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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.

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.

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 o...

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 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.

Importance The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes. Objective To demonstrate the presence of presumed SARS-CoV-2 viral particles and its relevant proteins in the eyes of patients with COVID-19. Design, setting, and participants The retina from enucleated eyes of patients with confirmed COVID-19 infection were submitted to immunofluorescence and transmission electron microscopy processing at a hospital in Sao Paulo, Brazil, from June 23 to July 2, 2020. After obtaining written consent from the patients' families, enucleation was performed in patients deceased with confirmed SARS-CoV-2 infection. All patients were in the intensive care unit, received mechanical ventilation, and had severe pulmonary involvement by COVID-19. Main outcomes and measures Presence of presumed SARS-CoV-2 viral particles by immunofluorescence and transmission electron microscopy processing. Results Three patients who died of COVID-19 were analyzed. Two patients were men, and 1 was a woman. The age at death ranged from 69 to 78 years. Presumed S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy double-membrane vacuoles that are consistent with the virus, presumably containing COVID-19 viral particles. Conclusions and relevance The present observations show presumed SARS-CoV-2 viral particles in various layers of the human retina, suggesting that they may be involved in some of the infection's ocular clinical manifestations.

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 Conclusions: Besides IOP elevation and systemic effects in HR, WDT is associated with temporary modifications of the deep vascular plexus in young healthy subjects.

The main purpose of this study was to investigate ocular clinical findings in patients with confirmed COVID-19 infection, of various levels of disease severity, who required mechanical ventilation and admission to intensive care units or specialized wards. Longitudinal, observational study conducted from March 2020 to June 2020. Color fundus and red-free photography were performed in both eyes following pupillary dilation. 104 participants were recruited from 2 different centers: 60 (58%) from the Hospital Municipal de Barueri intensive care unit (ICU) and 44 (42%) from specialized wards for patients with COVID-19 at the Hospital Sao Paulo. 21.9% presented with eye lesions, in 3% these lesions were vision compromising. Our results have shown similar rate of intraocular lesions in patients in both the ward or intensive care unit, regardless of medication use, including anticoagulant drugs.

PURPOSE To evaluate the 52-week safety and efficacy of intravitreal ziv-aflibercept in patients with neovascular age-related macular degeneration. METHODS All patients received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (1.25 mg) followed by a pro re nata regimen. The best-corrected visual acuity and spectral domain optical coherence tomography were obtained at baseline and monthly. Full-field and multifocal electroretinograms were obtained at baseline and 4, 13, 26, and 52 weeks. For some full-field electroretinography parameters, we calculated the differences between baseline and 52 weeks and then compared those differences between treated and untreated fellow eyes. RESULTS Fifteen patients were included and 14 completed the 52-week follow-up. The mean best-corrected visual acuity improved from 0.95 ± 0.41 (20/200) at baseline to 0.75 ± 0.51 (20/125) logarithm of the minimum angle of resolution at 52 weeks (P = 0.0066). The baseline central retinal thickness decreased from 478.21 ± 153.48 μm to 304.43 ± 98.59 μm (P = 0.0004) at 52 weeks. Full-field electroretinography parameters used to assess retinal toxicity after intravitreal injections (rod response and oscillatory potentials) remained unchanged during follow-up. The average multifocal electroretinography macular response in 5° showed increased N1-P1 amplitude and decreased P1 implicit time (P < 0.05). One patient presented with intraocular inflammation after the seventh intravitreal procedure. CONCLUSION The results suggested that intravitreal ziv-aflibercept might be safe and effective for treating neovascular age-related macular degeneration. More patients and a longer follow-up are needed to confirm the long-term outcomes of intravitreal ziv-aflibercept.

To evaluate the initial experiences of several vitreoretinal surgeons in Brazil, both experienced and beginners, with a three-dimensional (3D) system, and to report the advantages and disadvantages of this technology. We also report surgical manipulations performed using the heads-up method in porcine eyes. For full-thickness idiopathic macular holes (MHs), we analyzed the times required for pars plana vitrectomy (PPV) and internal limiting membrane (ILM) rhexis by using traditional microscopy and 3D system, and to evaluate anatomical surgical results. During experimental vitreoretinal surgery on porcine eyes, two retinal surgeons applied the heads-up method. In clinical surgery, 14 retinal surgeons performed almost all types of vitreoretinal surgeries in association with facectomy, Ahmed glaucoma valve implant, or minimally invasive glaucoma surgery using an iStent®. The Ngenuity® 3D Visualization System was digitally integrated with intraoperative optical coherence tomography, the Verion™ Image-Guided System, and an endoscope (with a modified GoPro® camera). To compare the 3D system with traditional microscopy, ergonomics, educational value, image sharpness, depth perception, field of view, advantages and disadvantages, and technical feasibility were assessed using a questionnaire. One year later, the 14 surgeons answered the same questionnaire again, in order to assess whether they became more comfortable or not with 3D. For treating MHs, four surgeons (surgeon 1, fellows 1, 2, 3) performed the total of 40 surgeries. Each one performed 10 surgeries (5 with traditional microscopy and 5 with 3D visualization). The completion time for PPV and ILM rhexis were determined by using both methods. In porcine eyes, disabling the color channels allowed better visualization of the ILM, either with Brilliant Blue G (BBG), indocyanine green chorioangiography (ICG), or acai dye; transillumination through the sclera was also better without a color channel, but visualization of the peripheral vitreous was better with a blue channel. Regarding clinical experience, the questionnaire responses showed that the respondents generally favored the heads-up method compared with traditional microscopy (p

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.

To report a unique case of intraocular inflammation and outer retinal changes in a patient with coronavirus disease (COVID-19).A 57-year-old woman was seen 12 days after COVID-19 symptoms onset confirmed by positive IgM and IgG serological tests. No anterior chamber cells were seen. Color fundus photograph showed a yellowish lesion within the macular area, and fluorescein angiography revealed hyperfluorescence on the topography of the macular lesion in both eyes. Spectral-domain optical coherence tomography demonstrated hyperreflective pinpoints at the level of posterior vitreous hyaloid, corresponding to vitritis, hyperreflective lesions at the level of inner plexiform and ganglion cell layers, and disruption of the ellipsoid zone.COVID-19 is known to affect the inner retinal layers. The current case not only supports but also adds a vitreal and an outer retinal layer involvement that might also be caused by this infectious disease.

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.

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 β-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.

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.

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.

PurposeTo analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions.MethodsThis 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.ResultsA 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.ConclusionThis 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.

To evaluate the expansion of the hyperautofluorescent ring and the retinal structure changes over time in cone-rod dystrophy (CRD) patients, using fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT).Retrospective case series study. Six eyes of three CRD patients with a parafoveal hyperautofluorescent ring were studied. The diagnosis of CRD was established by the presence of the implicit time shift at 30-Hz flicker and prevalent decrease of photopic over scotopic responses on electroretinography. External and internal ring expansion was evaluated by measurements of its area at baseline and at 24-month follow-up using FAF. SD-OCT analyzed the retinal structure of the ring and the length of devoid ellipsoid zone (EZ) was measured over time.The mean age of study patients was 21 years old and the mean baseline visual acuity was 20/200. The external and internal FAF rings involving the fovea were identified in all study eyes. SD-OCT showed a normal retinal structure outside the ring. At the transitional zone of the ring, disorganization of both EZ and external limiting membrane (ELM) was observed. Inside the hyperautofluorescent ring, EZ and ELM were not identified. At 24-month follow-up examination, the mean % area increase of external and internal rings were 18.32% and 20.42%, respectively, and was concordant with the EZ band defect length enlargement.Progressive expansion of hyperautofluorescent macular ring with a correspondent EZ band defect enlargement was observed over time in CRD patients.

To determine whether early visual acuity response to intravitreal dexamethasone implant therapy in diabetic macular edema (DME) is associated with long-term outcome.Retrospective case series.Multicenter (8 sites) retrospective review of medical records of eyes with DME treated with 0.7 mg intravitreal dexamethasone implant and minimum 18-month follow-up. One hundred and two eyes were included. Eyes with vitreoretinal interface abnormalities or that had undergone vitrectomy were excluded. Eyes were categorized into 3 groups based on change in best-corrected visual acuity (BCVA) at 3 months (logMAR equivalence of5-letter, 5-9-letter, or ≥10-letter gain). Visual acuity outcomes were determined for each early response group. The relationship between early (3-month) and overall change in BCVA was assessed using regression analysis.In the study population (102 eyes),5-letter, 5- to 9-letter, and ≥10-letter BCVA improvements were seen in 44.1%, 18.6%, and 37.3% of eyes, respectively, at 3 months. Among suboptimal (5-letter) responders at 3 months, 6.7% showed ≥10-letter gains at study conclusion compared to 29% in the robust (≥10-letter) early response group (P = .009). Change in BCVA at 3 months showed significant positive correlation with overall change in BCVA (coefficient = 0.44, P = .002).A similar proportion of eyes demonstrated suboptimal (5-letter) and robust (≥10-letter) early response to treatment at 3 months. Eyes with a robust early response demonstrated ≥10-letter long-term gain in BCVA at a significantly higher rate compared to those with poor early response. Early treatment response directly correlated with overall change in BCVA.

Evaluate toxicity of acai fruit (Euterpe oleracea) dye concentrations in a rabbit model.Rabbits were injected intravitreously with 10%, 25%, and 35% acai dye concentrations. Control eyes received balanced salt solution (BSS). Electroretinogram (ERG), fundus imaging, fluorescein angiography (FA), optical coherence tomography (OCT), and light and transmission electron microscopy (LM/TEM) were performed.Fundus imaging showed increased vitreous opacity with increased dye concentrations. FA and OCT showed normality with all concentrations. Comparisons between BSS and dye concentrations were analyzed using Kruskal-Wallis and Mood's median test (p0.05). At 24 h, ERGs showed reduced amplitudes from baseline in all eyes. Median b-wave amplitudes nonsignificantly decreased and latency increased with 10% and 25%; findings were significant (p0.05) for 35%. LM and TEM showed no abnormalities for 10% and 25%. With 35%, TEM showed ganglion cell edema at 24 h that resolved after 7 days. Vacuolization, multilamellar bodies, and nerve bundle damage occurred at 24 h/7 days in the inner nuclear layer. Mitochondrial cristae disruption occurred in the inner photoreceptor segment at 24 h that decreased by 7 days.Ten and twenty-five percent concentrations were safe and may improve identification of the posterior hyaloid and internal limiting membrane during chromovitrectomy in humans.

Purpose: To report the fundus manifestations and spectral-domain optical coherence tomographic (SD-OCT) features of dengue fever presenting as Purtscher-like retinopathy.Methods: Retrospective review of two cases of dengue fever.Results: Color fundus photograph revealed the presence of cotton-wool spots in a Purtscher-like configuration in the posterior pole of all study eyes. SD-OCT demonstrated increased reflectivity signal in the inner retinal layers, and after a variable follow-up period, there was complete disappearance of cotton-wool spots and persistence of the hyperreflectivity signal.Conclusion: We report two unique cases of dengue fever associated with retinal lesions in a configuration of Purtscher-like retinopathy.

BACKGROUND AND OBJECTIVE: To report a unique case series of diffuse unilateral subacute neuroretinitis (DUSN) patients imaged with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this retrospective case series, multimodal imaging was performed in four patients with DUSN at the time of patient visit. The study patients underwent standard clinical treatment for DUSN. RESULTS: The clinical findings were consistent with the diagnosis of DUSN. Cross-sectional OCT showed disruption of outer retinal layers in the foveal area and an irregular structure of the outer plexiform layer. En face OCT revealed hyperreflective spots and a large hyperreflective lesion in the foveal area correspondent to the outer retina disruption seen on cross-sectional OCT. OCTA demonstrated decreased vascular perfusion in both the superficial and deep retinal capillary plexuses along with choriocapillaris preservation. CONCLUSION: OCTA may provide a more detailed assessment of the retinal microvascular changes, allowing a more precise anatomical-functional correlation in DUSN. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:76–83.]

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.

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

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.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.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 (P0.05). The central retinal thickness significantly decreased during the course of 24 weeks.Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

Purpose: The aim of this study was to access the safety profiles of 2 fusion proteins with anti-vascular endothelial growth factor action (ziv-aflibercept and aflibercept) on retinal pigment epithelium cells and Muller-Glia cells in culture by assessing cell viability post drug exposure. Methods: Primary human retinal pigment epithelium cells (pRPE) and Muller-Glia cells (Mio-M1) were exposed to the clinical standardized concentrations of ziv-aflibercept (25 mg/mL) and aflibercept (40 mg/mL). Progressively higher concentrations of NaCl (300, 500, 1,000, 1,500, 2,000, 5,000, and 10,000 mosm/kg) were also applied to cells to assess the possibility of potentiating hyperosmotic cytotoxity effect. The study was applied to measure pRPE and Mio-M1 viability by a tetrazolium dye-reduction assay (XTT). Results: Cell viability of both pRPE and Mio-M1 presented no significant changes after exposure of ziv-aflibercept and aflibercept. Progressive NaCl concentrations did not significantly alter cell viability. The exposure to the negative control of 75 µL/mL of dimethyl sulfoxide showed significant reduction in cell viability. Conclusions: At clinical doses, neither ziv-aflibercept nor aflibercept caused any significant reduction in cell viability in vitro. Furthermore, injection solutions of NaCl with higher osmolality caused no significant reduction in cell viability.

Univ Fed Sao Paulo, Dept Ophthalmol, Rua Jacques Felix 278-54, BR-04509001 Sao Paulo, SP, Brazil

To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs). This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye’s staining abilities. The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p

To compare surgeons’ opinions regarding idiopathic full-thickness macular hole (MH) surgery by using traditional microscopy and three-dimensional (3-D) visualization system. To analyze the required time for pars plana vitrectomy (PPV) and for internal limiting membrane (ILM) rhexis by using both visualization methods. To evaluate anatomical surgical results. Four surgeons (surgeon 1, fellows 1, 2, 3) performed the total of 40 surgeries for treating MHs. Each one performed 10 surgeries (5 with traditional microscopy and 5 with 3-D visualization). The completion time for PPV and ILM rhexis was determined by using both methods. Ergonomics, educational value, image sharpness, depth perception, field of view and technical skills were analyzed through answering a questionnaire. Forty patients were included in the study. The MH size for surgeon 1, fellows 1, 2 and 3 groups, individually, ranged from 237 to 602 μm; 228 to 590 μm, 271 to 611 μm and 289 to 600 μm, respectively. In the 3-D and in the traditional microscopy subgroups (which includes all 4 physicians on the use of one or the other method), the MH size ranged from 228 to 602 μm and 237 to 611 μm, respectively. Comparisons between the average time for full PPV and ILM rhexis by using the two methods were non-significant, neither in each individual case of 3-D surgery for each surgeon. Surgeon 1 had always been faster than his fellows. Depth perception was rated as similar for both methods. Field of view and educational values were rated as superior when using the 3-D system. Image resolution and ergonomics were rated as superior when using traditional microscopy. Technical skills strongly tended toward ‘superiority’ when using traditional microscopy. Thirty-six (90%) full-thickness MHs were successfully closed with one surgery. The 3-D system for MH surgery had a short learning curve and was a refined educational tool, when used with reduced illumination and precise focus. Concerning MH surgery, heads-up method was similar to traditional microscopy regarding length of time and anatomical surgical results. Heads-up surgery may become a new pattern for ophthalmic surgery as ongoing improvements are applied.

Objective: To compare two different laser strategies of panretinal photocoagulation for diabetic retinopathy. Methods: Single-center, randomized study including 41 eyes treated with 577-nm multispot laser with a 20-ms pulse duration (group 1) or a 532-nm single-spot laser with a 100-ms pulse duration (group 2). The outcomes included best-corrected visual acuity (BCVA) and imaging changes at baseline, 6 and 12 months, laser parameters, and results of subjective pain analysis. Results: At 12 months, the treatments did not differ significantly in BCVA, central retinal thicknesses (CRTs), improved macular edema, vitreomacular interface changes, patient-reported pain scores, or angiographic responses. Group 1 had significantly fewer treatment sessions but used more laser spots (p < 0.001). Conclusion: The multispot laser required fewer applications with more spots delivered to compensate for lower fluency, showing similar patient tolerance to single-spot laser. Both groups maintained the initial visual acuities and CRTs; about 50% of cases had vitreomacular interface changes and improved macular edema, with similar angiographic improvements after 12 months.

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.

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.

BACKGROUND AND OBJECTIVE: To evaluate the preoperative and intraoperative findings as prognostic indicators of functional and anatomic results of idiopathic epiretinal membrane (ERM) surgery. PATIENTS AND METHODS: Vitrectomies included ERM and internal limiting membrane (ILM) removal with vital dyes. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography, and autofluorescence were performed at baseline and postoperatively. Intraoperative ILM status after ERM removal was also evaluated. RESULTS: Thirty-one eyes were monitored for a mean of 16.78 months. BCVA and central foveal thickness (CFT) improved significantly ( P < .001) from baseline at 3 and 12 months. Preoperative hyperautofluorescence was associated with greater CFT reduction ( P < .005). ILM status after ERM peeling did not influence visual recovery but was associated with anatomical results as measured by OCT. CONCLUSION: Preoperative poor initial BCVA and RPE defects by FAF may not be bad prognostic factors. Preoperative hyperautofluorescence was associated with greater CFT reduction. Intraoperative classification of ILM status after ERM and ILM staining/peeling was reported and may be useful for future studies, though it was not associated neither with preoperative nor postoperative BCVA. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:457–462.]

To determine the effects of lens status on the success rate of primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment using either perfluoropropane gas (C3F8) or silicone oil (SO) tamponade.A retrospective chart analysis was made of 97 eyes from 92 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy that were treated with primary 23-gauge PPV. Eyes included in this were phakic (n = 28), pseudophakic (n = 41), or phakic eyes subject to simultaneous phacoemulsification, intraocular lens implantation, and PPV during primary rhegmatogenous retinal detachment repair (n = 28). Tamponade at the end of PPV was with either C3F8 (n = 65) or SO (n = 32). Success was defined as retinal reattachment at 1 year follow-up after a single procedure in eyes submitted to C3F8 injection; in eyes treated with SO injection, the success rate was defined as retina reattached 1 year after oil removal. Statistical comparisons were made between groups using chi-square, Fisher's exact test, Kruskal-Wallis, Mann-Whitney, and multivariate analysis. All eyes were operated by 2 experienced retina surgeons and had a minimum follow-up of 12 months.The vitreoretinal redetachment rate in eyes subjected to C3F8 tamponade was significantly higher (28.6%) for phakic eyes (P = 0.011) compared with pseudophakic or phakic eyes that underwent to phacoemulsification and intraocular lens implantation (4.5%). Eyes in which SO was used at the end of the surgical procedure demonstrated a similar trend of higher reoperation rates in phakic eyes (28.6%) compared with pseudophakic or phakic eyes (8%) subjected to phacoemulsification and intraocular lens implantation; however, no statistically significant difference was observed (P = 0.201). No statistically significant differences were found between groups in relation to the number of tears (P = 0.863) and their location (inferior: P = 0.189, superior: P = 0.708, nasal: P = 0.756, and temporal: P = 0.08).The success rates of primary 23-gauge PPV with either C3F8 or SO tamponade in pseudophakic eyes with rhegmatogenous retinal detachment was higher than the same procedure performed in phakic eyes. Still, the retrospective and limited data presented is too preliminary to suggest or recommend that practitioners perform simultaneous combined cataract surgery with retinal detachment and requires further studies in a larger and prospective design to confirm these present findings.

To report a unique case series of acute syphilitic posterior placoid chorioretinopathy (ASPPC) correlating en-face optical coherence tomography (OCT) with standard imaging modalities.In this retrospective case series, multimodal imaging was performed in three ASPPC patients at the time of disease presentation.Clinical and laboratory findings were consistent with the diagnosis of ASPPC. In all the study patients, multiple hyperreflective dot-like lesions distributed in the macular area and observed with en-face OCT at the level of retinal pigment epithelium (RPE) corresponded to the nodular RPE elevations on cross-sectional OCT and to the hyperautofluorescent spots on fundus autofluorescence. In addition, the cross-sectional OCT scans showed disorganization of the outer retinal bands and punctate choroidal hyperreflectivity.By combining en-face OCT with multimodal imaging analysis, we propose that a primary inflammation at the level of the choroid may be the pathogenic mechanism for the occurrence of outer retinal band abnormalities.

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.]

Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel.A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale.In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897).Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.

The aim of this study is to analyze the agreement between the classifications based on morphology and diameter of vitreomacular traction (VMT) syndrome, as well as to correlate the morphological findings of VMT with specific maculopathies. Fifty-three eyes with VMT syndrome were categorized into two classifications based on optical coherence tomography images: the VMT morphology (V- or J-shaped) and the diameter of adhesion (focal≤1500 μm or broad>1500 μm). High correlation was seen between V-shaped and focal-VMT and between J-shaped and broad-VMT (kappa=0.850; P

To investigate the relationship between retinal sensitivity and persistence of subretinal fluid and then to analyze microperimetry as a prognostic predictor of acute central serous chorioretinopathy.A prospective observational study. Fourteen eyes of 14 patients presenting with first episode acute central serous chorioretinopathy were enrolled and underwent ocular examination, spectral domain optical coherence tomography, and MAIA microperimetry were performed. After three months of follow-up, without any treatment, visual acuity and spectral domain optical coherence tomography macular thickness assessments and microperimetry were repeated. The main outcome was to find a relation between initial macular sensitivity and persistence of subretinal fluid. A receiver operating characteristic curve was plotted to indicate the best macular sensitivity cutoff point that would be able to predict whether a patient with acute central serous chorioretinopathy would progress to the chronic form. According to the cutoff, we calculated the sensitivity, specificity, and positive and negative predictive values for macular sensitivity as a method to predict persistence of subretinal fluid.On the basis of the receiver operating characteristic curve, a cutoff of 20 dB macular sensitivity was obtained, as the best balance between sensitivity and specificity to predict chronicity. Using this cutoff, the method had a sensitivity of 71% and specificity of 100% with a positive predictive value of 100% and negative predictive value of 78%. Furthermore, it was found that eyes with acute central serous chorioretinopathy and microperimetry of less than 20 dB had a relative risk of 4.5 to develop subretinal fluid persistence.Microperimetry with a cutoff of 20 dB may be a useful test to predict the persistence of subretinal fluid, allowing the ophthalmologist to use treatment tools earlier, preventing extracellular damage and visual impairment.

Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. We review the properties of dyes, techniques of application, indications and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.

Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies onpegaptanib,ranibizumab,bevacizumab, andafliberceptfor the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.

We retrospectively evaluated a heavy silicone oil (HSO) as a long-term intraocular endotamponade agent to treat complicated RD by inferior PVR in 25 eyes of 25 patients. Patients underwent PPV and injection of Oxane HD as an internal tamponade agent. A comparison of preoperative and postoperative BCVA at month 1, month 6, and last visit was made in the group in which HSO was removed and in the group in which HSO was not removed. Statistical calculations were performed using the Wilcoxon test. The HSO was removed from 11 patients after a mean of 26.55 ± 21.38 months. The HSO remained inside the vitreous cavity in 14 eyes due to a high chance of PVR recurrence (mean follow-up period, 11.07 ± 7.44 months). Anatomic success was achieved in 92%. The BCVA in the group, in which HSO was not removed, improved significantly during the first 6 months. Among the patients who had the oil removed, there was improvement in BCVA after 1 month. Oil emulsification was the most common adverse effect in 52% of eyes. HSO is an effective tamponade in complex rhegmatogenous and tractional RD complicated by PVR. HSO can remain in the eye for long periods with relative tolerability and safety.

Fifteen patients with exudative age-related macular degeneration were treated with intravitreal injections of ziv-aflibercept (1.25 mg). Ziv-aflibercept improved the best-corrected visual acuity, multifocal electroretinography amplitudes, and central retinal thickness from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period., 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 mm3 to 8.08 ± 1.34 mm3, 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.

The goals of this study were to determine the potential for use of the natural anthocyanins from the açai fruit (Euterpe oleracea) during vitreoretinal surgery and the ideal physicochemical properties of the dye.We evaluated the color variations of the dye at different pHs and osmolarities with or without the use of mordants as a potential new tool for internal limiting membrane peeling. The extracts of anthocyanin from the açai fruit were analyzed by spectrophotometry to determine the degree of color variations associated with various pHs and osmolarities. The experiments were conducted in test tubes filled with tryptophan soya media and Petri dishes prepared with agar media.We observed various shades of green, red, and purple in the extracts of the anthocyanin dye at different pHs and osmolarities. The assay to adjust the anthocyanin solution similar to the physiologic retinal environment (osmolarity, 300 mOsm; pH, 7.00) resulted in a shade of purple that may be useful to stain the intraocular microstructures during vitreoretinal surgery. The physicochemical property of the purple anthocyanin solutions from the açai fruit was observed at physiologic pH and osmolarity.Anthocyanins from the açai fruit may be useful to enhance visualization of the intraocular microstructures during vitreoretinal surgery.

PURPOSE To evaluate drusenoid retinal pigment epithelial detachments (DPED) secondary to age-related macular degeneration (AMD) using spectral-domain optical coherence tomography imaging. METHODS In this prospective natural history study, eyes from patients with the diagnosis of nonexudative AMD and DPEDs were followed for at least 6 months. Eyes were scanned using the Cirrus spectral-domain optical coherence tomography instrument and the 200 × 200 A-scan raster pattern. A custom software was used to quantify volumetric changes in DPEDs and to detect the evolution and formation of geographic atrophy and choroidal neovascularization. Changes in DPED area and volume and development of the advanced forms of AMD were the main outcome. RESULTS Of the 130 patients (186 eyes) with nonadvanced AMD, 11 patients (16 eyes) presented with DPEDs during the study. Mean follow-up was 18.5 months. Most DPEDs had an area exceeding 1 disk area (14 of 16 eyes) based on color fundus images with a mean area of 4.19 mm(2) (SD = 1.35) measured by spectral-domain optical coherence tomography. The mean volume at the time the DPED was diagnosed was 0.48 mm(3) (SD = 0.28). Four different patterns of progression were observed: DPEDs remained unchanged in 8 of 16 eyes (50%), DPEDs tended to increase in volume before progressing to geographic atrophy in 5 eyes (31.25%) and choroidal neovascularization in 2 eyes (12.5%), and a DPED decreased by more than 50% without progressing to geographic atrophy or choroidal neovascularization in 1 eye (6.25%). CONCLUSION Spectral-domain optical coherence tomography imaging is able to detect subtle changes in the area and volume of DPEDs. Quantitative spectral-domain optical coherence tomography imaging of DPEDs is useful for identifying the natural history of disease progression and as a clinical tool for monitoring eyes with AMD in clinical trials.

Purpose: To investigate the in vitro effect of vital dyes on toxicity and apoptosis in a human retinal pigment epithelial cell line. Methods: ARPE-19 cells were exposed to brilliant blue (BBG), Evans Blue (EB), bromophenol blue (BroB), indocyanine green (ICG), infracyanine green (IfCG), light green (LG), fast green (FG), indigo carmine (IC) and Congo red (CR). Balanced salt solution was used as the control. Five different concentrations and 2 exposure times were tested. Cell viability was determined by the MTS (1-solution methyl thiazolyl tetrazolium) assay and apoptosis by Bax expression on Western blot. Results: All dyes significantly reduced cell viability after 3 min of exposure at all concentrations (p < 0.01), except for BBG that was safe at concentrations up to 0.25 mg/ml and CR up to 0.05 mg/ml, while LG was safe at all concentrations. Toxicity was higher after 30 min of exposure. Expression of Bax was upregulated after all dye exposures, except BBG; ICG had the highest Bax expression (p < 0.01). Conclusions: Overall the safest dye was BBG followed by LG, IfCG, FG, CR, IC, BroB, EB and ICG. ICG was toxic at all concentrations and exposure times tested. Moreover, BBG was the only dye that did not induce apoptosis in ARPE-19 cells.

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.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).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.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.

Purpose: Intravitreous injection of vital dyes, e.g. brilliant blue (BBG), promotes better visualization of the internal limiting membrane (ILM). This paper investigates the staining properties of BBG depending on different incubation times and 2 types of solvents - 5% glucose (GL) or saline solution - in a prospective study in patients. Methods: This paper investigates various aspects of BBG in various methods. An interventional prospective study was conducted in patients to examine the binding properties of the blue dye diluted in either saline or 5% GL to epiretinal membranes (ERMs) and ILMs. Forty-nine consecutive patients older than 18 years scheduled for macular ERM, vitreomacular traction and macular hole surgeries were prospectively recruited. The primary outcomes of this study were the degree of ILM and ERM staining. The secondary outcomes of the study were the need of reinjection of BBG or any other dye, the ability of BBG to stain the vitreous, and frequency of complications. The staining of the ILM and ERM were graded as no staining, little, moderate or strong staining. Results: There was no correlation between age (p = 0.32) or gender (p = 0.33) in the staining affinity of BBG to either the ILM or ERM. BBG may be an appropriate staining agent for the ILM in the majority (82%) of surgeries; however, in approximately half of the cases (45%) surgeons considered BBG not enough for ERM coloring and visualization. There is a tendency of BBG to stain the ILM better when saline solution is used compared to GL 5%; however, this was not statistically significant (p = 0.64). There was no difference in the staining efficacy of BBG to the ERMs by either solution (p = 0.70), despite the low staining affinity. Conclusion: BBG became the state-of-the-art dye for ILM identification. Differences in staining properties may imply that BBG should not be considered as first-line stain for ERM surgery. BBG is effective in ILM staining in over 80% of macular hole surgeries.

To compare same-day pain control and safety of 2 different anesthetic gels utilizing 5% and 2% lidocaine gel. Main outcome is to determine whether 5% lidocaine gel is more effective in decreasing pain during conjunctival clamping compared to 2% lidocaine gel 5 and 10 min after gel application.This is a prospective, randomized double-blind clinical trial. Patients were randomized to receive 2% or 5% lidocaine gel in each eye. Discomfort during the gel instillation and pain during conjunctival clamping 5 and 10 min after gel application were compared. Extent of corneal conjunctival staining was graded according to the Oxford scale.Eighty eyes of 40 patients were enrolled. The groups were similar in gender, with a mean age of 48 ± 16.26 years. The 5% lidocaine gel resulted in higher discomfort during initial instillation (P = 0.092), however, the pain during conjunctival clamping was lower in the 5% lidocaine gel eyes (P = 0.564) in both 5 and 10 min later (P 0.001). The majority of patients (80%) had no corneal conjunctival dye staining. The tear break-up time was not statistically different after lidocaine gel 2% (20.35 ± 7.37 s) and lidocaine 5% (19.75 ± 7.00 s).Five percent and 2% lidocaine gel have similar efficacy controlling pain 5 min after instillation, however, 5% lidocaine gel appears to be more effective with a longer duration of action, without corneal toxicity. There was no corneal toxicity noted with either concentration.

PURPOSE To determine whether a natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue stains and facilitates peeling of intraocular membranes in human eyes. METHODS In this study of 60 cadaveric eyes, open-sky vitrectomy including posterior hyaloid detachment was performed. Different lutein and zeaxanthin concentrations (0.01-20%) were tested alone or combined with different Brilliant Blue concentrations (0.0125-0.025%) in the corneal endothelium, corneal epithelium, anterior and posterior capsule, vitreous cavity through the macula including the posterior hyaloid, and internal limiting membrane. The various dye solutions were in contact with the intraocular membranes for

To evaluate the in vivo and in vitro toxicity of sunitinib malate, a multikinase inhibitor molecule.Experimental, Prospective, Controlled.Human retinal pigment epithelial (ARPE-19) and human umbilical vein endothelialcells (HUVECS) were used in a culture toxicity test and exposed to different concentrations of sunitinib malate for 18 hours. The HUVECs also were cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate. Fundus photography and angiographic, electrophysiologic, and histopathologic evaluations with light and electron microscopy were performed in two groups of five rabbits each that received different intravitreal concentrations of the drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of physiologic saline solution in the left eye. After sacrifice, the eyes were enucleated and fixed with modified Karnovsky solution.No toxicity related to sunitinib malate was observed using an in vitro model with the 12.5 and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25 mg/ml solution damaged the photoreceptors layer. No functional changes in the electroretinogram were observed in any group.Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.