Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

ASSESSMENT OF SIMULATED SURGICAL DEXTERITY AFTER MODIFIABLE EXTERNAL EXPOSURES AMONG NOVICE VERSUS EXPERIENCED VITREORETINAL SURGEONS.

PURPOSE: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience. METHODS: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured. RESULTS: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005). CONCLUSION: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.

Perifoveal exudative vascular anomalous complex and resembling lesions treated with intravitreal triamcinolone.

PURPOSE: To report the use of intravitreal triamcinolone to treat macular edema associated with isolated perifoveal exudative vascular anomalous complex (PVAC) and resembling lesion (PVAC-RL). METHODS: In this case series, three diabetic patients (3 eyes) with PVAC-RLs and one healthy patient (1 eye) with PVAC lesion associated with cystic spaces underwent three intravitreal injections of aflibercept before switching to one intravitreal triamcinolone injection in each patient. RESULTS: Macular edema improved from 297.5 ± 8.10 µm, at baseline, to 269.2 ± 8.89 µm, after triamcinolone; whereas visual acuity improved from 20/38 to 20/26 (ETDRS). CONCLUSION: PVAC and PVAC-RL are rare and often misdiagnosed lesions that may be associated with decreased vision. Our outcomes suggest that intravitreal injection of triamcinolone may be an effective and affordable treatment for PVAC and PVAC-RL with intraretinal fluid.

A Polysomnographic Study of Effects of Sleep Deprivation on Novice and Senior Surgeons during Simulated Vitreoretinal Surgery.

PURPOSE: To assess the impact of a 3-hour polysomnography (PSG)-recorded night of sleep deprivation on next-morning simulated microsurgical skills among vitreoretinal (VR) surgeons with different levels of surgical experience and associate the sleep parameters obtained by PSG with Eyesi-generated performance. DESIGN: Self-controlled cohort study. PARTICIPANTS: Eleven junior VR surgery fellows with < 2 years of surgical experience and 11 senior surgeons with > 10 years of surgical practice. METHODS: Surgical performance was assessed at 7am after a 3-hour sleep-deprived night using the Eyesi simulator and compared with each subject's baseline performance. MAIN OUTCOME MEASURES: Changes in Eyesi-generated score (0-700, worst to best), time for task completion (minutes), tremor-specific score (0-100, worst to best), and out-of-tolerance tremor percentage. Polysomnography was recorded during sleep deprivation. RESULTS: Novice surgeons had worse simulated surgical performance after sleep deprivation compared with self-controlled baseline dexterity in the total score (559.1 ± 39.3 vs. 593.8 ± 31.7; P = 0.041), time for task completion (13.59 ± 3.87 minutes vs. 10.96 ± 1.95 minutes; P = 0.027), tremor-specific score (53.8 ± 19.7 vs. 70.0 ± 15.3; P = 0.031), and out-of-tolerance tremor (37.7% ± 11.9% vs. 28.0% ± 9.2%; P = 0.031), whereas no performance differences were detected in those parameters among the senior surgeons before and after sleep deprivation (P ≥ 0.05). Time for task completion increased by 26% (P = 0.048) in the post-sleep deprivation simulation sessions for all participants with a high apnea-hypopnea index (AHI) and by 37% (P = 0.008) among surgeons with fragmented sleep compared with those with normal AHI and < 10 arousals per hour, respectively. Fragmented sleep was the only polysomnographic parameter associated with a worse Eyesi-generated score, with a 10% (P = 0.005) decrease the following morning. CONCLUSIONS: This study detected impaired simulated surgical dexterity among novice surgeons after acute sleep deprivation, whereas senior surgeons maintained their surgical performance, suggesting that the impact of poor sleep quality on surgical skills is offset by increased experience. When considering the 2 study groups together, sleep fragmentation and AHI were associated with jeopardized surgical performance after sleep deprivation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Weight-adjusted caffeine and ß-blocker use in novice versus senior retina surgeons: a self-controlled study of simulated performance.

BACKGROUND/OBJECTIVES: Tremor and expertise are potentially influenced variables in vitreoretinal surgery. We investigated whether surgeon experience impacts the association of microsurgical performance with caffeine and ß-blockers weight-adjusted intake. SUBJECTS/METHODS: Novice and senior surgeons (<2 and >10 practice years, respectively) were recruited in this self-controlled, cross-sectional study. A simulator's task sequence was repeated over 2 days, 30 min after the following exposures: day 1, placebo, 2.5 mg/kg caffeine, 5.0 mg/kg caffeine, and 0.6 mg/kg propranolol; and day 2, placebo, 0.2 mg/kg propranolol, 0.6 mg/kg propranolol, and 5.0 mg/kg caffeine. Outcomes were total score (0-700, worst-best), simulation time (minutes), intraocular trajectory (centimeters), and tremor-specific score (0-100, worst-best). RESULTS: We recruited 15 novices (9 men [60%], 1.33 ± 0.49 practice years) and 11 seniors (8 men [72.7%], 16.00 ± 4.24 practice years). Novices performed worse after 2.5 mg/kg caffeine and improved following 0.2 mg/kg propranolol in total score (557 vs. 617, p = 0.009), trajectory (229.86 vs. 208.07, p = 0.048), time (14.9 vs. 12.7, p = 0.048), and tremor-score (55 vs. 75, p = 0.009). Surgical performance improved with propranolol post-caffeine but remained worse than 0.2 mg/kg propranolol in total score (570 vs. 617, p = 0.014), trajectory (226.59 vs. 208.07, p = 0.033), and tremor-score (50 vs. 75, p = 0.029). Seniors' tremor-score was lower after 2.5 mg/kg caffeine compared to 0.2 mg/kg propranolol (8 vs. 37, p = 0.015). Tremor-score following propranolol post-caffeine remained inferior to 0.6 mg/kg propranolol alone (17 vs. 38, p = 0.012). CONCLUSION: While caffeine and propranolol were associated with performance changes among novices, only tremor was affected in seniors, without dexterity changes. The pharmacologic exposure impact on surgical dexterity seems to be offset by increased experience.

Retinal microvascular abnormalities, cotton wool-like lesions, and macular edema following COVID-19 in a patient previously vaccinated with AstraZeneca and idiopathic myopathy.

In this case study, the authors describe peculiar bilateral cotton wool-like retinal lesions associated with macular edema in a patient with COVID-19 who was vaccinated with a single dose of AstraZeneca one month earlier. This patient had no pulmonary or systemic cardiovascular complications from COVID-19, as reported in other papers that found retinal lesions. However, the patient was diagnosed with idiopathic myopathy when discovering the SARS-CoV-2 infection. The patient was a 22-year-old white female with no previous history of morbidity, complaining of blurred vision in both eyes seven days after testing positive for SARS-CoV-2 by PCR (using nasal and oral swab) and confirmed through ELISA blood test (IgM positive). There was no ancillary test revealing diabetes mellitus. The patient presented with scattered whitish cotton wool-like lesions and a few hemorrhages on the posterior pole in fundus examination. On spectral domain optical coherence tomography (SD-OCT), there were hyperreflective lesions in the nerve fiber layer, ganglion cell layer, inner nuclear layer, and inner and outer plexiform layers at the site corresponding to the whitish cotton wool-like lesions in the posterior fundus photos. Moreover, the macula of both eyes had intraretinal and subretinal fluid, reversible with corticosteroid therapy. In conclusion, COVID-19 has been associated with capillary disorders at different target sites such as retina, lungs, and central nervous system. Similarly, vaccination against SARS-CoV-2 has been linked to retinal complications in the literature; however, cotton wool-like lesions have not yet been reported. There are many questions yet to be answered about the implications of COVID-19 infection and its vaccines.

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/.

Transient central retina artery occlusion in patients undergoing intravitreal anti vegf injections.

PURPOSE: To evaluate the occurrence of transient central retinal artery occlusion following intravitreal anti-vascular endothelial growth factor injection. METHODS: Prospective, observational study of 807 patients (807 eyes) who were given intravitreal injections of ranibizumab or aflibercept to treat any cause of retinal vascular diseases between 1 January 2017 and 30 November 2018 at the Federal Fluminense University Hospital in Niteroi, and a private facility in Rio de Janeiro, Brazil. Patients who did not present transient central retinal artery occlusion were excluded. RESULTS: Among 4069 injections, only 18 patients (0.44%) presented transient central retinal artery occlusion, 14 mild cases (77.7%), and 4 severe cases (22.3%). The clinical factors associated with more severe cases of transient central retinal artery occlusion were the duration of the transient central retinal artery occlusion (p = 0.001), number of prior injections (p = 0.01), and a positive carotid Doppler test (p = 0.01). Twelve cases (66.6%) had positive carotid artery obstruction (atheroma plaque size ≥70%) while 6 cases (33.3%) had negative carotid artery obstruction (atheroma plaque size <70%). The age group >60 years old (p = 0.06), cup/disc ratio >0.6 (p = 0.06), and pseudophakic lens status were also factors with association with transient central retinal artery occlusion, although did not meet criteria for statistical significance. The only patient who experienced a recurrent episode of transient central retinal artery occlusion had diabetic macular edema, positive carotid Doppler test, and cup/optic disc ratio >0.6. CONCLUSION: Transient central retinal artery occlusion is a rare adverse event that can appear in patients with retinal vascular disease receiving anti-vascular endothelial growth factor therapy. The atheroma plaque size and the number of prior injections can be associated with the severity of the event.

A MULTIFACTORIAL APPROACH FOR IMPROVING THE SURGICAL PERFORMANCE OF NOVICE VITREORETINAL SURGEONS.

PURPOSE: To quantitatively analyze and compare the novice vitreoretinal surgeons' performance after various types of external exposures. METHODS: This prospective, self-controlled, cross-sectional study included 15 vitreoretinal fellows with less than 2 years of experience. Surgical performance was assessed using the Eyesi simulator after each exposure: Day 1, placebo, 2.5, and 5 mg/kg caffeine; Day 2, placebo, 0.2, and 0.6 mg/kg propranolol; Day 3, baseline simulation, breathalyzer reading of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentration; Day 4, baseline simulation, push-up sets with 50% and 85% repetition maximum; Day 5, 3-hour sleep deprivation. Eyesi-generated total scores were the main outcome measured (0-700, worst to best). RESULTS: Performances worsened after increasing alcohol exposure based on the total score (χ2 = 7; degrees of freedom = 2; P = 0.03). Blood alcohol concentration 0.06% to 0.10% and 0.11% to 0.15% was associated with diminished performance compared with improvements after propranolol 0.6 and 0.2 mg/kg, respectively (∆1 = -22 vs. ∆2 = +13; P = 0.02; ∆1 = -43 vs. ∆2 = +23; P = 0.01). Propranolol 0.6 mg/kg was positively associated with the total score, compared with deterioration after 2.5 mg/kg caffeine (∆1 = +7 vs. ∆2 = -13; P = 0.03). CONCLUSION: Surgical performance diminished dose dependently after alcohol. Caffeine 2.5 mg/kg was negatively associated with dexterity, and performance improved after 0.2 mg/kg propranolol. No changes occurred after short-term exercise or acute 3-hour sleep deprivation.

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.

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.

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.

Role of Vital Dyes in Chromovitrectomy.

ABSTRACT: Chromovitrectomy, the intraocular application of dyes to assist visualization of preretinal tissues during vitreoretinal surgery, was introduced to avoid ocular complications related to internal limiting membrane peeling, inadequate removal of the vitreous, and incomplete removal of epiretinal membranes. Since 2000, chromovitrectomy has become a popular approach among vitreoretinal specialists. The first vital dye used in chromovitrectomy, indocyanine green, facilitated identification of the fine and transparent internal limiting membrane. Following indocyanine green, trypan blue was introduced to identify epiretinal membranes, and triamcinolone acetonide stained the vitreous well. Recently, additional natural dyes such as lutein and anthocyanin from the açaí fruit have been proposed for intraocular application during vitrectomy. The main goal of this review was to study the role of vital stains in chromovitrectomy and report the latest findings in the literature.

Effectiveness and safety of ranibizumab 0.5 mg in treatment-naïve patients with diabetic macular edema: Results from the real-world global LUMINOUS study.

PURPOSE: To assess the one-year effectiveness and safety of ranibizumab 0.5 mg in treatment- naïve patients with diabetic macular edema (DME) enrolled in the real-world LUMINOUS study. PATIENTS AND METHODS: A 5-year, prospective, observational, open-label, global study which recruited 30,138 patients across all approved indications. Consenting patients (≥18 years) who were treatment-naïve or previously treated with ranibizumab or other ocular treatments were treated as per the local ranibizumab label. Here, we present the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letter score; primary treated eye) at Year 1, as well as the change in VA based on injection frequencies (≤4 and ≥5), treatment exposure, and the overall adverse events (AEs) and serious AEs (SAEs) in treatment-naïve DME patients. RESULTS: Of the 4,710 DME patients enrolled in the study, 1,063 were treatment-naïve. At baseline, mean age was 64.5 years, 54.7% were male, and 69.2% were white. At 1 year, mean VA letter score improved by +3.5 (n = 502) from a baseline of 57.7 with a mean of 4.5 injections. Presented by injection frequencies ≤4 and ≥5, VA letter score gains were 0.5 (n = 264) and 6.9 (n = 238) from baseline letter scores of 56.6 and 59.0, respectively. Over 5 years, the incidence of ocular/non-ocular AEs and SAEs was 7.2%/10.1% and 0.3%/5.8%, respectively. No endophthalmitis cases were reported. CONCLUSIONS: The LUMINOUS study included patients with DME with more diverse baseline characteristics than those in randomized clinical trials. The 1-year data showed improvement in VA with low number of injections in treatment- naïve patients with DME. Greater VA gains were observed in patients who received ≥5 injections. No new safety findings were identified. LUMINOUS confirms the effectiveness and safety of ranibizumab for the treatment of patients with DME in a real-world clinical practice.

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.