Características clínico- patológicas y evolución del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: En Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en la mujer, se trata de una enfermedad multifactorial que guarda relación con la herencia genética, historial hormonal estrogénico, estilo de vida, factores ambientales y culturales. Objetivos: investigar las características clínico-patológicas de pacientes con CM diagnosticadas en el Hospital de Clínicas y evaluar la sobrevida global total (SVG) y de acuerdo al subtipo biológico. Metodología: se recolectaron datos relacionados con las características clínico-patológicas y la evolución de pacientes tratadas por CM en el período comprendido entre el 1º de enero del 2011 y 31 de diciembre de 2020 asistidas en la Unidad de Mastología del Hospital de Clínicas. Se calculó la SVG para todas las pacientes, globalmente, y según el subtipo biológico. Resultados: se incluyeron 390 pacientes. Las características clínico-patológicas fueron: carcinoma ductal: 83%, estadio: in situ (1.8 %), I (27.7 %), II (29.7 %), III (23.6%), IV (12.6 %). Con respecto al perfil biológico: 235 tumores (60.3%) fueron RRHH+ HER 2−, 88 tumores (22.6%) fueron HER2 +, mientras que otros 41 tumores (10.5%) fueron clasificados como triple negativos (TN). La SVG para la totalidad de las pacientes tuvo una mediana de 92 meses. Las tasas de SVG a 2 y 5 años fueron para las luminales de 92% y 64%; en las TN la tasa de SVG a 24 meses fue de 69%, siendo a 5 años de 53.3% y en las HER2 + 76.6% y 67.3% respectivamente. Conclusiones: La mayoría de los tumores fueron diagnosticados en estadios precoces, siendo estos datos son concordantes con los reportados en estudios realizados a nivel nacional. La frecuencia de tumores RE/RP+ algo inferior a la reportada en estudios previos (70%) a nivel nacional, mientras que la de tumores HER 2 + TN fue similar a la reportada en estudios europeos, norteamericanos y en Latinoamérica donde se la prevalencia encontrada es del 20%

Introduction: In Uruguay, breast cancer (BC) ranks first in incidence and mortality from cancer in women. It is a multifactorial disease that is related to genetic inheritance, estrogenic hormonal history, lifestyle, environmental and cultural factors. Objectives: to investigate the clinicopathological characteristics of patients with BC diagnosed at the Hospital de Clínicas and to evaluate the overall overall survival (SVG) and according to the biological subtype. Metodology: data related to the clinicopathological characteristics and the evolution of patients treated for BC in the period between January 1, 2011 and December 31, 2020 assisted in the Mastology Unit of the Hospital de Clínicas were collected. Overall survival (SVG) was calculated for all patients, globally, and according to biological subtype. Results: 390 patients were included. The clinicopathological characteristics were: ductal carcinoma: 83%, stage: in situ (1.8%), I (27.7%), II (29.7%), III (23.6%), IV (12.6%). Regarding the biological profile: 235 tumors (60.3%) were HR+ HER 2−, 88 tumors (22.6%) were HER2 +, while another 41 tumors (10.5%) were classified as triple negative (TN). The SVG for all the patients had a median of 92 months. SVG rates at 2 and 5 years were 92% and 64% for luminals; in TN the 24-month survival rate was 69%, being 53.3% at 5 years and in HER2 + 76.6% and 67.3% respectively. Conclusions: Most of the tumors were diagnosed in early stages, these data being consistent with those reported in studies carried out at the national level. The frequency of ER/RP+ tumors was somewhat lower than that reported in previous studies (70%) at the national level, while that of HER 2 + TN tumors was similar to that reported in European, North American and Latin American studies where the prevalence found is 20%

Introdução: No Uruguai, o câncer de mama (CM) ocupa o primeiro lugar em incidência e mortalidade por câncer em mulheres. É uma doença multifatorial que está relacionada à herança genética, história hormonal estrogênica, estilo de vida, fatores ambientais e culturais. Objetivos: investigar as características clinicopatológicas dos pacientes com CM diagnosticados no Hospital de Clínicas e avaliar a sobrevida global (OSV) e segundo o subtipo biológico. Material e método: foram coletados dados referentes às características clínico-patológicas e à evolução dos pacientes atendidos por CM no período de 1º de janeiro de 2011 a 31 de dezembro de 2020 atendidos na Unidade de Mastologia do Hospital de Clínicas. A sobrevida global (SVG) foi calculada para todos os pacientes, globalmente e de acordo com o subtipo biológico. Resultados: 390 pacientes foram incluídos. As características clínico-patológicas foram: carcinoma ductal: 83%, estádio: in situ (1,8%), I (27,7%), II (29,7%), III (23,6%), IV (12,6%). Quanto ao perfil biológico: 235 tumores (60,3%) eram HR+ HER 2−, 88 tumores (22,6%) eram HER2+, enquanto outros 41 tumores (10,5%) foram classificados como triplo negativo (TN). O SVG para todos os pacientes teve uma mediana de 92 meses. As taxas de SVG aos 2 e 5 anos foram de 92% e 64% para luminais; em TN a sobrevida em 24 meses foi de 69%, sendo 53,3% em 5 anos e em HER2 + 76,6% e 67,3%, respectivamente. Conclusões: A maioria dos tumores foi diagnosticada em estágios iniciais, sendo esses dados consistentes com os relatados em estudos realizados em nível nacional. A frequência de tumores ER/RP+ foi um pouco menor do que a relatada em estudos anteriores (70%) em nível nacional, enquanto a de tumores HER 2 + TN foi semelhante à relatada em estudos europeus, norte-americanos e latino-americanos, onde a prevalência encontrado é 20%

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders.

Purpose: A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting. Methods: A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up). Results: Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 µm from 409.4 ± 85.8 µm to 290.0 ± 64.5 µm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039). Conclusion: Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.

OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

PURPOSE: To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). METHODS: We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. RESULTS: One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. CONCLUSION: Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

Prescribers' opinions to identify competitive groups: a comparative analysis in the pharmaceutical industry.

BACKGROUND: A firm must identify its key competitors (those that belong to the same competitive group), especially when operating in highly competitive industries, such as drug products. Experts who prescribe products to the final consumer play a crucial role in identifying the key competitors of a firm. In this context, the present paper aimed to determine if significant differences exist between two groups of prescribers (commercial and social) regarding the competitive structure that both groups identify using subjective information obtained through (i) categorization methods and (ii) evaluation methods. METHOD: A sample of 104 prescribers related to the sale of cosmetic pharmaceuticals was interviewed (53 commercials and 51 social prescribers). Multidimensional scaling was used to obtained perceptual maps that visually represented the competitive space for each group of prescribers. Cluster analysis was employed to identify the competitive structure (competitive clusters) for each group of prescribers. Bilateral Pearson correlations and Mobility Rates were applied to compare the perceptual maps and the identified clusters, respectively. RESULT: Competitive spaces and structures from both groups of prescribers were partially convergent, regardless the information was collected with categorization methods or evaluation ones. The competitive perceptual map identified by the commercial prescribers converges, to a certain extent, with the competitive perceptual map identified by the social prescribers when categorization data is used (correlation between maps = 0.322; p < 0.01). The same occurs when both targets (commercial prescribers and social prescribers) are compared using evaluation data (correlation between maps = 0.69; p < 0.01). In addition, the mobility rate (MR) shows 31.25% of convergence between the clusters identified on these maps using categorization methods; and 6.25% of convergence when evaluation data are used. CONCLUSIONS: There are certain perceptual differences depending on prescribers' occupation, although these differences are not significant. On the contrary, some differences due to the information collecting method (categorization versus evaluation) have been identified.

Endoscopy-assisted vitrectomy vs. vitrectomy alone: comparative study in complex retinal detachment with proliferative vitreoretinopathy.

BACKGROUND: Recurrent retinal detachment (RD) is still a widespread event despite the therapeutic options available. Proliferative vitreoretinopoathy (PVR) is one of the main causes of redetachment. Little is known about the use of endoscopy-assisted vitrectomy (E-PPV) in complex recurrent RD with PVR. The purpose of this study was to identify the potential advantages of E-PPV in complex RD with PVR compared with pars plana vitrectomy (PPV) alone. METHODS: Single-center, retrospective, observational, descriptive study. The medical records of 293 patients were reviewed. Patients who underwent PPV for complex rhegmatogenous RD and associated PVR between 2009 and 2017 were included. Patients with diabetic tractional RD, trauma, uveitis or detachment postendophthalmitis were excluded. After 2013, an endoscopic visualization system was used in a nonrandomized fashion at the surgeon's discretion. Outcome measures (reattachment rate, number of surgeries, lens status, PVR stage, intraocular pressure, phthisis rate) were compared between the E-PPV and PPV-only groups with independent samples t-tests (continuous variables) and Fisher's exact test (categorical variables), as well as time-adjusted analyses. Postoperative time to retinal redetachment was assessed with Kaplan-Meier survival analysis. RESULTS: One hundred one eyes from 100 patients met the inclusion criteria. The mean participant age was 63.3 years old (95% CI 60.4-66.1 years), without a significant difference between groups. E-PPV was performed in 36.6% (n = 37) of eyes, and 63.4% (n = 64) underwent PPV only. The mean follow-up was significantly longer in the PPV-only group (31.9 vs. 21.1 months; p = 0.021). Upon adjustment for follow-up duration, the mean number of surgeries was significantly lower in the PPV-only group (2.6 vs. 4.3 number of surgeries; p < 0.001) than in the E-PPV group. A significantly higher risk for redetachment was observed in the PPV-only group (HR [95% CI] 4.1 [1.4-11.8]) than in the E-PPV group (p = 0.037). The evolution to phthisis was 7% (n = 4) in the PPV-only group and 2.7% (n = 1) in the E-PPV group (p > 0.05). CONCLUSIONS: Compared to PPV alone, endoscopy-assisted vitrectomy seems to be advantageous in achieving better reattachment rates in complex RD with advanced PVR. Endoscopic visualization allows a thorough examination and extensive anterior PVR and vitreous base dissection.

Can Health Perceptions, Credibility, and Physical Appearance of Low-Fat Foods Stimulate Buying Intentions?

This study examines the influence of labelling and packaging strategies on perceived product health and overall attitudes to low-fat products in the field of healthy food claims among young consumers. The aim was to determine if these aspects can influence buying intentions. After a literature review, a quantitative study was carried out. With a sample of 300 young consumers (18-25 years old) and the use of partial least square methodology, this paper demonstrated that: (1) nutritional information and visual cues affect consumers' perceptions (information credibility and physical appearance), (2) information credibility influences product health perceptions and attitudes toward a product, (3) physical appearance affects attitudes toward a product, and (4) overall attitude to the product influences purchase intentions The results achieved show that credibility and physical appearance could stimulate low-fat foods purchase intentions through a positive global attitude to the product. Additionally, nutritional information and visual cues play a more relevant role than nutritional information response and informative cues. These results and the conclusions that follow must be understood in the analysed context (low-fat foods) with the sample used (300 young consumers).

Identifying profiles of complementary and alternative medicine believers and/or users.

The present study focuses on the identification of profiles of CAM believers and/or users. Using data from the Spanish CIS Barometer (2018) and a sample of 2486 Spaniards, a hierarchical and non-hierarchical cluster analysis and discriminant analysis have been performed. Profiles of people with a high level of belief in CAM and/or CAM users were identified. Results reflect relationships between personal factors (healthy lifestyle and status, political and religious ideology) and satisfaction with conventional medicine with the belief/use of CAM. Personal factors and satisfaction are not related to the level of belief in CAM. We have tried to fulfil some gaps detected in the literature: much of the research has been methodologically limited and there is a need to deepen the study of factors and processes that favor the initial uptake and subsequent use of CAM. Doing this, this paper offers diverse recommendations for organizations worried about this theme.

Prognostic factors of postoperative intraretinal cystoid spaces after primary pars plana vitrectomy for vitreomacular traction.

PURPOSE: To study the anatomical and surgical prognostic factors related to developing postoperative intraretinal cystoid spaces (ICS) six months after 25-gauge pars plana vitrectomy (PPV) for vitreomacular traction (VMT). METHODS: The study is a retrospective case series of patients presenting with VMT treated primarily with PPV. All patients underwent 25-gauge PPV by the same retina surgeon. Intra-operative parameters were all recorded. Postoperative visual acuity (VA), foveal thickness, and ICS were collected over six months of follow-up. ICS were defined as hyporeflective cysts divided by hyperreflective septa on optical coherence tomography (OCT). Patients with ICS persistence 3 months postoperatively received topical treatment extension. The primary outcome measure was odds of preoperative ICS in patients with postoperative ICS compared to controls. Secondary outcome measures were odds of presence of an attached hyaloid to the optic disc, presence of pseudophakia, the use of intra-operative air, and the use of more than one intra-operative indocyanine green (ICG) injections in patients with postoperative ICS compared to controls. RESULTS: Two hundred and eighty treatment-naïve patients with preoperative diagnosis of epiretinal membrane (ERM) were reviewed. Thirty patients with VMT, confirmed both preoperatively on OCT and intra-operatively, were included. Postoperatively, 40% (n = 12) presented with ICS at 6 months. Among these, 83% (n = 10) had ICS prior to PPV. Patients presenting with preoperative ICS were significantly more at risk of having persistent ICS postoperatively (P < 0.05). The following factors did not statistically affect ICS occurrence: optic disc hyaloid attachment status, phakia/pseudophakia, intra-operative air vs. sulfur hexafluoride (SF6), and the number of intra-operative ICG injections. CONCLUSIONS: Our data demonstrate a predictive relationship between the occurrence/persistence of ICS post-PPV for VMT and the initial foveal status. Specifically, having preoperative ICS is a major risk factor for its persistence postoperatively. Our data highlight the pathophysiological importance of the vitreous phase and its effect on visual prognosis.

Sutureless intrascleral fixation of intraocular lens through self-sealing sclerotomy wounds using haptic externalization and reinternalization technique.

In eyes with absent or insufficient capsule support, three-piece posterior chamber intraocular lens (PC IOL) may be fixed to the sclera. Previous techniques involve the use of sutures, flaps, glue, needles, trocars, or intrascleral tunnels to fixate the distal tips of the haptics intrasclerally. Herein we describe a modified technique for the sutureless scleral fixation of a standard 3-piece PC IOL using self-sealing sclerotomies created with a crescent blade and a 20-gauge microvitreoretinal blade, and then reinserting the haptics to leave the tips inside the vitreous cavity. We believe the relative simplicity of this technique makes it widely applicable for the placement of an IOL with insufficient capsule support.

Food packaging cues as vehicles of healthy information: Visions of millennials (early adults and adolescents).

Because packaging has become an important marketing tool, firms must know what type of packaging can affect consumers' packaging cues. Also, still today there is little attention paid to the relevance of educating millennials about the importance of a healthier lifestyle and eating. The aim is to analyse the effects of young consumers with varying degrees of healthy lifestyles and food involvement on packaging cues. Also, the paper analyses differences between early adults and adolescents millennials. Using a sample of 890 millennials (300 early adults and 590 adolescents) and SEM methodology, interesting results are reached. Some healthy habits affect food involvement, and this is related to informative packaging cues. Some differences among both groups of millennials are found. The results/ findings would be valuable for the marketers and administration in the food industry to formulate marketing packaging strategies and to promote a healthier lifestyle and food consumption among millennials.

Effects of ranibizumab and amfenac on the functional abilities and radiosensitivity of uveal melanoma cells / Efeitos do ranibizumabe e do amfenac nas habilidades funcionais e na radiossensibilidade de células de melanoma uveal

ABSTRACT Purpose: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. Methods: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). Results: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. Conclusion: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

RESUMO Objetivo: Avaliar os efeitos do ranibizumabe em associação com o amfenac nas células de melanoma uveal humano e explorar a capacidade desses compostos em sensibilizar as células de melanoma uveal à radioterapia. Métodos: Células de melanoma uveal humano do tipo 92.1 foram cultivadas e submetidas ao tratamento proposto (ranibizumabe, amfenac e a combinação de ambos). Ensaios de proliferação, migração e invasão com as células de melanoma uveal do tipo 92.1 foram avaliados após tratamento com ranibizumabe (125 mg/ml), amfenac (150 nM) e a combinação de ambos. Além disso, as taxas de proliferação foram avaliadas após tratamento com ranibizumabe e amfenac com subsequente exposição das células a diferentes doses de radiação (0 Gy, 4 Gy e 8 Gy). Resultados: Ensaio de proliferação: células tratadas com ranibizumabe e amfenac combinados apresentaram taxas de proliferação inferiores em comparação ao grupo controle (p=0,016), do que as tratadas apenas com ranibizumabe (p=0,033). Ensaio de migração: foi observada uma taxa de migração significativamente mais baixa nas células tratadas com amfenac do que no grupo controle (p=0,014) e do que nas tratadas com ranibizumabe (p=0,044). Ensaio de invasão: não houve diferenças significativas entre os grupos estudados. Exposição à irradiação: no grupo da dose de 4 Gy, não houve diferença significante entre os grupos. No grupo da dose de 8 Gy, o tratamento com ranibizumabe, afenac e sua combinação antes da aplicação da radiação de 8 Gy levou a uma redução acentuada nas taxas de proliferação (p=0,009, p=0,01 e p=0,034, respectivamente) em comparação aos grupos controle. Conclusão: A combinação de ranibizumabe e amfenac reduziu a taxa de proliferação das células de melanoma uveal; no entanto, apenas o amfenac diminuiu significativamente a migração celular. A radiossensibilidade das células de melanoma uveal do tipo 92.1 aumentou após a administração de ranibizumabe, amfenac e sua combinação. Mais investigações são necessárias para determinar se esta é uma estratégia de pré-tratamento viável para tornar grandes tumores passíveis de radioterapia.

Effects of ranibizumab and amfenac on the functional abilities and radiosensitivity of uveal melanoma cells.

PURPOSE: To evaluate the effects of ranibizumab and amfenac in human uveal melanoma cell lines and to explore the ability of these compounds to sensitize uveal melanoma cells to radiation therapy. METHODS: The 92.1 human uveal melanoma cell line was cultured and subjected to the proposed treatment (ranibizumab, amfenac, and a combination of both). Proliferation, migration, and invasion assays of the 92.1 uveal melanoma cell line were assessed after pretreatment with ranibizumab (125 mg/mL), amfenac (150 nM), or a combination of both. In addition, proliferation rates were assessed after treatment with ranibizumab and amfenac, and the cells were subsequently exposed to various radiation doses (0, 4, and 8 Gy). RESULTS: Proliferation assay: cells treated with a combination of ranibizumab and amfenac had lower proliferation rates than controls (p=0.016) and than those treated with only ranibizumab (p=0.033). Migration assay: a significantly lower migration rate was observed in cells treated with amfenac than the control (p=0.014) and than those treated with ranibizumab (p=0.044). Invasion assay: there were no significant differences among the studied groups. Irradiation exposure: in the 4 Gy dose group, there were no significant differences among any groups. In the 8 Gy dose group, treatment with ranibizumab, amfenac, and their combination prior to application of the 8 Gy radiation led to a marked reduction in proliferation rates (p=0.009, p=0.01, and p=0.034, respectively) compared with controls. CONCLUSION: Combination of ranibizumab and amfenac reduced the proliferation rate of uveal melanoma cells; however, only amfenac monotherapy significantly decreased cell migration. The radiosensitivity of the 92.1 uveal melanoma cell line increased following the administration of ranibizumab, amfenac, and their combination. Further investigation is warranted to determine if this is a viable pretreatment strategy to render large tumors amenable to radiotherapy.

Ocriplasmin versus vitrectomy for the treatment of macular holes.

OBJECTIVE: To compare the anatomical and visual outcomes of patients with bilateral macular holes (MH) who have been treated with pars plana vitrectomy in one eye and intravitreal ocriplasmin in the fellow eye. DESIGN: Multicentre, retrospective case series. PARTICIPANTS: Twenty-two eyes of 11 patients with bilateral MH treated with vitrectomy in one eye and ocriplasmin in the other were included. Patients were followed-up by 5 vitreoretinal surgeons from 3 retinal practices in Canada. METHODS: All charts were reviewed for data collection, and optical coherence tomography (OCT) scans pre- and posttreatment were evaluated. RESULTS: MH closed primarily in 36.4% (n = 4) of the ocriplasmin-treated eyes and in 90.9% (n = 10) of the vitrectomy-treated eyes (p = 0.031). The 4 successfully treated ocriplasmin MH were preceded by a vitreomacular traction (VMT) release. Three additional ocriplasmin-treated eyes achieved a VMT release without MH closure. All persistent MH (100%) closed with subsequent vitrectomy, with no significant difference in final best-corrected visual acuity (BCVA) between those who achieved MH closure with primary or secondary interventions (p = 0.073). Final BCVA improved from logMAR 0.85 ± 0.34 to 0.37 ± 0.22 (p = 0.005) in the vitrectomy eyes and from 0.56 ± 0.28 to 0.28 ± 0.16 (p = 0.009) in the ocriplasmin eyes, with no significant difference in final BCVA between treatments (p = 0.306). Postoperative ellipsoid zone disruption persisted more frequently in vitrectomy-treated eyes. CONCLUSION: Both procedures were associated with improved visual outcomes, but eyes initially treated with vitrectomy had a higher primary MH closure rate. On OCT, patients had more outer structural changes in vitrectomy eyes than in ocriplasmin eyes.

Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model.

BACKGROUND: Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD. METHODS: Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines. RESULTS: A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions. CONCLUSIONS: Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.

Evaluation of nicotinamide as an anti-inflammatory and anti-angiogenic agent in uveal melanoma cell lines.

PURPOSE:: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. METHODS:: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. RESULTS:: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. CONCLUSIONS:: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

Evaluation of nicotinamide as an anti-inflammatory and anti-angiogenic agent in uveal melanoma cell lines / Avaliação da nicotinamida como agente anti-inflamatório e anti-angiogênico em linhas celulares de melanoma uveal

ABSTRACT Purpose: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. Methods: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. Results: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. Conclusions: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

RESUMO Objetivo: Acredita-se que a nicotinamida (NIC) seja capaz de diminuir a angiogênese induzida pelo fator de crescimento endotelial vascular (VEGF). Investigar os efeitos da nicotinamida sobre a secreção de citocinas pró-angiogênicas e pró-inflamatórias em linhagens de células de melanoma uveal humano (UM). Métodos: Duas linhagens de células humanas de UM (92,1 e OCM-1) foram tratadas com NIC (10 mmol/L) ou apenas com meio de cultura por 48 horas. O sobrenadante das culturas obtido após a administração de nicotinamida foi comparado com o sobrenadante das culturas controle quanto à expressão de 20 fatores pró-angiogênicos e pró-inflamatórios, pela técnica de enzyme-linked immunosorbent assay (ELISA). Resultados: Sete citocinas pró-angiogênicas foram detectadas nas condições de controle em ambas as linhagens de células de UM. O tratamento com nicotinamida promoveu uma redução significativa da secreção das seguintes citocinas angiogênicas: Angiogenina, ANG2, EGF e VEGF-A em células 92.1; bFGF em células OCM-1; PIGF em ambas as linhagens celulares. Quanto às proteínas pró-inflamatórias, a expressão de MCP-1 e IL-8 foi significativamente reduzida com a administração de nicotinamida em relação às culturas de células que não receberam o tratamento. Conclusões: Nicotinamida apresenta propriedades anti-inflamatórias e anti-angiogênicas em modelo experimental in vitro. Tais efeitos sugerem a possibilidade de utilizar esta substância na quimioprevenção do UM. Entretanto, estudos com modelos experimentais in vivo são necessários para melhor avaliar o benefício do tratamento do UM com nicotinamida.