154 research outputs found
Macular Pigment Distribution as Prognostic Marker for Disease Progression in Macular Telangiectasia Type 2
PURPOSE
To evaluate macular pigment distribution pattern as a prognostic marker for disease progression in patients with macular telangiectasia type 2 (MacTel).
DESIGN
Retrospective cohort study.
METHODS
In this single-center study, 90 eyes of 47 patients were analyzed. Macular pigment optical density (MPOD) was measured with dual-wavelength fundus autofluorescence. Eyes were graded into MPOD distribution classes 1 to 3 with increasing loss of macular pigment and grading was performed masked by 2 independent graders. Best-corrected visual acuity, reading acuity, total scotoma size in fundus-controlled perimetry (microperimetry), and break of the ellipsoid zone (EZ) in optical coherence tomography (en face measurement) were defined as functional and morphologic outcome parameters and evaluated at baseline and after 60 months.
RESULTS
After a mean review period of 59.6 months (±standard deviation 5.2 months), no change between MPOD classes was observed compared to baseline. Morphologic and functional deficits were limited to the area of MPOD loss. At last follow-up, a significant mean decrease of visual acuity and reading acuity as well as a significant mean increase of scotoma size and EZ break were observed in eyes assigned to MPOD classes 2 and 3, while outcome parameters remained stable in eyes of class 1.
CONCLUSIONS
The results indicate that MPOD and its distribution may serve as a prognostic marker for disease progression and functional impairment in patients with MacTel
Quantification of Retinal and Choriocapillaris Perfusion in Different Stages of Macular Telangiectasia Type 2
Purpose: To quantify the retinal and choriocapillaris perfusion in different disease stages of macular telangiectasia type 2 (MacTel) using optical coherence tomography-angiography (OCT-A). /
Methods: We examined 76 eyes of 76 patients and 24 eyes of 24 age-related controls. Participants underwent multimodal imaging, including OCT and OCT-A. Patients' eyes were divided into three groups considering predefined criteria from funduscopy, OCT, and fluorescein angiography, thus reflecting the disease severity (“early,” “advanced,” and “neovascular”). Quantitative analyses of vessel density (VD), skeleton density (SD), and fractal dimension (FD) were conducted in the superficial and deep retinal plexus and in the avascular layer. The choriocapillaris was analyzed for mean signal intensity and percentage of nondetectable perfused choriocapillaris-area (PNPA). /
Results: The deep retinal plexus showed a progressive decrease of mean VD, SD, and FD in the temporal parafovea in all disease stages. In the superficial layer, VD, SD, and FD were significantly decreased in the temporal parafovea of advanced and neovascular stages, while these parameters did not differ from controls in early stages. In MacTel, signals of blood flow were also detectable at the level of the avascular layer and showed a significant increase with disease progression. The choriocapillaris in MacTel showed a significant increase of mean PNPA and a decrease of mean signal intensity in comparison to controls. These findings were consistent in all disease stages. /
Conclusions: Quantitative OCT-A data show a progressive rarefication of the retinal microvasculature in MacTel. We propose an altered choriocapillaris perfusion as a possibly early alteration of the disease
Stereoscopic Vision in Macular Telangiectasia Type 2
PURPOSE: To investigate stereoscopic vision in patients with macular telangiectasia
type 2 and correlate a paracentral sensitivity loss to reduced stereoscopic function.
METHODS: In a prospective single-center study, 50 patients with macular
telangiectasia type 2 and 25 age-matched controls were investigated. Stereoscopic
function was evaluated with Lang I, Titmus and TNO-test. Sensitivity of the central
16° was tested using fundus-controlled perimetry (microperimetry). Functional loss
was quantified as depth, size and localization of scotomata.
RESULTS: Both Titmus and TNO-test revealed significantly reduced stereoscopic
vision in patients compared to controls (both, p<0.0001). This applied even to
patients with only relative or monocular paracentral scotomata. A strong correlation
was observed for reduced stereoscopic vision with horizontal scotoma size and with
the distance of scotomata from the foveal center.
CONCLUSIONS: The results indicate that stereoscopic vision is impaired early in
patients with MacTel type 2. A paracentral sensitivity loss, even if mild and limited to
one eye, may considerably interfere with stereoscopic function despite normal visual
acuity. Projection of paracentral scotomata within the patient`s central visual field
plays an important role in stereoscopic vision and should be considered when
interpreting stereoscopic test results
Macular telangiectasia type 2 - Visual acuity, disease endstage and the MacTel Area. MacTel Project Report No. 8
Purpose:
To report the visual acuity measures from the MacTel registry study and to investigate and describe phenotypic findings in eyes with substantial vision loss due to MacTel type 2
Design:
Cross-sectional multi-center study.
Subjects:
Participants of the Natural History Observation (and Registry) of MacTel Study.
Methods:
Best–corrected visual acuity (BCVA) data, retinal imaging data and clinical data were accessed from the MacTel study databases in May 2019.
Main Outcome Measures:
Frequency distribution of BCVA and its relation to age. Morphological changes in eyes with very late disease stages, defined by a BCVA ≤ 20/200. Average retinal thickness of ETDRS fields on OCT. Dimensions of the area affected by MacTel (MacTel area).
Results:
BCVA was ≤20/50 in 37.3% and ≤20/200 in 3.8% of 4449 eyes of 2248 patients. 18.4% and 0.7% of all patients had bilateral BCVA ≤20/50 and ≤20/200, respectively. There was an asymmetry between right and left eyes (median BCVA 71 versus 74 letters), a finding supported by more advanced morphological changes in right eyes. BCVA correlated with participant’s age, but the effect size was small. If a neovascularization or macular hole was present, bilateral occurrence was frequent (33% or 17%, respectively), and BCVA was >20/200 (79% or 78% respectively) or ≥20/50 (26% or 13%, respectively). Eyes with advanced disease (BCVA ≤20/200) showed the following characteristics: 1) Atrophy of the foveal photoreceptor layer with or without associated subretinal fibrosis; 2) an affected area, termed here the “MacTel area”, limited to a horizontal diameter not exceeding the distance between the temporal optic disc margin and foveal center, and the vertical diameter not exceeding approximately 0.85 times this distance. Exceptions were eyes with large active or inactive neovascular membranes; 3) reduced retinal thickness measures within the MacTel area; and 4) less frequent retinal greying and more frequent hyperpigmentations compared to eyes with better BCVA.
Conclusions:
Severe vision loss is rare in MacTel and is related to photoreceptor atrophy in most people. Results indicate disease asymmetry with slightly worse vision and more advanced disease manifestation in right eyes. MacTel-related neurodegeneration does not spread beyond the limits of the “MacTel area”
Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis
Objective
Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical outcomes.
Methods
An integrated analysis was conducted by pooling data from 3 completed phase III trials comparing placebo with baricitinib treatment (RA‐BEAM, RA‐BUILD, and RA‐BEACON) and 1 ongoing long‐term extension study (RA‐BEYOND) in patients with active RA (n = 2,186).
Results
Baricitinib treatment was associated with an early transient increase in total lymphocyte count at week 4, which returned to baseline by week 12. Transient changes within normal reference ranges in T cells and subsets were observed with baricitinib treatment, up to week 104. B cells and relevant subpopulations increased after 4 weeks of baricitinib treatment, with no further increases noted through 104 weeks of treatment. Natural killer (NK) cells temporarily increased after 4 weeks of baricitinib treatment, before decreasing below baseline levels and then stabilizing over time. With baricitinib treatment, few correlations were observed between changes in lymphocyte subsets and clinical end points, and most correlations were also observed within the placebo group. A modest potential association between low NK cell numbers and treatment‐emergent infections was observed in the baricitinib 4 mg/day treatment group, but not for serious infections or herpes zoster.
Conclusion
Overall, these findings demonstrate that changes in lymphocyte subsets were largely within normal reference ranges across the baricitinib phase III RA clinical program and were not associated with increased risk of serious infections
Coordinated optimization of visual cortical maps (I) Symmetry-based analysis
In the primary visual cortex of primates and carnivores, functional
architecture can be characterized by maps of various stimulus features such as
orientation preference (OP), ocular dominance (OD), and spatial frequency. It
is a long-standing question in theoretical neuroscience whether the observed
maps should be interpreted as optima of a specific energy functional that
summarizes the design principles of cortical functional architecture. A
rigorous evaluation of this optimization hypothesis is particularly demanded by
recent evidence that the functional architecture of OP columns precisely
follows species invariant quantitative laws. Because it would be desirable to
infer the form of such an optimization principle from the biological data, the
optimization approach to explain cortical functional architecture raises the
following questions: i) What are the genuine ground states of candidate energy
functionals and how can they be calculated with precision and rigor? ii) How do
differences in candidate optimization principles impact on the predicted map
structure and conversely what can be learned about an hypothetical underlying
optimization principle from observations on map structure? iii) Is there a way
to analyze the coordinated organization of cortical maps predicted by
optimization principles in general? To answer these questions we developed a
general dynamical systems approach to the combined optimization of visual
cortical maps of OP and another scalar feature such as OD or spatial frequency
preference.Comment: 90 pages, 16 figure
Hyperbolic planforms in relation to visual edges and textures perception
We propose to use bifurcation theory and pattern formation as theoretical
probes for various hypotheses about the neural organization of the brain. This
allows us to make predictions about the kinds of patterns that should be
observed in the activity of real brains through, e.g. optical imaging, and
opens the door to the design of experiments to test these hypotheses. We study
the specific problem of visual edges and textures perception and suggest that
these features may be represented at the population level in the visual cortex
as a specific second-order tensor, the structure tensor, perhaps within a
hypercolumn. We then extend the classical ring model to this case and show that
its natural framework is the non-Euclidean hyperbolic geometry. This brings in
the beautiful structure of its group of isometries and certain of its subgroups
which have a direct interpretation in terms of the organization of the neural
populations that are assumed to encode the structure tensor. By studying the
bifurcations of the solutions of the structure tensor equations, the analog of
the classical Wilson and Cowan equations, under the assumption of invariance
with respect to the action of these subgroups, we predict the appearance of
characteristic patterns. These patterns can be described by what we call
hyperbolic or H-planforms that are reminiscent of Euclidean planar waves and of
the planforms that were used in [1, 2] to account for some visual
hallucinations. If these patterns could be observed through brain imaging
techniques they would reveal the built-in or acquired invariance of the neural
organization to the action of the corresponding subgroups.Comment: 34 pages, 11 figures, 2 table
Reversibility of liver fibrosis
Liver fibrosis, and its end stage cirrhosis are a major cause of morbidity and mortality and therapeutic options are limited. However, the traditional view of liver disease as an irreversible process is obsolete and it is now evident that the development of liver fibrosis is a dynamic and potentially bidirectional process. Spontaneous resolution of scarring is seen in animal models of liver fibrosis and in human trials in which the stimuli responsible for chronic or repeated hepatic inflammation is successfully removed. Key players in the process are hepatic stellate cells, macrophages, MMPs and their inhibitors Timps. It is also evident that in advanced fibrotic liver disease, specific histological features define what is currently described as "irreversible" fibrosis. This includes the development of paucicellular scars enriched in extensively cross-linked matrix components, such as fibrillar collagen and elastin. Our recent work has focused on the role of macrophage metalloelastase (MMP-12) in the turnover of elastin in reversible and irreversible models of fibrosis. We have shown that elastin turnover in liver injury and fibrosis is regulated by macrophages via Mmp-12 expression, activity and ratio to its inhibitor Timp-1. Failure of elastin degradation, together with increased deposition leads to accumulation of elastin in the fibrotic scars
Coordinated optimization of visual cortical maps (II) Numerical studies
It is an attractive hypothesis that the spatial structure of visual cortical
architecture can be explained by the coordinated optimization of multiple
visual cortical maps representing orientation preference (OP), ocular dominance
(OD), spatial frequency, or direction preference. In part (I) of this study we
defined a class of analytically tractable coordinated optimization models and
solved representative examples in which a spatially complex organization of the
orientation preference map is induced by inter-map interactions. We found that
attractor solutions near symmetry breaking threshold predict a highly ordered
map layout and require a substantial OD bias for OP pinwheel stabilization.
Here we examine in numerical simulations whether such models exhibit
biologically more realistic spatially irregular solutions at a finite distance
from threshold and when transients towards attractor states are considered. We
also examine whether model behavior qualitatively changes when the spatial
periodicities of the two maps are detuned and when considering more than 2
feature dimensions. Our numerical results support the view that neither minimal
energy states nor intermediate transient states of our coordinated optimization
models successfully explain the spatially irregular architecture of the visual
cortex. We discuss several alternative scenarios and additional factors that
may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with
arXiv:1102.335
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