Quantitative assessment of silicone oil release with siliconized and silicone oil-free syringes by microflow imaging microscopy / Avaliação quantitativa da liberação de óleo de silicone por seringas siliconizadas e sem óleo de silicone usando microflow imaging microscopy

ABSTRACT Purpose: Since particles are released in syringes during intravitreal injections, we assessed them quantitatively after agitating syringes commonly used for intravitreal injections. Methods: With and without agitation, the SR 1-ml insulin, Becton-Dickinson Ultra-Fine 0.3-ml Short Needle with a half-unit scale, HSW Norm-Ject Tuberculin, and Becton-Di­ckinson 1-ml Luer Lok Tip were examined with buffer and bevacizumab, aflibercept, and ziv-aflibercept. Flow imaging microscopy was performed to assess the particle numbers, concentrations, morphology, and size distribution. Results: Using the Becton-Dickinson Ultra-Fine syringe, the average particle count after agitation was higher than in the no-agitation group. For particles greater than 10 and 25 µm, differences were observed using the SR syringe between the two studied conditions. There were no significant differences in the means for the other syringes. Without agitation, the SR syringe had the highest number of particles (2,417,361.7 ± 3,421,575.5) followed by the Becton-Dickinson Ultra-Fine with 812.530,9 ± 996.187,2. The Becton-Dickinson Luer Lok Tip and HSW Norm-Ject performed equally with 398,396.8 ± 484,239.2 and 416,016.4 ± 242,650.1 particles, respectively. Conclusions: Flicking syringes to eliminate air bubbles results in increased numbers of particles released during intravitreal injections into the human vitreous.

RESUMO Objetivo: Visto que partículas são liberadas nas seringas durante as injeções intravítreas (IVIs), estas foram avaliadas quantitativamente após a agitação das seringas mais comumente usadas para injeções intravítreas. Métodos: A seringa SR de 1 ml de insulina, a agulha curta Becton-Dickinson Ultra-Fine 0,3 ml com escala de meia unidade, HSW Norm-Ject Tuberculin e a Becton-Dickinson Luer Lok Tip de 1 ml foram estudadas com placedo e com bevacizumabe, aflibercept e ziv-aflibercept, com e sem agitação. MicroFlow Imaging Mi­croscopy foi realizada para avaliar o número de partículas, con­centração, morfologia e distribuição das mesmas por tamanho. Resultados: A contagem média de partículas após agitação foi maior do que no grupo sem agitação usando a seringa Becton-Di­ckinson Ultra-Fine. Diferenças foram observadas usando a seringa SR entre as duas condições estudadas para partículas maiores que 10 e 25 µm. Para as demais seringas, não foram observadas diferenças significativas nas médias. A seringa SR apresentou o maior número de partículas sem agitação (2.417.361,7 ± 3.421.575,5) seguida da Becton-Dickinson Ultra-Fine com 812.530,9 ± 996.187,2. A BD Luer Lok Tip e a HSW Norm-Ject se comportaram de forma semelhante com 398.396,8 ± 484.239,2 e 416.016,4 ± 242.650,1 partículas, respectivamente. Conclusões: Agitar seringas para remover bolhas de ar resulta em um maior número de partículas liberadas durante Becton-Dickinson no vítreo humano.

Quantitative assessment of silicone oil release with siliconized and silicone oil-free syringes by microflow imaging microscopy.

PURPOSE: Since particles are released in syringes during intravitreal injections, we assessed them quantitatively after agitating syringes commonly used for intravitreal injections. METHODS: With and without agitation, the SR 1-ml insulin, Becton-Dickinson Ultra-Fine 0.3-ml Short Needle with a half-unit scale, HSW Norm-Ject Tuberculin, and Becton-Di-ckinson 1-ml Luer Lok Tip were examined with buffer and bevacizumab, aflibercept, and ziv-aflibercept. Flow imaging microscopy was performed to assess the particle numbers, concentrations, morphology, and size distribution. RESULTS: Using the Becton-Dickinson Ultra-Fine syringe, the average particle count after agitation was higher than in the no-agitation group. For particles greater than 10 and 25 µm, differences were observed using the SR syringe between the two studied conditions. There were no significant differences in the means for the other syringes. Without agitation, the SR syringe had the highest number of particles (2,417,361.7 ± 3,421,575.5) followed by the Becton-Dickinson Ultra-Fine with 812.530,9 ± 996.187,2. The Becton-Dickinson Luer Lok Tip and HSW Norm-Ject performed equally with 398,396.8 ± 484,239.2 and 416,016.4 ± 242,650.1 particles, respectively. CONCLUSIONS: Flicking syringes to eliminate air bubbles results in increased numbers of particles released during intravitreal injections into the human vitreous.

Ocular inflammation after agitation of siliconized and silicone oil-free syringes: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Noninfectious endophthalmitis may be misdiagnosed, leading to serious clinical implications. So far, its causative factors remain unknown. Therefore, this study assessed the role of silicone oil and syringe agitation in the development of inflammation after intravitreal injection of aflibercept. METHODS: A randomized, double-blind, controlled clinical trial included subjects with an indication of intravitreal antiangiogenic therapy prior to vitrectomy for proliferative diabetic retinopathy. Aflibercept was injected 48 h before surgery. The control group received the injection without agitation, while the intervention group was injected with a previously agitated syringe by flicking with either a siliconized or silicone oil-free syringe. The primary endpoint was the presence of anterior chamber reaction (ACR) at 48 h. Aqueous samples were collected and underwent cytometric bead array analysis for quantification of interleukins and chemokines. RESULTS: Forty-one individuals were included (21 in the agitation group and 20 in the no-agitation group). None of the included eyes showed baseline signs of AC cells, hyperemia or pain complaint, while 10% of control group and 80% of agitation group showed AC cells 48 h after injection of aflibercept with SR syringe. There were no differences in the mean variations of all cytokines and chemokines by agitation status. However, there was a marginally significant increase between the mean variations of IP-10 (p = 0.057) and IL-8 (p = 0.058) in the siliconized one. CONCLUSION: This clinical trial discloses a potential role of agitation and siliconized syringes in the development of inflammation after an intravitreal injection of aflibercept. These findings have important clinical implications for all healthcare practitioners who perform intravitreal injections. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-95ddhp. Registered 12 May 2019, http://www.ensaiosclinicos.gov.br/rg/RBR-95ddhp/.

Retinal microvascular density modifications during the water drinking test.

PURPOSE: The water drinking test (WDT) is a well-known stress test that increases intraocular pressure (IOP) momentarily and can indicate risk of glaucoma progression. This study focuses on correlating changes in the retinal microvascular plexus with the WDT in young healthy subjects. METHODS: A total of 20 eyes of 20 healthy young subjects (mean age 24.37 ± 2.17 years) were included in this study. In our protocol, WDT consisted of drinking 1 L of water within 5 min. Outcome measures in this prospective observational study were mean arterial pressure (MAP), heart rate (HR), IOP, and retinal vessel density of both superficial and deep macular retina using optical coherence tomography angiography (OCTA), which were assessed before water ingestion and four times after at 15-min intervals. OCTA images were later quantified by fractal analysis (box counting [Dbox]). One-way repeated measures analysis of variance (ANOVA) was used to assess the effects of WDT on each of the parameters. RESULTS: The WDT resulted in significant peak changes of the following parameters compared to baseline: IOP: 15.63 ± 3.37 versus 18.38 ± 4.53 mmHg at 30 min, p < 0.001; HR: 75.74 ± 12.23 versus 64.95 ± 11.37 bpm at 15 min, p < 0.001; deep retinal vessel density 1.758 ± 0.14 versus 1.749 ± 0.16 at 15 min, p = 0.040. CONCLUSIONS: Besides IOP elevation and systemic effects in HR, WDT is associated with temporary modifications of the deep vascular plexus in young healthy subjects.

In-vitro assessment of release of silicone oil droplets with the use of variety of syringes and needles used in intravitreal injections.

PURPOSE: To assess the variability of silicone oil (SO) particles released across syringes from the same lot and the role of different needle gauges. MATERIALS AND METHODS: Four syringe models and six needle models were assessed for SO release. About 50 microliters of a buffer solution were loaded into the syringe, needle or syringe/needle setup. The data were analyzed by imaging flow cytometry with fluorescently labeling for SO. RESULTS: All syringe models had a high coefficient of variation in SO release across syringes from the same lot. The amount of SO was significantly greater in the syringe when the needle was attached. SO particles with the BD 30G needle attached to the syringe were statistically greater than the 27G counterpart (p = 0.005). None of the other comparisons was statistically different. Finally, the number of SO particles was higher in the syringe/needle setup than in needles only (p = 0.0024). CONCLUSION: We found a high variability in SO content across syringes from the same lot. Additionally, there was no clear association between needle gauge and the number of SO particles, as well as their coefficient of variation. Finally, the needles accounted for a small number of SO particles in comparison to the combined syringe-needle setup.

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.

High particle variability across siliconized and oil-free syringes and needles from the same lots.

Previous studies have reported silicone oil (SO) applied to needles and syringes in the vitreous of patients after intravitreal injections. We evaluated four syringes (SR 1-mL insulin, Saldanha-Rodrigues; BD 1-mL Tuberculin Slip Tip, Becton-Dickinson; BD Ultra-Fine 0.3 mL, HSW Norm-Ject Tuberculin, Henke Sass Wolf) and 10 needles (BD PrecisionGlide 27- and 30-gauge (G); BD Eclipse and JBP Nanoneedle 27-, 30-, 33- and 34-G; TSK Invisible Needle and 27 and 30-G Steriject Control Hub). The protein-free buffer samples injected into the syringes and needles under study were collected in an Eppendorf tube and taken to Flow imaging microscopy, that characterized the concentration and morphology of the microsized particles. The number of particles was analyzed. The coefficients of variation (CV) were the primary outcome. The Feltz and Miller test compared the CVs. The significance level was 5%. Numerous particles and high CVs were associated with both devices, needles and syringes; the comparisons among them did not reach significance. The BD Ultrafine 0.3 mL syringe (149.7%) had the highest CV and the SO-free HSW Norm-Ject (66.4%) syringe the lowest, and the TSK Invisible needle (149.5%) had the highest and the BD Precision Glide 30G needle (35.9%) needle the lowest. In conclusion, particle release, including those with SO morphology, varied greatly among instruments, even from the same lots, which is relevant considering that fewer particles are injected into some eyes compared with others.

Heads-up Digitally Assisted Surgical Viewing with Intraoperative Optical Coherence Tomography for Myopic Schisis Repair.

PURPOSE: To describe the surgical approach with a screen-based heads-up, three-dimensional (3-D) digital viewing with intraoperative optical coherence tomography (I-OCT) for the successful repair of a myopic macular schisis (MMS) case. CASE REPORT: A 62-year-old woman with vision loss in the left eye was scheduled for pars plana vitrectomy (PPV) and MMS repair. Surgery was performed using the NGENUITYⓇ system for surgical viewing, and foveal-sparing internal limiting membrane (fs-ILM) peeling was performed without gas tamponade, after confirming the absence of iatrogenic macular hole with I-OCT. There were no intraoperative or postoperative complications. Visual acuity improved to 20/40 and the subfoveal macular thickness improved from 706 µm (preoperative) to 221 µm after seven months of follow-up. CONCLUSION: Heads-up digitally assisted viewing technology with I-OCT may be useful or preferred for patients requiring vitreoretinal surgery in the setting of MMS.

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.

Effect of chronic cocaine use on fine motor coordination tested during ophthalmic vitreoretinal simulated performance.

We conducted a case-control study using the Eyesi simulator to assess the surgical performance of 24 chronic cocaine users (CCUs) and 24 sex-/age-matched controls to numerically quantify ophthalmic microsurgical simulator performance and fine motor deficiencies. The inclusion criteria were no exposure to illicit drugs other than cocaine, marijuana, or alcohol within the previous month and no health conditions that could impact manual task performance. The outcomes included surgical scores (0-100, worst-best) and task completion time (minutes). Fisher's exact test, analysis of variance, Mann-Whitney U test, and Kruskal-Wallis test followed by Dunn-Bonferroni post-hoc were conducted for statistical analysis. The Eyesi scores were lower among CCUs compared to controls for bimanual tasks (4.50 ± 14.30 vs. 18.46 ± 26.64, p = 0.012), for exercises demanding upper and lower limb coordination (both hands and two foot pedals, respectively) (74.13 ± 35.01 vs. 85.21 ± 24.1, p = 0.045), and in the overall score for all three tasks (27.38 ± 15.06 vs. 39.5 ± 18.66, p = 0.021). CCUs took longer to complete tasks when performing exercises demanding upper and lower limb coordination compared to controls (1.26 ± 0.38 vs. 1.02 ± 0.44 min, p = 0.006). Individuals who used cocaine during the previous month had an independent lower bimanual score compared to controls (1.42 ± 4.91 vs. 18.46 ± 26.64, p = 0.018). No differences in performance among the CCUs were attributable to sporadic cannabis or alcohol use. Chronic use of cocaine negatively impacted fine dexterity as measured by bimanual tasks or maneuvers that required simultaneous coordination of the upper and lower limbs. This was most notable among individuals who used cocaine during the 1-month period before the simulation.

Effects of phosphodiesterase type 5 inhibitors on choroid and ocular vasculature: a literature review.

To provide information on the effects of phosphodiesterase type 5 (PDE5) inhibitors on choroidal vessels and central serous chorioretinopathy (CSC) and possible implications for development of exudative age-related macular degeneration (AMD). Two independent investigators conducted a qualitative review of PubMed to identify studies on the choroidal effect of PDE5 inhibitors in June 2019. The search used key words that included PDE5 inhibitors, sildenafil, tadalafil, vardenafil, choroid, choroidal flow, choroidal vessels, choroidal thickness, CSC, AMD or a combination. Only studies which assessed choroidal findings were included. Many ocular diseases are related to changes in choroidal thickness and perfusion. Patients with AMD, who have decreased choroidal perfusion, may manifest more severely diminished choroidal ability to deliver oxygen and other metabolites to the retina, leading to growth of neovascular tissue. As a result of this engorgement of the choroidal vasculature, some patients may have leakage across the retinal pigment epithelium (RPE) and accumulation of subretinal fluid, resulting in CSC. Transient visual symptoms, i.e., changes in color perception and increased light sensitivity, are well-known adverse effects, but there have been rare reports of vision-threatening ocular complications in users of PDE5 inhibitors, such as nonarteritic anterior ischemic optic neuropathy and cilioretinal artery occlusion. The choroid is a vascular tissue analogous in many respects to the corpus cavernosum, and PDE5 inhibitors may increase the choroidal thickness and perfusion. While it is intuitively obvious that thickness of the choroid alone does not guarantee better choriocapillaris oxygenation, it is a reasonable step towards ameliorating ischemia. These drugs have numerous physiologic effects on the choroid related to blood flow, such as clinical consequences in CSC and AMD.

Association of Weight-Adjusted Caffeine and ß-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.

Importance: Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. Objectives: To establish weight-adjusted cutoffs for caffeine and ß-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. Design, Settings, and Participants: This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). Interventions: Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. Main Outcomes and Measures: An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. Results: Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). Conclusions and Relevance: The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective.

PURPOSE: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. METHODS: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. RESULTS: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. CONCLUSIONS: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

Clinical Study on the Initial Experiences of French Vitreoretinal Surgeons with Heads-up Surgery.

Purpose: To evaluate the initial experience of four experienced vitreoretinal surgeons, in France, with a three-dimensional (3-D) system, and to explore the potential advantages and disadvantages of this technology. We also report anatomical surgical outcomes of full-thickness idiopathic macular holes (MH) and primary rhegmatogenous retinal detachment (RRD), by using traditional microscopy and heads-up method. Methods: Four French retinal surgeons performed several types of ophthalmic surgeries with this new technology. To compare the 3-D system with ocular viewing, ergonomics, educational value, image sharpness, depth perception, field of view, technical feasibility, advantages and disadvantages, and expectations for the future, were assessed using a questionnaire. We also compared the same questionnaire with the answers of six Brazilian experienced vitreoretinal surgeons. For treating MHs, the surgeons performed 88 surgeries (44 with microscopy and 44 with 3-D). They performed 100 PPV for treating primary RRD (50 with ocular viewing and 50 with 3-D). The visualization method for each patient, as well as the assignment of each surgeon for a specific patient, were all randomly selected. Results: On the questionnaire, 3-D was preferred to traditional microscopy, except for technical feasibility; the type of surgery benefitting most from the 3-D was macula surgery and the least was anterior segment surgery; the most used by all is the black and white filter in patients with atrophic RPE during ILM peeling. Eighty-one (92.1%) MHs was successfully closed with one surgery and out of the 100 eyes with a primary RRD, the anatomical success after 3 months of follow-up was 91%, with no statistical significance between 3-D and ocular viewing. Conclusions: The surgeons in this study preferred 3-D to ocular viewing. Vitrectomy surgery to treat MHs and RRDs can be performed using the 3-D with the same efficiency as microscopy. Digital integration of 3-D and iOCT can be useful in some cases. With continuous refinement to improve the ability to visualize inside of the eye, this promising technology may enhance what we do as surgeons.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective / Estudo de custo-efetividade de tratamentos para a degeneração macular relacionada à idade: uma perspectiva brasileira

ABSTRACT Purpose: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. Methods: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. Results: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. Conclusions: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

RESUMO Objetivo: Estudar o custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade neovascular. Métodos: Utilizamos um modelo de árvore de decisão para analisar a relação custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade, sob a perspectiva do Sistema Único de Saúde. O ranibizumabe e bevacizumabe foram administrados a pacientes com o mesmo procedimento de tratamento, e a diferença nos custos do tratamernto foi calculada com base no custo dos medicamentos. Os custos diretos foram estimados utilizando as informações fornecidas pelo SUS. A efetividade foi determinada em anos de vida ajustados pela qualidade (QALY) baseados em valores de utilidade em deficiênciavisual. A razãoincremental custo-efetividadefoicalculada comparando os dois tratamentos. O horizonte analítico foi de um ano. Resultados: A análise da árvore de decisão mostrou que a diferença na efetividade do tratamento foi de 0,01 QALY. A razão incremental de custo-efetividade mostrou que o tratamento com ranibizumabe exigiu um custo anual incremental de R$ 2 milhões para gerar um QALY adicional, em comparação ao bevacizumabe. Conclusões: Do ponto de vista do SUS, o bevacizumabe é mais custo-efetivo que o ranibizumabe no tratamento da degeneração macular relacionada à idade neovascular. O seu uso poderia gerar uma grande economia anual para o orçamento em saúde.

INTRAVITREAL DEXAMETHASONE IMPLANT MIGRATION INTO THE ANTERIOR CHAMBER: A Multicenter Study From the Pan-American Collaborative Retina Study Group.

PURPOSE: To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. METHODS: This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. RESULTS: The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. CONCLUSION: The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.

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.

Safety of 6000 intravitreal dexamethasone implants.

PURPOSE: To evaluate the real-life safety profile of intravitreal dexamethasone implant injection for various retinal conditions. METHODS: Retrospective multicenter analysis of intravitreal dexamethasone implant injections (700 µg) due to various retinal conditions including central retinal venous occlusion (1861 injections), diabetic macular oedema (3104 injections), post-surgical cystoid macular oedema (305 injections) and uveitis (381 injections). The eyes were evaluated mainly for the occurrence of adverse events such as glaucoma, cataract, retinal detachment and endophthalmitis along during the follow-up period. RESULTS: A total of 6015 injections in 2736 eyes of 1441 patients (mean age of 65.7±12.9 years) were in total analysed over an average period of 18 months (range 6 months to 102 months). A total of 576 eyes (32.5% of the phakic eyes) developed cataract requiring surgical intervention. However, visually insignificant cataract progression was observed in another 259 phakic eyes (14.6%) which did not require surgical removal. A total of 727 eyes (26.5%) experienced an intraocular pressure (IOP) rise of >25 mm Hg, with 155 eyes (5.67%) having a prior history of glaucoma and 572 eyes (20.9%) having new onset IOP rise. Overall, more than 90% of eyes with IOP rise were managed medically, and 0.5% eyes required filtering surgery. Endophthalmitis (0.07%), retinal detachment (0.03%) and vitreous haemorrhage (0.03%) were rare. There was no significant change in visual acuity (p=0.87) and central macular thickness (p=0.12) at the last follow-up. CONCLUSION: This is the largest real-life study assessing the safety of intravitreal dexamethasone implant injections in various retinal conditions. Cataract progression and intraocular pressure rise are the most common side effects, but are often rather easily manageable.

Effectiveness of monthly and fortnightly anti-VEGF treatments for age-related macular degeneration / Efetividade de tratamentos anti-VEGF mensais e quinzenais para a degeneração macular relacionada à idade

ABSTRACT Purpose: To study the efficacy and safety of treatments with ranibizumab and bevacizumab for exudative age-related macular degeneration. Methods: A parallel randomized clinical trial was conducted to compare the efficacy and safety of three regimens (bevacizumab every month, bevacizumab every 2 weeks, and ranibizumab every month), followed by as-needed retreatments, for 1 year, in previously untreated individuals with age-related macular degeneration. The primary outcome was change in visual acuity and in central macular thickness after 1 year of follow-up. Subjects were assigned randomly to one of the three groups in a 1:1:1 ratio, and investigators and examiners were blinded to the randomization results. Results: We included 15 patients in each group. After 1 year of follow-up, we found statistically significant improvements in visual acuity and central macular thickness reduction in all groups. However, we found no statistically significant differences between the three groups. Conclusions: The bi-weekly follow-up was effective and we found no significant differences in efficacy or safety between the treatments with ranibizumab and bevacizumab.

RESUMO Objetivo: Estudar a eficácia e segurança dos tratamentos com ranibizumabe e bevacizumabe para a degeneração macular relacionada à idade exsudativa. Métodos: Ensaio clínico paralelo randomizado foi conduzido para comparar a eficácia e segurança de três regimes (bevacizumabe a cada mês, bevacizumabe a cada 2 semanas e ranibizumabe todos os meses), seguidos por retratamentos conforme necessidade, durante 1 ano, em indivíduos previamente não tratados com degeneração macular relacionada à idade. O desfecho primário foi alteração na acuidade visual e na espessura macular central após um ano de seguimento. Os indivíduos foram designados aleatoriamente para um dos 3 grupos em uma proporção de 1:1:1, e os investigadores e examinadores foram mascarados para os resultados da randomização. Resultados: Foram incluídos 15 pacientes em cada grupo. Após um ano de seguimento, encontramos melhorias estatisticamente significativas na acuidade visual e na redução da espessura macular central em todos os grupos. No entanto, não encontramos diferenças estatisticamente significativas entre os 3 grupos. Conclusões: O seguimento quinzenal foi eficaz e não encontramos diferenças significativas na eficácia ou segurança entre os tratamentos com bevacizumabe e ranibizumabe.