Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline

Background: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) A f42 (A) and tau (T) ratio. Methods: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. Results: Mean age (\ub1 standard deviation) in the CH-PAT group (n = 27; 75.2 \ub1 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 \ub1 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) \u3bcm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. Conclusions: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology

Choroidal thickness and the retinal ganglion cell complex in chronic Leberʼs hereditary optic neuropathy: a prospective study using swept-source optical coherence tomography

Background/Objectives: Choroidal thinning has been suggested in Leber�s hereditary optic neuropathy (LHON). No study has been conducted of the choroid in relation to the retinal ganglion cell-inner plexiform layer (RGC-IPL). We sought to measure choroidal thickness in chronic LHON and to correlate thickness changes with the RGC-IPL. Subjects/Methods: Chronic LHON, 11778 mitochondrial DNA (mtDNA) mutation, patients (26 eyes; mean age: 35.1 ± 16.1 years) were prospectively recruited at Doheny Eye Center, University of California Los Angeles from March 2016 to July 2017. Age-matched healthy controls (27 eyes; mean age: 32.4 ± 11.1 years) were enroled for comparison. Swept-source optical coherence tomography (SS-OCT) imaging was performed in chronic LHON patients and compared with age-matched healthy controls. Results: The macular choroid was significantly thinner in chronic LHON (250.5 ± 62.2 μm) compared with controls (313.9 ± 60.2 μm; p < 0.0001). The peripapillary choroid was also significantly thinner in chronic LHON (135.7 ± 51.4 μm) compared with controls (183.0 ± 61.8 μm, p < 0.001). Choroidal thickness strongly correlated with retinal nerve fibre layer (RNFL) thickness in both the macular (R2 = 0.72; 95 CI, 0.57�0.84) and peripapillary regions (R2 = 0.53; 95 CI, 0.31�0.70). Choroidal thickness was also significantly correlated with macular RGC-IPL thickness (R2 = 0.51; 95 CI, 0.26�0.73). Conclusions: Choroidal thinning in chronic LHON correlated strongly with both RNFL and RGC-IPL thicknesses. These findings may suggest a pathophysiological mechanism involving vascular pathology of the choroid in relation to the retinal ganglion cell complex in LHON. © 2019, The Author(s), under exclusive licence to The Royal College of Ophthalmologists

Changes in Choroidal Thickness follow the RNFL Changes in Leber's Hereditary Optic Neuropathy

Leber's hereditary optic neuropathy (LHON) is typically characterized by vascular alterations in the acute phase. The aim of this study was to evaluate choroidal changes occurring in asymptomatic, acute and chronic stages of LHON. We enrolled 49 patients with LHON, 19 with Dominant Optic Atrophy (DOA) and 22 healthy controls. Spectral Domain-Optical Coherence Tomography (SD-OCT) scans of macular and peripapillary regions were performed in all subjects, to evaluate macular and peripapillary choroidal thickness, and retinal nerve fiber layer (RNFL) thicknes. Macular and peripapillary choroidal thicknesses were significantly increased in the acute LHON stage. On the contrary, macular choroidal thickness was significantly reduced in the chronic stage. Furthermore, peripapillary choroidal thickness was decreased in chronic LHON and in DOA. Both RNFL and choroid had the same trend (increased thickness, followed by thinning), but RNFL changes preceded those affecting the choroid. In conclusion, our study quantitatively demonstrated the involvement of the choroid in LHON pathology. The increase in choroidal thickness is a feature of the LHON acute stage, which follows the thickening of RNFL. Conversely, thinning of the choroid is the common outcome in chronic LHON and in DOA

Multiwavelength behaviour of the blazar 3C 279: Decade-long study from γ -ray to radio

We report the results of decade-long (2008-2018) γ -ray to 1 GHz radio monitoring of the blazar 3C 279, including GASP/WEBT, Fermi and Swift data, as well as polarimetric and spectroscopic data. The X-ray and γ -ray light curves correlate well, with no delay ≳ 3 h, implying general cospatiality of the emission regions. The γ -ray-optical flux-flux relation changes with activity state, ranging from a linear to amore complex dependence. The behaviour of the Stokes parameters at optical and radio wavelengths, including 43 GHz Very Long Baseline Array images, supports either a predominantly helical magnetic field or motion of the radiating plasma along a spiral path. Apparent speeds of emission knots range from 10 to 37c, with the highest values requiring bulk Lorentz factors close to those needed to explain γ -ray variability on very short time-scales. The MgII emission line flux in the 'blue' and 'red' wings correlates with the optical synchrotron continuum flux density, possibly providing a variable source of seed photons for inverse Compton scattering. In the radio bands, we find progressive delays of the most prominent light-curve maxima with decreasing frequency, as expected from the frequency dependence of the τ= 1 surface of synchrotron self-absorption. The global maximum in the 86 GHz light curve becomes less prominent at lower frequencies, while a local maximum, appearing in 2014, strengthens toward decreasing frequencies, becoming pronounced at ∼5 GHz. These tendencies suggest different Doppler boosting of stratified radio-emitting zones in the jet. © 2020 The Author(s).We thank the referee for attentive reading and comments that helped to improve presentation of the manuscript. The data collected by the WEBT collaboration are stored in the WEBT archive at the Osservatorio Astrofisico di Torino -INAF (ht tp://www.oato.inaf.it/blazars/webt/); for questions regarding their availability, please contact the WEBT President Massimo Villata([email protected]).TheSt.Petersburg University team acknowledges support from Russian Science Foundation grant 17-12-01029. The research at BU was supported in part by National Science Foundation grant AST-1615796 and NASA Fermi Guest Investigator grants 80NSSC17K0649, 80NSSC19K1504, and 80NSSC19K1505. The PRISM camera at Lowell Observatory was developed by K. Janes et al. at BU and Lowell Observatory, with funding from the NSF, BU, and Lowell Observatory. The emission-line observations made use of the DCT at Lowell Observatory, supported by Discovery Communications, Inc., BU, the University of Maryland, the University of Toledo, and Northern Arizona University. The VLBA is an instrument of the National Radio Astronomy Observatory. The National Radio Astronomy Observatory is a facility of the US NSF, operated under cooperative agreement by Associated Universities, Inc. This research has used data from the UMRAO which was supported by the University of Michigan; research at this facility was supported by NASA under awards NNX09AU16G, NNX10AP16G, NNX11AO13G, and NNX13AP18G, and by the NSF under award AST-0607523. The Steward Observatory spectropolarimetric monitoring project was supported by NASA Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G, and NNX15AU81G. The Torino group acknowledges financial contribution from agreement ASI-INAF n.2017-14-H.0 and from contract PRIN-SKA-CTA-INAF 2016. I.A. acknowledges support by a Ramon y Cajal grant (RYC-2013-14511) of the 'Ministerio de Ciencia, Innovacion, y Universidades (MICIU)' of Spain and from MCIU through the 'Center of Excellence Severo Ochoa' award for the Instituto de Astrofisica de Andalucia-CSIC (SEV-20170709). Acquisition and reduction of the POLAMI and MAPCAT data were supported by MICIU through grant AYA2016-80889-P. The POLAMI observations were carried out at the IRAM 30-m Telescope, supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). The MAPCAT observations were carried out at theGerman-Spanish Calar Alto Observatory, jointly operated by the Max-Plank-Institut fur Astronomie and the Instituto de Astrofisica de Andalucia-CSIC. The study is based partly on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC. The OVRO 40-m monitoring program is supported in part by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G, and NSF grants AST-0808050 and AST-1109911. TH was supported by the Academy of Finland projects 317383 and 320085. AZT-24 observations were made within an agreement between Pulkovo, Rome and Teramo observatories. The Submillimeter Array is a joint project between the Smithsonian Astrophysical Observatory and the Academia Sinica Institute of Astronomy and Astrophysics and is funded by the Smithsonian Institution and the Academia Sinica. The Abastumani team acknowledges financial support by the Shota Rustaveli National Science Foundation under contract FR/217950/16. r This research was partially supported by the Bulgarian National Science Fund of the Ministry of Education and Science under grants DN 081/2016, DN 18-13/2017, KP-06-H28/3 (2018), and KP-06-PN38/1 (2019), Bulgarian National Science Programme 'Young Scientists and Postdoctoral Students 2019', Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Projects DO1-157/28.08.2018 and DO1-153/28.08.2018 of the Ministry of Education and Science of the Republic of Bulgaria. GD and OV gratefully acknowledge observing grant support from the Institute of Astronomy and Rozhen National Astronomical Observatory via bilateral joint research project `Study of ICRF radio-sources and fast variable astronomical objects' (head -G. Damljanovic). This work was partly supported by the National Science Fund of the Ministry of Education and Science of Bulgaria under grant DN 08-20/2016, and by project RD-08-37/2019 of the University of Shumen. This work is a part of projects nos 176011, 176004, and 176021, supported by theMinistry of Education, Science and Technological Development of the Republic of Serbia. MGM acknowledges support through the Russian Government Program of Competitive Growth of Kazan Federal University. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the 'Unite des Communes vald 'otainesMont-Emilius'. The research at the OAVdA was partially funded by several `Research and Education' annual grants from Fondazione CRT. This article is partly based on observations made with the IAC80 and TCS telescopes operated by the Instituto de Astrofisica de Canarias in the Spanish Observatorio del Teide on the island of Tenerife. A part of the observations were carried out using theRATAN-600 scientific equipment (SAO of the Russian Academy of Sciences)

Multiwavelength behaviour of the blazar 3C 279: decade-long study from γ-ray to radio

We report the results of decade-long (2008–2018) γ-ray to 1 GHz radio monitoring of the blazar 3C 279, including GASP/WEBT, Fermi and Swift data, as well as polarimetric and spectroscopic data. The X-ray and γ-ray light curves correlate well, with no delay ≳ 3 h, implying general cospatiality of the emission regions. The γ-ray–optical flux–flux relation changes with activity state, ranging from a linear to a more complex dependence. The behaviour of the Stokes parameters at optical and radio wavelengths, including 43 GHz Very Long Baseline Array images, supports either a predominantly helical magnetic field or motion of the radiating plasma along a spiral path. Apparent speeds of emission knots range from 10 to 37c, with the highest values requiring bulk Lorentz factors close to those needed to explain γ-ray variability on very short time-scales. The Mg ii emission line flux in the ‘blue’ and ‘red’ wings correlates with the optical synchrotron continuum flux density, possibly providing a variable source of seed photons for inverse Compton scattering. In the radio bands, we find progressive delays of the most prominent light-curve maxima with decreasing frequency, as expected from the frequency dependence of the τ = 1 surface of synchrotron self-absorption. The global maximum in the 86 GHz light curve becomes less prominent at lower frequencies, while a local maximum, appearing in 2014, strengthens toward decreasing frequencies, becoming pronounced at ∼5 GHz. These tendencies suggest different Doppler boosting of stratified radio-emitting zones in the jet.First author draf

The correlated optical and radio variability of BL Lacertae - WEBT data analysis 1994-2005

Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968-2003) revealed a fair optical-radio correlation in 1994-2003, with a delay of the hard radio events of ~100 days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8 years. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results. In this campaign we have collected and assembled about 11000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200-300 days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the "period" seems to progressively lengthen from 7.4 to 9.3 years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) ca

The high activity of 3C 454.3 in autumn 2007: Monitoring by the WEBT during the AGILE detection

The quasar-type blazar 3C 454.3 underwent a phase of high activity in summer and autumn 2007, which was intensively monitored in the radio-to-optical bands by the Whole Earth Blazar Telescope (WEBT). The gamma-ray satellite AGILE detected this source first in late July, and then in November-December 2007. In this letter we present the multifrequency data collected by the WEBT and collaborators during the second AGILE observing period, complemented by a few contemporaneous data from UVOT onboard the Swift satellite. The aim is to trace in detail the behaviour of the synchrotron emission from the blazar jet, and to investigate the contribution from the thermal emission component. Optical data from about twenty telescopes have been homogeneously calibrated and carefully assembled to construct an R-band light curve containing about 1340 data points in 42 days. This extremely well-sampled optical light curve allows us to follow the dramatic flux variability of the source in detail. In addition, we show radio-to-UV spectral energy distributions (SEDs) at different epochs, which represent different brightness levels. In the considered period, the source varied by 2.6 mag in a couple of weeks in the R band. Many episodes of fast (i.e. intranight) variability were observed, most notably on December 12, when a flux increase of about 1.1 mag in 1.5 hours was detected, followed by a steep decrease of about 1.2 mag in 1 hour. The contribution by the thermal component is difficult to assess, due to the uncertainties in the Galactic, and possibly also intrinsic, extinction in the UV band. However, polynomial fitting of radio-to-UV SEDs reveals an increasing spectral bending going towards fainter states, suggesting a UV excess likely due to the thermal emission from the accretion disc

Multiwavelength observations of 3C 454.3. III. Eighteen months of agile monitoring of the "crazy diamond"

We report on 18 months of multiwavelength observations of the blazar 3C 454.3 (Crazy Diamond) carried out in the period 2007 July-2009 January. In particular, we show the results of the AGILE campaigns which took place on 2008 May-June, 2008 July-August, and 2008 October-2009 January. During the 2008 May-2009 January period, the source average flux was highly variable, with a clear fading trend toward the end of the period, from an average γ-ray flux F E>100 MeV ≳ 200 × 10-8photonscm -2s-1 in 2008 May-June, to F E>100 MeV 80 × 10-8photonscm-2s-1 in 2008 October-2009 January. The average γ-ray spectrum between 100 MeV and 1 GeV can be fit by a simple power law, showing a moderate softening (from ΓGRID ∼ 2.0 to ΓGRID ∼ 2.2) toward the end of the observing campaign. Only 3σ upper limits can be derived in the 20-60 keV energy band with Super-AGILE, because the source was considerably off-axis during the whole time period. In 2007 July-August and 2008 May-June, 3C 454.3 was monitored by Rossi X-ray Timing Explorer (RXTE). The RXTE/Proportional Counter Array (PCA) light curve in the 3-20 keV energy band shows variability correlated with the γ-ray one. The RXTE/PCA average flux during the two time periods is F 3-20 keV = 8.4 × 10-11ergcm-2s -1, and F 3-20 keV = 4.5 × 10 -11ergcm-2s-1, respectively, while the spectrum (a power law with photon index ΓPCA = 1.65 0.02) does not show any significant variability. Consistent results are obtained with the analysis of the RXTE/High-Energy X-Ray Timing Experiment quasi-simultaneous data. We also carried out simultaneous Swift observations during all AGILE campaigns. Swift/XRT detected 3C 454.3 with an observed flux in the 2-10 keV energy band in the range (0.9-7.5) × 10-11ergcm-2s-1 and a photon index in the range ΓXRT = 1.33-2.04. In the 15-150 keV energy band, when detected, the source has an average flux of about 5mCrab. GASP-WEBT monitored 3C 454.3 during the whole 2007-2008 period in the radio, millimeter, near-IR, and optical bands. The observations show an extremely variable behavior at all frequencies, with flux peaks almost simultaneous with those at higher energies. A correlation analysis between the optical and the γ-ray fluxes shows that the γ-optical correlation occurs with a time lag of τ = -0.4+0.6-0.8 days, consistent with previous findings for this source. An analysis of 15 GHz and 43 GHz VLBI core radio flux observations in the period 2007 July-2009 February shows an increasing trend of the core radio flux, anti-correlated with the higher frequency data, allowing us to derive the value of the source magnetic field. Finally, the modeling of the broadband spectral energy distributions for the still unpublished data, and the behavior of the long-term light curves in different energy bands, allow us to compare the jet properties during different emission states, and to study the geometrical properties of the jet on a time-span longer than one year. © 2010. The American Astronomical Society. All rights reserved