Silicone Oil Droplets After Intravitreal Injections

Subject: Review of Silicone Oil Droplets (SODs) as a Complication of Intravitreal Injections (IVIs)

Executive Summary

Intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents and other medications are a cornerstone treatment for various retinal conditions. However, a significant and increasingly recognized complication is the inadvertent introduction of silicone oil droplets (SODs) into the vitreous cavity. These droplets originate from the silicone-based lubricant used in most commercial syringes. While often asymptomatic, SODs can cause significant visual disturbances, discomfort, and have potential long-term implications, including elevated intraocular pressure (IOP) and immune/inflammatory responses. The prevalence of SODs is high, with studies reporting their presence in over 70% of patients receiving IVIs with siliconized syringes. The risk of SODs is influenced by factors such as the number of injections, syringe design, handling techniques, and drug viscosity. The use of silicone-free syringes is recommended to mitigate this complication.

Main Themes and Key Findings

1. High Prevalence and Source of Silicone Oil Droplets (SODs)

• Ubiquitous Presence: SODs are a common occurrence after IVIs. García et al. (2022) reported that “Silicone oil droplets were reported in 109 eyes (71.7%)” of patients who had received at least one IVI. Similarly, Melo et al. (2023) found “Presumed SiO (pSiO) was detected in 43 (78%) eyes” in their study. Akbulut et al. (2022) also noted “studies about detection of intravitreal silicone oil droplets following repeated injections.”
• Syringe Lubrication: The primary source of SODs is the silicone-based lubricant (polydimethylsiloxane) that coats the inside of syringe barrels and plungers to ensure smoother drug delivery. “The silicone oil droplets originate from the silicone-based lubricant that coats the syringe barrel and plunger, facilitating smoother and more efficient drug delivery” (Kamath et al., 2025). Melo et al. (2023) explicitly state, “The primary source of SiO contamination in IVIs is most likely the syringe.”
• Needles as a Source: Siliconized needles can also contribute to SOD contamination, even with silicone-free syringes (Melo et al., 2023; Panigrahi et al., 2023).

2. Factors Influencing SOD Introduction

• Number of Injections: There is a direct correlation between the number of IVIs and the quantity of SODs. García et al. (2022) found a “positive correlation… between the number of IVIs received and the quantity of droplets found.” Kamath et al. (2025) note, “The incidence of silicone oil droplets increases with the number of injections.” Melo et al. (2023) empirically confirmed “pSiO accumulation with repeated IVIs.”
• Syringe Design: The design of the syringe plays a crucial role. Staked-on needle designs may release more silicone oil compared to luer lock designs (Kamath et al., 2025; Scott et al., 2009 cited in Kamath et al., 2025). Prefilled syringes generally show fewer particles (Kamath et al., 2025).
• Handling Techniques:Flicking/Agitation: Actions like flicking or tapping the syringe to remove air bubbles significantly dislodge silicone oil into the drug solution. “The common practice of flicking the syringe before the injection… has been implicated in the release of silicone oil into the vitreous cavity” (Kamath et al., 2025). Melo (2022) states, “the SiO is especially released by agitation, such as when the syringe is flicked or tapped.”
• Plunger Depression: Depressing the plunger to its end, particularly with smaller drug volumes, can release more oil (García et al., 2022; Emerson, 2017 cited in Bijon et al., 2023).
• Drug Viscosity: Highly viscous medications, such as pegcetacoplan, may interact more with silicone oil, leading to increased droplet release, especially with agitation during preparation. “The high viscosity of pegcetacoplan engendered copious amounts of air bubbles in the syringe, so priming the syringe was crucial to ensure smooth efflux of the medication during the injection. Intravitreal injection of the medication was done using the usual aseptic technique…” (Dessouki et al., 2023). “We hypothesize that, due to its viscosity, pegcetacoplan may interact with the silicone oil present in the syringe. Any agitation, such as flicking or pulling and pushing of the plunger, may amplify this interaction” (Dessouki et al., 2023).
• Manufacturing Defects & Storage Conditions: Uneven siliconization, suboptimal storage, and transport conditions (e.g., fluctuating temperatures, freeze-thaw cycles, mechanical agitation/shocks) can degrade the silicone layer and increase droplet release (Kamath et al., 2025; Melo, 2022).

3. Clinical Manifestations and Patient Impact

• Visual Floaters: The most common symptom is the presence of iridescent or black floaters, often described as distressing (Kamath et al., 2025; Dessouki et al., 2023; Melo, 2022). “Although frequently asymptomatic, silicone oil droplets can occasionally cause significant visual disturbances and discomfort” (Kamath et al., 2025). Bijon et al. (2023) reported “multiple small floaters that began the day following the injection” in a patient receiving pegcetacoplan.
• Asymptomatic vs. Symptomatic: Many cases remain asymptomatic, with studies showing that “only 40% of these individuals reported experiencing visual symptoms” despite 71% prevalence (Kamath et al., 2025). García et al. (2022) noted that 39.5% of eyes with SODs reported floaters, but the “prevalence of symptoms is much lower than the prevalence of droplets.”
• Severity: Symptoms can range from mild annoyance to significant distress that may warrant intervention. “Approximately 5% of their US members [ASRS] have performed vitrectomy to treat patients with symptomatic floaters, and 2% have seen patients seeking legal action” (Melo, 2022).
• Intraocular Pressure (IOP) Elevation: While not always statistically significant, there is a concern that SODs can increase IOP, potentially by blocking the trabecular meshwork. “A correlation has been observed between a higher number of silicone oil droplets and an increase in mean IOP” (Kamath et al., 2025). García et al. (2022) observed that the “Abundant” group had a higher mean IOP, though not statistically significant.
• Inflammatory Responses: Silicone oil microdroplets can act as a foreign body, potentially exacerbating inflammatory responses and promoting protein aggregation, which can lead to immunogenicity. Melo (2022) highlights that “agitation of a siliconized syringe could lead to the detection of inflammatory cells in the anterior chamber of the eye.” Experimental studies have shown SODs can “invoke early- and late-stage immune responses” and form complexes with pharmaceutical proteins that are potentially immunogenic (Dessouki et al., 2023; Melo, 2022).
• Neuroadaptation: Over time, patients may become less symptomatic due to neuroadaptation, where the brain learns to ignore the floaters (Kamath et al., 2025).
• Posterior Vitreous Detachment (PVD): A positive correlation exists between PVD and the number of silicone droplets, suggesting PVD may facilitate droplet movement and visualization (García et al., 2022).

4. Management and Recommendations

• Prevention is Key:Silicone-Free Syringes: The most significant recommendation is the use of silicone-free syringes. “Therefore, the authors recommend using SiO-free syringes for IVIs to mitigate SiO-related complications” (Melo et al., 2023). Dessouki et al. (2023) suggest “using silicone-free syringes, if possible, when administering pegcetacoplan to prevent such complications in the future.”
• Prefilled Syringes: These may reduce the need for manual manipulation and plunger friction, thus lowering contamination risk (Kamath et al., 2025).
• Avoid Agitation: Unnecessary priming, flicking, or tapping of the syringe should be avoided to preserve the lubricant layer (Kamath et al., 2025; Melo, 2022).
• Syringe Design Choice: Selecting syringes designed to minimize oil release is important (Kamath et al., 2025).
• Patient Counseling: Patients should be informed about the potential for SODs and associated symptoms as part of the consent process (Kamath et al., 2025; Dessouki et al., 2023; Panigrahi et al., 2023).
• Medical Management: For elevated IOP, anti-glaucoma medications can be effective (Kamath et al., 2025).
• Vitrectomy: In rare cases of significant visual loss or severe symptomatic floaters, vitrectomy may be considered, but it is an invasive procedure with inherent risks (Kamath et al., 2025; Melo, 2022).

5. Emerging Concerns and Future Research

• Micro-sized Droplets: Conventional slit-lamp examinations primarily detect macro-sized droplets. There is growing interest in the potential inflammatory power of micro-sized droplets (García et al., 2022).
• Long-term Effects: More studies with longer follow-up periods are needed to fully understand the long-term implications of SODs, especially concerning IOP changes and potential immune responses (García et al., 2022; Dessouki et al., 2023; Akbulut et al., 2022).
• Regional Variations: The incidence of SODs in specific populations, such as South Asian, remains understudied (Kamath et al., 2025).
• Standardization: There is a need for standardized techniques and materials in intravitreal injections to minimize SOD contamination (Melo et al., 2023; Dessouki et al., 2023).