To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular ...sensitivity losses in ABCA4 gene−associated Stargardt disease (STGD1).
This was a multicenter prospective cohort study.
Participants comprised 127 molecularly confirmed STGD1 patients enrolled from 6 centers in the United States and Europe and followed up every 6 months for up to 2 years.
The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°-10° eccentricity), and the MD for scotopic sensitivity for the extrafovea, were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. Main outcome measures were baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD.
At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (P < .001). Longitudinally, all eyes showed a statistically significant worsening trend: the rates of foveal mMD and extrafoveal mMD and sMD changes were 0.72 (95% CI = 0.37-1.07), 0.86 (95% CI = 0.58-1.14), and 1.12 (95% CI = 0.66-1.57) dB per year, respectively.
In STGD1, in extrafovea, loss of scotopic macular function preceded and was faster than the loss of mesopic macular function. Scotopic and mesopic macular sensitivities using microperimetry provide alternative visual function outcomes for STGD1 treatment trials.
To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical ...trials investigating the efficacy on retinal sensitivity.
Design: International, multicenter, prospective cohort study with 5 study visits every 6 months over 24 months. Participants: A total of 233 individuals with genetically confirmed STGD1 (≥1 disease-causing ABCA4 variant). Main Outcome Measures: The total volume (VTOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of VTOT over time and its correlation with the ABCA4 genotype and baseline features.
At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average VTOT of 0.91 decibel-steradian (dB-sr) and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity 95% confidence interval was 0.077 0.064, 0.090 dB-sr/y for VTOT and 0.87 0.72, 1.02 dB/year for MS. The progression rate of VTOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline VTOT; P < .001) and exhibited a difference in the first vs second year of follow-up (0.065 dB-sr/year vs 0.089 dB-sr/year, respectively; P < .001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (P < .001), whereas a significant association with the genotype was not detected (P = .7).
In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.
There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo ...investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.
To compare different metrics and acquisition modes of fixation stability as a new visual function biomarker in a large cohort of patients with ABCA4-related Stargardt disease from the multicenter ...prospective ProgStar study.
Fixation was tested during a separate fixation exam and also dynamically during a sensitivity exam, using fundus-tracking microperimetry (Nidek MP-1). Fixation data were analyzed using the bivariate contour ellipse area (BCEA), the 2/4 degree method, and the Fujii classification.
In a total of 235 patients, the mean BCEA was larger when measured during the sensitivity exam (418 eyes; 12.5 vs. 4.6 deg2 during the fixation task in 427 eyes). Correlations between the two tests were generally weak. Fixation stability during the sensitivity test was significantly correlated with visual acuity. Comparing the BCEA values and the corresponding Fujii categories for these eyes revealed ranges of overlap where an eye with one defined BCEA value can fall into each of the three Fujii categories.
Patients may have limited ability to fixate over defined time periods, which leads to significant differences between shorter and longer measurements of fixation stability. The most appropriate way to use this functional biomarker appears to be using continuous metrics for fixation stability, such as the BCEA, during a macular sensitivity test.
To evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed PROM1-associated retinal degeneration (RD) over a ...24-month period.
International, multicenter, prospective case series.
A total of 13 eyes (13 patients) affected with PROM1-associated RD were enrolled at 5 sites and SD-OCT images were obtained at baseline and after 24 months. Loss of mean thickness (MT) and intact area were estimated after semi-automated segmentation for the following individual retinal layers in the central subfield (CS), inner ring, and outer ring of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OS), inner segments (IS), outer nuclear layer (ONL), inner retina (IR), and total retina (TR).
Statistically significant losses of thickness of RPE and TR were detected in the CS and inner ring and of ONL and IS in the outer ring (all P < .05); a statistically significant decrease in the intact area of RPE and IS was observed in the inner ring, and of ONL in the outer ring (all P < .05); the change in MT and the intact area of the other layers showed a trend of decline over an observational period of 24 months.
Significant thickness losses could be detected in outer retinal layers by SD-OCT over a 24-month period in patients with PROM1-associated retinal degeneration. Loss of thickness and/or intact area of such layers may serve as potential endpoints for clinical trials that aim to slow down the disease progression of PROM1-associated retinal degeneration.
Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible ...manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe
GaTe
, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.
In this small study, investigators genetically disrupted the HIV receptor CCR5 in CD4 T cells of aviremic persons who were infected with HIV. After reinfusion and during viremia, the modified cells ...declined at a significantly slower rate than did the unmodified cells.
The ability to make site-specific modifications to (or “edit”) the human genome has been an objective in medicine since the recognition of the gene as the basic unit of heredity.
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The challenge of genome editing is the ability to generate a single double-strand break at a specific point in the DNA molecule. Numerous agents, including meganucleases, oligonucleotides that form DNA triplexes, and peptide nucleic acids, have been tested and shown to be limited by inefficiency.
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Another class of reagents, the zinc-finger nucleases (ZFNs), have proved versatile for genome editing, and the use of ZFNs is now well established . . .
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