There is currently no national strategy or standardized approach to diabetic retinopathy screening in the Brazilian public health system, and multiple socioeconomic barriers prevent access to eye ...examination in Brazil's poorest regions.ProblemThere is currently no national strategy or standardized approach to diabetic retinopathy screening in the Brazilian public health system, and multiple socioeconomic barriers prevent access to eye examination in Brazil's poorest regions.From September 2021 to March 2022 we carried out a pilot project with an artificial intelligence system for diabetic retinopathy screening, embedded in a portable retinal camera. Patients with a diagnosis of diabetes according to the municipality registry were invited to attend nearby clinics for screening on designated days. Trained health-care technicians acquired images which were automatically evaluated by the system, with instant remote evaluation by retinal specialists in selected cases.ApproachFrom September 2021 to March 2022 we carried out a pilot project with an artificial intelligence system for diabetic retinopathy screening, embedded in a portable retinal camera. Patients with a diagnosis of diabetes according to the municipality registry were invited to attend nearby clinics for screening on designated days. Trained health-care technicians acquired images which were automatically evaluated by the system, with instant remote evaluation by retinal specialists in selected cases.Our study was based in Sergipe State, located at a region with high illiteracy rates and no local availability of specialized retina care. The average number of laser treatments performed annually in the last 5 years is 126, for a total State population of 2.3 million.Local settingOur study was based in Sergipe State, located at a region with high illiteracy rates and no local availability of specialized retina care. The average number of laser treatments performed annually in the last 5 years is 126, for a total State population of 2.3 million.Even though screening was performed free of charge in a convenient location for patients, from a total 2052 eligible individuals, only 1083 attended for screening.Relevant changesEven though screening was performed free of charge in a convenient location for patients, from a total 2052 eligible individuals, only 1083 attended for screening.Efforts to raise awareness on the condition screened and to provide health education for patients and local health-care personnel are fundamental for increased attendance. Tailoring screening systems to the local setting, such as determining the trade-off between sensitivity and specificity, is challenging in regions with no current benchmarks. Standards for retinopathy screening based on the strategies adopted by high-income countries may not be realistic in low- and middle-income countries.Lessons learntEfforts to raise awareness on the condition screened and to provide health education for patients and local health-care personnel are fundamental for increased attendance. Tailoring screening systems to the local setting, such as determining the trade-off between sensitivity and specificity, is challenging in regions with no current benchmarks. Standards for retinopathy screening based on the strategies adopted by high-income countries may not be realistic in low- and middle-income countries.
Background/aimsTo assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions.MethodsEight 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.ResultsFive 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.ConclusionSyringes 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.
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.
•Syringes should have as little silicone oil as possible or none at all.•Drug in the vial or the syringe should never be agitated.•New devices might play a role in assisting the intravitreal injection.•Materials and techniques might cause complications when used inappropriately.•The choice of the anesthetic technique is important for better patient comfort.
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.
Intraocular inflammation is an uncommon but potentially vision-threatening adverse event related to anti-VEGF therapy. This is of increasing importance given both the volume of injections performed, ...as well as the increased prevalence of inflammation seen with newer anti-VEGF agents. Brolucizumab, the newest anti-VEGF agent, has been associated with an inflammatory retinal vasculitis and the underlying mechanism is unclear. Reviewing potential mechanisms and clinical differences of intraocular inflammation may assist clinicians and scientists in reducing the risk of these events in the future.
Two types of inflammation are seen with intravitreal injections, acute onset sterile inflammation and delayed onset inflammatory vasculitis. Acute onset inflammation can be subcategorized into subclinical anterior chamber inflammation and sterile uveitis/endophthalmitis. Subclinical anterior chamber inflammation can occur at rates as high as 19% after intravitreal anti-VEGF injection. Rates of sterile uveitis/endophthalmitis range from 0.05% to 4.4% depending on the anti-VEGF agent. Inflammatory vasculitis is only associated with brolucizumab and occurred in 3.3% of injections according to the post hoc review of the HAWK/HARRIER data. In addition, silicone oil from syringes can induce immunogenic protein aggregates. Agitation of the syringe, freeze thawing, shipping and improper storage prior to injection may increase the amount of silicone oil released from the syringe.
The main factors which play a role in intraocular inflammation after anti-VEGF injection can be divided into three causes: patient-specific, medication-specific and delivery-specific. The majority of clinically significant inflammation seen after intravitreal injection is an acute onset inflammatory response with most patients recovering baseline VA in 3-5 weeks. The presence of pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss may help distinguish infectious from non-infectious etiologies of post injection inflammation. Avoiding temperature fluctuation, mechanical shock, agitation during transport and handling of syringes/drugs, and the use of SO-free syringes may help minimize intraocular inflammation. While a definitive mechanism has not yet been established, current knowledge of the clinical presentation and vitreous histopathology of brolucizumab-retinal vasculitis favors an auto-immune type IV hypersensitivity reaction.
To determine factors causing inflammation after intravitreal aflibercept injections.
This case-control study included aflibercept-treated eyes with inflammation post-injection and aflibercept-treated ...control eyes. Medical records were analyzed to identify contributing factors. Biophysical tests were performed to characterize properties of particle aggregation. Institutional review board approval was obtained.
Inflammation developed in six eyes; three patients had anterior uveitis, and five had vitreous cells. Oil droplets were seen in all cases. Saldanha Rodrigues (SR) syringes were used in all cases. Among controls, SR and Becton-Dickinson syringes were used in 10 and 17 eyes, respectively. Regression analysis showed an association between SR syringes and inflammation (odds ratio = 21.66; 95% confidence interval, 1.10-425.06; P = .043). Biophysical analyses primarily showed aggregation possibly from free oil droplets or protein-oil droplet aggregation.
Post-injection inflammation was associated with SR syringes. Silicone oil droplets, especially after syringe agitation, might play a role in the inflammatory reaction. Ophthalmic Surg Lasers Imaging Retina. 2019;50:288-294..
Abstract
Injections are widely performed in the healthcare practice. Silicone has long been thought to be an inert and harmless material. Although used for decades in medical implants, including ...heart valves, breast implants, and as a tamponade for retinal detachment surgery, silicone oil might have deleterious effects. Agitation of the syringe to expel air at the moment of drug preparation not only leads to silicone oil release but also to therapeutic protein aggregation. Lab studies have shown that silicone oil microdroplets can act as an adjuvant to promote a break in immunological tolerance and induce antibody response. Similarly, recent studies have suggested a causal link between agitation of siliconized syringes and ocular inflammation after intravitreal injection. Systemically, silicone oil has been reported in association with autoimmune diseases and skin granuloma after either direct injection of dermal fillers or secondary leakage from silicone breast implant. However, it has not been established yet a potential link between the silicone oil released by the syringes and such relevant systemic adverse events. Few professionals are aware that agitation of a siliconized syringe might lead to silicone oil release, which, in turn, acts an adjuvant to an increased immunogenicity. We strongly recommend that every healthcare professional be aware of the use of silicone oil in the syringe manufacturing process, the factors that promote its release and the potential complications to the organism. Ultimately, we recommend that safer syringes be widely available.
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.
This study reports the implementation of a diabetic retinopathy (DR) screening program in Aracaju, Brazil, emphasizing the challenges and premature termination.
The program, a collaboration between ...local health authorities, national DR screening experts, private clinics, trained retinal imaging technicians, a portable retinal camera with artificial intelligence (AI), telemedicine, and AI-assisted image analysis, was established. Screening occurred at primary care centers, with free specialized treatment for high-risk DR cases.
After a public tender, two clinics were selected for screening, and four for secondary management. Initially, diabetic patient attendance at primary care clinics varied considerably, posing a challenge. Nonetheless, the screening continued, with 3,561 patients screened within six months. However, due to complaints and disputes between providers and authorities, the program was prematurely terminated, achieving less than a quarter of the initial screening target.
The DR screening program faced significant challenges, including low adherence and organizational issues at primary care centers. This experience highlights the need to standardize clinical workflows, enhance organization and integration among primary care units, and address cultural factors to improve adherence rates. These insights are valuable for implementing screening programs, particularly in low- and middle-income countries.
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