Simultaneous Therapy with Intravitreal Dexamethasone Implant and Bevacizumab for the Treatment of Macular Edema

To investigate the safety profile and benefits of a short-term simultaneous treatment regimen combining two drugs—an intravitreal implant of dexamethasone with an intravitreal injection of bevacizumab—in patients with macular edema. This was a retrospective, non-randomized, open-label case series study.  Patients were treated between April 2014 and July 2015 and were diagnosed with recurrent macular edema secondary to diabetic retinopathy and retinal vein occlusion. They underwent simultaneous treatment with an intravitreal injection of bevacizumab (1.25 mg) and an intravitreal implant of dexamethasone (0.7 mg). Patients were evaluated at baseline and at each subsequent visit with a complete ophthalmological examination and spectral-domain optical coherence tomography (OCT) scans. They were examined 24 hours after the treatment, and then followed up after 30 days and 60 days. Twenty patients (representing 20 eyes) were included in the study. At the time of injection (i.e., baseline), the best-corrected visual acuity (BCVA) was 0.758 ± 0.42 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.51 ± 0.33 logMAR at 1 month and to 0.5 ± 0.34 logMAR at 2 months (P ≤ 0.03). The median baseline central macular thickness (CMT) was 542 µm (interquartile range, 466 – 751 µm). The median CMT decreased significantly to 321 µm (interquartile range, 288–381 µm) at 1 month and 310 µm (interquartile range, 286 – 354 µm) at 2 months (P ≤ 0.0002). The mean intraocular pressure (IOP) increased from 14.9 ± 2.29 mmHg (at baseline) to 16.5 ± 2.99 mmHg (P = 0.04) after 2 months. Two (10%) eyes showed cataract progression. There were no other ocular or systemic complications for the duration of this study. Simultaneous therapy combining a dexamethasone implant plus bevacizumab for macular edema may be an attractive treatment regimen with an acceptable safety profile

Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study

Background: To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation.Methods: We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) = 0.6 and >= 30 months of follow-up with no evidence of glaucomatous neuropathy. for controls, VCDR was limited to <= 0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis.Results: A total of 74 patients (mean age, 45.6 +/- 14.9 years) with pLPC and 45 controls (mean age, 44.8 +/- 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). the proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm(2) in disc area.Conclusion: Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.Universidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilHosp Med Olhos, Glaucoma Unit, BR-06018180 Osasco, SP, BrazilMayo Clin, Dept Ophthalmol, Jacksonville, FL 32224 USAUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilWeb of Scienc

Eyes with Large Disc Cupping and Normal Intraocular Pressure: Using Optical Coherence Tomography to Discriminate Those With and Without Glaucoma

We evaluated the ability of spectral-domain optic coherence tomography (SD-OCT) to differentiate large physiological optic disc cupping (LPC) from glaucomatous cupping in eyes with intraocular pressure (IOP) within the normal range.  We prospectively enrolled patients with glaucoma or presumed LPC. Participants  had optic discs with confirmed or suspected glaucomatous damage (defined as a vertical cup-to-disc ratio≥0.6), and all eyes had known untreated IOP&lt;21 mmHg. For glaucomatous eyes, a reproducible glaucomatous visual field (VF) defect was required. LPC eyes required normal VF and no evidence of progressive glaucomatous neuropathy (follow-up≥30 months). Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses were obtained using SD-OCT. For all studied parameters of pRNFL and GCC thicknesses, eyes with glaucoma (n=36) had significantly thinner values compared to eyes with LPC (n=71; P&lt;0.05 for all comparisons). In addition, pRNFL parameters had sensitivity of 66.7% and specificity of 83.1%, and GCC parameters had sensitivity of 61.2% and specificity of 81.7%. The combination of the two analyses increased the sensitivity to 80.6%. In conclusion, while evaluating patients with large optic disc cupping and IOP in the statistically normal range, SD-OCT had only limited diagnostic ability to differentiate those with and without glaucoma. Although the diagnostic ability of the pRNFL and the GCC scans were similar, these parameters yielded an increase in sensitivity when combined, suggesting that both parameters could be considered simultaneously in these cases

Mecanismos de fechamento angular sem bloqueio pupilar: análise de prevalência e resultados terapêuticos

Purpose: To assess the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients.Methods: A retrospective chart review was conducted to evaluate patients who had undergone laser peripheral iridotomy (LPI) due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for >= 180 degrees on dark-room gonioscopy. Key exclusion criteria were any form of secondary glaucoma and the presence of >90 degrees of peripheral anterior synechiae. Collected data were age, race, gender, angle-closure mechanism (based on indentation goniocopy and ultrasound biomicroscopy), intraocular pressure (IOP), number of antiglaucoma medications and subsequent management during follow-up. If both eyes were eligible, the right eye was arbitrarily selected for analysis.Results: A total of 196 eyes of 196 consecutive patients (mean age 58.3 +/- 11.6 years) who underwent LPI were included. in most of the patients [86% (169 patients; 133 women and 36 men]), LPI sucessfully opened the angle. Mean IOP was reduced from 18.3 +/- 6.4 mmHg to 15.4 +/- 4.5 mmHg after LPI (p<0.01). Among the 27 patients with persistent occludable angles, the most common underlying mechanisms were plateau iris (56%) and lens-induced component (34%). Most of these patients (85%) were treated with argon laser peripheral iridoplasty (ALPI); approximately 90% showed non-occludable angles following the laser procedure (mean IOP reduction of 18.9%), with no significant differences between patients with plateau iris and lens-induced components (p=0.34; mean follow-up of 11.4 +/- 3.6 months).Conclusions: Our findings suggest that, in this population of Brazilian patients, several eyes with angle closure were not completely treated with LPI. in the present large case series involving middle-age patients, plateau iris was the leading cause of persistent angle closure and was effectively treated with ALPI. A detailed eye examination with indentation gonioscopy should always be performed after LPI to rule out persistent angle closure due to non-pupillary block mechanisms.Hosp Med Olhos, Glaucoma Unit, Osasco, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilMayo Clin, Jacksonville, FL 32224 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by zika virus

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water sup-plies of NE compared to other regions of Brazil. Experimentally, we described that STX dou-bled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Fil: Pedrosa, Carolina da S. G.. D’Or Institute for Research and Education; BrasilFil: Souza, Leticia R. Q.. D’Or Institute for Research and Education; BrasilFil: Gomes, Tiago A.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Oswaldo Cruz; BrasilFil: de Lima, Caroline V. F.. D’Or Institute for Research and Education; BrasilFil: Ledur, Pitia F.. D’Or Institute for Research and Education; BrasilFil: Karmirian, Karina. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito Andrés, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Costa, Marcelo do N.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza M.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, Átila D.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, Amilcar. Universidade Federal do Rio de Janeiro; BrasilFil: Prata Barbosa, Arnaldo. D’Or Institute for Research and Education; BrasilFil: Tovar Moll, Fernanda. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, Patricia P.. Universidade Federal do Rio de Janeiro; BrasilFil: Lara, Flavio A.. Instituto Oswaldo Cruz; BrasilFil: Molica, Renato J. R.. Universidad Federal Rural Pernambuco; BrasilFil: Rehen, Stevens K.. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; Brasi

Repeatability of short-duration transient visual evoked potentials in normal subjects

To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1–2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant™ System (Diopsys, Inc., Pine Brook, New Jersey, USA). A checkerboard stimulus was modulated at two reversals per second. Two different contrasts of checkerboard reversal patterns were used: 85% Michelson contrast with a mean luminance of 66.25 cd/m2 and 10% Michelson contrast with a mean luminance of 112 cd/m2. Each test lasted 20 s. Both eyes, independently and together, were tested 10 times (5 times at each contrast level). The following information was identified from the filtered N75-P100-N135 complex: N75 amplitude, N75 latency, P100 amplitude, P100 latency, and Delta Amplitude (N75-P100). The median values for each eye’s five SD-tVEP parameters were calculated and grouped into two data sets based on contrast level. Mean age was 27.3 ± 5.2 years. For OD only, the median (95% confidence intervals) of Delta Amplitude (N75-P100) amplitudes at 10% and 85% contrast were 4.6 uV (4.1–5.9) and 7.1 uV (5.15–9.31). The median P100 latencies were 115.2 ms (112.0–117.7) and 104.0 ms (99.9–106.0). There was little within-session variability for any of these parameters. Intraclass correlation coefficients ranged between 0.64 and 0.98, and within subject coefficients of variation were 3–5% (P100 latency) and 15–30% (Delta Amplitude (N75-P100) amplitude). Bland–Altman plots showed good agreement between the first and fifth test sessions (85% contrast Delta Amplitude (N75-P100) delta amplitude, mean difference, 0.48 mV, 95% CI, −0.18–1.12; 85% contrast P100 latency delay, −0.82 ms, 95% CI, −3.12–1.46; 10% contrast Delta Amplitude (N75-P100) amplitude, 0.58 mV, 95% CI, −0.27–1.45; 10% contrast P100 latency delay, −2.05 mV, 95% CI, −5.12–1.01). The inter-eye correlation and agreement were significant for both SD-tVEP amplitude and P100 latency measurements. For the subset of eyes in which the inter-session repeatability was tested, the intraclass correlation coefficients ranged between 0.71 and 0.86 with good agreement shown on Bland–Altman plots. Short-duration transient VEP technology showed good within-session, inter-session repeatability, and good inter-eye correlation and agreement

An examination of polygenic score risk prediction in individuals with first-episode psychosis

Background Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. Methods The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. Results PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10−6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002). Conclusions PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP