Retinotopic cortical mapping in objective functional monitoring of macular therapy.

Background/aims: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance.

Methods: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography.

Popular media misinformation on neonatal abstinence syndrome, 2015-2021.

Background: As the overdose crisis unfolded, narratives mischaracterizing neonatal abstinence syndrome (NAS) as "addicted babies" with echoes to the "crack babies" panic proliferated in mainstream media. his study examines NAS misinformation dynamics and characteristics over a seven-year period.

Methods: Based on a comprehensive query, Media Cloud was used to compile mainstream media content relating to NAS between 2015 and 2021.

Safety Analyses of the Phase 3 VISION Trial of [Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer.

Background And Objective: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of Lu-PSMA-617 and the impact of longer observation time for patients receiving Lu-PSMA-617 plus SoC.

Methods: VISION was an international, open-label study.

Diffuse retinal dysfunction following immune reconstitution uveitis in patients with prior cytomegalovirus retinitis: a novel observation.

Purpose: To report continuing diffuse retinal dysfunction following resolution of immune reconstitution uveitis (IRU) in patients with cytomegalovirus retinitis (CMVR).

Methods: Retrospective case series describing two patients with IRU following CMVR who underwent serial fundus photography and macular optical coherence tomography. One patient had serial electrophysiology.

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease.

Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage.

Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3).

Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis.

Purpose: Macular involvement in optic neuritis (ON) is well-recognised but poorly understood and may be of clinical relevance. This study explores macular structure-function correlates in acute ON.

Methods: This cross-sectional cohort study recruited ON patients within 14 days of symptom onset.

Three-Year Changes in Visual Function in the Placebo Group of a Randomized Double-Blind International Multicenter Safety Study: Analysis of Electroretinography, Perimetry, Color Vision, and Visual Acuity in Individuals With Chronic Stable Angina Pectoris.

Purpose: To determine whether significant deteriorations in objective (electroretinography [ERG]) and subjective (standard automated and semi-automated kinetic perimetry; color discrimination; and best-corrected visual acuity) tests of visual function, potentially attributable to aging, occurred in the group randomized to placebo of a 3-year prospective multicenter ocular safety study of ivabradine for chronic stable angina pectoris.

Methods: The multicenter trial was conducted at 11 international ophthalmic centers. Changes in visual function between baseline and month 36 were analyzed by means of a two-tailed Wilcoxon signed-rank test, based on the Hodges and Lehman estimator of the median difference, with the 95% confidence intervals derived by Walsh averages.

Macular Telangiectasia type 2: multimodal assessment of retinal function and microstructure.

Purpose: To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG).

Methods: Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation.

Combination of pasireotide and octreotide: effects on GH and IGF-I secretion and glucose metabolism in healthy volunteers.

Purpose: To assess the pharmacokinetics, pharmacodynamics and tolerability of different doses of octreotide and pasireotide (subcutaneous [sc] and long-acting release [LAR]) when co-administered in healthy volunteers.

Methods: This was an exploratory, Phase I, single-centre study. Healthy adults were enrolled in a staggered approach into seven cohorts to receive octreotide and pasireotide (sc and LAR formulations), alone or in combination.

Pathogenic variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously.

cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates.

Background: Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs).

Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model.

Background: Human pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in the delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells, and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined.

Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase.

The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs , the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits . Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).

Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases.

Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These conditions include retinitis pigmentosa (RP) and advanced forms of age-related macular degeneration (AMD), such as geographic atrophy (GA). Together, these disorders represent a significant proportion of currently untreatable blindness globally.

Comparison of predictors for terminal disease progression in simian immunodeficiency virus/simian-HIV-infected rhesus macaques.

Objectives: CD4+ T-cell decline and increasing virus levels are considered hallmarks of HIV/AIDS pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by simian immunodeficiency virus (SIV) infection associated with increased monocyte turnover also appear to impact pathogenesis. It remains unclear, however, which factors best predict onset of terminal disease progression and survival time. The objective of this study, therefore, was to directly compare these co-variates of infection for predicting survival times in retrospective studies of SIV/simian-HIV (SHIV)-infected adult rhesus macaques.

Severe retinal vasculitis in systemic lupus erythematosus leading to vision threatening paracentral acute middle maculopathy.

Systemic lupus erythematosus can affect any organ system at presentation and throughout its course. Lupus retinal vasculitis is responsible for the visual loss of variable severity and typically ascribed to the involvement of pre-capillary superficial arterial vasculature. Using multimodal imaging techniques and electrophysiology, we demonstrate the first-ever case of severe lupus retinal vasculitis resulting in the rare association of paracentral acute middle maculopathy.

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month.

Quality Control Procedures and Baseline Values for Electroretinography, Perimetry, Color Vision, and Visual Acuity in an International Multicenter Study: Observations from a Safety Trial in Chronic Stable Angina Pectoris.

Purpose: To describe quality control procedures and baseline values of electroretinography (ERG), kinetic and static perimetry, color discrimination, and best-corrected visual acuity from a multicenter ocular safety study.

Methods: A multicenter prospective longitudinal randomized placebo-controlled study was conducted at 11 ophthalmic centers that had received certification following training, instruction, and monitoring. ERGs were obtained with the Espion E2 Ganzfeld console, perimetry with the Octopus 101 perimeter, color discrimination with the Lanthony desaturated D15 test, and best-corrected visual acuity with the Early Treatment Diabetic Retinopathy Study chart.

Macular maldevelopment in -mediated retinal dysfunction.

: Achromatopsia has been previously associated with mutations in the gene. Rod-monochromatism, foveal hypoplasia, and disruption of the subfoveal photoreceptor layer are described as phenotypical features. We report detailed structural and electrophysiological assessment of two patients from two families, one manifesting severe macular maldevelopment and one with foveal hypoplasia.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500  deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.