CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. METHODS: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. RESULTS: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. CONCLUSION: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR DIABETIC MACULAR EDEMA: A Pilot Study.

PURPOSE: Diabetic macular edema is the leading cause of blindness in young adults in developed countries. Beyond metabolic control, several therapies have been studied such as laser treatment and intravitreal injections of corticosteroids or anti-vascular endothelial growth factor drugs. In terms of public health the long-term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study sought to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of diabetic macular edema. METHODS: Seven consecutive patients with diabetic macular edema were enrolled. A complete examination, including full-field electroretinography, visual acuity, central retinal thickness, and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv-aflibercept. The seven patients were submitted to six consecutive intravitreal injections of ziv-aflibercept with a 4-week interval. RESULTS: No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at 24 weeks (P < 0.05). The central retinal thickness significantly decreased during the course of 24 weeks. CONCLUSION: Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

Posterior hyaloid detachment and internal limiting membrane peeling assisted by anthocyanins from acai fruit (Euterpe oleracea) and 10 other natural vital dyes: experimental study in cadaveric eyes.

PURPOSE: The purpose of this study was to determine whether natural dyes facilitate posterior hyaloid detachment (posterior vitreous detachment [PVD]) and retinal internal limiting membrane (ILM) peeling in human eyes. METHODS: Open-sky vitrectomy with posterior hyaloid and ILM removal was performed in 86 human cadaveric eyes. After core vitrectomy, 11 different dyes were injected into the vitreous cavity to aid hyaloid detachment and ILM removal. The dyes were allowed to settle on the macula for 5 minutes after PVD and were removed by mechanical aspiration. Intraocular forceps were used for ILM peeling, which was confirmed by light microscopy of the peeled tissue. Acai fruit (Euterpe oleracea) extract and 10 additional dyes from plants or animal sources were tested: pomegranate (Punica granatum), logwood (Haematoxylum campechianum), chlorophyll extract from alfalfa (Medicago sativa), cochineal (Dactylopius coccus), hibiscus (Hibiscus rosa-sinensis), indigo (Indigofera tinctoria), paprika (Capiscum annuum), turmeric (Curcuma longa), old fustic (Maclura tinctoria), and grape (Vitis vinifera). RESULTS: The dyes facilitated PVD and ILM peeling. Acai fruit (E. oleracea) extract, logwood (H. campechianum), cochineal (D. coccus), and old fustic (M. tinctoria) facilitated PVD in all cases; dye-assisted PVD was compared with triamcinolone-assisted PVD performed previously in a comparative model. Acai fruit (E. oleracea) extract, cochineal (D. coccus), and chlorophyll extract from alfalfa (M. sativa) showed the best capability for ILM staining; dye-assisted ILM removal was compared with the ILM peeling guided by indocyanine green staining performed previously in a comparative model. Light microscopy confirmed the ILM removal in all cases. CONCLUSION: Anthocyanin dye of the acai fruit (E. oleracea) and the dyes from cochineal (D. coccus) and chlorophyll extract from alfalfa (M. sativa) resulted in the best capability for posterior hyaloid and ILM staining in human cadaveric eyes and may be a useful tool for vitreoretinal surgery.

Outcomes of Pars Plana Vitrectomy and 4-Point Sutured Scleral Fixation of Akreos AO60 Intraocular Lens in Clinical Settings: A Case Series.

PURPOSE: To determine the long-term anatomic outcomes and surgical complications of pars plana vitrectomy (PPV) and 4-point Gore-Tex-sutured Akreos AO60 intraocular lens (IOL) scleral fixation. DESIGN: Retrospective, multicenter, multisurgeon case series. PARTICIPANTS: Ninety-seven patients in tertiary eye care centers. METHODS: The patients underwent PPV and intraocular fixation of the Akreos AO60 IOL using Gore-Tex CV-8 sutures between January 2015 and April 2020. The inclusion criteria were aphakia, no capsular support, and a minimal 1 year of follow-up. MAIN OUTCOME MEASURES: Uncorrected visual acuity (VA), complication rates or types, and refraction. RESULTS: Data from 101 eyes of the 97 patients were analyzed (mean follow-up duration, 33.4 months; range, 12-62 months). The mean ± standard deviation uncorrected logarithm of the minimum angle of resolution VA improved from 1.04 ± 0.73 (20/200 Snellen equivalent) before surgery to 0.66 ± 0.65 (20/80) at 6 months after surgery (P < 0.001). The most prevalent complications included hypotony (12.9%), ocular hypertension (12.9%), corneal edema (8.9%), cystoid macular edema (6.9%), and vitreous hemorrhage (5.9%). Refraction was measured between 3 and 6 months after surgery, and 61.8% of the patients had spherical equivalent of ± 2.0 diopters. Most complications occurred in the first postoperative month and resolved spontaneously or with medical treatment. CONCLUSIONS: The results demonstrated that this surgical technique is well tolerated by the eyes, with a low complication rate in the long term. The rates of IOL opacification were infrequent for up to 62 months of follow-up.

Use of surgical videos available on social media among retina surgeons: results of a vitreoretinal specialist survey.

PURPOSE: This study aimed to assess and interpret how vitreoretinal surgeons use surgical videos available on social media as complementary learning tools to improve, review, or update their abilities, considering their different levels of expertise. METHODS: In this cross-sectional survey, an online survey was sent to vitreoretinal specialists and fellows. RESULTS: This survey included 258 participants, of whom 53.88% had been in practice for >10 years (senior surgeons), 29.07% between 4 and 10 years (young surgeons), and 17.05% for <3 years (surgeons in training). Retinal surgical videos available on social media were used by 98.84% of the participants (95% confidence interval, 97.52%-100%). YouTube (91%) was the most common source of videos, and surgeons in training watched more videos on YouTube than senior surgeons. Regarding the preferred method when preparing for a procedure, 49.80% of the participants watched surgical videos available on social media, 26.27% preferred to "consult colleagues", and 18.82% preferred to seek information in scientific articles. Participants valued the most the "image quality" (88%) and presence of "surgical tips and tricks" (85%). CONCLUSION: Surgical videos can provide benefits in acquiring strategic skills, such as decision-making, surgical planning, and situational awareness. Retina surgeons used them as teaching aids regardless of their level of expertise, despite being relatively more valuable to surgeons in training or young surgeons.

Telementoring versus face-to-face mentoring in the training of scleral fixation surgery of intraocular lenses.

PURPOSE: To assess telementoring as a complementary tool for surgical training of a scleral fixation technique. DESIGN: Randomized, controlled, two-arm, blinded clinical trial. METHODS: Using a 3D visualization system, 132 participants were randomized in order of enrollment into traditional face-to-face mentoring (n = 66) and telementoring (n = 66). A single surgeon mentored all participants in the 2 groups. The procedure was performed in a model suitable for training in intraocular lens fixation SimulEYE® (INSEYET, WESTLAKE VILLAGE, CA, USA). In the telementoring group, the images captured on a local computer were sent to a second computer located in another room through a teleconferencing platform in real-time. Nine steps of the recorded procedure were evaluated and scored by two masked independent surgeons experienced in the technique. MAIN OUTCOMES MEASURES: The primary outcomes evaluated were the global score (the sum of each score on the rubric), surgical failure, and surgical time (in seconds). RESULTS: Surgical success was achieved in 98.5% in the face-to-face group and in 95.5% in the telementoring group (p-value = 0.619). Minimal technical problems were reported in 8 procedures in the telementoring group (12%), without interfering with the surgical result, and completion of the procedure. CONCLUSIONS: Telementoring is an encouraging educational tool that can overcome geographical barriers to ease the transfer of abilities and knowledge. We lack evidence in terms of group differences for superiority comparing face-to-face and telementoring, in addition to presenting comparable results regarding surgical success and failure. More studies are needed to explore the impact of telementoring in other ophthalmological surgeries. TRIAL REGISTRATION: The Federal University of São Paulo institution's Research Ethics Committee reviewed and approved this study protocol (approval number, 5.383.484).

The risks behind the widespread use of siliconized syringes in the healthcare practice.

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.

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review.

BACKGROUND: 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. OBSERVATIONS: 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. CONCLUSION: 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.

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.

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.

Release of silicone oil and the off-label use of syringes in ophthalmology.

BACKGROUND/AIMS: To assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions. METHODS: Eight syringes were analysed: from the USA, Terumo 0.5 mL, Becton-Dickinson (BD) Tuberculin 1 mL, BD Luer-lok 1 mL, BD Ultra-Fine 0.3 mL and Exel Insulin 0.3 mL; from Germany, Braun Omnifix-F 1 mL and Braun Injekt-F 1 mL and from Spain, BD Plastipak 1 mL. The impact of air, priming the plunger, agitation by flicking and fluid temperature on SO release were assessed by light microscopy. Fourier transform infrared spectroscopy (FTIR) was performed to identify the molecular compound in each syringe. RESULTS: Five hundred and sixty syringes were analysed. Terumo 0.5 mL and BD Ultra-Fine 0.3 mL released more SO than all others. BD Luer-lok 1 mL, BD Plastipak and Braun Omnifix-F 1 mL released little SO; BD Tuberculin 1 mL, Exel 0.3 mL and Braun Injekt-F 1 mL released the least SO. Priming the syringe and different temperatures did not significantly affect SO release. Agitation by flicking caused a significantly higher proportion of samples to have SO droplets and an increased number of oil droplets. Air had an additive effect on the release of oil in the agitation groups. FTIR identified polysiloxane in all syringes but Injekt-F. CONCLUSION: Syringes commonly used for intravitreal injections frequently release SO droplets, especially when agitated by flicking. To avoid unnecessary ocular risks, syringes should not be agitated before intravitreal injection. It is desirable that syringes be manufactured specifically for ophthalmic use.

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

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

Inflammatory Reaction After Aflibercept Intravitreal Injections Associated With Silicone Oil Droplets Released From Syringes: A Case-Control Study.

BACKGROUND AND OBJECTIVE: To determine factors causing inflammation after intravitreal aflibercept injections. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.].

Effectiveness of monthly and fortnightly anti-VEGF treatments for age-related macular degeneration.

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.

Use of surgical videos available on social media among retina surgeons: results of a vitreoretinal specialist survey / Uso de vídeos cirúrgicos nas mídias sociais entre cirurgiões de retina: resultados de uma pesquisa com especialista em retina

ABSTRACT Purpose: This study aimed to assess and interpret how vitreoretinal surgeons use surgical videos available on social media as complementary learning tools to improve, review, or update their abilities, considering their different levels of expertise. Methods: In this cross-sectional survey, an online survey was sent to vitreoretinal specialists and fellows. Results: This survey included 258 participants, of whom 53.88% had been in practice for >10 years (senior surgeons), 29.07% between 4 and 10 years (young surgeons), and 17.05% for <3 years (surgeons in training). Retinal surgical videos available on social media were used by 98.84% of the participants (95% confidence interval, 97.52%-100%). YouTube (91%) was the most common source of videos, and surgeons in training watched more videos on YouTube than senior surgeons. Regarding the preferred method when preparing for a procedure, 49.80% of the participants watched surgical videos available on social media, 26.27% preferred to "consult colleagues", and 18.82% preferred to seek information in scientific articles. Participants valued the most the "image quality" (88%) and presence of "surgical tips and tricks" (85%). Conclusion: Surgical videos can provide benefits in acquiring strategic skills, such as decision-making, surgical planning, and situational awareness. Retina surgeons used them as teaching aids regardless of their level of expertise, despite being relatively more valuable to surgeons in training or young surgeons.

RESUMO Objetivo: Avaliar e interpretar como os cirurgiões vitreorretinianos utilizam os vídeos cirúrgicos disponíveis nas mídias sociais como ferramentas complementares de aprendizagem para melhorar, revisar ou atualizar suas habilidades, considerando seus diferentes níveis de especialização. Métodos: Nesta pesquisa transversal, um survey online foi enviado à especialistas e aprendizes na área vítreo-retiniana. Resultados: Esta pesquisa incluiu 258 participantes, dos quais 53,88% atuavam há mais de 10 anos (cirurgiões seniores), 29,07% entre 4 e 10 anos (cirurgiões jovens) e 17,05% há menos de 3 anos (cirurgiões em treinamento). Vídeos cirúrgicos de retina nas mídias sociais foram usados por 98,84% dos participantes (intervalo de confiança de 95%, 97,52%-100%). A fonte mais comum de acesso aos vídeos foi o YouTube (91%), e o grupo de cirurgiões com menos de 3 anos de experiência assistiu mais vídeos no YouTube em comparação aos cirurgiões seniores. Assistir a vídeos cirúrgicos nas redes sociais foi o método preferido na preparação para um procedimento para 49,80% dos participantes versus 26,27% que preferiram "consultar colegas" e 18,82% que preferiram buscar informações em artigos científicos. A "qualidade de imagem" (88%) e a presença de "dicas e truques cirúrgicos" (85%) foram as características dos vídeos mais valorizadas pelos participantes. Conclusão: O uso de vídeos cirúrgicos pode trazer benefícios na aquisição de habilidades estratégicas, como tomada de decisão, planejamento cirúrgico e consciência situacional. Sua aplicação como auxiliar de ensino foi utilizada por cirurgiões de retina independentemente de seu nível de especialização, apesar de ser relativamente mais valioso para cirurgiões em formação ou com menos de 10 anos de experiência.

Safety of 5914 intravitreal ziv-aflibercept injections.

PURPOSE: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. METHODS: This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. RESULTS: A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke and two deaths) were infrequent. CONCLUSION: This constitutes the largest pooled safety report on IVZ use and includes patients from 14 centres distributed across the globe. It shows that IVZ has an acceptable ocular and systemic safety profile with incidences of adverse events similar to those of other vascular endothelial growth factor inhibitory drugs. The analysis supports the continued use of IVZ in various retinal disorders.

Molecular mechanisms of topical anti-inflammatory effects of lipoxin A(4) in endotoxin-induced uveitis.

Lipoxin A(4) (LXA(4)) is a lipid mediator that plays an important role in inflammation resolution. We assessed the anti-inflammatory effect of LXA(4) on endotoxin-induced uveitis (EIU) in rats. The inflammatory cell number and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), and protein, as well as expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), in the anterior chamber of the eye were determined 24 h after lipopolysaccharide (LPS; 200 mug/paw) intradermal injection. The immunohistochemical reactivities of nuclear factor-kappaB (NF-kappaB) and c-Jun were also examined. Topical LXA(4) (1-10 ng/eye) pretreatment decreased the number of inflammatory cells and the protein leakage into the aqueous humor (AqH). In addition, topical LXA(4) (10 ng/eye) inhibited the LPS-induced production of IL-1beta, TNF-alpha, and PGE(2), and expression of COX-2 and VEGF. A decreased activation of NF-kappaB and c-Jun was also found in LXA(4)-treated eyes. It is very interesting that an anti-inflammatory effect was achieved even when LXA(4) (10 ng/eye) was applied topically after LPS challenge, as indicated by the reduction in the cellular and protein extravasations into the AqH. Moreover, topical treatment of corticosteroid prednisolone (200 mug/eye) beginning before or after LPS injection reduced all of the molecular and biochemical alterations promoted on EIU rats in an efficacy similar to that of LXA(4). Together, the present results provide clear evidence that pharmacological activation of LXA(4) signaling pathway potently reduces the EIU in rats. Therefore, LXA(4) stable analogs could represent promising agents for the management of ocular inflammatory diseases.

INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR THE TREATMENT OF A PATIENT WITH MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To describe the visual, tomographic, and electroretinographic findings in a patient with macular edema secondary to branch retinal vein occlusion who was submitted to three consecutive intravitreal injections of ziv-aflibercept. METHODS: The patient underwent a complete ophthalmic examination, as well as optical coherence tomography and full-field electroretinography at baseline and 90 days after the first injection. RESULTS: The best-corrected visual acuity improved from 20/400 to 20/40, and the central retinal thickness decreased from 791 µm to 198 µm after three consecutive intravitreal injections of ziv-aflibercept. Full-field electroretinography showed an increase in cone amplitude and decrease in rod amplitude. No adverse side effects were observed after injections. CONCLUSION: Intravitreal injections of ziv-aflibercept showed both effectiveness and safety in the treatment of a patient with macular edema secondary to branch retinal vein occlusion. The observed anatomic (by ophthalmic examination, optical coherence tomography) and functional (best-corrected visual acuity, full-field electroretinography) improvements and lack of serious adverse side effects demonstrates the potential of intravitreal injections of ziv-aflibercept for the treatment of macular edema secondary to branch retinal vein occlusion.

Pilot Study Comparing Topical Anesthetic Agents in Pterygium Surgery: Subconjunctival Injection Versus 2% Lidocaine Gel Versus 5% Lidocaine Gel.

PURPOSE: To compare the efficacy of different concentrations of topical lidocaine gel with standard subconjunctival anesthesia. METHODS: This was a prospective randomized controlled pilot study with 3 different groups. Group SC received subconjunctival lidocaine and proparacaine drops as needed during surgery. Group L2 received 2% lidocaine gel and group L5 received 5% lidocaine gel. Both lidocaine gel groups could receive another gel dose as needed during the procedure. The primary outcome was pain, which was experienced during and after surgery. The assessment was done using a 10-point linear analog scale at predetermined stages of surgery (1-first incision, 2-pterygium body excision, 3-conjunctival suturing, 4-immediate postoperative period after patching, and 5-assessment by a trained nurse in the absence of a surgeon after operation). RESULTS: We enrolled 45 consecutive patients who underwent primary pterygium surgery. Statistical significance between groups was found in mean pain at administration (2.2 vs. 0.4 vs. 0.0 in SC, L2, and L5 groups, respectively, with P < 0.05). The number of reapplications of anesthetic drops did not differ between the groups. We found a correlation between reapplication of the anesthetic and pain at administration and duration of the procedure. CONCLUSIONS: We demonstrated that the use of lidocaine gel at concentrations of 2% and 5% in pterygium surgery was as effective as subconjunctival injection of lidocaine in reducing intraoperative and postoperative pain, producing significantly less pain during initial administration of the anesthetic.

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes.

BACKGROUND AND OBJECTIVE: To study the safety and efficacy of intravitreal injections of ziv-aflibercept (IVI-ZA) (Zaltrap; Sanofi-Aventis and Regeneron Pharmaceuticals, Tarrytown, NY) during a period of 48 weeks in patients with diabetic macular edema (DME). PATIENTS AND METHODS: Seven consecutive patients with DME were enrolled and submitted to 12 consecutive IVI-ZA with a 4-week interval. The safety parameters included changes in full-field electroretinogram (ERG) and systemic or ocular complications, and the efficacy parameters were the mean change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: No significant differences were found in any ERG component after IVI-ZA, and no systemic or ocular complication was observed. The improvement of BCVA was most significant after the first IVI-ZA and remained until week 48 (P < .05). The CRT significantly decreased during the course of 48 weeks. CONCLUSION: The 48-week results are consistent with our previous 24-week findings, supporting IVI-ZA as a safe, efficient, and well-tolerated therapy for patients with DME. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:245-250.].