B had the lowest frequency. CONCLUSION: 0.5 mL insulin syringes with staked-in needles used for supplying the product seem to be the main source of silicone oil contamination in repackaged anti-vascular endothelial growth factors. Silicone-free insulin syringes with staked-in needles would be strongly recommended for supplying anti-vascular endothelial growth factor intravitreal injections from compounding pharmacies.

Release of silicone oil and the off-label use of syringes in ophthalmology.

BACKGROUND/AIMS: To assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions. METHODS: Eight syringes were analysed: from the USA, Terumo 0.5 mL, Becton-Dickinson (BD) Tuberculin 1 mL, BD Luer-lok 1 mL, BD Ultra-Fine 0.3 mL and Exel Insulin 0.3 mL; from Germany, Braun Omnifix-F 1 mL and Braun Injekt-F 1 mL and from Spain, BD Plastipak 1 mL. The impact of air, priming the plunger, agitation by flicking and fluid temperature on SO release were assessed by light microscopy. Fourier transform infrared spectroscopy (FTIR) was performed to identify the molecular compound in each syringe. RESULTS: Five hundred and sixty syringes were analysed. Terumo 0.5 mL and BD Ultra-Fine 0.3 mL released more SO than all others. BD Luer-lok 1 mL, BD Plastipak and Braun Omnifix-F 1 mL released little SO; BD Tuberculin 1 mL, Exel 0.3 mL and Braun Injekt-F 1 mL released the least SO. Priming the syringe and different temperatures did not significantly affect SO release. Agitation by flicking caused a significantly higher proportion of samples to have SO droplets and an increased number of oil droplets. Air had an additive effect on the release of oil in the agitation groups. FTIR identified polysiloxane in all syringes but Injekt-F. CONCLUSION: Syringes commonly used for intravitreal injections frequently release SO droplets, especially when agitated by flicking. To avoid unnecessary ocular risks, syringes should not be agitated before intravitreal injection. It is desirable that syringes be manufactured specifically for ophthalmic use.

Enhancing Chlorobenzene Biodegradation by Delftia tsuruhatensis Using a Water-Silicone Oil Biphasic System.

In this study, a water-silicone oil biphasic system was developed to enhance the biodegradation of monochlorobenzene (CB) by Delftia tsuruhatensis LW26. Compared to the single phase, the biphasic system with a suitable silicone oil fraction (v/v) of 20% allowed a 2.5-fold increase in the maximum tolerated CB concentration. The CB inhibition on D. tsuruhatensis LW26 was reduced in the presence of silicone oil, and the electron transport system activity was maintained at high levels even under high CB stress. Adhesion of cells to the water-oil interface at the water side was observed using confocal laser scanning microscopy. Nearly 75% of cells accumulated on the interface, implying that another interfacial substrate uptake pathway prevailed besides that initiated by cells in the aqueous phase. The 8-fold increase in cell surface hydrophobicity upon the addition of 20% (v/v) silicone oil showed that silicone oil modified the surface characteristics of D. tsuruhatensis LW26. The protein/polysaccharide ratio of extracellular polymeric substances (EPS) from D. tsuruhatensis LW26 presented a 3-fold enhancement. These results suggested that silicone oil induced the increase in the protein content of EPS and rendered cells hydrophobic. The resulting hydrophobic cells could adhere on the water-oil interface, improving the mass transfer by direct CB uptake from silicone oil.

Development of a modified p-dimethylaminocinnamaldehyde solution for touch DNA analysis and its application to STR analysis.

We developed an acid-free p-dimethylaminocinnamaldehyde (DMAC) solution containing silicone oil that was suitable for spraying on clothing for analysis of biological samples such as touch DNA. We investigated the effect of this solution and irradiation with blue light emitting diode (LED) light on short tandem repeat (STR) analysis. To examine the effect of adding acid to the DMAC solution on visualizing biological samples, saliva sample was deposited on T-shirt. The T-shirt was sprayed with acid-added DMAC or acid-free DMAC solution and left for 2 h before irradiation with the blue LED light. We observed no differences between the fluorescence intensities achieved with these two solutions. To examine the effect of acid addition to the DMAC solution on STR analysis, sweat samples were smeared on glass slides and dried. The slides were sprayed with acid-added or acid-free DMAC solution and irradiated with the blue LED light. Samples were collected from the slides with swabs, and DNA was extracted from each sample using a PrepFiler Express™ Forensic DNA Extraction Kit and quantified using a Human DNA quantification kit (Takara RR281). The extracted DNA was amplified using an AmpFℓSTR® Identifiler® Plus PCR Amplification Kit for STR typing. We found that addition of acid to DMAC had little effect on DNA contained in the biological samples and STR analysis. To investigate whether DMAC could be used to visualize biological samples on clothes, saliva, sweat, and finger and palm prints were deposited on separate T-shirts. Biological samples were treated with DMAC and observed after 2 h, 1, 2, or 3 days under the blue LED. All biological samples were visualized and emitted fluorescence after 2 h. To examine the effects of the DMAC solution and LED irradiation on STR analysis, including DNA extraction, quantification, and STR typing, saliva and sweat were smeared on glass slides and dried. Touch DNA samples were deposited on glass slides directly. The slides were then sprayed with DMAC solution, sprayed with DMAC solution and irradiated with the blue LED, or left untreated. Samples were collected from the slides with swabs, and DNA was extracted, quantified, and amplified using the above kits. These results suggest that the DMAC solution and blue LED light will have no adverse effects on STR analysis. Therefore, this method will be very useful for touch DNA analysis in forensic investigations.

Quantification of Silicone Oil and Its Degradation Products in Aqueous Pharmaceutical Formulations by 1H-NMR Spectroscopy.

During the past years, there has been an increasing focus on the presence of silicone oil as a contaminant in pharmaceutical formulations kept in prefilled syringes (PFSs). As the PFSs are coated on the inner wall with silicone oil (polydimethylsiloxane), there is a potential risk that the oil can migrate from the inner surface of the primary packing material into the aqueous solution. Several studies have demonstrated that presence of silicone oil as droplets in a high-concentrated protein formulation can cause protein aggregation. Hence, because the use of silicone-coated primary packing material for protein formulations are increasing, the call for an easy and quantitative method for determination of silicone oil and its degradation products in pharmaceutical formulations is therefore needed. Several analytical techniques have in the past been developed with the aim of detecting the presence of silicone oil and degradation products hereof. Most of these methods require hydrolyzation, derivatization, and extraction steps followed by, for example, gas chromatography-mass spectrometry analysis. Applying these methods can cause a loss in detection or an overestimation of the hydrolytic degradation products of silicone oil, that is, trimethylsilanol and dimethylsilanediol. The 2 silanols are highly hydrophilic and prefers the aqueous environment. Analysis of an aqueous formulation obtained from a PFS by 1H-NMR spectroscopy provides data about the content and levels of silicone oil and the 2 silanols even in levels below 10 ppm. The 1H-NMR method offers an easy and direct, quantitative measurement of samples intended for clinical use and samples kept at elevated temperature for a prolonged time (i.e., stability studies). The result of the study presented here showed dimethylsilanediol to be the main silicone compound present in the aqueous formulation when kept in baked-on PFSs. The degradation product dimethylsilanediol, in full accordance with expected hydrolytic degradation of silicone oil, increased during storage and with elevated temperature. In addition, the method can be applied to aqueous samples where polydimethylsiloxane has been added as, for example, the major constituent of antifoam.

CONTAMINATION OF ANTI-VEGF DRUGS FOR INTRAVITREAL INJECTION: How Do Repackaging and Newly Developed Syringes Affect the Amount of Silicone Oil Droplets and Protein Aggregates?

PURPOSE: The particle counts and the nature of particles of three different antivascular endothelial growth factor agents (VEGF) in different containers in a laboratory setting were compared. METHODS: Original prefilled ranibizumab glass syringes, original vials with aflibercept, and repacked ready-to-use plastic syringes with bevacizumab from a compounding pharmacy and a compounding company (CC) were analyzed. Particle counts and size distributions were quantified by different particle characterization methods (nephelometry, light obscuration, Micro-Flow Imaging, nanotracking analysis, resonant mass measurement). Using high-performance size-exclusion chromatography (HP-SEC), levels of protein drug monomer and soluble aggregates were determined. RESULTS: Nearly all samples showed similar product quality. Light obscuration and Micro-Flow Imaging showed a 4-fold to 9-fold higher total particle count in compounding company bevacizumab (other samples up to 42,000 particles/mL). Nanotracking analysis revealed highest values for compounding company bevacizumab (6,375 million particles/mL). All containers showed similar amounts of silicone oil microdroplets. Ranibizumab showed lowest particle count of all tested agents with only one monomer peak in HP-SEC. Repackaged bevacizumab from different suppliers showed varying product quality. CONCLUSION: All three tested agents are available in similar quality regarding particulate purity and silicone oil microdroplet count. Repackaging can have a major impact on the quality.

Characterization of the initial level and migration of silicone oil lubricant in empty prefilled syringes for biologics using infrared spectroscopy.

Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals. LAY ABSTRACT: Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals.

Differentiation of subvisible silicone oil droplets from irregular standard dust particles.

New methods are being applied to distinguish silicone oil droplets from subvisible particles in therapeutic protein formulations. The need to standardize these methods and compare them to established methods is critical to increase the understanding of the risks from protein aggregation and other subvisible particulate matter. We present the use of medium test dust (MTD) as a stable subvisible particle standard that can be distinguished from silicone oil by flow imaging methodology and the combination of light obscuration and microscopic methods. We further present the use of binary classification techniques to characterize the ability of flow imaging to distinguish between particle types (i.e., silicone vs. protein, silicone vs. standard, etc.) as a function of particle size. For the differentiation of silicone oil and MTD, the aspect ratio attribute was as good as or better than any other characteristic or combination of two characteristics applied to distinguish this particle population. However, the value of the discrimination by flow imaging was limited to particles larger than 5 µm.

Discrimination between silicone oil droplets and protein aggregates in biopharmaceuticals: a novel multiparametric image filter for sub-visible particles in microflow imaging analysis.

PURPOSE: Accurate monitoring of the sub-visible particle load in protein biopharmaceuticals is increasingly important to drug development. Manufacturers are expected to characterize and control sub-visible protein particles in their products due to their potential immunogenicity. Light obscuration, the most commonly used analytical tool to count microscopic particles, does not allow discrimination between potentially harmful protein aggregates and harmless pharmaceutical components, e.g. silicone oil, commonly present in drug products. Microscopic image analysis in flow-microscopy techniques allows not only counting, but also classification of sub-visible particles based on morphology. We present a novel approach to define software filters for analysis of particle morphology in flow-microscopic images enhancing the capabilities of flow-microscopy. METHODS: Image morphology analysis was applied to analyze flow-microscopy data from experimental test sets of protein aggregates and silicone oil suspensions. RESULTS: A combination of four image morphology parameters was found to provide a reliable basis for automatic distinction between silicone oil droplets and protein aggregates in protein biopharmaceuticals resulting in low misclassification errors. CONCLUSIONS: A novel, custom-made software filter for discrimination between proteinaceous particles and silicone oil droplets in flow-microscopy imaging analysis was successfully developed.

Demonstrating the stability of albinterferon alfa-2b in the presence of silicone oil.

Silicone oil is often used to decrease glide forces in prefilled syringes and cartridges, common primary container closures for biopharmaceutical products. Silicone oil has been linked to inducing protein aggregation (Diabet Med 1989;6:278; Diabet Care 1987;10:786-790), leading to patient safety and immunogenicity concerns. Because of the silicone oil application process (Biotech Adv 2007;25:318-324), silicone oil levels tend to vary between individual container closures. Various silicone oil levels were applied to a container closure prior to filling and lyophilization of an albumin and interferon alfa-2b fusion protein (albinterferon alfa-2b). Data demonstrated that high silicone oil levels in combination with intended and stress storage conditions had no impact on protein purity, higher order structure, stability trajectory, or biological activity. Subvisible particulate analysis (1-10 µm range) from active and placebo samples from siliconized glass barrels showed similar particle counts. Increases in solution turbidity readings for both active and placebo samples correlated well with increases in silicone oil levels, suggesting that the particles in solution are related to the presence of silicone oil and not large protein aggregates. Results from this study demonstrate that silicone oil is not always detrimental to proteins; nevertheless, assessing the impact of silicone oil on a product case-by-case basis is still recommended.

Silicone oil microdroplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling.

PURPOSE: To quantify levels of subvisible particles and protein aggregates in repackaged bevacizumab obtained from compounding pharmacies, as well as in samples of bevacizumab and ranibizumab tested in controlled laboratory experiments. METHODS: Repackaged bevacizumab was purchased from four external compounding pharmacies. For controlled laboratory studies, bevacizumab and placebo were drawn into plastic syringes and incubated at -20°C, 4°C, and room temperature (with and without exposure to light) for 12 weeks. In addition, mechanical shock occurring during shipping was mimicked with syringes containing bevacizumab. Particle counts and size distributions were quantified by particle characterization technology. Levels of monomer and soluble aggregates of bevacizumab were determined with size-exclusion high-performance liquid chromatography (SE-HPLC). RESULTS: Repackaged bevacizumab from the compounding pharmacies had a wide range of particle counts (89,006 ± 56,406 to 602,062 ± 18,349/mL). Bevacizumab sampled directly from the original glass vial had particle counts of 63,839 ± 349/mL. There was up to a 10% monomer loss in the repackaged bevacizumab. Laboratory samples of repackaged bevacizumab and placebo had initial particle counts, respectively, of 283,675 ± 60,494/mL and 492,314 ± 389,361/mL. Freeze-thawing of both bevacizumab and placebo samples led to >1.2 million particles/mL. In all repackaged samples, most of the particles were due to silicone oil. SE-HPLC showed no significant differences for repackaged samples incubated in the laboratory under various conditions, compared with bevacizumab directly from vial. However, repeated freeze-thawing caused a more than 10% monomer loss. CONCLUSIONS: Bevacizumab repackaged in plastic syringes could contain protein aggregates and is contaminated by silicone oil microdroplets. Freeze-thawing or other mishandling can further increase levels of particle contaminants.

[Subconjunctival deposit of silicone oil after vitreoretinal surgery]. / Depósito subconjuntival de óleo de silicone após cirurgia vitreorretiniana.

PURPOSE: To assess the histopathological findings of conjunctival specimens from patients submitted to vitreoretinal surgery with intraocular silicone oil injection. METHODS: Prospective analyses of 30 eyes of 30 patients were evaluated. Before the patients underwent removal of the intraocular silicone oil, conjunctival excision was performed and submitted to histopathologic examination. RESULTS: The presence of empty spaces corresponding to silicone oil location was positive in 10 (33%) specimens. The presence of inflammatory cells, vascular congestion, leukostasis, lymphocyte and monocyte infiltrates were positive in 27 (90%) specimens. The presence of silicone oil was positive in 10 (33%) specimens. Therefore, in those patients who undergo vitreoretinal surgery, silicone oil may be present in the conjunctiva or subconjunctival space, even if biomicroscopic examination seems to be normal. According to our knowledge, this is the first study with the purpose to assess the histopathological findings of conjunctival specimens from patients submitted to vitreoretinal surgery with intraocular silicone oil injection. CONCLUSION: Ophthalmologists should be aware of this possible complication after intraocular use of silicone oil after vitreoretinal surgery.

Depósito subconjuntival de óleo de silicone após cirurgia vitreorretiniana / Subconjunctival deposit of silicone oil after vitreoretinal surgery

OBJETIVO: Comprovar a presença do óleo de silicone no espaço subconjuntival de pacientes submetidos previamente à cirurgia vitreorretiniana por meio de estudo histopatológico das amostras conjuntivais obtidas, nos quais o exame biomicroscópico não foi capaz de comprovar sua presença. Determinar qual a incidência da presença do óleo de silicone no espaço subconjuntival em uma série de casos e quais implicações clínico-patológicas. MÉTODOS: Estudo prospectivo em 30 olhos de 30 pacientes. Foram incluídos no estudo os pacientes que haviam sido submetidos previamente à cirurgia vitreorretiniana com implante intra-ocular de óleo de silicone e que possuíssem indicação para retirada do óleo de silicone e que não apresentassem ao exame biomicroscópico sinais da presença do óleo de silicone no espaço subconjuntival. Após sua retirada, a amostra era encaminhada para análise histopatológica pelo método de hematoxilina-eosina. RESULTADOS: Foi observada a presença de espaços vazios correspondentes às áreas de localização do óleo de silicone, removido durante processamento histológico, em 10 (33 por cento) amostras. Observou-se também a presença de sinais inflamatórios na substância própria caracterizada por congestão vascular, leucostase e infiltrado linfomononuclear em 27 (90 por cento) amostras. CONCLUSÃO: Portanto, em pacientes submetidos ao implante intra-ocular do óleo de silicone, devemos suspeitar que o óleo esteja presente no espaço subconjuntival, mesmo que o exame biomicroscópico pareça normal.

PURPOSE: To assess the histopathological findings of conjunctival specimens from patients submitted to vitreoretinal surgery with intraocular silicone oil injection. METHODOS: Prospective analyses of 30 eyes of 30 patients were evaluated. Before the patients underwent removal of the intraocular silicone oil, conjunctival excision was performed and submitted to histopathologic examination. RESULTS: The presence of empty spaces corresponding to silicone oil location was positive in 10 (33 percent) specimens. The presence of inflammatory cells, vascular congestion, leukostases, lymphocyte and monocyte infiltrates were positive in 27 (90 percent) specimens. The presence of silicone oil was positive in 10 (33 percent) specimens. Therefore, in those patients who undergo vitreoretinal surgery, silicone oil may be present in the conjunctiva or subconjunctival space, even if biomicroscopic examination seems to be normal. According to our knowledge, this is the first study with the purpose to assess the histopathological findings of conjunctival specimens from patients submitted to vitreoretinal surgery with intraocular silicone oil injection. CONCLUSION: Ophthalmologists should be aware of this possible complication after intraocular use of silicone oil after vitreoretinal surgery.