Here, we summarise the current knowledge on QC maintenance in Arabidopsis and compare it with that of agriculturally relevant cereal crops.The NIH Virtual SARS-CoV-2 Antiviral Summit, held on 6 November 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for coronavirus disease 2019 (COVID-19), including combinations of antivirals. Scientific experts from the public and private sectors convened virtually during a live videocast to discuss severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets for drug discovery as well as the preclinical tools needed to develop and evaluate effective small-molecule antivirals. The goals of the Summit were to review the current state of the science, identify unmet research needs, share insights and lessons learned from treating other infectious diseases, identify opportunities for public-private partnerships, and assist the research community in designing and developing antiviral therapeutics. This report includes an overview of therapeutic approaches, individual panel summaries, and a summary of the discussions and perspectives on the challenges ahead for antiviral development.

This study assessed the cytotoxicity of the impurities detected in the perfluorooctane (PFO) batches for vitreoretinal surgery that were associated with serious adverse incidents of ocular toxicity, namely, the perfluorooctanoic acid (PFOA), 1H,1H,7H-dodecafluoro-1-heptanol (DFH), 1H-perfluorooctane (1H-PFO), ethylbenzene, anhydrous p-xylene, and perfluoro-2-butyltetrahydrofurane, and two additional substances 1H,1H,1H,2H,2H-perfluorooctane (5H-PFO) and hexafluoro-1,2,3,4-tetrachlorobutane.

Serial dilutions were tested by in vitro direct contact cytotoxicity test, validated in accordance with the ISO 10993-52009 standard using BALB3T3 and ARPE-19 cell lines, after sample application for 24 hours.

Six of the eight tested substances were cytotoxic according to the above-mentioned ISO standard. Anhydrous p-xylene, ethylbenzene, and PFOA were the most cytotoxic impurities as traces 1.55 ppm, 1.06 ppm, and 28.4 ppm reached the cytotoxicity limit, respectively. Hexafluoro-1,2,3,4-tetrachlorobutane, DFH, and 1according to the ISO 10993-52009 standard is a sensible and fast method for reliable detection of the cytotoxicity in perfluorocarbon liquids to guarantee maximal safety for the patients.

Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable.

The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable.

Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups.

Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients.

Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

Caveolin (Cav) regulates various aspect of endothelial cell signaling and cell-permeable peptides (CPPs) fused to domains of Cav can reduce retinal damage and inflammation in vivo. Thus, the goal of the present study was to identify a novel CPP that improves delivery of a truncated Cav modulator in vitro and in vivo.

Phage display technology was used to identify a small peptide (RRPPR) that was internalized into endothelial cells. Fusions of Cav with the peptide were compared to existing molecules in three distinct assays, vascular endothelial growth factor-A (VEGF) induced nitric oxide (NO) release, VEGF induced vascular leakage, and in a model of immune mediated uveitis.

RRPPR was internalized efficiently and was potent in blocking NO release. Fusing RRPPR with a minimal Cav inhibitory domain (CVX51401) dose-dependently blocked NO release, VEGF induced permeability, and retinal damage in a model of uveitis.

CVX51401 is a novel Cav modulator that reduces VEGF and immune mediated inflammation.

CVX51401 is an optimized Cav modulator that reduces vascular permeability and ocular inflammation that is poised for clinical development.

CVX51401 is an optimized Cav modulator that reduces vascular permeability and ocular inflammation that is poised for clinical development.

To evaluate the feasibility of capturing and interpreting retinal images in a workplace environment using a multimodal, cloud-based, diabetic retinal screening program combined with electronic self-reported questionnaires. The burden of diabetic retinopathy (DR) and other retinal conditions, healthcare utilization, and visual function were also assessed.

A cross-sectional feasibility study was conducted at the Genentech, Inc., Campus Health Center. Eyes of participants were imaged using ultra-widefield (UWF) color fundus photography (CFP) and spectral-domain optical coherence tomography (SD-OCT). A cloud-based platform was used for the automated, seamless transfer of images to a remote reading center for evaluation for DR and other retinal pathologies. Electronic surveys collected participants’ self-reported medical histories, healthcare utilization, and visual function data.

Among 100 participants (mean age, 43.9 years; 44% male), 33% of them self-reported diabetes. Eye examinations within the past 12 months were reported by 71% of all participants (n = 71/100) and by 85% (n = 28/33) of those with self-reported diabetes. Among participants with complete screening images from both UWF-CFP and SD-OCT, 20% (n = 6/30) of those with self-reported diabetes and 8.5% (n = 5/59) of participants with no history of diabetes were unaware they had mild/moderate nonproliferative DR. Among all participants, 20% (20/100) had a retinal finding, on either UWF-CFP or SD-OCT, or both, which prompted a referral for further evaluation.

A retinal screening program deployed via a secure, scalable, and interoperable cloud-based platform was feasible and conveniently integrated into the workplace.

Cloud-based platforms could be used to promote a secure, scalable, and interoperable system for retinal screening in nontraditional environments.

Cloud-based platforms could be used to promote a secure, scalable, and interoperable system for retinal screening in nontraditional environments.

To assess en face ellipsoid zone (EZ) maps of remaining retinal structure as outcome measures for the future clinical research in patients with choroideremia.

Twenty eyes from 12 patients with a confirmed genetic diagnosis of choroideremia were included retrospectively from a single site. From spectral domain-optical coherence tomography volume scans, slabs including the EZ were manually segmented to create the en face EZ maps. The preserved EZ area was measured by two graders. Lengths of the EZ were recorded at 0°, 45°, 90°, and 135°. The intraclass correlation coefficients and Bland-Altman plots were used to show intergrader agreement. The Pearson correlation coefficient evaluated the correlation between length and area. A Bland-Altman plot compared en face EZ and the preserved fundus autofluorescence area.

Measurements of EZ area by two graders showed excellent agreement with an intraclass correlation coefficient of 0.992 (95% confidence interval, 0.980-0.997). A Pearson correlation analysis showed that the existing marker for preserved photoreceptor (horizontal EZ length) was correlated with the area (r = 0.722). The average EZ length in four meridians showed a much better correlation with the EZ area (r = 0.929). The fundus autofluorescence area was found to be a mean of 0.45 ± 0.99 mm2 greater than the EZ area.

EZ area measurement provides excellent intergrader reliability, although the process is time consuming. We propose a less time-consuming alternative to estimate the EZ by using the average EZ band length in meridians. Our data also suggest that the loss of photoreceptor inner segments is an early change in choroideremia and may happen before the loss of the retinal pigment epithelium.

En face EZ mapping is a potential tool for future clinical trials to quantify preserved photoreceptor structure in choroideremia.

En face EZ mapping is a potential tool for future clinical trials to quantify preserved photoreceptor structure in choroideremia.

The purpose of this study was to evaluate the predictive value of optical coherence tomography (OCT) and OCT angiography (OCTA) parameters at baseline on lesion’s activity at the 1-year follow-up in type 1 macular neovascularizations (MNVs) treated with 1-year fixed regimen of intravitreal aflibercept injections (q8 IAIs).

All patients were imaged by structural OCT to evaluate central macular thickness (CMT), subretinal fluid (SRF), subretinal hyper-reflective material (SHRM), intraretinal fluid (IRF) and intraretinal hyper-reflective dots (HRDs), and by Swept-Source OCTA to measure baseline MNV area, perfusion density (PD), vessel length density (VLD), and vessel diameter index. At the end of q8 IAI, patients were classified in two groups active-MNV (A-MNV) and inactive-MNV (I-MNV), considering the OCT signs of activity. Three binary logistic regression models were developed (1) OCT-based, (2) OCTA-based, and (3) OCT/OCTA-based model.

Thirty-one treatment-naïve type 1 MNVs were enrolled (13 A-MNV and 18 I-MNV). No differences were observed in baseline OCT and OCTA characteristics between A-MNV and I-MNV. Among the models developed, model 3 that combined OCT/OCTA parameters showed a performance of 87.5% and excellent sensitivity for A-MNV lesions (100%). By analyzing the model, the A-MNV group appears more likely to show at baseline SRF, greater CMT, wider MNV area, and lower PD and VLD compared to I-MNV.

Our study demonstrated that the combination of baseline OCT and OCTA parameters allowed to achieve a good models’ performance in the prediction of MNV activity permitting to correctly classifying the active lesions at the end of follow-up period, with excellent sensitivity.

OCT/OCTA could integrate statistical models potentially useful for artificial intelligence.

OCT/OCTA could integrate statistical models potentially useful for artificial intelligence.