Retinal Degeneration Associated With Biallelic RDH12 Variants: Longitudinal Evaluation of Retinal Structure and Visual Function in Pediatric Patients.

Purpose: The purpose of this study was to determine the natural history of the photoreceptor disease in a large group of pediatric patients with RHD12-associated Leber congenital amaurosis (RDH12-LCA), to estimate the changes expected over the duration of a clinical trial, and to define the relationship between the photoreceptor loss and visual dysfunction.

Methods: Forty-six patients representing 36 families were included. The great majority of patients were under the age of 18 years.

Erratum: Safety and improved efficacy signals following gene therapy in childhood blindness caused by mutations.

[This corrects the article DOI: 10.1016/j.isci.

Mapping intertidal microphytobenthic biomass with very high-resolution remote sensing imagery in an estuarine system.

Microphytobenthos (MPB) contributes significantly to estuarine primary production, so that quantifying its biomass is crucial for assessing their ecosystem functioning. Conventional sampling methods are labour-intensive, logistically challenging, and cannot provide a comprehensive spatial distribution map of MPB biomass. Satellite imagery has offered a feasible alternative for mapping large areas at various temporal and spatial resolutions.

Implementing active surveillance for low-risk thyroid carcinoma into clinical practice: collaborative recommendations for Latin America.

The incidence of thyroid cancer is increasing globally, but mortality rates have remained steady. Many patients with thyroid cancer have low-risk, nonmetastatic intrathyroidal tumors smaller than 2 cm. Active surveillance has shown benefits in these patients, but the adoption of this approach remains below standard in Latin America.

Effect of body orientation and joint movement on local bioimpedance measurements.

The purpose of this pilot study was to determine if body orientation, skin treatment, joint angle, and shoulder arch movements affect localized bioimpedance spectroscopy (BIS) measurement. Nowadays, there are various wearable and portable impedance measurement tools in different shapes and sizes. Therefore, the body position and orientation of the subject during measurement may be of great importance for the comparability of the results.

Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.

Background: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

Methods: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study.

ShetlandsUAVmetry: unmanned aerial vehicle-based photogrammetric dataset for Antarctic environmental research.

The study of the functioning and responses of Antarctica to the current climate change scenario is a priority and a challenge for the scientific community aiming to predict and mitigate impacts at a regional and global scale. Due to the difficulty of obtaining aerial data in such extreme, remote, and difficult-to-reach region of the planet, the development of remote sensing techniques with Unmanned Aerial Vehicles (UAVs) has revolutionized polar research. ShetlandsUAVmetry comprises original datasets collected by UAVs during the Spanish Antarctic Campaign 2021-2022 (January to March 2022), along with the photogrammetric products resulting from their processing.

Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation-Effect of an Modifier Variant.

Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in over 300 genes. A single missense mutation (K42E) in the gene encoding the enzyme dehydrodolichyl diphosphate synthase (DHDDS), which is required for protein N-glycosylation in all cells and tissues, causes -IRD (retinitis pigmentosa type 59 (RP59; OMIM #613861)).

Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in 90-LCA: Replication in two eyes.

Purpose: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A > G variant in the gene. A previous report showed vision improvements following a single injection in one eye with unexpected durability lasting at least 15 months.

Color Vision in Blue Cone Monochromacy: Outcome Measures for a Clinical Trial.

Purpose: Blue cone monochromacy (BCM) is an X-linked retinopathy due to mutations in the OPN1LW/OPN1MW gene cluster. Symptoms include reduced visual acuity and disturbed color vision. We studied BCM color vision to determine outcome measures for future clinical trials.

Night vision restored in days after decades of congenital blindness.

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction We studied two patients with -LCA who were undergoing gene augmentation therapy.

Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial.

Purpose: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the () gene.

Design: Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.

Participants: A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses.

Mobility test to assess functional vision in dark-adapted patients with Leber congenital amaurosis.

Background: Inherited retinal degenerations (IRDs) affect daylight and night vision to different degrees. In the current work, we devise a method to quantify mobility under dark-adapted conditions in patients with severe childhood blindness due to Leber congenital amaurosis (LCA). Mobility thresholds from two different LCA genotypes are compared to dark-adapted vision measurements using the full-field stimulus test (FST), a conventional desktop outcome measure of rod vision.

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial.

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10.

Water quality monitoring with Sentinel-2 and Landsat-8 satellites during the 2021 volcanic eruption in La Palma (Canary Islands).

In this study, seawater quality was monitored with high-resolution satellite imagery during the 2021 volcanic eruption (September-December) on La Palma Island (Spain), the longest recorded in the history of the island, and the most destructive in the last century in Europe. The Sentinel-2A/B twin satellites and Landsat-8 satellite were jointly used as an optical constellation, which allowed us to successfully characterize the short- and medium-term evolution of the new lava delta and subsequent impact on the seawater. Robust atmospheric and sunglint correction approaches were applied to thoroughly quantify the environmental changes caused on the adjacent coastal waters.

Applications of unmanned aerial vehicles in Antarctic environmental research.

Antarctica plays a fundamental role in the Earth's climate, oceanic circulation and global ecosystem. It is a priority and a scientific challenge to understand its functioning and responses under different scenarios of global warming. However, extreme environmental conditions, seasonality and isolation hampers the efforts to achieve a comprehensive understanding of the physical, biological, chemical and geological processes taking place in Antarctica.

A Novel Gene Mutation Associated With Autosomal Dominant Retinal Degeneration.

Despite major progress in the discovery of causative genes, many individuals and families with inherited retinal degenerations (IRDs) remain without a molecular diagnosis. We applied whole exome sequencing to identify the genetic cause in a family with an autosomal dominant IRD. Eye examinations were performed and affected patients were studied with electroretinography and kinetic and chromatic static perimetry.

Macular Rod Function in Retinitis Pigmentosa Measured With Scotopic Microperimetry.

Purpose: To investigate the validity and reliability of macular rod photoreceptor function measurement with a microperimeter.

Methods: Macular sensitivity in dark-adapted retinitis pigmentosa (RP) patients (22 eyes; 9-67 years of age) and controls (five eyes; 22-55 years of age) was assessed with a modified Humphrey field analyzer (mHFA), as well as a scotopic microperimeter (Nidek MP-1S). Sensitivity loss (SL) was estimated at rod-mediated locations.

Full-field stimulus testing: Role in the clinic and as an outcome measure in clinical trials of severe childhood retinal disease.

Disease mechanisms have become better understood in previously incurable forms of early-onset severe retinal dystrophy, such as Leber congenital amaurosis (LCA). This has led to novel treatments and clinical trials that have shown some success. Standard methods to measure vision were difficult if not impossible to perform in severely affected patients with low vision and nystagmus.

Measures of Function and Structure to Determine Phenotypic Features, Natural History, and Treatment Outcomes in Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are at the forefront of innovative gene-specific treatments because of the causation by single genes, the availability of microsurgical access for treatment delivery, and the relative ease of quantitative imaging and vision measurement. However, it is not always easy to choose a priori, from scores of potential measures, an appropriate subset to evaluate efficacy outcomes considering the wide range of disease stages with different phenotypic features. This article reviews measurements of visual function and retinal structure that our group has used over the past three decades to understand the natural history of IRDs.

Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report.

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969 ) was studied for 15 months after a single intravitreal sepofarsen injection.

Leber Congenital Amaurosis Due to Mutations: Longitudinal Analysis of Retinal Structure and Visual Function.

Gene augmentation therapy is being planned for -associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of -LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and efficacy outcome measures previously determined to be useful for monitoring this disorder. In this group of molecularly-identified LCA patients ( = 10; ages 7-37 years at first visit), optical coherence tomography (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus.