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

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

Photoreceptor Function and Structure in Autosomal Dominant Vitelliform Macular Dystrophy Caused by BEST1 Mutations.

Purpose: The purpose of this study was to evaluate rod and cone function and outer retinal structure within macular lesions, and surrounding extralesional areas of patients with autosomal dominant Best vitelliform macular dystrophy caused by BEST1 mutations.

Methods: Seventeen patients from seven families were examined with dark- and light-adapted chromatic perimetry and optical coherence tomography. Subsets of patients had long-term follow-up (14-22 years, n = 6) and dark-adaptation kinetics measured (n = 5).

Photoreceptor function and structure in retinal degenerations caused by biallelic BEST1 mutations.

The only approved retinal gene therapy is for biallelic RPE65 mutations which cause a recessive retinopathy with a primary molecular defect located at the retinal pigment epithelium (RPE). For a distinct recessive RPE disease caused by biallelic BEST1 mutations, a pre-clinical proof-of-concept for gene therapy has been demonstrated in canine eyes. The current study was undertaken to consider potential outcome measures for a BEST1 clinical trial in patients demonstrating a classic autosomal recessive bestrophinopathy (ARB) phenotype.

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.

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.

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.

Reduced fixation stability induced by peripheral viewing does not contribute to crowding.

Attending to peripheral visual targets while maintaining central fixation, a process that involves covert attention, reduces fixation stability. Here, we tested the hypothesis that changes in fixation stability induced by peripheral viewing contribute to crowding in peripheral vision by increasing positional uncertainty. We first assessed whether fixation was less stable during peripheral versus central (foveal) viewing for both crowded and uncrowded stimuli.

Assessing Binocular Central Visual Field and Binocular Eye Movements in a Dichoptic Viewing Condition.

Macular degeneration typically results in heterogeneous binocular central visual defects. Currently available approaches to assess central visual field, like the microperimetry, can test only one eye at a time. Therefore, they cannot explain how the defects in each eye affect the binocular interaction and real-world function.

Transient pupillary light reflex in CEP290- or NPHP5-associated Leber congenital amaurosis: Latency as a potential outcome measure of cone function.

Mutations in photoreceptor cilium genes CEP290 and NPHP5 cause a form of Leber congenital amaurosis (LCA) which typically lacks rods but retains central cones. The current study evaluated the transient pupillary light reflex (TPLR) as an objective outcome measure to assess efficacy of ongoing and future therapies. Eleven eyes of six patients selected for retained cone function were tested with TPLR using full-field stimuli in the dark-adapted state.

Treatment Potential for Macular Cone Vision in Leber Congenital Amaurosis Due to CEP290 or NPHP5 Mutations: Predictions From Artificial Intelligence.

Purpose: To use supervised machine learning to predict visual function from retinal structure in retinitis pigmentosa (RP) and apply these estimates to CEP290- and NPHP5-associated Leber congenital amaurosis (LCA) to determine the potential for functional improvement.

Methods: Patients with RP (n = 20) and LCA due to CEP290 (n = 12) or NPHP5 (n = 6) mutations were studied. A patient with CEP290 mutations but mild retinal degeneration was included.

Electrocardiogram-guided Technique: An Alternative Method for Confirming Central Venous Catheter Tip Placement.

Background: The current standard followed for assessing central venous catheter (CVC) tip placement location is through radiological confirmation using chest X-ray (CXR). Placement of CVCs under electrocardiogram (ECG) guidance may save cost and time compared to CXR.

Objective: The objective of this study is to compare the accurate placement of the CVC tip using anatomical landmark technique with ECG-guided technique.

Impact of simulated micro-scotomas on reading performance in central and peripheral retina.

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field.

Functional changes at the preferred retinal locus in subjects with bilateral central vision loss.

Purpose: Subjects with bilateral central vision loss (CVL) use a retinal region called the preferred retinal locus (PRL) for performing various visual tasks. We probed the fixation PRL in individuals with bilateral macular disease, including age-related macular degeneration (AMD) and Stargardt disease (STGD), for localized sensitivity deficits.

Methods: Three letter words at the critical print size were presented in the NIDEK MP-1 microperimeter to determine the fixation PRL and its radial retinal eccentricity from the residual fovea in 29 subjects with bilateral CVL.