Anti-complement drugs for the treatment of geographic atrophy and the release of silicone oil.

Intravitreal injections are a common procedure in ophthalmology, often using syringes coated with silicone to aid piston movement and needles coated with silicone oil to facilitate penetration of the sclera. Pegcetacoplan and avacincaptad pegol, recently approved for clinical use by the US Food and Drug Administration, have higher viscosity and seem more susceptible to entrap air bubbles compared to anti-VEGF drugs.It is plausible that both anti-complement drugs could be associated with a higher likelihood of introducing silicone oil in the vitreous because of higher viscosity, with potentially higher friction at the inner surface of syringe barrel, in the vicinity of silicone oil. In addition to this, undesirable agitation might be inadvertently promoted by some retina specialists to remove air bubbles from the drug solution.In conclusion, recent reports of silicone oil droplets in the vitreous of patients receiving pegcetacoplan injection might be related to both its viscosity and to agitation of the syringe to remove air bubbles. Since avacincaptad pegol also is viscous, though with different pH, syringe and filter needle, we might expect similar reports for this agent soon. We also recommend further studies be carried not only to clarify the current matter but also the potential association between the combination of agitation, silicone oil and inflammation or any immune response.

PRO score: predictive scoring system for visual outcomes after rhegmatogenous retinal detachment repair.

BACKGROUND/AIMS: To compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system. METHODS: Analysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA ≤20/200). RESULTS: A total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1±1.1 (20/250) and 0.5±0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (≤20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), >1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age >70 (1.13; 1.04 to 1.23). The data were split into training (75%) and validation (25%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8% with a total score of 0, 17% with 1, 29% with 2, 47% with 3, and 71% with 4 or higher. CONCLUSIONS: Independent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss >1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.

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.

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.

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.

Prevalence of silicone oil droplets in eyes treated with intravitreal injection.

OBJECTIVE: To assess the number of eyes with silicone oil in the vitreous after intravitreal injection. METHODS: This cross-sectional, comparative study was divided into 2 groups: (1) treatment-eyes subjected to antiangiogenic therapy; (2) control-no history of intravitreal injection. Subjects were assessed regarding age, gender, clinical diagnosis, lens status, visual acuity and number of previous intravitreal injections. All eyes underwent a meticulous slit-lamp and ultrasound examination for the identification of silicone oil. ImageJ software was used to quantify the index of silicone oil (IOS) by ultrasonography. RESULTS: Sixty-seven eyes (30 controls, 37 treated) were included. Slit-lamp examination found silicone oil droplets in 25 out of 37 (67.57%) treated eyes and in none of the control group. Ultrasonography identified silicone oil in 28 out of 37 (75.68%) treated eyes and in 1 out of 30 (3.33%) controls. An observed agreement of 85.07% and a Cohen's Kappa coefficient of 69.10% (p < 0.0001) between ultrasonography and biomicroscopy were found. Wilcoxon test showed a statistically significant difference (p = 0.0006) in IOS between controls (0.41 ± 0.43%) and treated eyes (2.69 ± 2.55%). Spearman's correlation test (0.61; p < 0.0001) showed that the greater the number of injections, the higher the IOS. CONCLUSIONS: Silicone oil droplets were found in the majority of the eyes previously treated with antiangiogenic intravitreal injection. The greater the number of injections, the higher the likelihood of finding silicone oil. An improvement in the technique of injection and better-quality syringes post-injection silicone oil droplets.

Release of silicone oil droplets from syringes.

BACKGROUND: Intravitreal silicone oil droplets have been found in the vitreous. The aim of this study is to compare the rates of silicone oil released by different brands of commonly used syringes for intravitreal injection after agitation by flicking. METHODS: Three models of two brands of syringes were analyzed for their rates of silicone oil release: Saldanha Rodrigues (SR) 1 mL insulin syringe (SR, Brazil, syringe 1), Becton-Dickinson (BD) Plastipak 1 mL insulin syringe (Brazil, syringe 2), and BD Safety-Glide 1 mL insulin syringe (USA, syringe 3). All syringes were tested under four different conditions: positive control (fluid with addition of silicone oil) without agitation (group 1, n = 5); positive control with agitation (group 2, n = 3); fluid only without agitation (group 3, n = 5); and fluid only with agitation (group 4, n = 5). Masked graders performed all analyses using light microscopy. RESULTS: All syringes (1, 2, and 3) released silicone oil droplets in the positive control group regardless of the agitation status (groups 1 and 2). When no oil was added and the syringes were not agitated, only syringe 1 released silicone oil droplets (40% of samples). After agitation, syringes 1 and 3 released silicone oil droplets in all samples. Quantitative analysis showed a significantly (P = 0.011; 11.2 ± 2.9 vs. 0.6 ± 0.9, respectively) higher mean number of silicone oil droplets released by syringe 1 after agitation compared to no agitation. Syringe 1 also had significantly (P = 0.002, 11.2 ± 2.9 vs. 0.0 ± 0.0 vs. 2.2 ± 0.8, respectively) more droplets than syringes 2 and 3 after agitation. CONCLUSIONS: Syringes commonly used for intravitreal injections frequently release silicone oil droplets when agitated by flicking, especially the SR insulin ones. We recommend that they not be agitated at the time of intravitreal injection and that the manufacturers consider producing syringes adapted for intraocular use.